Alzheimer's Club

To Gemma. In memory of Mark

2010-12-28T22:46:00.002+02:00

Produced on December 28, 2010, Mark's Day 9.

Side bar Eulogy for Mark Smith by George Perry, Wenquan Zou, and an excerpt of memories by Nate Berger is accompanied by Alex Koudinov love song on melody of not recorded song "Grown old with you" by John Lennon. Russian lyrics was written in 4+10 minutes on 8 and 11 October 2010. The song was originally dedicated to Alex Koudinov children, brothers, sister, a woman, and John Lennon 70th Birthday, and written for a sister (all, thanks God, are doing well), and is now re-dedicated to Gemma in memory of Mark. Translation of lyrics into English is provided at the end of this video clip. Sound Recording virtually made via software programming at Abbey Road Studio 1, London. To experience the sound of a listener in a studio, please download surround edition of the song. Surround sound 5.1 is available for download as Dolby Digital 5.1, 6 channel .wav or 6 channel .wma files, the link for a free VLC player is provided
http://surround.rusradio.me

Please visit Journal of Alzheimer's disease memorial web page In Memory: Mark A. Smith at
http://www.j-alz.com/marksmith.html to read Mark's guestbook memories by friends and colleagues.

In memory: Mark Smith, 1965 - 2010

2010-12-24T17:33:00.005+02:00

by Alexei Koudinov, MD, PhD, DrSci

3D tagged/enabled video at youtube

How to view 3D video?

To view the video above please use 3D glasses. Otherwise, push 3D buttom (to appear after the playback start) at right of youtube player navigation bar to explore other viewing options.

I recommend, however, using 3D video below, programmed for viewing with no 3D red/green glasses (this video has no 3D tag and is intended to be viewed with no 3D glasses). I find this is not tiring for eyes and of brighter colors. The player below is of smaller size then standard youtube player, as it is more appropriate to easy catch 3D image for my eyes.

Stereographic video below has two separate image fields arranged side-by-side. The user is required to force his or her eyes either to cross, or to diverge, so that the two images appear to be three. Then as each eye sees a different image, the effect of depth is achieved in the central image of the three. It may take certain time to "see" a 3D image. Please don't "focus" on either video images, look ahead (beyond the screen) at the center, it takes less then a second for me to see 3D video at the player below:

3D video with no Youtube 3D tag enabled

Sound Recording and 3D motion pictures of 23 December 2010 5PM Jerusalem time by Alexei Koudinov. Melody by Tomaso Albinone, Adagio in G Minor. Candle is from Golgoga of the Holy Sepulture Church, Jerusalem.

Quoting Alzforum.org news of 21 December 2010:

"As shocked researchers notify each other privately, the Alzforum editors are saddened to inform the community at large that Mark Smith died last Sunday.

According to the Cleveland Plain Dealer, Smith, a prolific and outspoken researcher on Alzheimer’s disease and the biology of aging, was walking home at about 2 a.m. from an early Christmas party at a local tavern, when a man, who had apparently been at the tavern as well that night, struck him from behind and left the scene. Another motorist noticed the body of a man lying in the road, notified the police, and Smith was pronounced dead at a local hospital shortly thereafter. Incredibly, the driver was later found dead in his home or his car, according to various early news reports (see, e.g., The News-Herald). Police are investigating.

Mark Smith was well known to Alzforum readers. Starting in 2002, he became a frequent commentator and co-led ARF Live discussions as early as 1999.

Born in 1965, Smith grew up in England, trained there and in Vienna, Austria, and then began his U.S. career with a postdoctoral position in 1992 in the lab of George Perry at Case Western Reserve University in Cleveland, Ohio. Smith rose through the ranks at Case Western, where he was professor of pathology. In 2006, Perry moved on to become dean at the University of Texas at San Antonio, but the two continued to work together closely. “We exchanged 20 e-mails per day and spoke daily on the phone, the last time Friday,” said Perry.

Smith and Perry coauthored some 500 papers and shared the work of editor-in-chief of the Journal of Alzheimer’s Disease. They co-edited, with Jesus Avila and June Kinoshita, the centennial book Alzheimer’s Disease, A Century of Scientific and Clinical Research, IOS Press, 1996. “Mark and I were indistinguishable in many ways. We worked on everything together,” said Perry. Indeed, a follow-up to this book, chronicling the major discoveries in AD research in the years since 1996, is already in planning; Perry will dedicate it to Smith.

Smith’s main contributions to the understanding of Alzheimer’s disease lie in the areas of oxidative stress and the cell cycle...

Also see: alzforum.org | j-alz.com

...to be continued with personal address to Mark

Mark Smith, 45, Is Struck and Killed by Hit-and-Run Driver

2010-12-21T14:36:00.005+02:00

Original article: World-renowned researcher fatally struck while walking, driver found dead. 19ActionNews.com (20 December 2010) [FullText | Video]

Also see another 5ABC News video: WEWS News Staff. Alzheimer’s researcher, Case Western Reserve University professor mourned around world: Wife wants professor remembered as true scientist (21 December 2010) [Video]

BAINBRIDGE TOWNSHIP, OH (WOIO) - An investigation is underway after a deadly hit and run accident.

19 Action News has learned that Dr. Mark A. Smith, a well-respected and world renowned researcher, was walking Eastbound on Chagrin Road shortly after 2AM Sunday when he was struck by a vehicle.

The 45-year-old Bainbridge Township father of two was rushed to the Solon Medical Campus, where he was pronounced death.

Police found the car that fatally struck Dr. Smith a short time later on Ober Lane in Bainbridge Township. The driver of the car, 50-year-old Daniel V. Neesham, was found death at his home.

The Bainbridge Police Department has no conclusion on cause of death for either person and the cause of the accident is still being investigated. Investigators are waiting on toxicology and autopsy reports before they can determine a cause of death for the men.

Why there is no cure for Alzheimer's disease?

2010-11-10T14:21:00.001+02:00

Based on Society for Neuroscience Ethics in Neurosciences Abstract 2010:

Koudinov, Alexei. Why ethical and policy issues topic of the Society for Neuroscience annual meetings is overdue? Program No. 28.4. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Available online at abstractsonline.com

Neuroscience is a human activity that has lots of features only insiders can talk about with confidence. While general public may consider science is a privilege of those with high IQ, for many behind a university campus wall (or commercial lab secrecy) it is a matter of surviving, battling for funds, lab space, equipment access, and tenure. It is so great to have a confidence you are set up until a pension age. It was long time ago that you had a scientific quest excitement and late night lab hours of experimentation. Surely, you built your research on the data by others, heavily quoted a field leader, prominent Professor of the national premier research center you dreamed about as a postdoc or a faculty member. You could not know that this Professor had industry appointments and that he sold his million dollar stock shortly before the clinical trial on devastating human brain disorder failed (1). Well, you thought this failure could be a failure of the major theory of the disease. But who cares? A number of years ago you read an article in the Wall Street Journal (2) that called this theory a dogma retarding the development of the true disease cure. Would it be practical to you to combat the field corruption? Can one be a warrior? The natural answer for you as an ordinary human being is not: NOT at a postdoc time, because otherwise who of the field leadership would say “yes” to your tenure promotion and approval? NOT now (when you are a senior professor) because you have so many ties. Our World is in fact small, so, you take your tenure/grants as a fragile substance and prefer to be not so loud. You recall five years ago or so British Parliament published written evidence, a fact based encyclopedia of the corruption in your research field (3). But its’ impact is remote, as no one wants to take ethical issues seriously or talk on them openly. Several no-response open statements by a caring scientist to US Office of Research Integrity ORI, SEC and British Office of Fair Trading are all examples that in neurosciences patients are forgotten, commercial interests or one’s Ego are ruling (1). Well, you hope the SFN takes a leadership by introducing new annual meeting topic of Ethical issues in Neurosciences, and that as of now evidence based facts of wrongdoing will be not that easy to hide. Openness means change for good. Good in science means public non-private interest in scientific findings.

References:

1. http://business.timesonline.co.uk/tol/business/article1017839.ece
2. http://neurobiologyoflipids.org/editors/alexeikoudinov/pdfdocs/submittedletters/koudinov2wsj23april04.html
3. http://www.publications.parliament.uk/pa/cm200304/cmselect/cmsctech/399/399we125.htm
4. http://twitter.com/alzforum

Eli Lilly drug Semagacestat failure means amyloid theory of Alzheimer's disease is a bankrupt

2010-09-06T11:39:00.004+03:00

Dr. Bill E. Beckwith. Memory Minute: Drug failure casts doubt on Alzheimer’s theory. Naplesnews.com (25 Aug 2010)

Excerpt: Do we really have a breakthrough in diagnosis and treatment of Alzheimer’s disease? In our desperation for a cure, we have gotten ahead of biology and cast all of our hopes on the amyloid hypothesis ignoring the complexity of Alzheimer’s disease.

The amyloid hypothesis drives a multitude of clinical trials currently underway by pharmaceutical companies to find the cure for Alzheimer’s disease. Simply stated, the hypothesis proposes that build up of beta amyloid, an abnormal protein in the brain, is the cause of Alzheimer’s disease. Hence, treatments are sought that either stop or reverse the production of amyloid proteins in the brain. One of the medications under investigation was semagacestat, a drug developed by Lilly Pharmaceuticals.

The trials had advanced to the point where there were 2,600 patients enrolled in the clinical trials comparing semagacestat with a placebo. This medication attacks the abnormal amyloid. In theory, this is a good thing. However, the trials were terminated because the results indicated (1) that the medication did not slow the disease as expected, (2) the medication made cognition worse, and (3) the medication made treated patients less able to care for their personal needs. This led to many commentaries defending the amyloid hypothesis despite this important failure. This is a natural reaction to information that goes contrary to one’s beliefs. We regroup and find new ways to support our belief and minimize or ignore contrary evidence.

But in this case, the failure of semagacestat should cast doubt on the amyloid theory. We need to pursue the science behind this theory and its failure but we need to be careful in moving ahead with a single minded theory. This could be a costly blind alley. As discussed ...earlier... the amyloid hypothesis has a number of other problems. For example, there are other data from clinical trials with amyloid drugs that reverse the buildup of beta amyloid but have no clinical benefit.

Furthermore, a substantial number of people develop enough plaques as they age that they meet the pathological criteria for Alzheimer’s disease on autopsy but have no symptoms of the disease... Read full article

Unabridged Alzheimer's University review article manuscript: amyloid beta improves memory through fixing cholesterol supply of brain cells

2010-09-02T11:22:00.001+03:00

Alzheimer's amyloid beta improves memory in lab animal brain tissue: Amyloid beta, neural lipid metabolism, cholesterol and synaptic plasticity

This is Part 6 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Part 1 | Part 2 | Part 3 | Part 4 | Part 5 | Part 6

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at: http://alzheimercode.blogspot.com

*****

Amyloid beta, neural lipid metabolism, cholesterol and synaptic plasticity

In line with our early reasoning that Abeta is an apolipoprotein constituent of lipoproteins (and as such may have a diverse function in lipid metabolism) we studies the effects of the synthetic analog of amyloid beta protein, peptide Abeta1-40 (thought to be a major form of soluble Abeta [[24]]) on lipid synthesis in the hippocampal slices of rodents using metabolic labeling with C14-acetate, a radioactive lipid precursor [[56]]. Over the prolonged incubation with the label slices remained viable and actively synthesized phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and cholesterol. Abeta treatment increased the synthesis of PC, PE and cholesterol on 33, 67 and 46 % above the control values (100 %), respectively.

Abeta1-40 also modulated the synthesis of choline-containing phospholipids (cPLs, namely phosphatidylcholine and sphingomyelin), the major neural membrane component, an integral part of the brain cholinergic system, and a reservoir for lipid second messengers. We traced the synthesis of cPLs with radioactive choline in the presence of Abeta1-40 and found that Abeta increases the synthesis of cPLs to 47% above the controls (no Abeta). These data imply that the modulation of neural lipids by Abeta can be mediated via different metabolic pathways [].

Additional experimentation showed that Abeta also enhanced the uptake of tritiated [3H]cholesterol by slices, ~32.5% in 6 hrs above the control value (100 %, no Abeta). We used two kinds of controls. First, we stimulated slices with 50 mM potassium (that models basic neural synaptic function), followed by a biochemical analysis of lipid synthesis with a radioactive label. K+ evoked depolarization did not significantly change specified above lipid syntheses (contrary to lipid peroxidation modification that we report below), suggesting that membrane depolarization, modeling basal synaptic activity and neurotransmission, do not enhance hippocampal lipid syntheses as it occurs during the treatment of slices with Abeta peptide, and after long-lasting synaptic enhancement (LTP), as verified by autoradiography of hippocampal slices after the metabolic labeling with radioactive lipid precursor [14C] acetate and the induction of the LTP with a tetanic stimulus (100 Hz, 1 sec) in stratum radiatum (SR) recording pathway of the CA1 [[56, 58]].

Therefore, we set to test the role for Abeta in the synaptic plasticity in brain slices from adult male rat hippocampus under the condition that we characterized previously with regard to cholesterol and phospholipid synthesis [[56, 59]]. The prolonged maintenance of slices in a test tube for about twenty hours in our experimental setup preserved synaptic function (input/output curve, I/O, a basic measure of synaptic function, Figure 1, inset) but abrogated synaptic plasticity (measured as LTP, Figure 1, Panel A). Synthetic homolog of the Abeta (1-40 amino acids’ molecule length, representing the major form of soluble Abeta[[24]], Panel B) rescued LTP while cholesterol synthesis inhibition with a statin abolished LTP restoration by the peptide [[59]].

LTP models synaptic plasticity that underlies learning and memory, and depends on cholesterol and phospholipids supply via synthesis and lipoprotein transport as well as membrane lipid peroxidation (discussed at length of this article). The above effect of Abeta may represent its biological function of activity-dependent sensing membrane physical and chemical properties that is translated into membrane lipid homeostasis modulation to fine tune current synaptic action. Our observation implies an intriguing perspective that Abeta protein is a functional player in an activity-dependent cholesterol neurochemical pathways and contributes to the knowledge base on the important role for Abeta in synaptic structure-functional plasticity shown by others [[21, 43, 44, 45, 46, 60, 61, 62]].

Our findings also support early formulation of our hypothesis that the change in Abeta biochemistry in Alzheimer's disease and related disorders is a functional (but NOT pathologic) compensatory phenomenon aiming to counterbalance impaired cholesterol dynamics and associated neurotransmission and synaptic plasticity [[56, 59, 63, 64]]. Such cholesterol mediated failure of synaptic function and neural degeneration in our view represents the cause of the major sporadic form of Alzheimer's disease [[56, 59, 63, 64, also see Scheme 1 in the following lecture]].

Amyloid beta restores memory in the model of hippocampal slices of lab animals

Figure 1. Effect of Alzheimer's Abeta1-40 on synaptic plasticity in CA1 area of adult rat hippocampus. A, Field excitatory postsynaptic potentials (fEPSPs) recorded from a single site in stratum radiatum of CA1 under the condition of the prolonged incubation of slices without the peptide Abeta1-40 (Control) or in the presence of the peptide (Abeta) are presented as normalized slopes versus time to yield LTP charts. Abeta1-40 peptide reversed the impairment of the LTP, a characteristic of synaptic plasticity, in slices subjected to 21+ hrs of maintenance ex-vivo, and made it statistically not different (P>0.05, nonparametric Mann-Whitney signed rank test, one-tailed) from the slices maintained for 6-8 hrs only [[56]]. Inset (I/O maximum) illustrates the maximum values of the input-stimulus/output-response (I/O) curves (indicative of basic synaptic function) that show no statistical differences (n=6, P>0.05, one-tailed) between slices maintained for a prolonged time with Abeta or without the peptide. D, Representative fEPSPs at the bottom right show that statin mevinolin (a cholesterol synthesis inhibitor) abolished LTP restoration by Abeta (for details and experimental protocol please see the text and the scheme in [[59]]). The presented waveforms are recorded during the baseline stimulation (1), immediately after the tetanic stimulus (2), as well as three (3) and twenty (4) minutes thereafter. Panel B illustrates amino acid sequence differences between rat and used in the study human Abeta1-40. “Stars” on the schematic hippocampal slice (Panel C) illustrate stimulating and recording electrodes positioning. The figure is reproduced by permission from the Neurobiology of Lipids, 1, 8 (2003), http://neurobiologyoflipids.org/content/1/8/ [[59]].

References:

24. AR. Koudinov, NV. Koudinova, A. Kumar, R. Beavis, J. Ghiso. (1996) Biochemical characterization of Alzheimer's soluble amyloid beta protein in human cerebrospinal fluid: association with high density lipoproteins. Biochem. Biophys. Res. Commun. (1996) 223:592-597

43. FR. Kamenetz, T. Tomita, DR. Borchelt, SS. Sisodia, T. Iwatsubo, R. Malinow. Activity dependent secretion of beta-amyloid: roles of -amyloid in synaptic transmission. Soc. Neurosci. Abstr. (2000) 26: 491.

44. HA. Pearson, C. Peers. Physiological roles for amyloid beta peptides. J. Physiol. (2006) 15: 5–10.

45. JP. Steinbach, U. Muller, M. Leist, ZW. Li, P. Nicotera, A Aguzzi. Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ. (1998) 5:858–866.

46. S. Lesne, C. Ali, C. Gabriel, N Croci, ET. MacKenzie, CG. Glabe, M. Plotkine, C. Marchand-Verrecchia, D. Vivien, A. Buisson. NMDA receptor activation inhibits alpha-secretase and promotes neuronal amyloid-beta production. J. Neurosci. (2005) 25:9367–9377.

56. AR. Koudinov, NV. Koudinova. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. (2001) 15: 1858-1860. Available at: http://www.fasebj.org/cgi/content/abstract/00-0815fjev1. Also available as slide show at: http://neurobiologyoflipids.org/content/1/6/neurolipids112002-02.html#fr1

57. NV. Koudinova, AR. Koudinov. Amyloid beta protein attenuates the synthesis of phospholipids containing choline: another effector of neural membrane homeostasis? Soc. Neurosci. Abst. online. (2002) Program No.884.2. Available at: http://neurobiologyoflipids.org/content/1/5/

58. AR. Koudinov, NV. Koudinova. Cholesterols' role in synapse formation. Science (2002) 295: 2213.

59. AR. Koudinov, NV. Koudinova. Amyloid beta protein restores hippocampal long term potentiation: a central role for cholesterol? Neurobiol. Lipids (2003) 1: 8 Available at: http://neurobiologyoflipids.org/content/1/8/

60. J. Wu, R. Anwyl, MJ. Rowan. beta-amyloid-(1-40) increases long-term potentiation in rat hippocampus in vitro. Europ. J. Pharm. (1995) 284: R1-R3.

61. J. Wu, R. Anwyl, MJ. Rowan. beta-amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus. NeuroReport (1995) 6: 2409-2413.

62. PE. Schulz. beta-peptides enhance the magnitude and probability of long term potentiation. Soc. Neurosci. Abstr. (1996) 22: 2111.

63. AR. Koudinov, NV. Koudinova. Brain cholesterol pathology is the cause of Alzheimer's disease. Clin Med Health Res (2001) clinmed/2001100005. Available at: http://clinmed.netprints.org/cgi/content/full/2001100005v1

64. AR. Koudinov, NV. Koudinova. Cholesterol, synaptic function and Alzheimer's disease. Pharmacopsychiatry (2003) S36: 107-12.

56. AR. Koudinov, NV. Koudinova. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. (2001) 15: 1858-1860. Available at fasebj.org , also available as a slide show at koudinov.info (to be reprinted at Alzheimer's Code):

Link to this publication: amyloid-beta-lipids-cholesterol-synapse

Part 1 | Part 2 | Part 3 | Part 4 | Part 5 | Part 6

Unabridged Alzheimer disease article 5: Abeta and APP implicated in the function of peripheral synapses and the neuromuscular junction NMJ pathology

2010-08-31T17:57:00.004+03:00

Amyloid beta and its precursor molecule APP implicated in the function of peripheral synapses and the neuromuscular junction (NMJ) pathology

Abeta and APP implicated in the function of peripheral synapses and the neuromuscular junction (NMJ) pathology

This is Part 5 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Part 1 | Part 2 | Part 3 | Part 4 | Part 5

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at: http://alzheimercode.blogspot.com

*****

Alzheimer's Amyloid beta and its' precursor molecule APP implicated in the function of peripheral synapses and the neuromuscular junctions (NMJ) pathology

Further investigation is warranted to elucidate the normal role for amyloid beta protein (Abeta) and its’ precursor at peripheral synapses, neuromuscular junctions (NMJ) and NMJ pathologies (ex. inclusion-body myositis, IBM). Two basic observations include the study published more then a decade ago [[48]]. This was the first demonstration of APP and Abeta concentration postsynaptically at human neuro-muscular junctions, that led authors to conclude that “APP may have a role in normal junction biology and possibly in some diseases affecting NMJs”. Another study later showed that APP homolog in Drosophila (APPL) promotes synapse differentiation at the neuromuscular junction [[49]], leading the authors to propose a model “by which APPL, in conjunction with activity-dependent mechanisms, regulates synaptic structure and number”.

Recent comprehensive study performed analyses of neurotransmission in mature neuromuscular synapse of APP deficient mice. This research “found that APP deletion led to reduced paired-pulse facilitation [PPF, a measure of synaptic transmission and synaptic vesicles recycling efficacy] and increased depression of synaptic transmission with repetitive stimulation. Readily releasable pool size and total releasable vesicles were not affected, but probability of release was significantly increased. Strikingly, the amount of asynchronous release, a measure sensitive to presynaptic calcium concentration, was dramatically increased, and pharmacological studies revealed that it was attributed to aberrant activation of N- and L-type Ca(2+) channels.” Authors therefore proposed that APP modulates synaptic transmission at the NMJ by ensuring proper Ca(2+) channel function [[50]].

Another study [[51]] reported on an essential role of APP family of proteins in the development of neuromuscular synapses. “Mice deficient in APP and its homolog APP-like protein 2 (APLP2) exhibited aberrant apposition of presynaptic marker proteins with postsynaptic acetylcholine receptors and excessive nerve terminal sprouting. The number of synaptic vesicles at presynaptic terminals was dramatically reduced. [In agreement with the previous study by Yang L et al.[[Ref. 50]] ], these structural abnormalities were accompanied by defective neurotransmitter release and a high incidence of synaptic failure [[51]]. This is also in accord with the reduction of the synaptic vesicle density, active zone size, and docked vesicle number per active zone in submandibular ganglion synapses of mice lacking APP and APPLP2 demonstrated in lab animals with double gene deletions [[52]].

Another recent report demonstrated that APP is essential in regulating the presynaptic expression and activity of the high-affinity choline transporter (CHT), a molecule that mediates the rate-limiting step of cholinergic synaptic transmission in both the NMJ and central cholinergic neurons. Loss of APP was the cause of the aberrant localization of CHT at the neuromuscular synapses and reduced CHT activity at cholinergic projections. [[53]]

Interestingly, abnormal accumulation of APP and Abeta epitopes (as well as excessively phosphorylated tau in the form of paired helical filaments, PHF, see below) in vacuolated muscle fibers (VMF) is a characteristic feature of not just AD, but also the neuromuscular pathology such as IBM [[54, 55]]. Also important is the observation that in IBM there is an abnormal accumulation of a number of lipoprotein receptors (such as LDLR, VLDLR, LRP) and cholesterol within IBM vacuolated muscle fibers [[54]]. However, LDLR and VLDLR are also expressed at normal NMJ, suggesting “physiologic roles for them in transsynaptic signaling pathways and increased internalization of lipoproteins” at NMJ. Similarly, based on our physiological research with rat hippocampal slices, we earlier proposed that there is an activity-dependent demand for lipoprotein cholesterol and phospholipids at the central synapses [[56]]. Most important, the study by Jaworska-Wilczynska [[54]] confirms that there is a peripheral application of the functional crosstalk between Abeta, lipoproteins and cholesterol, that our own explanation of Abeta involvement in AD is about (see below).

References:

48. V. Askanas, WK. Engel, RB. Alvarez. Strong immunoreactivity of beta-amyloid precursor protein, including the beta-amyloid protein sequence, at human neuromuscular junctions. Neurosci. Lett. (1992) 143: 96-100.

49. L. Torroja, M. Packard, M. Gorczyca , K. White, V. Budnik. The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J. Neurosci. (1999) 19: 7793-7803.

50. L. Yang, B. Wang, C. Long, G. Wu, H. Zheng. Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses. Neuroscience (2007) 149(4):768-78.

51. P. Wang, G. Yang, DR. Mosier, P. Chang, T. Zaidi, YD. Gong, NM. Zhao, B. Dominguez, KF. Lee, WB. Gan, H. Zheng. Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J. Neurosci. (2005) 25(5):1219-25.

52. G. Yang, YD. Gong, K. Gong, WL. Jiang, E. Kwon, P. Wang, H. Zheng, XF. Zhang, WB. Gan, NM. Zhao. Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci. Lett. (2005) 384(1-2):66-71.

53. B. Wang, L. Yang, Z. Wang, H. Zheng. Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc. Natl. Acad. Sci. USA (2007) 104(35):14140-5.

54. M. Jaworska-Wilczynska, GM. Wilczynski, WK. Engel, DK. Strickland, KH. Weisgraber, V. Askanas. Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle. Neurology (2002) 58: 438-445.

55. AR. Koudinov, NV. Koudinova, U. Beisiegel. Cholesterol homeostasis failure at neuromuscular junctions and CNS synapses: a unifying cause of synaptic degeneration? Neurology online. (2002) Available at neurology.org

56. AR. Koudinov, NV. Koudinova. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. (2001) 15: 1858-1860. Available at fasebj.org , also available as a slide show at koudinov.info (to be reprinted at Alzheimer's Code):

Link to this publication: amyloid-beta-app-implicated-in-synapse

Part 1 | Part 2 | Part 3 | Part 4 | Part 5

An editorial in the journal Lancet debates the problems of drug development for Alzheimer's disease

2010-08-29T16:50:00.000+03:00

Excerpt of the coverage by medicalnewstoday: The feature questions why so many trials are failing at the phase 3 clinical trial stage and asks whether the animal models used prior to this are the most effective way to test the drugs. It also suggests treatments should perhaps start to focus more on the changes in the brain that happen before symptoms like memory loss start to appear. However, it notes that these are difficult to replicate in animal models.

Alzheimer's Society Dr Susanne Sorensen, Head of Research comments: 'Scientific research is essential in the search for a cure and treatments for Alzheimer's disease and we must not be too disheartened that many drug trials fall at the final hurdle. The fact only one in five clinical trials across all diseases will be successful highlights the need for more investment so we can defeat dementia.'

'Every day scientists are learning more about the early stages of Alzheimer's disease and this is an important area for further study and development.'

Unabridged Alzheimer's disease manuscript: Amyloid beta and Amyloid Precursor Protein (APP) modulate the function of central synapses in brain

2010-08-28T16:42:00.003+03:00

This is Part 4 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Part 1 | Part 2 | Part 3 | Part 4

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at: http://alzheimercode.blogspot.com

*****

Amyloid beta and Amyloid Precursor Protein (APP) modulate the function of central synapses in brain

There are many articles reporting on amyloid beta role in modulating synaptic function [[reviewed in Ref. 17]]. In quoted above article by Malinow group of Cold Spring Harbor [[21, 43]] researchers found that evoked activity of neurons in hippocampal slices stimulated the production of Aβ. This happened primarily by an increased trafficking of APP towards beta secretase sites at the cell membrane. In addition of the increased Aβ formation, there could be an increase of the production of other APP derivates, such as AICD which could also modulate synaptic activity. It is well possible [[44]], that at “physiological expression levels of APP, this provided a negative feedback, since Abeta depresses synaptic activity. Without such depression, synaptic activity could become excessive, leading to excitotoxicity. Indeed, gamma secretase inhibition led to increased EPSC frequency [[21]], and kainate-induced seizures are potentiated in APP knockout mice [[45]]. Further to these studies, a recent report indicated that specific stimulation of NMDA receptors up-regulated APP, inhibited alpha-secretase activity and promoted amyloid beta production [[46]]. Collectively, these studies argue strongly that APP processing, and the presence of amyloid beta itself, are closely associated with synaptic activity and may serve to provide physiological control of activity, guarding against excessive glutamate release” [[44]].

Most recently it was show, that endogenous secreted APP-alpha regulates hippocampal NMDA receptor function, long-term potentiation and spatial memory [[47]]. Specifically, “intrahippocampal infusion of antibodies targeted to endogenous sAPP alpha reduced long-term potentiation (LTP) in the dentate gyrus of adult rats by approximately 50%. Conversely, infusion of recombinant sAPP alpha dose-dependently increased LTP and facilitated in vitro tetanically evoked NMDA receptor-mediated currents. Pharmacological inhibition of alpha-secretase and other alpha-disintegrin-and-metalloproteases by TAPI-1 reduced both LTP and tetanus-evoked NMDA receptor-mediated currents in dentate granule cells. Both effects were prevented by co-application of exogenous recombinant sAPP alpha. Similarly, spatial memory was inhibited by intrahippocampal TAPI-1, an effect that was prevented by co-application of recombinant sAPP alpha” [[47]].

References:

17. AR. Koudinov, TT. Berezov. Alzheimers amyloid-beta (Abeta) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiologica Exp. (2004) 64(1): 71-79.

21. F. Kamenetz, T. Tomita, H. Hsieh, G. Seabrook, D. Borchelt, T. Iwatsubo, S. Sisodia, R. Malinow. APP processing and synaptic function. Neuron (2003) 37:925-937

43. FR. Kamenetz, T. Tomita, DR. Borchelt, SS. Sisodia, T. Iwatsubo, R. Malinow. Activity dependent secretion of beta-amyloid: roles of beta-amyloid in synaptic transmission. Soc. Neurosci. Abstr. (2000) 26: 491.

44. HA. Pearson, C. Peers. Physiological roles for amyloid β peptides. J. Physiol. (2006) 15: 5–10.

45. JP. Steinbach, U. Muller, M. Leist, ZW. Li, P. Nicotera, A Aguzzi. Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ. (1998) 5:858–866.

46. S. Lesne, C. Ali, C. Gabriel, N Croci, ET. MacKenzie, CG. Glabe, M. Plotkine, C. Marchand-Verrecchia, D. Vivien, A. Buisson. NMDA receptor activation inhibits alpha-secretase and promotes neuronal amyloid-beta production. J. Neurosci. (2005) 25:9367–9377.

47. CJ. Taylor. Endogenous secreted amyloid precursor protein-alpha regulates hippocampal NMDA receptor function, long-term potentiation and spatial memory. Neurobiol. Dis. (2008) (2):250-260.

Link to this publication: amyloid-beta-is-needed-for-synapse

Part 1 | Part 2 | Part 3 | Part 4

Alzheimer's code: a semi-fiction novel of academic plunders and Amyloid beta Biotech professors' mafia members

2010-08-26T12:25:00.000+03:00

Question: What Alzheimer's disease code is?

Answer: Alzheimer's code is a semi-fiction novel of Alzheimer's disease research network of plunders from the United States University campuses and international Amyloid beta Biotech mafia members

*****

Alzheimer's code is not-yet written semi-fiction mystery novel "The Alzheimer Code" by Alexei Koudinov (under his name Alex Kudinov-Sheffer). The idea of thi book come to Dr. Koudinov in summer 2006. The book scenario is not a fiction: it is a sad documentary of the contemporary very corrupted Alzheimer's disease research, leading scientists and academic Professors, Professional, Public and Governmental Institutions doing nothing to stop the preudoscience in-the-private interest.

Quoting original Alzheimer's code outline at early (archived) edition of Dr.Koudinov's Alzheimer's Club side bar:

"A semi-fiction mystery novel "The Alzheimer Code" is under preparation. In this book the death of the President of the United States of America is followed by his preventive anti-amyloid vaccination against Alzheimer's disease. At the same time and for the same reason, in his agony of death Editor-in-Chief of London-based Nature science journal recalls he in fact witnessed the corruption of Alzheimer's pseudo-science, brought to the community by a keen student. This is a story of a corrupted Harvard University professor, a research center co-director and a godfather of the international network of science criminals. Be the first to know when Alzheimer Code is published..."

In fact, a reader does not need to wait for Alzheimer's code, as Dr. Koudinov Written evidence for United Kingdom Parliamentary inquiry on Science Publication and his "Open letter to President George W. Bush on conduct by scientists, STM journals, and Scientific Institutions", is a documentary summary of the facts behind the true story of Alzheimer's disease research mafia.

Additional original facts are scheduled to appear at www.alzheimercode.info, and will include original correspondence with the Wall Street journal Sharon Begley, Newsweek's Geofrey Cowley, Alzheimer's neurocientists, Editors of major Scientific Journals, Professional Organizations, Governmental Institutions and Funding bodies, and the observations of the conduct by scientists in major Alzheimer's laboratories and outside university campus.

Stay tuned, continue reading, as the story unfolds

us-university-campus-alzheimers-plunder

New AlzClub.org news web site by Dr. Koudinov to publish annontated Alzheimer's news from third party sources

2010-08-24T23:26:00.001+03:00

There is a kind of magic in my awaking at 5AM this Sunday, 15 August 2010. After having morning physical excersises and breakfast and logged in to make a new life of my http://www.alzclub.org web site. Previously (since 2004 I beleive), it looked as this archieved copy at my koudinov.info/alzclub web folder.

For years I was (and still I am) confident, that Alzheiemr's is such a corrupted research field, that one can take an academic leave for three, five, or even ten years, and then come back exactly to the date he or she left. Those bastards and mafia-like strucrure of academic science and hidden big pharmaceutical bucks behind them leaves no space for an open minded innovative ideas. Don't ask how it is possible, it is the way Alzheimer's research exists for two decades.

So, I decided to remove digital dust out of my advocacy, scientific and lay language writings and make it public here, so, you, Dear Reader, has original content from the author, directly and with no "dealers", such as poor and often corrupted academic journals.

...It was no surprise that three days later Eli Lilly announced the halt of Alheimer's therapy trial, as patients worsen on a chemical called secretase inhibitor, which is an anti-amyloid beta therapy based on ill-fated and poor-minded (yet commercially, but not public succesful) amyloid hypothesis (read dogma) of Alzheimer's disease.

Today, by the end of the day August 19, I decided to start another theme web site, devoted exclusively to reprinting Alzheimer's news and press releases from different sources. I thus would like to separate my original content from content by others. I will still announce interesting news at major AlzClub.org web site by providing brief summary and linking to a full text at the news site and the article source. All other web sites, including Alzheimer's History, Alzheimer's Amyloid beta courses for Public and Professionals, Alzheimer's Code and emerging projects will be syndicating the content of each other, so, every new material will be visible, and just click away no matter at which particular site you are at the moment.

Surely, all the projects are non-profit, public and ad supported: while I do not expect to make revenue, it will be nice to have an advertisement support coveingr my internet publishing and associated expenses.

Remaining independent and truly yours,

Alexei Koudinov, MD, PhD, DrSci

neuroscientist, Alzheimer's researcher

a man of 44 who loves this world

P.S. First annotated by me news item to follow in just another 10 minutes or so, with Press release of Alzheimer's Association of Chicago, IL on Eli Lilly Alzheimer's clinical trial termination, stay connected, and yes, follow me on twitter

Dr Koudinov: I don't believe Alzheimer's Association dissapointed of Phase III clinical trial (of anti-amyloid Semagacestat by Eli Lilly) halt!

2010-08-23T23:58:00.000+03:00

"The Alzheimer's Association is disappointed to learn of the negative interim results from the Phase III clinical trial of Semagacestat," William Thies, Ph.D., Alzheimer's Association Chief Medical and Scientific Officer says in a Press Release.

Comment by Alexei Koudinov follows:

Are they truly dissapointed at Alzheimer's association of Phase III clinical trial of Semagacestat by Eli Lilly? I doubt it! Or more precisely, I do not believe it! I mean I don't believe he is dissapointed of the development setback, as media reports. Perhaphs he is dissapointed of fundraising problem (as it will be much harder to full the public that the research funded by Alzheimer's association is just bullshit), meaning less profit personally for him? You can ask him and Alzheimer's association CEO, they should be available via Alz.Org web site. I tried myself. In April 2004 I wrote the letter to the editor of The Wall Street Journal on WSJ coverage of Alzheimer's research. There were two (plus letters to editor, and another article in late summer, after Alzheimer's Global convention) articles, and the person behind that research by WSJ's Sharon begley was myself: I brought the story to them, described facts, provided contacts, you will learn all this at Alzheimer's Code History web site. My letter to WSJ editor responded on Alzheimer's Association letter (by Sheldon Goldberg, President and CEO, Alzheimer’s Association, 16 April 2004) to The Wall Street Journal editor on April 16 WSJ article "Scientists World-Wide Battle a Narrow View of Alzheimer's Cause" by Sharon Begley. In this letter I provided facts why Alzheimer's asscoation is a part of narrow amyloid view on Alzheiemr's. And now Dr.Thies says he is dissapointed. I don't believe him, period.

Read the Press release by Alzheimer's Association

WSJ Blog Article Commented by Alexei Koudinov

2010-08-22T15:21:00.004+03:00

Katherine Hobson. Alzheimer’s Drug Development a Tough Road, Lilly News Shows. WSJ Blog on Health and the business of Health (17 August 2010) FullText

Excerpt: Eli Lilly has scrapped a drug being tested for use against Alzheimer’s disease because it increased patients’ symptoms and was also tied to a higher risk of skin cancer...

...P. Murali Doraiswamy, a psychiatry professor at Duke and author of “The Alzheimer’s Action Plan.”: Scientists don’t fully understand the role of the plaques (made of amyloid protein) and tangles (consisting of another protein, tau) that are found in the brains of patients with the disease... “But what we don’t understand is the interaction between the [plaques and tangles], the timeline of events and how they interact with other things, such as inflammation and oxidative stress.”

These days drug developers are primarily focusing on those plaques, hoping that preventing or clearing them will affect memory and cognition in patients...

...He hopes the data from clinical trials — failed or not — will be made available so that scientists can try to get a grasp on those complexities. “It would be a shame if companies keep repeating the mistakes” of others, he says.

Please visit WSJ Blog to read full WSJ Blog article and comments

Comment by Alexei Koudinov

I appreciate Katherine Hobson WSJ article. I am a person behind a series of WSJ 2004 articles on Alzheimer's by Sharon Begley. Just to avoid repetitive statements, please see my Open Letter to Forbes editor, regarding Forbes Blog articles by Robert Langreth, quoted at length of the WSJ Blog article under discussion, it is available at www.alzclub.org

As for the comment by Dick G, I must say, that one should be cautious while reading one's contribution online.

There is surely no confidence in an unbiased scientific view even in most credible science publications (see sad examples of Alzheimer's field, Science magazine and Nature Journal as a part of my written evidence to UK Parliamentary Committee on science and technology). The view presented in the WSJ Blog comment on Cholesterol and Alzheimer's is apparently from a non Professional. I remember this, because a number of years ago the same writing (qouted in the WSJ blog comment by Dick G) got to a major professional forum of Alzheimer's disease research alzforum.org as a hypothesis of Alzheimer's. It was then shortly removed for the reason I indicate.

I noticed that the quoted article presents the following statement "...depriving the brain of cholesterol through a low-fat, low-cholesterol diet or cholesterol-lowering drugs, could have the potential to make Alzheimer's disease worse", as the idea of the author. This is in fact an interpretation of our earlier scientific contribution available at a number of articles. The author of the writing at the Dick G link promised to revise the text to make proper acknowledgement of my and my colleagues research ("...These will be reviewed and this article will be changed to properly credit Dr. Koudinov..."), but probably just forgot to do it.

No problem, just see the update for our views on both Alzheimer's and cholestrol, see these two articles: "Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions" (Journal of Alzheimers Disease 18(2): 381-440, 2009 Oct), and "Cholesterol homeostasis failure as a unifying cause of synaptic degeneration" (J Neurological Sciences, 229-230: 233-40 2004 Dec). Both are written in simple non technical language, and will be available in even easy to understand original near-lay (non edited by journal) editions at www.AlzClub.org, Alzheimer Code and Alzheimer's Amyloid Beta Course

Alexei Koudinov Open letter to Forbes on Alzheimer's therapy failure by Eli Lilly

2010-08-21T12:00:00.000+03:00

Attention: Robert Langreth, Forbes, Senior Health Editor

This letter to you is also available at www.alzclub.org

Dear Forbes Editor,

I appreciate Forbes and Forbes series of articles on Alzheimer's and your and your commentators open minded view on the disease.

It's a pity there is no way at Forbes Blog to find a direct contact for articles' authors, as I am particularly interested to contact Robert Langreth of Treatments section, who authored several Blog articles on Alzheimer's clinical trial failure. Please forward this email to Mr. Robert Langreth!

I am Alzheimer's research who is talking on Alzheimer's amyloid beta protein as a normal and essential protein (see PDF of the article Alzheimer's amyloid beta is an essential synaptic protein, not neurotoxic junk for background reading and a preceeding short publication in Science magazine, my other selected reprints can be found here.

I also battle for disclosure of competing ineterests in Alzheimer's. I am a person behind three articles on Alzheimer's in the Wall Street Journal (2004, by Sharon Begley).

For background reading see my "Open letter to President George W. Bush on conduct by scientists, STM journals, and Scientific Institutions" (that should be now re-addressed to a new President of the US, I'll appreciate for your help in making such a letter public, as I am ready to re-address it, hope President Abama has more time on Ethics and Public health issues), and my written evidence to UK Parliamentary Committee on Science publishing "Editorial and Publisher Corruption"

It's a pity that you journalists are like on other Planet, not seeing what scientists like me are talking about for years, while this information is freely available on the Internet. Would you get such a deserved attention and talk on it in time, Eli Lilly would probably not enter just terminated Clinical Trial of a bad thought Alzheimer's drug.

Sincerely,

Alexei Koudinov, MD, PhD, DrSci

Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse, excellent Senior Journal article says

2010-08-20T12:28:00.007+03:00

Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse, excellent Senior Journal article says

Alzheimer's, Dementia & Mental Health: Battle Against Alzheimer’s Disease Hits Wall as Drug Test Stopped; Maybe Plaque Not Cause seniorjournal.com

Note by Alexei Koudinov: I noticed this excellent article at www.seniorjournal.com 20 August 2010 AM Jerusalem time. Please make a visit to the original publication to appreciate this excellent report, thanks!

Excerpt: ...The efforts to prevent or successfully treat Alzheimer’s disease – the disease most feared by senior citizens - with drugs has never advanced very far, but these efforts suffered a major setback this week when Eli Lilly and Company announced it was halting development of semagacestat. This potential treatment for AD was in advanced clinical trials when it was discovered to be making patients worse instead of better. Many see this failure as a major blow to the most popular theory on the cause of the disease. The Lilly announcement said, “Studies showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.”...

Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has also informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies. In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease.

Semagacestat was designed to reduce the body's production of amyloid beta plaques, which scientists believe play an important role in causing Alzheimer's disease. Semagacestat is believed to block the activity of gamma secretase, an enzyme that is essential to the body's production of amyloid beta plaques, according to the company. It was being tested in two Phase III clinical trials called IDENTITY and IDENTITY-2.

Lilly’s interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened. However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo...

...Semagacestat was one of many drugs being tested that focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease. Lilly actually has another amyloid-beta compound, solanezumab, in Phase III trials and says this testing will continue. The company says these two compounds have “different mechanisms of action”...

About the IDENTITY trials

IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) and IDENTITY-2 are Lilly's Phase III placebo-controlled trials studying semagacestat, a gamma-secretase inhibitor being investigated as a potential treatment to slow the progression of mild to moderate Alzheimer's disease. Both Phase III trials are fully enrolled, with more than 2,600 patients from 31 countries, and include a treatment period of approximately 21 months. An open-label extension study (IDENTITY-XT) is available to all participants completing either study.

All study participants had to be at least 55 years old and meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, with certain assessment scores indicating mild to moderate Alzheimer's disease. Patients with more advanced Alzheimer's disease were not included in the studies.

alzheimers-semagacestat-makes-patients

Unabridged Alzheimer's manuscript series: Lipoprotein-associated Amyloid beta: a way to preserve soluble state of amphipathic molecule , Part 3

2010-08-19T19:11:00.004+03:00

Lipoprotein-association of Alzheimer’s amyloid beta: a way to preserve phiological soluble state of a amphipathic apoAbeta molecule

This is Part 3 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Part 1 | Part 2 | Part 3

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at: http://alzheimercode.blogspot.com

*****

Part 3 | Part 1 | Part 2

In line with the notion that Abeta is an apolipoprotein constituent of the HDL, we further showed that natural apoAbeta does not cross link with other apoliporoteins in normal CSF HDL (indicating a priority of apoAbeta-to-lipid interaction under normal condition) [[32]] and that an interaction of apoAbeta with apolipoproteins is a characteristic of Alzheimer’s CSF HDL samples [[25]]. In Alzheimer’s, therefore, there is a break of the lipoprotein structural integrity in a way that favors interaction of Abeta-to-Abeta(that creates oligomers [[33]] or apoAbeta-to-other apolipoprotein, shown for ApoE and ApoJ [[25]], and most recently for ApoA1 [[34]].

Of major support for the argument of the “mistaken identity” is the potent inhibition of neural toxicity of Abeta by lipoproteins [[34, 35, 36]], apoA1 and apoE, two major apolipoproteins and lipid binding proteins in the circulation and the brain, respectively [[34, 38]], and a risk factor for AD [[38]]. It is very unfortunate that these facts neither discussed nor experimentally addressed in key experimental [[12, 33]] and recent articles on oligomeric amyloid hypothesis [[13, 14]].

Additionally, there is a major experimental deficiency by oligomeric amyloid hypothesis proponents, and all others, who use “antibodies that can selectively target soluble oligomers of Abeta” [[1, 33]]. We do believe that these antibodies are poorly characterized and therefore may mistake natural lipoprotein-associated soluble apoAbeta (and other membrane-bound proteins) for lipid free Abeta oligomers. This is because micellar Abeta used for production of anti-oligomer antibodies [[33]] may well mimic the conformational motif of lipoprotein-bound apoAbeta and of other membrane-bound proteins [[39]].

Similarly, the experimental lack of the association of Abeta with lipoproteins (that potently arrests Ab neurotoxicity [[34,35,36,37]] questions physiological relevance of the study of the role for oligomers in synapse dysfunction and toxicity [[12,13,14]]. Moreover, it is well documented that “Abeta associat[ion] with membranes is dynamic and capable of adopting a number of conformations, each of which may have significance in understanding the progression of Alzheimer's disease.” [[29, 40]]. It is also shown that experimental Abeta neurotoxicity is modulated by the rate of peptide aggregation [[41]] and neuronal functional state [[42]]. Thus, potassium-induced membrane depolarization, a treatment modeling basic neuronal function, significantly reduced vulnerability to aggregated beta-amyloid peptides of cultured rat hippocampal neurons pretreated with high potassium [[42]]. Therefore, the lack of such a consideration is any experimental protocol on amyloid oligomers can generate a systemic error and lead to wrong conclusions (also see below).

References:

1. SR. Robinson, GM. Bishop, G. Munch. Alzheimer vaccine: amyloid  on trial. Bioessays (2003) 25:283-288.

12. DM. Walsh, I. Klyubin, JV. Fadeeva, WK. Cullen, R. Anwyl, MS. Wolfe, MJ. Rowan, DJ. Selkoe. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature (2002) 416:535-539.

13. Rowan MJ, Klyubin I, Wang Q, Hu NW, Anwyl R (2007) Synaptic memory mechanisms: Alzheimer's disease amyloid beta-peptide-induced dysfunction. Biochem Soc Trans 35(Pt 5), 1219-1223.

14. Selkoe DJ (2008) Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res 192(1), 106-113.

25. AR. Koudinov, TT. Berezov, NV. Koudinova. The levels of soluble A in different HDL subfractions distinguish Alzheimer's and normal aging CSF: implication for brain cholesterol pathology? Neurosci Lett. (2001) 314:115-118.

32. AR. Koudinov, TT. Berezov, NV. Koudinova. Alzheimer's amyloid beta protein association with high density lipoprotein in normal human cerebrospinal fluid: primary binding to lipid? Soc. Neurosci. (1997) 23:537.

33. R. Kayed, E. Head, JL. Thompson, TM. McIntire, SC. Milton, CW. Cotman, CG. Glabe. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science (2003) 300:486-489.

34. Paula-Lima AC, Tricerri MA, Brito-Moreira J, Bomfim TR, Oliveira FF, Magdesian MH, Grinberg LT, Panizzutti R, Ferreira ST. Human apolipoprotein A-I binds amyloid-beta and prevents Abeta-induced neurotoxicity. Int. J. Biochem. Cell Biol. (2008 Dec 14) PMID 19130896

35. A. Cedazo-Minguez, M. Huttinger, RF. Cowburn. Beta-VLDL protects against Abeta(1-42) and apoE toxicity in human SH-SY5Y neuroblastoma cells. NeuroReport (2001) 12:201-206.

36. ZS. Farhangrazi, H. Ying, G. Bu, LL. Dugan, AM. Fagan, DW. Choi, DM. Holtzman. High density lipoprotein decreases beta-amyloid toxicity in cortical cell culture. NeuroReport (1997) 8:1127-1130.

37. RP. Koldamova, IM. Lefterov, MI. Lefterova, JS. Lazo. Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits Abeta aggregation and toxicity. Biochemistry (2001) 40: 3553-3560.

38. JS. Whitson, MP. Mims, WJ. Strittmatter, T. Yamaki, JD. Morrisett, SH. Appel. Attenuation of the neurotoxic effect of Abeta amyloid peptide by apolipoprotein E. Biochem. Biophys. Res. Commun. (1994) 199(1):163-70.

39. B. Soreghan, C. Pike, R. Kayed, W. Tian, S. Milton, C. Cotman, CG. Glabe. The influence of the carboxyl terminus of the Alzheimer Abeta peptide on its conformation, aggregation, and neurotoxic properties. Neuromolecular Med. (2002) 1:81-94

40. JA. Lemkul, DR. Bevan DR. A comparative molecular dynamics analysis of the amyloid beta-peptide in a lipid bilayer. Arch. Biochem. Biophys. (2008) 470(1):54-63.

41. LW. Hung, GD. Ciccotosto, E. Giannakis, DJ. Tew, K. Perez, CL. Masters, R. Cappai, JD. Wade, KJ. Barnham. Amyloid-beta peptide (Abeta) neurotoxicity is modulated by the rate of peptide aggregation: Abeta dimers and trimers correlate with neurotoxicity. J. Neurosci. (2008) 28(46):11950-8.

42. CJ. Pike, R. Balázs, CW. Cotman. Attenuation of beta-amyloid neurotoxicity in vitro by potassium-induced depolarization. J. Neurochem. (1996) 67(4):1774-7

Link to this publication: Alzheimer-amyloid-beta-lipoprotein

Part 1 | Part 2 | Part 3

Eli Lilly termination of the drug test is a major Alzheimer's field advancement, Alexei Koudinov comments on Professor Paul Aisen television talk

2010-08-19T17:59:00.012+03:00

Eli Lilly termination of the drug test is a major Alzheimer's field advancement, Koudinov comments on Paul Aisen television interview

Full interview transcript is available at original online publication. Full in-text comments by Dr.Koudinov are available at Alzhemer's news web site, excerpt follows:

DR. PAUL AISEN: Well, we think that the cause of Alzheimer's disease is a -- is the accumulation of a toxic fragment called amyloid peptide, and this drug was designed to prevent that fragment from being released and from accumulating.

Dr. Alexei Koudinov: Well, Dr. Aisen, may I ask you to talk for yourself, and avoid using "we". We means who? You, Dr.Selkoe, other shareholders of a related BioTech Stock, PIs of NIH and other Funding Bodies research grants on amyloid, or your fellow participants of NIH State-of-the-Science Conference Preventing Alzheimer's Disease 2010? Would it be practical for you to think differently, Dr. Aisen? Be specific! I and many other researchers do not think that amyloid beta causes Alzheiemer's, and we did not grant you the privelege to talk on our behalf.

DR. PAUL AISEN: ...this was a large treatment study, with thousands of participants. And, in such a program, you follow the data. You have an independent group monitoring the trial and monitoring the data, both for safety and for impact of drug on memory. And this monitoring led to the conclusion that the drug was carrying a risk, a risk of skin cancer, and wasn't improving memory. So, that means that this dose of this particular drug is not effective at this stage of disease.

Dr. Alexei Koudinov: You are wrong! This means the whole concept and amyloid theory is wrong, Dr.Aisen! You know that, don't you?

DR. PAUL AISEN: It's a big setback, because there are only a few drugs that are at this pivotal stage, this final stage of drug development. So, having one of the major trials fail is a significant setback for the field...

Dr. Alexei Koudinov: It's a major advance, Dr. Aisen! It's happened a number of years ago, Elan trial collapsed, do you remember? It should happened again, so, it happened this August 2010 with Lilly trial. it will happen again to prove simple truth: amyloid is not an enemy, amyloid beta protein is a friend of the diseased brain, aiding the function, impaired by the other primary disease cause. So, you simply can not remove it from the brain!

DR. PAUL AISEN: Sure. ...the basic abnormality in the Alzheimer's disease brain is, as I said, the accumulation of a toxic fragment called amyloid. And we have always been able to be sure that Alzheimer's is present after death when we can examine brain tissue and see the amyloid in brain...

Dr. Alexei Koudinov: Why you are not mentioning amyloid accumulation in other human brain disease states, as well is amyloid accumulation in non-demented individuals?

DR. PAUL AISEN: ...the trial that was just stopped was conducted in the dementia stage. It may well be that the dementia stage is too late for such a drug to work. We now know that amyloid accumulates 10 or 15 years before dementia. And we think that, for anti-amyloid drugs to be effective, the earlier the better we intervene.

These tools give us a way of testing the drugs at the earliest stage, and ultimately can be used -- when we prove that these drugs work, they can be used to guide therapy in people before the onset of symptoms (AK: see related article by Dr.Aisen).

Dr. Alexei Koudinov: Well, one faked tool we have for more then a decade, a so called Gold standard for testing Alzheiemr's therapies. You know what I am talking about, right? A so called Alzheimer's transgenic mouse. No wonder, assisted by faked peer review at Nature, amyloid mafia got a ticket for testing drugs in Humans.

DR. PAUL AISEN: ...this is a disease that can't be directly observed. ...Now we have new, much more precise measures of disease that allow us to identify people at the very early stages, as we said, but also to much more precisely measure the impact of treatment. So, I think that clinical trial methodology has advanced, and that's going to help us demonstrate effective treatments.

Dr. Alexei Koudinov: You know, what I got in mind is a Russian (Soviets-time) anecdote of a TV appearence of a Big Professor (just like you at PBC this time) reporting the Tooth Extraction over anus. So much amazed TV reporter is asking "why" and "what for"? ...and the answer is straight forward and cristal clear: First, because all we do we do this way, and Second, because (for tooth extraction) it is for the first time ever. So, Dr.Aisen, don't oversimplify the story. As you are on the wrong pass with Alzheimer's theory, no methodology will yield the cure. Period!

Drug's Failure Casts Doubt on a Tactic in Alzheimer's Battle, says Gina Kolata of NYTimes, commented by Alexei Koudinov

2010-08-19T00:50:00.009+03:00

Citation: Gina Kolata. Drug’s Failure Casts Doubt on a Tactic in Alzheimer’s Battle. New York Times (August 18, 2010) FullText | Comment by Alexei Koudinov

Excerpt: "The failure of a promising Alzheimer’s drug in clinical trials highlights the gap between diagnosis — where real progress has recently been made — and treatment of the disease.

It was not just that the drug, made by Eli Lilly, did not work — maybe that could be explained by saying the patients’ illness was too far advanced when they received it. It was that the drug actually made them worse, the company said. And the larger the dose they took, the worse were patients’ symptoms of memory loss and inability to care for themselves. Not only that, the drug also increased the risk of skin cancer.

So when Lilly announced on Tuesday that it was ending its large clinical trials of that drug, semagacestat, researchers were dismayed...

...Beyond the setback for Lilly, the study raises questions about a leading hypothesis of the cause of Alzheimer’s and how to treat it. The idea, known as the amyloid hypothesis, says the disease occurs when a toxic protein, beta amyloid, accumulates in the brain. The idea is that if beta amyloid levels are reduced, the disease might be slowed, halted or even prevented if treatment starts early enough..."

Comment by Alexei Koudinov: it was never promising, who told you that? Did you check their scientific and ethical credit history first? You should! I checked and never believed those bastards of Alzheimer's leadership, "Professors" on campuses of major Universities and Medical centers. Want a referenced proof? Here it is, United Kingdom Parliament Written Evidence for the Science and technology Committee, check it out. I would infact ban them from doing science in early 2000, I asked Office of Research Integrity and SEC to do it. No reply yet

Alzheimer's Amyloid beta protein course for the general public launched by Alexei Koudinov, MD, PhD

2010-08-18T18:14:00.002+03:00

Alzheimer's Amyloid beta protein course for the public launched

You surely heard that amyloid beta protein is just an evil, responsible for Alzheimer's disease. Well, this is ...what corrupted Professors, Big Pharma money behind them, and those junior (and not so junior) scientists who depend on them when applying for funds, tenure appointments and academic promotions are forced to say to this world.

In reality, amyloid beta is an essential protein, preserved from as simple living systems as cells, to as complex as Humans and Human Brain. Amyloid bete is ecen necessary for brain to function. can you imagine where an attempt to eliminate it will lead to? Read on to learn more. You will make fascinating discoveries and will realize why conventional Alzheimer's therapy development is on the wrong pass.

This continuing education (lay language edition) course will be for the general public. No age limit or prior science education required. It is available for free at this link. Stay tuned, Have fun!

Why Eli Lilly stopped developing Alzheimer's drug? (17 August 22pm Jerusalem time)

2010-08-17T23:18:00.010+03:00

Why Eli Lilly stopped developing Alzheimer's drug? (17 August 22pm Jerusalem time)

http://www.google.com/hostednews/ap/article/ALeqM5gCJAoz-hiG3ZKoIt6aNf-82CVogQD9HLDCC83

Answer by Alexei Koudinov: "Because contemporary mainstream Alzheimer's disease science is bullshit! Read on for details"

Reprinted for educational Alzheiemr's scholar information purpose only, no copyright infringement intended

Citation: Tom Murphy. Eli Lilly halts development of Alzheimer's drug. Associated Press (AP) (17 August 2010) FullText | Comment by Dr. Koudinov
By TOM MURPHY (AP)

Excerpt: Eli Lilly and Co. has stopped developing a potential Alzheimer's disease treatment... The Indianapolis company said Tuesday preliminary results from late-stage studies of semagacestat showed it did not slow the progression of Alzheimer's, and patients taking the drug actually fared worse than those on a placebo...

...Lilly said Tuesday patients taking semagacestat [Alexei Koudinov in-text note: Semagacestat blocks the enzyme γ-secretase, which (along with β-secretase) is responsible for APP proteolysis, to be explained at Alzheimer's Amyloid beta course] saw their cognition, or memory and reasoning skills, and their ability to complete daily living activities like getting dressed worsen "to a statistically significantly greater degree" than patients taking a placebo.

The drug also was tied to an increased risk of skin cancer. Lilly said the decision to halt semagacestat's development will not affect its other potential Alzheimer's treatment, solanezumab [Alexei Koudinov in-text note: humanized monoclonal antibody against Amyloid beta, this Alzheiemr's therapy trial to fail in due course].

There is no known cure for Alzheimer's disease. Drugs on the market that treat it only temporarily alleviate symptoms. Scientists aren't even sure what causes Alzheimer's.

Earlier this year, Pfizer Inc. and partner Medivation Inc. said the promising Alzheimer's treatment Dimebon failed to work in a late-stage study, but the companies are continuing another study of the drug as an add-on treatment for Alzheimer's.
Johnson & Johnson also is developing the potential treatment bapineuzumab, and there are several other drugs in late-stage testing...

This publication URL

Amyloid beta of Alzheimer's Disease Online Course launched by Alexei Koudinov, MD, PhD, DrSci

2010-08-17T17:50:00.003+03:00

Alexei Koudinov, MD, PhD, DrSci, just launched new theme web site, called "Amyloid beta of Alzheimer's Disease Online Course". The description of the web site particularly says: "Amyloid beta protein is in fact not that bad as Alzheimer's disease research dogma painted it. It is in fact an essential protein, preserved from a fly to Humans. Can you believe that? Then read on to learn more. You will make fascinating discoveries and will realize while conventional Alzheimer's therapy development is on the wrong pass. No prior science education required.". The project will be interactive, so, virtual students can answer quiz questions and pass tests of their knowledge of Alzheimer's amyloid beta peptide

Unabridged Alzheimer's manuscript series: Amyloid beta oligomers and lipoprotein apoAbeta: mistaken identity well possible, Part 2

2010-08-17T11:52:00.005+03:00

Part 1 is available at this link

This is Part 2 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at: http://alzheimercode.blogspot.com

*****

Amyloid beta oligomers and lipoprotein apoAbeta: mistaken identity well possible

For a decade and a half we all know that Abeta is normally produced by cells and exists as normal soluble molecule and that it indeed is an important brain chemical with a diverse function [[reviewed in Ref.17]]. Even a key scientist of AD field, quoted above Dr. Selkoe acknowledged a number of years ago “that Abeta is produced physiologically and may have a normal function, but when it accumulates excessively in certain regions of the brain, it can oligomerize and attain new, potentially neurotoxic functions, as many labs worldwide -- including ours -- have shown. So, Abeta is normal, but it also appears to contribute to disease. Lowering its brain concentrations back to normal levels is one approach to treating and preventing AD. We are certainly not ignoring its physiological role.” [[18]]. Selkoe group was one of those who confirmed A association with the lipoproteins as a circulatory form of Abeta [[19]].

However, sadly and contrary to what Selkoe says, the physiological role for Abeta is largely ignored. We first hand experienced the opposition to deliver our public scientific concern on the validity of amyloid oligomers when attempting to contribute communication arising matter on the article published in Nature [[10, 12, 20]]. Our letter finally was published, but in a different journal, British Medical Journal [[15]]. A key date is March 26, 2003 when Neuron published an article that opened scientific discussion of synaptic function for Abeta and its precursor (APP) in the major neuroscience journal [[21]]. Interestingly, this research by the lab of an accomplished neuroscience leader was published three years after it was first reported at the 32nd Society for Neuroscience Annual Meeting 2000, enlightening the tight opposition by opponents for a public scientific presentation of the data on Abeta physiological function, and well supporting the conclusion of assisted by Dr. Koudinov widely recognized journalistic research by Sharon Beagley, major US-based science journalist (then a WSJ staff science writer) [[2,3,4,5,22]].

Our past study and research by others provided evidence that Abeta is a structure-functional apolipoprotein constituent (apoAbeta) of high density lipoproteins in both blood and cerebrospinal fluid [[23, 24, also see Refs. 17, 25 for detailed bibliography]]. Abeta is also secreted by hepatic cells [[26]] and by the astrocytes [[27]] as a part of lipoprotein complexes [[26, 27]]. Lipoproteins provide a proper thermodynamic environment for Abeta that shares with other apolipoproteins a unique structural property of amphipathicity [[28, 29]]. The amphipathicity explains an association of some apolipoproteins' hydrophobic parts with lipids of the outer layer of lipoprotein particles, and with apolar parts of other apolipoprotein molecules. Another characteristic of amphipathic molecules is the high tendency to self-associate which also takes place during protein oligomerization and amyloid fibril formation. Magnificent experimental evidence indicates that, out of the lipid environment, apolipoproteins are easily subjected to cross- and self- aggregation, oligo- and polymerization [[reviewed in Ref. 28]]. Moreover, some of them form amyloid fibrils and represent separate types of human amyloidosis, ex. apoA-I and serum amyloid A (AA). Interestingly, amyloid story of Alzheimer’ was introduced in 1984 by George Glenner [[30]], who studied different type amyloidoses. Should one carefully research his scientific contribution and legacy, he or she could be impressed by Dr. Glenner dedication and willingness to demonstrate Alzheimer’s is just another amyloid disease in line with other pathologies that he studied previously. Dr. Glenner died in 1995 at the age of 67, he suffered himself of systemic senile amyloidoses [[31]].

Well, Alzheimer’s story is not that simple as amyloid hypothesis proponents are trying to convince others. ...to be continued

References

17. AR. Koudinov, TT. Berezov. Alzheimers amyloid-beta (Abeta) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiologica Exp. (2004) 64(1): 71-79. http://www.nencki.gov.pl/pdf/an/vol64/koudin.pdf

18. Correspondence with Dennis Selkoe. Alexei Koudinov web site (Aug. 2002-July 2004) Available at: http://koudinov.info/archive/selkoe.html

19. AL. Biere, B. Ostaszewski, ER. Stimson, BT. Hyman, JE. Maggio, DJ. Selkoe. Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma. J. Biol. Chem. (1996) 271(51): 32916-22.

20. Correspondence with Nature Editorial office. (April 2002 – Dec. 2002) Available at: http://neurobiologyoflipids.org/editors/alexeikoudinov/pdfdocs/submittedletters/koudinov2nature02.pdf

21. F. Kamenetz, T. Tomita, H. Hsieh, G. Seabrook, D. Borchelt, T. Iwatsubo, S. Sisodia, R. Malinow. APP processing and synaptic function. Neuron (2003) 37:925-937

22. Correspondence with Sharon Begley. Alzclub.org (2003) To be available at: http://www.alzclub.org

23. AR. Koudinov, E. Matsubara, B. Frangione, J. Ghiso. The Soluble form of Alzheimer's amyloid beta protein is complexed to high density lipoprotein 3 and very high density lipoprotein in normal human plasma plasma. Biochem. Biophys. Res. Commun. (1994) 205:1164-1171.

24. AR. Koudinov, NV. Koudinova, A. Kumar, R. Beavis, J. Ghiso. (1996) Biochemical characterization of Alzheimer's soluble amyloid beta protein in human cerebrospinal fluid: association with high density lipoproteins. Biochem. Biophys. Res. Commun. (1996) 223:592-597

25. AR. Koudinov, TT. Berezov, NV. Koudinova. The levels of soluble A in different HDL subfractions distinguish Alzheimer's and normal aging CSF: implication for brain cholesterol pathology? Neurosci Lett. (2001) 314:115-118.

26. AR. Koudinov, NV. Koudinova. Soluble amyloid beta protein is secreted by HepG2 cells as an apolipoprotein. Cell. Biol. Inter. (1997) 25:265-271.

27. MJ. Ladu, C Reardon, L Van Eldik, AM. Fagan, G Bu, DM. Holtzman. Lipoproteins in the central nervous system. Ann. NY Acad. Sci. (2000) 903: 167-175.

28. AR. Koudinov, TT. Berezov, A. Kumar, NV. Koudinova. (1998) Alzheimer's amyloid beta interaction with normal human plasma high density lipoprotein: association with apolipoprotein and lipids. Clin. Chim. Acta (1998) 270: 75 –84.

29. AR. Koudinov, NV. Koudinova, TB. Berezov, YuD. Ivanov. HDL Phospholipid: a Natural Inhibitor of Alzheimer's Amyloid beta Fibrillogenesis? Clin. Chem. Lab. Med. (1999) 37: 993-4.

30. GG. Glenner, CW. Wong. (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. (1984) 120: 885-890.

31. W. Saxon. Dr. George G. Glenner, 67, Dies; Researched Alzheimer's Disease. New York Times. (14 July 1995). Available at: http://query.nytimes.com/gst/fullpage.html?res=990CE5DC1F30F937A25754C0A963958260

This publication URL at Alzheimer's Code | At AlzClub.org

After Alzheimer's amyloid hypothesis, introduction. An unabridged original edition of the manuscript, published in Journal of Alzheimer's disease

2010-08-16T14:24:00.003+03:00

This is Part 1 of the unabridged original manuscript, submitted by invitation in April 2009 to the theme issue of The Journal of Alzheimer's disease. Edited by the Journal edition was later published and is available upon request (will be published here at a later date)

Alexei Koudinov, Elena Kezlya, Natalia Koudinova, Temirbolat Berezov Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. Journal of Alzheimer’s Disease. 2009 18(2): 381-400. Unabridged Notedited Original Author Edition. Available at: http://alzheimercode.blogspot.com

*****

Amyloid hypothesis dominated the stage of Alzheimer’s disease research for over two decades but failed to explain the pathogenesis of Alzheimer’s disease (AD) or provide neurodegeneration cure. The original formulation of the hypothesis stated that at the origin of Alzheimer’s pathogenesis are the fibrillogenesis of amyloid beta protein (Abeta) and the formation of amyloid plaques that cause synaptic failure and clinical picture of memory loss. Interestingly, vast majority of Abeta experimentation was performed in vitro with the synthetic analogs of heterogeneous Abeta peptides (in terms of molecule length due to amino acid number variations). Also interesting is that despite of claimed abundance in AD brain, human Abeta was never purified in preparative quantities from Alzheimer’s brain sections. In 2002 failed experimental vaccine treatment of Alzheimer’s with antibodies against Abeta [[1]] caused severe brain inflammation in a significant number of patients, worthening of AD symptoms and patients’ death. This was the time of the first major public criticism of amyloid hypothesis and AD field. Two years later, Sharon Begley of the major international Wall Street Journal (WSJ) with the assistance of a number of premier scientists worldwide concluded in a series of the WSJ Science magazine [[2,3,4,5]] that over the years amyloid hypothesis has become dogma that retarded the development of the entire field for more then a decade. At the same time the hypothesis was challenged by a number of Alzheimer’s neuroscience research groups and finest science journalists worldwide [[2,3,4,5,6,7,8,9]]. Moreover, UK Parliament hearing [[10]] reported on the competing financial interest by a number of key players of AD field and science and professional establishment (such as American Academy of Neurology [[11]]), and uncovered the sad role of major STM journals (ex., Science, Nature, Neuron) in retarding the publication of alternative Alzheimer’s theories [[10]].

Yet, the pharmaceutical industry research is still dominated by amyloid hypothesis, primarily through the usage of mutant Abeta transgenic mice as a “gold standard” animal model for testing prospective Alzheimers therapies.

In reply on a challenge, amyloid proponents refurbished their big bucks backed argument. The latest edition of the amyloid theory states that the major AD culprit are amyloid beta oligomers [[12]]. They particularly say that “there is growing evidence that mild cognitive impairment in early AD may be due to synaptic dysfunction caused by the accumulation of non-fibrillar, oligomeric Abeta (amyloid beta-peptide), long before widespread synaptic loss and neurodegeneration occurs. Soluble Abeta oligomers can rapidly disrupt synaptic memory mechanisms at extremely low concentrations via stress-activated kinases and oxidative/nitrosative stress mediators.” [[13]]. In his latest review article, Dennis Selkoe of Harvard says that "during the last 25 years, neuropathological, biochemical, genetic, cell biological and even therapeutic studies in humans have all supported the hypothesis that the gradual cerebral accumulation of soluble and insoluble assemblies of the amyloid beta-protein in limbic and association cortices triggers a cascade of biochemical and cellular alterations that produce the clinical phenotype of Alzheimer's disease." [[14]]. He adds, that “the reasons for elevated cortical Abeta levels in most patients with typical, late-onset AD are unknown, but… these could turn out to include augmented neuronal release of Abeta during some kinds of synaptic activity”. He thus allows physiological function for Abeta, but apparently is hesitant to discuss it publicly in greater details. “Elevated levels of soluble Abeta42 monomers enable formation of soluble oligomers that can diffuse into synaptic clefts, …can disrupt hippocampal LTP in slices and in vivo and can also impair the memory of a complex learned behavior in rats,” Selkoe concludes [[14]].

Lacking-since-inauguration is the possibility that Abeta oligomers are experimental artifacts [[12, 15]]. This is because missed is the pivotal consideration that as a lipoprotein structural component, Abeta molecule gets easy amyloidogenic oligomerization out of lipid environment. Association of Abeta with high density lipoproteins (HDL) in plasma and cerebrospinal fluid (CSF) was first demonstrated by us in early 1990s [[16]], confirmed by many groups since then, and is an apparent structural reason for Abeta involvement in lipid metabolism, as outlined below.

References:

1. SR. Robinson, GM. Bishop, G. Munch. Alzheimer vaccine: amyloid  on trial. Bioessays (2003) 25:283-288.

2. S. Begley. Is Alzheimer's Field Blocking Research Into Other Causes? The Wall Street Journal (9 April 2004) p.B.1
http://online.wsj.com/article/SB108145279348578177.html

3. S. Begley. Scientists World-Wide Battle a Narrow View Of Alzheimer's Cause.
The Wall Street Journal (16 April 2004) p.A.9
http://online.wsj.com/article/SB108206188684384119.html

4. S Begley. Fevered Debate Over Alzheimer's Origins Causes Deep Divisions. The Wall Street Journal (6 August 2004) p.B.1 http://neurobiologyoflipids.org/news/news2004.html#wsj060804

5. RW. Mahley, S Goldberg, RJ. Hodes. Does Bias Confound Alzheimer's Research? The Wall Street Journal (27 April 2004) p.A.19 http://neurobiologyoflipids.org/news/news2004.html#wsj

6. Bishop GM, Robinson SR, Smith MA, Perry G, Atwood CS. Call for Elan to publish Alzheimer's trial details. Nature. 2002 Apr 18;416(6882):672704047.

7. AR. Koudinov, MA. Smith, G. Perry, NV. Koudinova. Alzheimer's disease and amyloid beta protein. Science (25 June 2002) Available at: http://www.sciencemag.org/cgi/eletters/296/5575/1991

8. Correspondence with Geoffrey Cowley, Newsweek Health and Science reporter (2003) To be available at: http://alzheimercode.blogspot.com

9. Crowley D. (16 Nov 2003) Selkoe's sale of Elan shares referred to SEC. Sunday Times. Available at: http://www.timesonline.co.uk/article/0,,2095-895532,00.html

10. Koudinov AR. Part 1: Editorial and publisher corruption. Written evidence for inquiry on Scientific Publication by Science and Technology Committee, UK House of Commons. (2004) Available at: http://www.publications.parliament.uk/pa/cm200304/cmselect/cmsctech/399/399we125.htm Also available at: http://neurobiologyoflipids.org/editors/alexeikoudinov/pdfdocs/submittedletters/koudinovwrittenevidence.pdf

11. Correspondence with Murray Sagsveen, General Counsel and Associate Executive Director, American Academy of Neurology (AAN). (Nov. 2002-March 2003) Available at: http://neurobiologyoflipids.org/editors/alexeikoudinov/pdfdocs/submittedletters/koudinov2aansagsveennov02march03.pdf

12. DM. Walsh, I. Klyubin, JV. Fadeeva, WK. Cullen, R. Anwyl, MS. Wolfe, MJ. Rowan, DJ. Selkoe. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature (2002) 416:535-539.

15. AR. Koudinov, NV. Koudinova. Amyloid hypothesis, synaptic function, and Alzheimer’s disease, or Beware: the dogma is revitalized. British Medical J. (2002) Available at: http://bmj.com/cgi/eletters/324/7338/656

16. NV. Koudinova, A. Kontush, TT. Berezov, AR. Koudinov. Amyloid beta, neural lipids, cholesterol and Alzheimer's disease. Neurobiology Lipids (2003) 1:6. Available at: http://neurobiologyoflipids.org/content/1/6/

Alzheimer's disease code by Alexei Koudinov, MD, PhD, DrSci

2010-08-15T11:43:00.006+03:00

(August 15, 2010, Rehovot, Israel) Dr. Alexei Koudinov announces, that he just launched long ago though web site Alzheimer's disease code, published under Blogger platform, and presently available at alzheimercode.blogspot.com . The project, as the home page states, is "a white paper of the wrong doing of Alzheimer's disease research and its' leadership, aiming to protect public interest in the neurosciences of devastating human brain neurodegenerative disorders". The project will run in conjunction with alzforum twitter account by Dr.Koudinov, to make the story message bolder.

Plans are to follow the present developments of the basic and clinical neurosciences of Alzheimer's disease and a number of related disorders, including Down syndrome, Niemann Pick's Type C disease, Neuromuscular Junction pathologies, and Parkinson's disease, and enlighten sad history of Alzheimer's field corruption, so, new generations of students, scientists and the public would have a more accurate picture of true developments (and retardation) of the cure of the most devastating human brain disorders

Was Alois Alzheimer Right or Wrong?

2009-05-15T01:00:00.003+03:00

- Why senile dementia was misclassified as "Alzheimer's disease,"

and how it confused the field.

In 1907, Aloysius "Alois" Alzheimer presented a rare case of dementia in a 51-year-old woman. This "presenile dementia" (younger than 60) was thought distinct enough from "senile dementia" (older than 65) to warrant a new name, thus it became known as, "Alzheimer's disease" (AD).

In the 1970s, however, some researchers argued that because of their similar symptoms and diagnostic hallmarks, "Alzheimer disease and senile dementia should be considered a single disease" [1]. This would mean that Alzheimer was wrong. Since then, AD research has been directed at finding a pathogenic cause, be it genetic, metabolic, toxic, or some other causative factor. But after 30 years, while the cause for presenile dementia, or early-onset familial AD, has been essentially found in the form of three mutant genes, the cause for senile dementia, or late-onset sporadic AD, remains unknown [2]. Perhaps Alzheimer was right, after all.

Consider other diseases with onset at both middle age and old age. Senile hearing loss, for example, would be etiologically different from hearing loss in middle age despite similar symptoms and pathology - just as a new car that breaks down must have some mechanical defect, whereas problems with a very old car will be less obvious. Many other old-age diseases - osteoporosis, atherosclerosis, cataracts, and muscle atrophy - can also occur in young and middle aged individuals, but only in rare cases, generally the result of genetic defects. Thus, it appears to be a general case that the senile disorders constitute a family of illnesses that are fundamentally distinctive from their similar mid-age counterparts by origins, onset age, and prevalence - similar to our two types of car breakdown. Clearly, lumping them together while ignoring these distinctions would result in far-reaching confusions in research, a concern of a growing number of investigators [2-5].
Emphasizing its age-related nature, however, does not mean that senile dementia would be hopeless and inevitable, because the disorder is largely influenced by genotypic difference such as ApoE genes and other contributing elements including diet, lifestyle, and social factors. As such, targeting these elements has proven effective in postponing, ameliorating, or preventing illnesses within one's lifespan. Nevertheless, because these elements are numerous, senile dementia is a multifactorial disorder and, as such, it should not surprise that there may not be any single factor that can be taken as its pathogenic cause.

Thus, defining senile dementia as AD has not just given it a new name, like amyotrophic lateral sclerosis for Lou Gehrig disease but has converted it conceptually into a reversible disease. While successfully arousing support from the public and Congress in hopes of a cure, this definition has singled senile dementia from other senile conditions and misguided its research toward pathogen-hunting. This may be why after 30 years of study and more than 60,000 papers published, the origins of senile dementia remain an enigma.

Current funding priorities should be restructured to emphasize research on senile dementia. Such studies should take aging, or passage of time, as the starting point for reasoning, and explain the hallmark lesions mechanistically and coherently. Studies should focus on the risk-enhancing factors, which seem to matter little for the young, but can push the oldest cells over the brink, and develop remedies that can activate and strengthen the cells to extend their lifespan - similar to what we do for other late-life disorders. Though much more challenging than tackling early-onset dementia, only such studies and the incremental progress that follows will answer the social crisis we face.

References

1. R. Katzman, "The prevalence and malignancy of Alzheimer's disease: a major killer," Arch Neurol, 33:217-8, 1976. [PubMed]
2. M. Chen, H.L. Fernandez, "Alzheimer's disease revisited 25 years later: Is it a "disease" or senile condition?" Front Biosci, 6:e30-40 2001. [PubMed]
3. P.J. Fox et al., "Defining dementia: social and historical background of Alzheimer disease," Genet Test, 3:13-9 1999. [PubMed]
4. D.A. Drachman, "Aging of the brain, entropy, and Alzheimer disease," Neurology, 67:1340-52, 2006. [PubMed]
5. R.H. Swerdlow, "Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?" Neurobiol Aging, July 28, 2006 doi:10.1016/j.neurobiolaging.2006.06.021 [PubMed]

Ming Chen is director of the Neurobiology of Aging Research Laboratory at Bay Pines VA Medical Center and the University of South Florida, USA. Email: ming.chen[at]va.gov

Submitted by Ming Chen. Originally published at The Scientist, June 2007, p.23

Robert Katzman: 1925-2008

2008-09-18T15:59:00.006+03:00

ROBERT KATZMAN: 1925-2008 - Physician's research brought more attention to Alzheimer's. Keith Darcй. UNION-TRIBUNE (September 18, 2008)

Dr. Robert Katzman, who in the mid-1970s recast Alzheimer's disease as a major illness rather than a natural part of aging, died Tuesday after battling heart disease for several years. He was 82.

Dr. Katzman's work triggered an explosion in interest in Alzheimer's disease, which led to increased funding to study the disease and search for treatments and a cure.

Dr. Katzman, who lived in La Jolla with his wife, Nancy, was the founding director of the Shiley-Marcos Alzheimer's Disease Research Center at the University of California San Diego. He held the Florence Riford Chair for Research in Alzheimer's Disease at UCSD from 1984 until his retirement in 1995. Read Article Full Text...

PET Scan Can Detect Alzheimer's Symptoms

2008-08-16T17:52:00.001+03:00

PET Scan Can Detect Alzheimer's Symptoms
eMaxHealth.com - Hickory,NC,USA
A type of brain imaging named positron emission tomography (PET) scan may allow physicians to detect early symptoms of Alzheimer's disease.

Alzheimer's rates expected to climb among minority elderly

2008-04-29T05:01:00.000+03:00

By Susan J. Landers

Health care disparities and low minority enrollment in clinical trials interfere with crafting solid treatment plans for blacks and other minorities.

Washington -- As research findings coalesce around a collection of risk factors for Alzheimer's disease, it is becoming obvious that poor and minority populations -- the ones most likely to harbor risk factors such as hypertension and diabetes --also are more likely than whites to encounter this brain disorder.

The age-specific prevalence of dementia already has been estimated to be from 14% to as much as 100% higher in blacks than in whites by the Alzheimer's Assn., an advocacy and educational group based in Chicago. And the disease is expected to surge among Hispanics in the coming years. Currently, about 200,000 Hispanics in the U.S. have Alzheimer's. That number could climb to 1.3 million by 2050, according to the association.

Cardiovascular disease, high cholesterol levels, hypertension, obesity, diabetes and fewer years of education all are factors that may increase an individual's risk for Alzheimer's disease, and minorities are overrepresented in all of these factors.

Since there is unlikely to be a cure for dementia anytime soon, a Plan B for addressing the needs of this group of aging, at-risk minorities was offered at the Annual Conference of the National Council on Aging and the American Society on Aging, held March 26-30 in Washington, D.C.

Presented by Richard E. Powers, MD, a geriatric psychiatrist and medical director of the Alabama Dept. of Mental Health and Mental Retardation in Tuscaloosa, the approach covers the reduction of risk factors, early recognition of disease, aggressive therapy, caregiver support and research. Dr. Powers also is the chair of the Medical Advisory Board of the Alzheimer's Foundation of America, a national, nonprofit organization founded in 2002 and based in New York City.

The fact that few members of minority groups are enrolled in clinical trials to examine the links between risk factors and cognitive decline can lead to treatment complications, Dr. Powers noted. That has to change, he stressed.

"We need to be able to show an African-American that if you don't take your antihypertensive when you are 50, you will end up like your father -- who had terrible dementia -- when you are 70 or 80."...

Source: Susan J. Landers, AMNews (28 April 2008) [FullText]

Local musician plans Alzheimer's walk

2008-04-24T22:30:00.000+03:00

By Nanci G. Hutson

For Bob Brophy, a musician and Manhattan sightseeing tour guide with an off-beat sense of humor, nothing is even slightly amusing about Alzheimer's disease.

"I'm angry about it," said Brophy, whose mother, Peggy, died of Alzheimer's six years ago and whose beloved father-in-law, Joe Michael, 90, the retired national sales director for Encyclopedia Britannica, was diagnosed with it 18 months ago.

Brophy used his anger to become a driving force behind New Milford's first Memory Walk for the Connecticut chapter of the Alzheimer's Association. The May 3 event will raise money for research.

The 10 a.m. walk -- 1.5 to 3 miles -- around the New Milford Village Green will be preceeded by registration at 9 a.m.

Brophy learned about the walk, a national event, from the Senior Center Alzheimer's support group his mother-in-law, Mieke Michael, attends.

He engaged Joe, a born salesman, to ask store owners to hang fliers in their windows.

"Who could say no to Joe?" Brophy queries.

Brophy enlisted his wife, Felicia Michael, and their band, The Blue Yodels, to play for the walk's early March kick-off.

They then formed a 12-member Blue Yodels' team, with his in-laws as honorary members. To date the team, one of about 30, is the event's top benefactor, raising $5,000 of its $10,000 goal. The walk has some $16,500 in pledges.

Brophy also arranged for a pasta dinner fundraiser Sunday from noon to 6 p.m. at S. J. Barrington's Cafe & Grill on Route 7. Admission, $10 per person, includes a dinner, cash bar and raffle prizes.

Brophy is a nearly constant companion for his father-in-law, regularly taking him to play pool, darts or run errands.

"Joe's always itching to do so something," Brophy said.

Mieke, 88, is Joe's main caregiver but requires regular respite.

Alzheimer's Association education and training coordinator Carolyn DeRocco said the Michaels are fortunate to have caring family members to offer support as they cope with the disease.

"They're so creative in compensating for what (Joe) can't do," DeRocco said. "They keep him very active."

In past years, Brophy and his wife have donated their time and talents to other charities, including two AIDS bike rides from Manhattan to Boston. This cause, though, touches a much deeper chord.

In the words of his wife, Brophy said, there are two reasons to perform: "Love or money."

This is clearly for love, he said.

"If this is the least we can do for my mom and for Joe, then we should do the least."

Memory Walk pasta dinner benefit
WHAT -- complete pasta meal with cash bar and raffle prizes. Music by The Blue Yodels and Doug Mahard.

WHEN -- Sunday from noon to 6 p.m.

WHERE -- S.J. Barrington's Cafe & Grill, 48 Kent Road (Route 7 North), New Milford.

HOW -- $10 tickets can be purchased in advance by calling the restaurant at (860) 355-9222.

For more information -- visit blueyodels@aol.com or call (646) 354-0041.

Alzheimer's Association Memory Walk

WHAT -- the nation's largest event to raise awareness and funds for Alzheimer's care, support and research.

WHEN -- May 3 with 9 a.m. registration and 10 a.m. walk (1.5 to 3 miles)

WHERE -- New Milford Village Green

HOW --Sign up with a team of friends or family, with an organization, or as an individual participant.

Source: newstimes.com (23 April 2008) [FullText]

Vitamin E May Help Alzheimer's Patients Live Longer

2008-04-24T14:20:00.000+03:00

People with Alzheimer's disease who take vitamin E appear to live longer than those who don't take vitamin E.

For the study, researchers followed 847 people with Alzheimer's disease for an average of five years. About two-thirds of the group took 1,000 international units of vitamin E twice a day along with an Alzheimer's drug (a cholinesterase inhibitor). Less than 10 percent of the group took vitamin E alone and approximately 15 percent did not take vitamin E.

The study found people who took vitamin E, with or without a cholinesterase inhibitor, were 26 percent less likely to die than people who didn't take vitamin E.

"Vitamin E has previously been shown to delay the progression of moderately severe Alzheimer's disease. Now, we've been able to show that vitamin E appears to increase the survival time of Alzheimer's patients as well," said study author Valory Pavlik, PhD, with Baylor College of Medicine's Alzheimer's Disease and Memory Disorders Center in Houston, TX, and member of the American Academy of Neurology. “This is particularly important because recent studies in heart disease patients have questioned whether vitamin E is beneficial for survival.”

In addition, the study found vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone. "Our findings show that people who took a cholinesterase inhibitor without vitamin E did not have a survival benefit,” said Pavlik. “More research needs to be done to determine why this may be the case.”

In addition to vitamin E supplements, some vegetables oils, nuts, and green leafy vegetables are main food sources of vitamin E. Some fortified cereals in the United States also contain vitamin E. “The daily amount of vitamin E taken by patients in this study was much higher than what is currently recommended for the general population,” said Pavlik.

Source: eMaxHealth (23 April 2008) [FullText]

Love that can't be forgotten: Alzheimer's fails to stop man from loving his wife of 68 years

2008-04-23T16:37:00.002+03:00

By Nanci G. Hutson

Snuggling arm and arm on a couch in their Sullivan Farm living room, every now and then sneaking a tender kiss, Joe and Mieke Michael seem the epitome of newlywed bliss.

They are, however, approaching their 68th wedding anniversary.

Theirs is an abiding love, one that has long inspired their four adult children, five grandchildren, three great-grandchildren, in-laws, friends and strangers.

"They're unbelievable," says their youngest daughter, Felicia, born on her father's 43rd birthday. "They were always in love. Sure, they've had their conflicts and struggles like any couple, but what prevailed was this underlying devotion to each other. It was astonishing to witness. Very rare."

Even today, when half of this whole is suffering from a disease that robs its victims of their memories, Joe and Mieke, at 90 and 88 respectively, are true lovers.

Eighteen months ago, Joe was diagnosed with Alzheimer's disease, a progressive terminal illness with no known cure.

On May 3, New Milford will have its first Memory Walk to benefit Alzheimer's research.

"I love him more than ever, and now is when he needs me most,'' said Mieke, a vivacious and elegant woman who was a Dutch folk singer in the 1950s, performing at Radio City Music Hall, Carnegie Hall and the old Danbury Fair. She still receives royalties from the recording "Greetings from Holland" she made with partner Nina Dunkel, who died years ago of pancreatic cancer.

Pulling her close to his side,

Joe displays a toothy smile. "I'm lucky to have this one," he says.
Joe Michael was born in Danbury and lived in Redding for 40 years. He was the national sales director for Encyclopedia Britannica, a chairman of the Redding school board, and in the Eisenhower years ran unsuccessfully as a Democrat for state Senate.

The couple retired to their summer home in West Hampton, Long Island, then moved to New Milford three years ago. Of their children, Felicia lives closest -- just two miles away, while Kim lives in Newtown, Vicki in Virginia, and Richard in Texas.

Joe wags his finger at the woman he proposed to on their first date. He still calls his bride.

"I love you," Joe declares.

"I love you, too," Mieke answers as she hems a pair of his pants.

Joe grins wider.

"Can you believe I was able to convince her to marry me?" Joe asks some visiting guests. He quickly adds, "That's before I had Alzheimer's."

The disease, Mieke said, is " a challenge every day. I never know what's going to happen."

The fireplace in their condominium is chain locked because one morning he apparently placed a burning log on the nearby floor and started a small fire.

"She gives me heck," Joe says with a chuckle. "But I enjoy it. I'm very fortunate."

Felicia's husband, Bob Brophy, becomes teary-eyed.

"They've always been so positive and pleasant all their lives,'' Brophy said of the couple, nicknamed Muzzy and Duzzy. "They can draw on that now. But a lot of these changes are hard."

Joe is a handsome, charming man with thick, wavy white hair who looks far younger than his chronological age. His healthy appearance can deceive those unaware of the debilitating illness that is ever so slowly taking him away.

He no longer remembers his phone number, address, or days of the week. He repeats stories from 65 years ago, but cannot remember what he did a few minutes earlier. He recognizes family, but new acquaintances he is likely to forget.

"He hasn't forgotten me yet," Mieke said.

His family is not certain Joe knows what is happening to him, though he is able to give a few answers.

"You forget," Joe said of his disease. "You don't maintain mentally, so you rely on your old mentality. The best way I deal with it is that I married a brilliant woman."

"We're dealing with it," Mieke said, "and dealing with it in style."

Contact Nanci G. Hutson

at nhutson@newstimes.com

or at (860) 354-2274.

Alzheimer's disease facts

Alzheimer's disease -- a progressive, terminal illness -- is the most common form of dementia, affecting some 5 million people a year. It is the seventh leading cause of death in the U.S. Age is the top risk factor.

The average illness lasts between three and 20 years.

The leading symptoms are:

Forgetfulness severe enough to affect work, hobbies and social life.

Inability to recall information.

Short-term memory loss.

A decline in ability to write, speak or understand written or spoken words.

Loss of visual spatial abilities, such as map reading skills, and ability to understand symbols and signals.

Inability to make plans, resolve problems or complete tasks.

There is no known cause or cure for Alzheimer's disease.

The Connecticut chapter of the national Alzheimer's Association tries to reduce the risk of dementia by promoting brain health. It participates in national research efforts to find a cure.

For more information, call (860) 828-2828 or visit www. alz.org/ct.

Source: newstimes.com (23 April 2008) [FullText]

Funding for Alzheimer's should be top priority

2008-04-23T13:15:00.002+03:00

Mature Adult continues to carry the torch in our personal media campaign to pressure our legislators on Capital Hill to fund intense research to find the cause of Alzheimer's disease.

The Alzheimer's Association wants $1.4billion dollars, but so far Congress has refused to allocate it.

We're certain there are members of Congress with family members or friends or constituents with Alzheimer's, the worst of the mental diseases.

In this region, Alzheimer's claims more victims every day. Without the dollars to increase the research required to find the cause, the statistics will climb dramatically during this decade.

The current issue of the Alzheimer Association's newsletter states that critical funding for Alzheimer's research at the National Institutes of Health will remain flat and fail to keep up with inflation.

President Bush in his fiscal 2009 budget proposal rejected the Alzheimer's Association's funding appeal. The budget also eliminated money for other services and care, including a 243-hour helpline, caregiver support groups and professional caregiver training, the association reported.

How cruel can the administration and Congress be? A lot, it seems, and we can't figure out why Congress feels this way.

"Alzheimer's advocates across the country are mobilized, galvanized and focusedon pushing the government to aggressively pursue an end to this insidious disease," said Fredericka Waugh of the Alzheimer's Association Delaware Valley chapter. "They are determined make their voices heard and their vote count."

"These Alzheimer's Championswill continue to spread the word among their neighbors, to write letters, send emails and on May 14, they will deliver the message to lawmakers on Capitol Hill that Alzheimer's disease must be addressed and funded as a national priority," Waugh said. To contact Waugh, call (215) 561-2919.

Source: thehammontonnews.com (23 April 2008) [FullText]

Midland County joins Project Lifesaver to aid in rescue of missing seniors, disabled individuals

2008-04-22T16:46:00.002+03:00

By Cathy Heng

Steve Kayden says his autistic daughter may not speak, but she has a talent for disappearing. "She has a tendency to escape," the Midland father said. "You turn your back, and she disappears. She's even left her classroom with several adults supervising."

Hollie Kayden, 8, is one of the first three Midland County participants in Project Lifesaver, an initiative that helps emergency responders quickly find people with Alzheimer's disease, dementia and other disabilities.

The girl and two other participants -- Kazuko Spraull, 87; and Melvin "Smiley" Fischer, 64, both of Midland -- now wear bands that emit a tracking signal. Hollie wears the band as an anklet.

Midland is the third Michigan county to use the device, joining Saginaw and Grand Traverse counties.

Clients wear numbered wristbands that emit a tracking signal that Central Dispatch can trace, Midland County Sheriff Jerry Nielsen said. When caregivers notify law enforcement that a person is missing, a rescue team responds with a mobile tracking system.

Mary Spraull said her mother, Kazuko Spraull, still talks about the time she was lost in the woods 10 years ago.

"It was awful. I could see the house in the woods, and then I couldn't -- it was dark," said Kazuko Spraull, who became lost on her daughter's 40-acre tract.

Fischer, the third wristband wearer, likes to walk but loses track of time and wanders off -- even in the cold -- because of dementia, his caregivers said.

"Since 2002, there have been more than 45 missing person reports in which a person walked away in Midland County," said Jan Lampman, executive director of The Arc of Midland, a nonprofit agency that promotes the welfare of people with developmental disabilities.

Nielsen recalled the three-day search for Linda R. Crouch, a 54-year-old woman with dementia who wandered from the Pinecrest Home, a county facility for seniors and people with disabilities, in November 2006. She turned up in a barn across from the Homer Township facility.

The search included a state police helicopter, firefighters scouring woods with thermal imaging cameras, a dive team, four dog handlers and 17 full-time and reserve deputies. It cost $10,000 in personnel and equipment expenses, the sheriff said.

"With this system, we might have found her in 10 minutes," he said.

In Saginaw County, 35 people have worn the bracelets since the Sheriff's Department launched the effort for $5,300 in 2004, said Karen M. Courneya, director of the Saginaw County Commission on Aging.

Presently, 15 county residents wear the devices. Deputies have relied on them six or seven times to find the wearers, she said.

The Arc received $9,255 from the Midland Area Community Foundation to start the project.

Other participants are Community Mental Health and Senior Services of Midland County, the Midland Police Department and the Midland County Sheriff's Department.
Project Lifesaver started in Chesapeake, Va., in 1999 when rescuers used FM transmitters to track missing people with Alzheimer's disease, Lampman said.

Midland County has about 1,500 people with Alzheimer's. The Arc may have another 300 clients who could use the tracker. Lampman said the initial cost of the device and its battery is $420, then $120 per year after that. Insurance may pay, or donations are available, she said.

Project Lifesaver has reported no serious injuries or deaths in more than 1,000 searches nationally, Lampman said. Recovery time with the device averages 30 minutes.

Courneya said she's excited about Midland County adopting the system because agents in the two counties can work together if their residents cross county lines. Saginaw officials helped train Midlanders in the technology.

In Saginaw County, residents 60 or older are eligible to receive a bracelet. To get one, call the Commission on Aging at 797-6880.

Source: Cathy Heng. For The Saginaw News (22 April 2008) [FullText]

Announcing Arizona Alzheimer's Consortium conference

2008-04-22T08:43:00.003+03:00

Physicians and other experts will talk about progress in the fight against Alzheimer's disease at an Arizona Alzheimer's Consortium conference.

Registration for next month's 10th-annual conference - for patients, caregivers, family members and scientists - is open now.

The morning session will include a physician and caregiver panel discussion, with time for audience members to ask questions. The afternoon session is a science forum, but it is open to non-scientists, too. advertisement

Details: 8 a.m.-5 p.m. May 30 at Renaissance Glendale Hotel & Spa, 9495 W. Coyotes Blvd. The conference, buffet breakfast and lunch are free, but reservations are required at 602-239-6901 or azalz.org.

Source: Connie Midey The Arizona Republic (22 April 2008) [FullText]

Living with Alzheimer's

2008-04-22T03:40:00.002+03:00

The UNK marketing team will be presenting their Alzheimer's Marketing Plan to Great Plains chapter CEO, Program Director and me at the School of Business on Wednesday, April 23 at 10:00 a.m.

The hometowns of the Alzheimer student team members are: Sidney, O'Neill, Ravenna, Fullerton, North Platte and Lawrence.

On April 24 from 2-6 p.m. at Kearney Homestead Assisted Living we will support their Virtual Dementia tour. This is a free event open to the public to increase awareness about what it is like to have dementia. Participants will put on a headset, goggles and other items to simulate common symptoms of dementia. They will be told to complete 5-10 tasks in a 5 minute period. They will be taken to a room in the facility to complete their tasks.

Kearney, NE, April 7, 2008 - The Alzheimer's Association® estimates that 10 million baby boomers will develop Alzheimer's disease in the United States, according to their new report released today, the 2008 Alzheimer's Disease Facts and Figures.

The new report says the disease is poised to strike one out of eight baby boomers. According to the Alzheimer's Association, now is the time to address this looming epidemic that currently has no effective disease-modifying treatments that halt or delay the progression of the disease.

"The 2008 Alzheimer's Disease Facts and Figures shows the tremendous impact this disease is having in Nebraska and nationwide. With 33,000 people with Alzheimer's disease living in Nebraska today and with the prevalence expected to grow to 37,000 by 2010, now is the time to develop an effective blueprint to deal with this disease," said Karen Noel, the executive director of the Alzheimer's Association's Great Plains Chapter.

Today, as many as 5.2 million Americans are living with Alzheimer's disease, the seventh leading cause of death in the country and the fifth leading cause of death for those over age 65. The Association's report offers numerous statistics that convey the burden Alzheimer's imposes on individuals, families, government, business, and the nation's health and long term care systems. For example,

Every 71 seconds, someone in America develops Alzheimer's disease; by mid-century someone will develop Alzheimer's every 33 seconds.

By 2010, there will be almost a half million new cases of Alzheimer's disease a year; and by 2050, there will be almost a million new cases each year.

Women are nearly twice as likely as men to develop Alzheimer's disease (17 percent vs. 9 percent). One in six women and one in ten men age 55 and older can expect to develop Alzheimer's disease in their remaining lifetime. Although it may appear that being female is a risk factor, more women will develop Alzheimer's because on average, women live longer than men, thereby having more time to develop the disease.

The report highlights that last year, in Nebraska alone there were 54,319 caregivers, providing 46,888,454 hours of unpaid care for a loved one with Alzheimer's or another dementia valued at 496,079,839 dollars. In 2007, there were nearly 10 million Americans age 18 and over providing 8.4 billion hours of unpaid care to people with Alzheimer's disease valued at $89 billion. An additional quarter of a million Alzheimer caregivers were children age 8 to 18.

With seventy percent of people with Alzheimer's and other dementias living at home where friends and family take care of them, the disease not only touches the individual but entire families.

According to the latest statistics from the Centers for Disease Control and Prevention, from 2000-2005 death rates have declined for most major diseases -- heart disease (-8.6 percent), breast cancer (-.8 percent), prostate cancer (-4.9 percent) and stroke (-14.4 percent), while Alzheimer's disease deaths continue to trend upward, increasing 45 percent during that period.

"It is more important than ever that research funding be increased to find effective treatments that delay the progression of the disease. The Alzheimer's Association continues to be vigilant in offering support to individuals living with the disease as well as the 54,319 Alzheimer caregivers in this state who are grappling with the tremendous challenges an Alzheimer's diagnosis brings to one's doorstep," said Noel.

The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer's disease through the advancement of research; to provide and enhance care and support for all affected; and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. For more information, visit alz.org.

Source: Nebraska.tv (21 April 2008) [FullText]

Upcoming National Conference Bridges Neuroscience and Education

2008-04-21T23:25:00.002+03:00

The brain is "plastic," according to recent findings in neuroscience, and that concept can help teachers and educators improve learning. Brain plasticity will be the focus of a gathering of nearly 800 educators, from across the U.S. and other countries, to be held in Massachusetts at the end of this month.

The Learning & the Brain conference was co-founded by Kenneth S. Kosik, co-director of the Neuroscience Research Institute at the University of California, Santa Barbara, and Harriman Professor of Neuroscience Research, along with Anne Rosenfeld and Kelly Williams. The 20th edition of the conference will be held in Cambridge, Mass., on April 26-29, and registration is still open. See: learningandthebrain.com/. Continuing education credits are available to participants. (The conference fee is waived for credentialed members of the press)

This year's conference theme is "neuroplasticity," or how the brain changes with learning, memory, and experience. The meeting will focus on the discovery that the brain is not "hardwired" from birth, but holds a remarkable lifelong power to change. Positive or negative environments, exercise, nurturance, learning, and other experiences continue to change the brain throughout life.

These revolutionary findings point to new possibilities for "rewiring" the brain to help overcome learning disorders and to enhance memory, learning, IQ, and achievement in all learners. "Neuroscience has the potential to transform education," said Anne Rosenfeld, conference president.

Conference participants will learn about:

Brain-based teaching for children, adolescents and adults
How stress and early adversity shape brains and later learning
New insights into reading and math disorders and interventions
Influences that change the brain and affect learning
Cutting-edge environments, technology and insights into adult learning
Techniques for treating mood, ADHD, stress, and learning problems
How the brain can be retrained to improve attention and memory
The role of brain plasticity in resilience, empathy, and teaching

While learning and the brain go together like hand and glove, it was not until 1999 that educators and neuroscientists created a gathering place to discuss new research findings with respect to the classroom and clinical practice. "This marriage between neuroscience and education is pretty new," said Kosik. "But people now see it as a discipline in its own right."

The Learning & the Brain conference evolved a decade ago when Kosik met with conference coordinators Anne Rosenfeld and Kelly Williams. Rosenfeld and Williams were referred to Kosik by the Belmont, Mass. superintendent of schools, who told them about the Saturday workshops that Kosik was holding in Belmont to teach children, parents, and teachers about the brain. He was a professor of neuroscience at Harvard University during this time.

Together Kosik, Rosenfeld, and Williams founded the national Learning & the Brain conference. The first conference, in 1999, featured a welcome video by then-first lady Hillary Clinton.

Regarding this year's conference and neuroplasticity, Kosik explained that perhaps no other topic within the vast field of neuroscience has lured more neuroscientists than the question

of how the brain changes with learning and memory. "While neuroscientists approach this topic at the level of genes, and synapses, and brain imaging, clearly the fruit of this research will impact how we can better educate our children," he said.

Kosik sums up a few of the reasons why the bridge between neuroscience and education is so important:

Measurable benefits accrue from art and music education, from learning a second language, and from physical exercise.

The performing arts foster the sustained attention necessary to improve performance in other areas of cognition.

Early interventions and enrichment have long-term measurable benefits and are most beneficial when implemented from birth.

Education offers protection against late life cognitive impairment such as Alzheimer's disease.

Adjusting the school day to be more in accord with the sleep-wake cycles of children and young adults has been solidly shown to have measurable benefits.
"These are just a few of the concrete contributions that neuroscience has made to education," said Kosik.

This year's conference features a prestigious list of faculty members that includes prominent neuroscientists, psychiatrists, psychologists, and educators. Several of them have written important books in the field of learning and the brain.

Kurt Fischer, director of the Mind Brain and Education Program at the Harvard University Graduate School of Education, will present special remarks. Fischer said that the conference has helped pioneer connecting biology and cognitive science with educational practice and policy. He edits the award-winning new journal, Mind, Brain and Education, published by Blackwell. "Every conference brings together top scientists who are doing cutting-edge research with practitioners who lead the way in connecting research to practice," said Fischer. "Neuroscience is creating powerful tools that can greatly improve education."

Conference co-sponsors are: Martinos Center for Biomedical Imaging at the Massachusetts Institute of Technology; Mind Brain and Education Program at Harvard Graduate School of Education; Comer School Development Program, Child Study Center at Yale Medical School; Dana Alliance for Brain Initiatives; Department of Speech, Language, and Hearing Sciences at Boston University; Boston University School of Education; Neuroscience Research Institute at the University of California, Santa Barbara; National Association of Secondary School Principals; and Public Information Resources, Inc.

Source: Media-Newswire.com (21 April 2008) [FullText]

Medivation's Dimebon Improved Thinking, Memory In Alzheimer's Patients

2008-04-21T19:56:00.002+03:00

Alzheimer's patients treated with Medivation's investigational drug Dimebon showed improvement in the key aspects of cognitive function over a one-year period compared with placebo. The improvement occurred in not only memory and language, but also in more complex functions such as awareness of time and place, and praxis -- the process of getting an idea and initiating and completing a new motor task. These clinical results were generated during a pivotal trial of Dimebon in patients with mild-to-moderate Alzheimer's disease (AD).

The data were presented today during an oral presentation at the 60th Annual Meeting of the American Academy of Neurology (AAN) by Steven H. Ferris, Ph.D., the Gerald J. and Dorothy R. Friedman Professor of Psychiatry at New York University and director of the NYU Alzheimer's Disease Center.

"The finding that Dimebon improved memory, orientation, language and praxis in Alzheimer's disease patients suggests that it provides a broad rather than a selective cognitive benefit," said Dr. Ferris. "This is an important finding given that deficits in memory and thinking are one of the hallmarks of Alzheimer's disease and cause patients and caregivers significant distress."

Dimebon Significantly Improved Cognitive Function at One Year

The data presented at the AAN Annual Meeting included results of an analysis of the 11 subdomains of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), a standardized measure of cognition in patients with AD and one of two endpoints the U.S. Food and Drug Administration (FDA) has used to approve all currently marketed drugs for mild-to-moderate AD. In the study, ADAS-cog was assessed at the beginning of the study and at weeks 12, 26, 39 and 52.

Results showed that Dimebon-treated patients were significantly improved compared with placebo on 9 of the 11 ADAS-cog subdomains after one year of treatment. Benefits were observed in memory (word recall, p=0.04; word recognition, p=0.03; remembering instructions, p=0.10); orientation (p= 0.01); constructional praxis (the ability to copy simple drawings or patterns, p=0.005) and ideational praxis (the ability to perform a familiar but complex sequence of actions, p=0.006); and language (following commands, p<0.0001; naming objects, p<0.0001; word finding, p=0.005; comprehension, p=0.15; overall language, p=0.0002).

"We have recently presented a number of different findings from our first pivotal trial of Dimebon at scientific conferences, demonstrating that this investigational drug has a beneficial impact on the key aspects of Alzheimer's disease -- from behavioral symptoms to thinking and memory problems to impairments in daily function," said Lynn Seely, M.D., chief medical officer of Medivation. "Medivation is committed to rapidly developing Dimebon as a treatment for mild-to-moderate Alzheimer's disease to make it available to the millions of people who suffer from this increasingly prevalent disease, for which new treatment options are desperately needed."

Dimebon Showed Statistically Significant Benefit Versus Placebo on All Key Efficacy Endpoints

Medivation previously announced efficacy and safety results from the pivotal, 12-month, double-blind, placebo-controlled trial of Dimebon in 183 patients with mild-to-moderate AD. Dimebon improved the clinical course of Alzheimer's disease patients by causing statistically significant improvements over placebo in each of the five primary aspects of the disease -- memory, thinking, activities of daily living, behavior and overall clinical function. Significant gains over placebo were evident after as little as 12 weeks of treatment, and were maintained after both six months and a full year of treatment. In addition, after six months of treatment, Dimebon patients were significantly better on all five disease aspects than they were at the beginning of the study. The real-world impact of these data was evaluated by independent assessment, including caregiver interviews, which confirmed improvement or stabilization in 81 percent of Dimebon-treated patients after six months of treatment. Importantly, Dimebon's overall benefit compared to placebo continued to increase over time, and was larger at one year than at six months.

Dimebon was well-tolerated throughout the entire one-year treatment period. The majority of adverse events were mild, with dry mouth (18.0 percent Dimebon, 1.1 percent placebo) and depressed mood the most common events. There were significantly fewer serious adverse events in the Dimebon group than in the placebo group at one year.

Medivation is planning to initiate a second, confirmatory pivotal Phase 3 trial of Dimebon in mild-to-moderate AD in the second quarter of 2008 with the goal of completing the trial and applying for U.S. and European marketing approval in 2010. The Company is also evaluating Dimebon in an ongoing Phase 2 clinical trial in mild-to-moderate Huntington's disease. Dimebon is an orally-available small molecule that has been shown to inhibit brain cell death in preclinical models relevant to Alzheimer's and Huntington's diseases, making it a potential treatment for these and other neurodegenerative diseases.

Source: eMaxHealth (21 April 2008) [FullText]

Researchers examine a key risk factor for Alzheimer's

2008-04-21T14:20:00.002+03:00

By John Scott

Researchers at the Washington University School of Medicine have spent four years working to determine what effects a specific protein can have on Alzheimer's brain plaques, a key risk factor for the disease.

An estimated five million Americans suffer from Alzheimer's, a disease that destroys brain cells and causes people to develop memory and behavior problems.

John Cirrito, research instructor in neurology and lead researcher of the study, said that the study, published in the April 10 issue of the journal Neuron, has been underway for 1.5 years. The topic has been studied for four years.

The team of researchers examined amyloid beta, a protein derived from amyloid precursor protein. Buildups of amyloid beta can create plaques in the brain that lead to a variety of problems including death of brain cells, eventually contributing to Alzheimer's disease. According to Cirrito, scientists have been trying to determine what regulates the protein's production.

Cirrito said that amyloid beta affects two key areas of the brain, the cortex and the hippocampus. The cortex is responsible for cognitive functions while the hippocampus controls memory. The plaques inhibit the functions of these areas, leading to the symptoms indicative of Alzheimer's disease.

"Before [the plaques] kill the cells, [researchers] think they're making neurons fire incorrectly," Cirrito said.

The study targeted a cellular process known as endocytosis, a process in which cells absorb materials from their surroundings by pinching off a section of their membrane. Production of amyloid beta is linked to both endocytosis and communication between brain cells. In the study, stopping endocytosis decreased the level of amyloid beta by 70 percent.

According to Cirrito, the function of amyloid beta and its precursor are still unknown. Endocytosis, however, is a necessary function for nearly all cells in the body. Therefore, it is very difficult to inhibit the process without causing harm to the cells, so treatments must be specifically targeted.

Source: John Scott. Student Life (21 April 2008) [FullText]

Study: Cholesterol raises Alzheimer's risk

2008-04-21T13:18:00.002+03:00

By Monifa Thomas

Avoiding heart disease isn't the only reason to keep your cholesterol in check. A new study has found the risk of developing Alzheimer's disease is higher for people who, in their 40s, have high cholesterol.

Alzheimer's is also more likely to start early for heavy drinkers and smokers, according to a separate study presented Wednesday at the American Academy of Neurology conference in Chicago.

A study of nearly 9,800 men and women from northern California found that people who had high cholesterol levels in their early 40s were at least 1.25 times more likely to develop Alzheimer's disease by the time they reached their 70s.

"High mid-life cholesterol increased the risk of Alzheimer's disease regardless of mid-life diabetes, high blood pressure, obesity, smoking and late-life stroke," said study author Dr. Alina Solomon of the University of Kuopio in Finland.

Another study presented at the neurology conference found that Alzheimer's starts earlier for people who have a history of heavy smoking and drinking. The study was based on 938 people 60 or older who were diagnosed with possible or probable Alzheimer's disease.

Those who had a history of heavy drinking developed Alzheimer's nearly five years earlier than people who were not heavy drinkers. Heavy smokers got Alzheimer's two years sooner.

People who smoked and drank -- and had a gene variant known to increase the risk of Alzheimer's -- developed the disease 8.5 years sooner than people who had none of these risk factors, the study found.

Source: Monifa Thomas, Health Reporter (mjthomas@suntimes.com) 21 April 2008 [FullText]

Alzheimer's & cholesterol: Problems with low cholesterol pop up

2008-04-21T02:33:00.002+03:00

By Joe Graedon and Teresa Graedon, Ph.D.

What may be good for the heart could be bad for the brain. Lowering cholesterol, especially bad LDL cholesterol, appears to reduce the risk of heart attacks. But new studies suggest that very low cholesterol might pose unexpected problems for the nervous system.

Researchers have analyzed data from a long-term study of Japanese-American men in Honolulu. Blood samples of healthy men were measured in the early 1990s. During the next decade, researchers noted who was diagnosed with Parkinson's disease. Those with low LDL cholesterol initially were significantly more likely to develop this neurological disorder (Movement Disorders online, March 31, 2008).

This is not the first time that low LDL cholesterol has been linked with a higher risk of Parkinson's disease. Other neurological problems also may be associated with low cholesterol. One study uncovered a link between low cholesterol and Alzheimer's disease (Neurology, Aug. 11, 1999).

Scientists in New Zealand have been monitoring adverse effects of cholesterol-lowering medications. They have noted that statins may be associated with depression, memory loss, confusion and aggressive behavior (Drug Safety, March 2007). The authors point out that "Cholesterol is crucial to brain functioning."

A new study (Neurology, March 25, 2008) links low LDL cholesterol to worsening of ALS (Lou Gehrig's disease). In fact, the researchers conclude: "The beneficial effect of hyperlipidemia (high cholesterol) on survival of more than 12 months is, to our knowledge, one of the most important documented."

Probably the most controversial issue hinges on whether lowering cholesterol with statin-type medications is linked to ALS-like syndrome. The French researcher who conducted the study on LDL and ALS, Vincent Meininger, M.D., Ph.D., was asked in a Neurology journal podcast whether there could really be a statin-related ALS connection. He responded, "I think yes."

It is very difficult for scientists to determine whether statin-type medicines trigger or worsen ALS. Many people have reported their experiences to www.peoplespharmacy.com (analyzed in Drug Safety, February 2008).

Here is one example:

"My husband took Lipitor for several years. After a knee replacement, his leg muscle deteriorated, and no amount of exercise could bring it back. Then he developed swallowing problems. He had trouble breathing, but at the emergency room they found nothing wrong.

"He had a lot of pain and no relief even with pain medicine. His muscles weakened so much that he could not eat food unless it was put in a blender. He went from 165 to 113 pounds, losing so much muscle that he fell many times and could only walk with a walker.

"He was an active man before all this happened and exercised every day. He had so many tests to find his problem, but it was not diagnosed as ALS until the morning of the day he died in July 2007. This is a horrible disease and a horrible way to die."

No one knows whether there truly is a relationship between statin-type cholesterol-lowering medicine and ALS-like syndrome. The Food and Drug Administration is investigating this issue. Anyone who would like to report serious problems with such medications can do so at the FDA's Web site (www.fda.gov/medwatch)....

Source: Joe Graedon and Teresa Graedon. Problems with low cholesterol pop up. King Features Syndicate (20 April 2008) [FullText and Q&A section]

Alzheimer's disease caregiver news 2008/04/21

2008-04-21T00:12:00.006+03:00

Finding support for `the most difficult job'
Charlotte Observer - Charlotte,NC,USA
"I am in the most difficult job I have ever had," a local caregiver said about caring for her spouse who has Parkinson's disease. ...
See all stories on this topic

Caregivers' corner: Incontinence can often be managed if not corrected
Annapolis Capital - Annapolis,MD,USA
My mother has Alzheimer's disease and has been incontinent for the past year. Her doctor said it was to be expected. Is there really a fix for it? ...
See all stories on this topic

Health Briefs for April 20
North County Times - Escondido,CA,USA
Herman will discuss the role of specialized environments when caring for someone with Alzheimer's disease or dementia. Reserve to (760) 479-1818 or ...
See all stories on this topic

This News Alert is brought to Alzclub readers by Google.

Otley MP backs author's call for Alzheimer's funding

2008-04-20T23:34:00.003+03:00

By Jim Jack

MP Greg Mulholland is backing best selling author Terry Pratchett's calls for increased funding for research into Alzheimer's disease.

Mr Mulholland, whose constituency includes Otley, Bramhope and Pool-in-Wharfedale, says not enough is being done to try to find a cure for the condition, despite more than 700,000 people in the UK living with dementia.

Mr Pratchett, author of the globally popular Discworld series of comic fantasy novels, was recently diagnosed with Alzheimer's diseaseand has donated a million dollars (around £500,000) to research into the disease.

Mr Mulholland said: "Dementia affects hundreds of thousands of people in the UK, yet it is still fundamentally misunderstood and receives scant attention, despite the devastating impact that it can have on the lives of those who suffer from it.

"While great advances in our understanding of Alzheimer's disease and the new approaches to treatment and prevention are being made here in the UK, it is still nowhere near enough. We are at real risk of failing sufferers of Alzheimer's, particularly vulnerable older people, and leaving them marginalised and ignored.

"So I am very happy to back Terry, and the Alzheimer's Research Trust, in calling for an increase in funding so that we can promote research and understanding of this vitally important issue."

Chief Executive of the Alzheimer's Research Trust, Rebecca Wood, said: "I welcome Mr Mulholland taking the lead on trumpeting dementia research funding by sponsoring this motion.

"We are delighted MPs have chosen to support the campaign by Terry Pratchett and the Alzheimer's Research Trust to increase research funding for dementia: a disease that 700,000 people in the UK live with.

"Research is the only way to beat this disease and help people like Terry - to prevent them losing their thinking skills and keep them doing the things they love.

"For every person with Alzheimer's, £11 is spent each year on UK research compared with £289 for each cancer patient, even though similar numbers of people are affected."

Source: Jim Jack. Otley MP backs author's call for Alzheimer's funding. wharfedaleobserver.co.uk [FullText]

Pfizer's Lipitor Failed to Slow Alzheimer's Disease in Study

2008-04-19T23:14:00.000+03:00

By Michelle Fay Cortez and Elizabeth Lopatto

Pfizer Inc.'s best-selling cholesterol drug Lipitor failed to slow mental and physical worsening in patients with Alzheimer's disease, a study found.

The results clash with previous research that showed high cholesterol raises the risk of Alzheimer's disease, an inexorable loss of memory and function that affects 4.5 million Americans. The study of 640 patients, the largest ever on cholesterol-lowering statin drugs for the condition, found patients fared the same whether they got Lipitor or placebo.

Pfizer, which funded the study presented at the American Academy of Neurology's annual meeting in Chicago, is looking for ways to expand Lipitor's use as competing medications lost patent protection. Lipitor accounts for about 40 percent of Pfizer's profits and its sales slid 7 percent to $3.1 billion in the first quarter, the company said.

The study ``did not demonstrate significant benefits on the symptoms of mild to moderate Alzheimer's disease,'' said Howard Feldman, who helped guide the study and is head of neurology at the University of British Columbia Hospital in Canada. ``There are some noteworthy findings that require further analysis and should inform further research to determine the potential for statin use in this population.''

Patients in the 18 month study received Aricept, New York- based Pfizer's Alzheimer's drug, in addition to either Lipitor or a matching placebo. There were no differences between the groups in the ability to think and reason by the end of the trial. Mental, behavioral and physical abilities were all similar, the researchers said.

Analysis in Men

After the study was completed, an unplanned analysis suggested men getting Lipitor may have had a slower rate of decline, the researchers said. Those results must be confirmed with additional trials. In addition, imaging scans of the brain suggested less shrinking in the hippocampus, previously considered an indicator of worsening disease.

Pfizer said it is not planning additional studies of Lipitor in patients with Alzheimer's disease.

The first symptom of Alzheimer's may be mild forgetfulness. As it progresses, patients forget how to brush their teeth, change their clothes, or recognize once-familiar people. They become confused and agitated and eventually require constant care, according to the Bethesda, Maryland-based National Institute on Aging.

The number of patients with Alzheimer's disease is expected to soar in the coming years as the baby boomers age. Someone is currently diagnosed with the disease every 71 seconds, and 10 million baby boomers will develop it eventually, according to the Alzheimer's Association.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.netElizabeth Lopatto in New York at elopatto@bloomberg.net.

Source: Bloomberg (17 April 2008) [FullText]

Health Tip: Talking to a Person With Alzheimer's Disease

2008-04-18T15:01:00.000+03:00

As Alzheimer's disease progresses, communicating becomes more of a challenge.

The U.S. National Institute on Aging offers these suggestions for talking to someone with Alzheimer's:

Speak in a calm, soothing tone of voice.Use simple, short words and sentences -- but avoid baby talk, or speaking like you would to a child.Avoid talking about the person in front of him or her.Turn off the TV, radio or any other possible distractions when trying to communicate.Get the person's full attention before speaking, and refer to the person by name. If the person is trying to communicate but is having trouble finding words, gently try to suggest words the person may be looking for.Be patient and give the person plenty of time to think and respond.

Source: Health Day News. washingtonpost.com (18 April 2008) [FullText]

Pfizer says study shows Lipitor has no significant impact on Alzheimer's

2008-04-17T03:09:00.000+03:00

Pfizer (NYSE:PFE) Inc. said that the largest statin study of patients with Alzheimer's Disease shows that its blockbuster cholesterol-lowering prescription drug has no significant impact on the disease.

'In a study in patients with mild-to-moderate Alzheimer's disease (AD), the addition of Lipitor (atorvastatin calcium tablets) 80 mg to Aricept(R)(donepezil HCl) 10 mg showed no significant differences in cognition or global function (key measures of Alzheimer's progression) compared to placebo plus Aricept 10 mg.Lipitor,' the company said.

However, Pfizer, which is expected to report lacklustre sales of Lipitor in first-quarter results out later on Thursday, said the study further confirmed the safety profile of 80 mg doses of Lipitor in elderly patients.

The 18-month study included 640 patients and was the largest statin study in Alzheimer's disease.

Pfizer is attempting to build up its product pipeline as its patent for Lipitor expires in 2010.

Source: CNN Money & Thomson Financial delivered by Newstex. Newstex ID: AFX-0013-24562002 (17 April 2008) [FullText]

Results from Largest Statin Study of Patients with Alzheimer's Disease Show Lipitor(R) Has No Significant Impact on Disease

2008-04-16T07:21:00.000+03:00

NEW YORK, Apr 16, 2008 (BUSINESS WIRE) -- In a study in patients with mild-to-moderate Alzheimer's disease (AD), the addition of Lipitor (atorvastatin calcium tablets) 80 mg to Aricept(R: 67.12, +3.05, +4.76%) (donepezil HCl) 10 mg showed no significant differences in cognition or global function (key measures of Alzheimer's progression) compared to placebo plus Aricept 10 mg. Furthermore, no statistically significant differences were seen on various cognitive, behavioral and functional secondary endpoints. However, the Lipitor arm was not associated with greater cognitive decline than the placebo arm in this trial. The results were presented today at the annual American Academy of Neurology meeting in Chicago.

The 18-month study, called Lipitor's Effect on Alzheimer's Dementia (LEADe), included 640 patients and is the largest statin study in Alzheimer's disease.

While rates of decline in cognition and global function were similar for both the Lipitor and placebo groups, there were some interesting findings from the trial:

In a sub set of 64 patients for whom MRI scans were available, patients in the Lipitor arm had significantly less decline in hippocampal volume in the brain compared to the placebo arm. While the clinical significance of this result is not yet fully understood, less decline in hippocampal volume may be beneficial since declines have been associated with the progression of Alzheimer's disease. This finding requires further investigation and analysis.

In a sub-analysis completed after the trial, men in the Lipitor arm had a significantly slower rate of decline in cognition compared to men in the placebo arm. There was no difference in the rate of decline in cognition in women in the Lipitor arm compared to women in the placebo arm. However, no definitive conclusions can be drawn from this post-hoc analysis.

"The results of our investigation of Lipitor on the symptoms of Alzheimer's disease have been long awaited," said Professor Howard Feldman, chair of the LEADe Steering Committee and professor and head of the division of neurology, University of British Columbia Hospital in Canada. "While the LEADe study did not demonstrate significant benefits on the symptoms of mild to moderate Alzheimer's disease, there are some noteworthy findings that require further analysis and should inform further research to determine the potential for statin use in this population."

Lipitor 80 mg was shown to be well tolerated and the incidence of liver and muscle adverse events in patients was low.

Aricept was selected as the background therapy since it is proven effective for treating the symptoms of Alzheimer's and is the most widely used cholinesterase inhibitor. The effect of Aricept on Alzheimer's was not investigated in this study.

"Over the past 15 years, Pfizer has been committed to researching the potential benefit of Lipitor in patients at various levels of cardiovascular risk as well as in non cardiovascular diseases such as Alzheimer's disease," said Dr. Rochelle Chaiken, vice president of the cardiovascular/metabolic team in Pfizer global medical. "While we are not planning additional studies with Lipitor in patients with Alzheimer's disease at this time, LEADe provides the medical community with important data. In addition, Pfizer is committed to advancing research and treatment in Alzheimer's disease."

About Alzheimer's Disease

Alzheimer's disease is a progressive degenerative brain disorder that gradually destroys a person's memory and ability to learn, reason, make judgments, communicate, and carry out daily activities. As the disease progresses, patient may experience changes in personality and behavior, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations.

About Lipitor

Lipitor is the most prescribed cholesterol-lowering therapy in the world, with nearly 144 million patient-years of experience. Lipitor is supported by an extensive clinical trial program involving more than 400 ongoing and completed trials with more than 80,000 patients.

Important U.S. Prescribing Information for Lipitor

Lipitor is a prescription medication. It is used in patients with multiple risk factors for heart disease such as family history, high blood pressure, age, low HDL ("good" cholesterol) or smoking to reduce the risk of a heart attack, stroke, certain types of heart surgery and chest pain.

Lipitor is also used in patients with type 2 diabetes and at least one other risk factor for heart disease such as high blood pressure, smoking or complications of diabetes, including eye disease and protein in urine, to reduce the risk of heart attack and stroke.

Lipitor is used in patients with existing coronary heart disease to reduce the risk of heart attack, stroke, certain kinds of heartsurgery, hospitalization for heart failure, and chest pain.

When diet and exercise alone are not enough, Lipitor is used along with a low-fat diet and exercise to lower cholesterol.

Lipitor is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, pregnant or may become pregnant.

Patients taking Lipitor should tell their doctors if they feel any new muscle pain or weakness. This could be a sign of rare but serious muscle side effects. Patients should tell their doctors about all medications they take. This may help avoid serious drug interactions. Doctors should do blood tests to check liver function before and during treatment and may adjust the dose. The most common side effects are gas, constipation, stomach pain and heartburn. They tend to be mild and often go away.

For additional product information, visit Lipitor.com.

About Aricept

Once-a-day prescription ARICEPT(R: 67.12, +3.05, +4.76%) (donepezil HCl tablets) is indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate and severe Alzheimer's disease (AD). ARICEPT helps with memory, thinking and everyday tasks.

ARICEPT is the number-one prescribed AD medication worldwide, with more than 3 billion patient days of ARICEPT therapy sold. Nearly 2.3 million people in the United States alone have begun ARICEPT therapy.

Important U.S. Prescribing Information for Aricept

ARICEPT is the first once-a-day Alzheimer's prescription medication available in the U.S. and can be taken with or without food. Available in 5 mg or 10 mg dosage strengths, ARICEPT 5 mg and 10 mg are approved for the treatment of mild to moderate AD. ARICEPT 10 mg (after four to six weeks at 5 mg) is approved for the treatment of severe AD. ARICEPT(R: 67.12, +3.05, +4.76%) ODT(TM: 101.55, +2.98, +3.02%) (donepezil HCl) Orally Disintegrating Tablets are available in the U.S. in 5 mg and 10 mg tablets, providing the same dosage strength of drug as ARICEPT tablets.

ARICEPT is well tolerated but may not be for everyone. People at risk for stomach ulcers or who take certain other medicines should tell their doctors because serious stomach problems, such as bleeding, may get worse. Some people who take ARICEPT may experience fainting. Some people may have nausea, vomiting, diarrhea, bruising, or not sleep well. Some people may have muscle cramps or loss of appetite or may feel tired. In studies, these were usually mild and temporary.

For additional product information, visit aricept.com

SOURCE: Pfizer Inc: Pfizer Vanessa Aristide, 212-733-3784 or Rebecca Hamm, 212-733-8811Copyright Business Wire 2008

Alzheimer's association Federal Policy April 2008 update

2008-04-10T23:57:00.000+03:00

contributed to AlzClub by Diane Christopher

As we reported last month, both the US House and Senate approved separate versions of a “Budget Resolution” (S Con Res 70/ H Con Res 312) � a document that provides guidance oon how much Congress should spend on specific federal programs, including Alzheimer research.

The Senate “Budget Resolution” recommended a $3 billion increase for all medical research - an effort led by Senators Specter (PA) and Harkin (IA). Congress is now in the process of resolving the differences between the two versions of the “Budget Resolution”.

The Alzheimer’s Association is urging Congress to accept the Senate-recommended increase for research. The overall amount recommended for research will be an important factor when the Appropriations Committees begin consideration of their annual appropriations bills.

If Congress is unable to reach agreement on the “Budget Resolution” by May, the Appropriations Committees are expected to begin debating individual bills. At this time, we do not know when the bill that funds research will be debated but will let you know when further action is needed!

While initial Alzheimer funding decisions will be made this spring, final votes on the appropriations bills are not expected until after the November presidential election.

The Association's goal is for Congress to increase funding for Alzheimer research by $125 million over current funding ($644 million) to accelerate clinical trials on new treatments and prevention methods and to improve techniques for earlier diagnosis.

What Can I do NOW?

Ask your friends and family to help multiply our numbers on Capitol Hill!

We need more voices joining advocates storming the US Capitol during our Day on the Hill in Washington DC on May 14th during the annual Public Policy Forum.

HOW? Share the Virtual Visit url: www.alz.kintera.org/virtualvisit

Personal messages from advocates will be hand-delivered to Congress by advocates from your state.

Alzheimer's Disease Congressional Hearing at Forum

On May 14th, the U.S. Senate Special Committee on Aging will convene a hearing to explore the impact of Alzheimer’s on the baby boom generation. The hearing will feature testimony from Alzheimer advocates. The focus will be: latest information about new Alzheimer drugs and diagnostic techniques in development; unique challenges faced by boomers with early onset Alzheimer’s disease; and an update on the Alzheimer’s Study Group’s (chaired by Newt Gingrich and former Senator Bob Kerrey) national strategic plan on Alzheimer’s.

Stay tuned for more information about how you can watch the hearing if you can’t make it to the Public Policy Forum.

Original text by Alzheimer's association

Alzheimers Disease… What’s It Really Like?

2008-02-11T13:00:00.000+02:00

By Diane L. Christopher
Buffalo, New York

I would like to dedicate this in Honor of my Beloved Mother, diagnosed with Alzheimers Disease, who passed away last April 22, 2006. Just exactly how many people are familiar with this horrible disease? Some may say they have never heard of it. Others may say it’s “hardening of the arteries.” Some may even say it’s just old age “creeping in.” But, the real truth of the matter is, it’s the most debilitating, demoralizing, destructive, and devastating disease within existence.

Does anyone really know what a person with this disease goes through?

How they spend their hours, their days, their nights, their very existence? Just once, we should try and view the world through their eyes. Just once, we should walk the path they walk. And just once, we should be told we can no longer live on our own. That we are incapable of taking proper care of ourselves.

The trouble is everyone is too busy and too caught up in their own daily lives to feel the pain, the anguish, the fears and tears of a person with this disease . “There but by the Grace of God go I.” Please take a moment to just think about it, as this world they now exist in is very confusing, dark, lonely and at times, almost completely void of reality as we know it. To a person with this disease the world can be a pretty frightening place. A clouded, distorted view of life free of warmth, free of past comforts, and even at times free of love because of lack of understanding.

What have we brought into this world? Nothing! What can we take out of this world when we leave it? Nothing! Just once try to put yourselves in their place. Try once to experience first hand the frustration, the emptiness, and the heartache that that fills their day each and every day.

When was the last time you had to have someone feed you, or the last time you had to have someone dress you, or bathe you? Or comb your hair , or for that matter, brush your teeth? This is merely the beginning as the real heartbreaker is when they can no longer walk or talk, or even swallow their food. Sound horrifying? It is!! Once again, “There but by the Grace of God go I.”

Please try and think long and hard. Please try thinking with your hearts and not your schedules. Please try to take out one hour a week, one hour every two weeks, or possibly just one hour a month. Go and visit a Facility where residents with Alzheimers Disease reside. There is no cost….it’s free. The only thing is it may possibly cost you is a smile, a hug, or a reassuring pat on the shoulder. Perhaps just a listening ear, or a tender loving and caring heart. The rewards reaped will be monumental.

Remember 911? Who could ever forget? But, as the days passed, people seemed to do exactly that. We all returned to our old lives, our old ways of living and our busy schedules. Please don’t let this happen here. The time is here and now. Please give of yourselves, your understanding, your love, your time, and put a smile back upon one face, put back a song within one heart and maybe even wipe away one tear or two from a pair of tired eyes. You will be so very much the richer. But most of all, you will fill someone else’s life with warmth and make a difference in someone’s life that otherwise was quite cold and empty.

May God continue to bless them and you.

Maybe this will help if even in a small way... it is my contribution to all those out there suffering from this disease. And to all the loved ones and friends who are caregivers.

Diane L. Christopher
22 Terry Lane
Buffalo, New York 14225-1340
diane22[at]roadrunner.com

Accidental Memory Stimulation Points at Possible Alzheimer's Treatment

2008-02-09T19:31:00.000+02:00

...A study published in the January 29th Annals of Neurology reveals that surgeons operating on an awake obese patient under general anesthesia discovered that brain stimulation evoked detailed autobiographical memories. The procedure was a last attempt to control the patient's morbidly obese weight and involved Bilateral hypothalamic deep brain stimulation. Researchers tried to find appetite-suppressant areas in the hypothalmus.

As surgeons implanted electrodes into the patient's brain, he suddenly began to experience a flood of memories from a visit to a park he had made decades earlier. He recounted events in amazing detail, from the weather to the types of clothes his friends were wearing. As the current on the electrodes intensified, the memories grew richer in detail. He performed better in simple recall tests with the electrodes turned on than when the current was turned off. Subsequently, the same memories were recounted when surgeons at the Toronto Western Hospital applied current to the same area of the brain two months later.

Deep brain stimulation has already shown to be effective against Parkinson's disease. A neurostimulator surgically implanted into the brain of Parkinson's patients results in marked reduction of tremors, rigidity, and stiffness. The patients are also able to increase speed of movement and have less difficulty walking. In the situation of the obese patient, surgeons monitored the changes in brainwave function through EEG monitors and noticed an increase in brainwave frequency. Sufferers of Alzheimer's have decreased brainwave frequency.

Source: associatedcontent.com (9 Feb 2008)

Paper Alert by Alzforum: ABCA1 Protects Against Amyloid Deposition

2008-02-01T21:35:00.000+02:00

A paper in the January 17 Journal of Clinical Investigation online supports the idea that ABCA1 (ATP-binding cassette A1), a protein transporter involved in lipidation, can protect against amyloid buildup. David Holtzman and colleagues from Washington University, St. Louis, Missouri, overexpressed ABCA1 in PDAPP transgenic mice. First author Suzanne Wahrle and colleagues report that the mice have a very similar phenotype to ApoE-negative animals. Both ABCA1 overexpression and ApoE loss lead to significantly less amyloid-β in the hippocampus than normal PDAPP mice. What little Aβ is present occurs predominantly in the hilus. There is also a dearth of amyloid plaques, as judged by thioflavin S staining. Alzforum first discussed these findings in our report from the Bar Harbor Workshop, Enabling Technologies for Alzheimer Disease Research (see ARF related news story).

ABCA1 seems crucial for loading ApoE with lipid and loss of the transporter leads to reduced levels of ApoE, but not amyloid, in the brain (see ARF related news story). These latest results support the idea that the lipidation status of ApoE is intimately linked with its effect on Aβ processing and aggregation. The data “support the conclusions that increased ABCA1-mediated lipidation of apoE in the CNS can reduce amyloid burden and that increasing ABCA1 function may have a therapeutic effect on AD,” write the authors.—Tom Fagan.

Reference:Wahrle SE, Jiang H, Parsadanian M, Kim J, Li A, Knoten A, Jain S, Hirsch-Reinshagen V, Wellington CL, Bales KR, Paul SM, Holtzman DM. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J. Clin. Invest. 2008 January 17 online. Full Text at J Clin Investigation Abstract

Source: Alzforum research news (22 January 2008) [FullText and comments]

Drug trials: If you pay, it's a good drug

2007-06-29T10:27:00.000+03:00

The effectiveness of a drug is usually established by a trial, often one that also uses a placebo, or sugar pill, or another drug from the same family. These trials are expensive, and they’re invariably funded by the drug’s manufacturer.And guess what? When the drug company is paying, the results are 20 times more likely to be favourable. Even better, the researchers are 35 times more likely to give their conclusions a favourable spin.The effectiveness of the drug over a sugar pill seems to disappear if the funding is from an independent source.Researchers from the University of California uncovered the ‘research for hire’ practice when they investigated 192 published trials for cholesterol-lowering statin drugs. Of those, just half were upfront about the trial’s sponsors.The drug trial is a very worthwhile investment for the drug company. Once its drug has received a favourable review in a so-called ‘scientific’ trial, it’s well on the road to millions of dollars of sales.(Source: PLos Medicine, June 7, 2007, published online).

Original text: Drug trials: If you pay, it's a good drug What Doctors Don't Tell You - London, UK (21 June 2007)

Alzheimer's media news in brief (25 June 2007)

2007-06-26T10:27:00.000+03:00

Alzheimer's fails to rob Robert Kapuniai of his proud link to the 100th Battalion
Honolulu Star-Bulletin - Honolulu, HI, USA
In what could be the last big gathering for many, about 80 World War II veterans of the widely known 100th Infantry Battalion attended a luncheon yesterday at the Hilton Hawaiian Village commemorating the unit's 65th anniversary. Among the majority who are nisei, or second generation Japanese Americans, is Robert Kapuniai, believed to be the last of the few Hawaiians who served in the volunteer battalion.
Kapuniai, who just turned 90 and has Alzheimer's disease, has sons who pass on his stories. That is the solemn mission of succeeding generations, said speaker Maj. Gen. Jason Kamiya. Robert Kapuniai's Alzheimer's disease does what he tried to do for years with alcohol. It makes him forget his pain. It makes him forget when he stood for days in the river, unable to move, because the Germans were near. Forget the pain of shrapnel as pieces pierced his body, permanently damaging his legs and back. But deep down, as the disease approaches its third stage, he remembers a little. When he hears "100th Battalion" or its nickname, "One Puka Puka," for the group of Japanese-American volunteer soldiers who fought in World War II, he remembers vaguely that he was one of them.

Alzheimer's drug challenge launched
Guardian Unlimited - UK
The Government's medicines watchdog is facing a major legal challenge in the High Court over its decision not to continue funding anti-dementia drugs on the NHS for patients in the early stages of Alzheimer's disease.
Drug companies supported by the Alzheimer's Society are challenging decisions by the National Institute for Health and Clinical Excellence. Nice says it made its recommendations because the drug treatment was shown to be not particularly effective for people with mild Alzheimer's disease, and resources should be put into other treatments available on the NHS. The four-day case before Mrs Justice Dobbs at London's High Court centres on the use of acetyl cholinesterase inhibitors (AChEIs) in the treatment of Alzheimer's disease.
Nice recommended that three anti-cholinesterase drugs - Aricept (donepezil), Exelon (rivastigmine) and Reminyl (galantamine) should not be prescribed for use by patients in the early stages of the disease.
The drug marketers, Eisai and Pfizer, argue the effectiveness appraisal process was unfair. They say those consulted by Nice were provided with a "read only" version of the economic model used by the watchdog to evaluate both clinical and cost effectiveness of AChEIs.

David Hyde Pierce Tackles Alzheimer's
News Channel 7 - SC, USA
WASHINGTON (AP) -- David Hyde Pierce is helping start a campaign against Alzheimer's disease, which he saw two family members suffer from. "I think the hardest thing in both cases, with my grandfather and with my dad, were the moments when they understood what was happening to them," Pierce said on ABC's "This Week" program in a segment that aired Sunday. "It's a disease that takes your brain apart, a piece at a time. And it doesn't stop till it kills you." The longtime co-star of the TV series "Frasier" said the Alzheimer's Association's Champions campaign aims to recruit one American for every person with Alzheimer's. A Web site lets people sign up for events, make donations and buy T-shirts. More than 5 million people in the U.S. live with the disease, according to the association. "All we have to do is find a way to slow it down," Pierce said. "We're not trying to keep people from dying. We're trying to keep people from dying this way." The 48-year-old actor won a Tony award earlier this month for his role in "Curtains."

Queen's graduate wins scholarship for pioneering Alzheimer research
Belfast Telegraph - UK
A Queen's University medical graduate has won a prestigious scholarship award to aid pioneering research on Alzheimer's - the first time it has ever gone outside the US. Dr Bernadette McGuinness, from Coalisland in Co Tyrone, was awarded the Paul B. Beeson Career Development Award for her proposed research into Alzheimer's disease and dementia.The £228,000 grant will allow Dr McGuinness and the Queen's team to continue their research which specifically focuses on neuropsychological changes and genetics in early Alzheimer's disease.The Beeson Award is a career development award given to "high calibre individuals seeking to advance research into ageing and medicine for older people". Dr McGuinness was delighted to receive it at a special conference in New York over the weekend.Graduating with an MD in 2006, Dr McGuinness has worked closely with the Dementia Research Group from Queen's School of Medicine (Drs Peter Passmore, Janet Johnston and David Craig). Her research proposal relates to an enzyme thought to be involved in the Alzheimer's process. The team studied activity of an enzyme in platelets and found that the activity was elevated in patients with Alzheimer's...

Emory Participates in Study to Slow Progression of Alzheimer's Disease
DentalPlans.com - Dania, FL, USA
Nutritionists have long endorsed fish as part of a heart-healthy diet, and recent studies have suggested that omega-3 fatty acids found in the oil of certain fish, algae and human breast milk may also benefit the brain by lowering the risk of Alzheimer's disease. In order to test whether an omega-3 fatty acid called docosahexaenoic acid (DHA) can impact the progression of Alzheimer's disease, researchers at Emory University are evaluating DHA in a clinical trial, the gold standard for medical research. The study is supported by the National Institute on Aging (NIA) of the National Institutes of Health. A nationwide consortium of leading Alzheimer's disease researchers is supported by NIA and coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. The clinical trial is taking place at 52 sites across the U.S. The study is seeking 400 participants ages 50 and older with mild to moderate Alzheimer's disease. James Lah, MD, associate professor of neurology at Emory, will lead Emory's participation. Oregon Health and Science University's Joseph Quinn, MD, associate professor of neurology, is directing the national study. Researchers primarily will evaluate whether taking DHA over many months slows the progression of both cognitive and functional decline in people with mild to moderate Alzheimer's...

Alzheimer's Drug Based On Secretase Inhibitor Begins Clinical Trials
Medical News Today (press release) - UK
A drug based on the design of a Purdue University researcher to treat Alzheimer's disease began the first phase of human clinical trials this week. "Millions of people suffer from this devastating disease and treatment options are very limited," said Arun Ghosh, the Purdue professor who led the creation of the treatment molecule. "Current drugs manage the symptoms, but this could be the first disease-modifying therapy. It may be able to prevent and reverse the disease."CoMentis Inc., a biopharmaceutical company based in San Francisco, is initiating the clinical trials of the experimental drug CTS-21166...

Intellect Neurosciences, Inc. Obtains Validation of European Patent for Clinical Candidate in 18 Countries
PR Newswire UK (press release) - London, UK
Intellect Neurosciences, Inc. (OTC Bulletin Board: ILNS), a biopharmaceutical company focused on development of disease-modifying therapeutic agents for the treatment and prevention of Alzheimer's disease and related disorders, announced today that European Patent No.1056452 covering the use of indole-3-propionic acid to treat multiple indications has been validated in several Europe countries...
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News Alert for Alzheimer's (19 June 2007)

2007-06-19T15:00:00.000+03:00

Stress and Alzheimer's disease
News-Medical.net - Sydney, Australia
Subjecting mice to repeated emotional stress, the kind we experience in everyday life, may contribute to the accumulation of neurofibrillary tangles, one of the hallmarks of Alzheimer's disease, report researchers at the Salk Institute for Biological Studies. While aging is still the greatest risk factor for Alzheimer's disease, a number of studies have pointed to stress as a contributing factor. "A long-term study of about 800 members of religious orders had found that the people who were most prone to stress were twice as likely to develop Alzheimer's disease, but the nature of the link between the two has been elusive," says Paul E. Sawchenko, Ph.D., a professor in the Neuronal Structure and Function Laboratory, who led a phalanx of Salk researchers contributing to the current study. The group's findings, detailed in this week's Journal of Neuroscience, suggest that the brain-damaging effects of negative emotions are relayed through the two known corticotropin-releasing factor receptors, CRFR1 and CRFR2, which are part of a central switchboard that mediates the body's responses to stress and stress-related disorders...

Certain Foie Gras Linked To Diseases Such As Alzheimer's And Arthritis, Animal Study Suggests
Science Daily (press release) - USA
University of Tennessee Graduate School of Medicine professor and researcher Alan Solomon, M.D., director of the Human Immunology and Cancer/Alzheimer's Disease and Amyloid-Related Disorders Research Program, led a team that discovered a link between foie gras prepared from goose or duck liver and the type of amyloid found in rheumatoid arthritis or tuberculosis. This experimental data has provided the first evidence that a food product can hasten amyloid development. Amyloidosis is a disease process involving the deposit of normal or mutated proteins that have become misfolded. In this unstable state, such proteins form hair-like fibers, or fibrils, that are deposited into vital organs like the heart, kidneys, liver, pancreas and brain. This process leads to organ failure and, eventually, death. There are many types of amyloid-related diseases in addition to rheumatoid arthritis, such as Alzheimer's disease, adult-onset (type-2) diabetes and an illness related to multiple myeloma called primary or AL amyloidosis, an illness that has been a particular focus of study in the Solomon laboratory. Foie gras is a culinary delicacy derived from massively enlarged fatty livers of ducks and geese. It is produced by gorging the fowl over several weeks. Solomon and his research team analyzed commercially sold foie gras from the U.S. and France and found that it contained a type of amyloid called AA. Amyloid deposits are commonly found in waterfowl, but this condition is noticeably increased in force-fed birds. In their study, mice prone to develop AA amyloidosis were injected or fed amyloid extracted from foie gras. Within eight weeks, a majority of the animals developed extensive amyloid deposits in the liver, spleen, intestine and other organs. Based on the findings of the study, Solomon and his team concluded that this and perhaps other forms of amyloidosis might be transmissible, like "mad cow" and other related diseases. Until now, no other infectious sources of food products have been found...

Alzheimer's associated enzyme can disrupt neural activity in brain
HULIQ - Hickory, NC, USA

An enzyme involved in the formation of the amyloid-beta protein associated with Alzheimer's disease can also alter the mechanism by which signals are transmitted between brain cells, the disruption of which can cause seizures. These findings from researchers at the MassGeneral Institute for Neurodegenerative Disorders (MGH-MIND) may explain the increased incidence of seizures in Alzheimer's patients and suggest that potential treatments that block this enzyme - called beta-secretase or BACE - may alleviate their occurrence. The report will appear in the journal Nature Cell Biology and is receiving early online release. "We have found a molecular pathway by which BACE can modulate the activity of sodium channels on neuronal cell membranes, says study leader Dora Kovacs, PhD, director of the Neurobiology of Disease Laboratory in the Genetics and Aging Research Unit at MGH-MIND. "That implies that elevated BACE activity may be responsible for the seizures frequently observed in Alzheimer's patients." Alzheimer's disease is characterized by plaques within the brain of the toxic amyloid-beta protein. Amyloid-beta is formed when the larger amyloid precursor protein (APP) is clipped by two enzymes - BACE and gamma-secretase - which releases the amyloid-beta fragment. Signaling impulses in nerve cells are transmitted via voltage-gated sodium channels, structures on the cell membrane that transmit electrochemical signal by admitting charged sodium particles into the cell's interior. Sodium channels consist of an alpha subunit, which makes up the body of the channel, and one or two beta subunits that help to regulate the channels' activity. Previous studies from Kovacs' team and others showed that the BACE and gamma-secretase enzymes that release amyloid-beta from APP also act on the beta2 subunit of neuronal sodium channels. The current study was designed to examine how this processing of the beta2 subunit may alter neuronal function. Lead author Doo Yeon Kim, PhD, and colleagues first confirmed that the beta2 subunit, similar to APP, can be acted on by BACE and gamma-secretase, releasing a portion of the beta2 molecule from the cell membrane. A series of experiments using brain tissue from animal models and from Alzheimer's patients revealed the following series of cellular events: Elevated levels of the free beta2 segment within the cell appear to increase production of the alpha subunits, but those molecules are not incorporated into new sodium channels on the cell surface. The resulting deficit of membrane sodium channels inhibits the passage of neuronal signals into and through the cells. Neuronal sodium-channel dysfunction is known to cause seizures in both mice and humans. In a supplement to the current paper the investigators present evidence that sodium channel metabolism is altered in the brains of Alzheimer's patients compared with non-demented individuals of similar age. "Our study suggests that the BACE inhibitors currently being developed to reduce amyloid-beta generation in Alzheimer's disease patients may also help prevent seizures by alleviating disrupted neural activity," Kovacs explains. "However, complete inhibition of BACE activity could interfere with the enzyme's normal regulation of sodium channels, so therapeutic strategies using those inhibitors will need to be carefully designed." Kovacs is an associate professor of Neurology at Harvard Medical School. -Massachusetts General Hospital.

Motion Sensors Used to Predict Alzheimer's Disease
FOX News - USA
The goal: Shave off that time by spotting subtle changes in mobility and behavior that Alzheimer's specialists are convinced precede the disease's telltale...

Discovery Made on Alzheimer's Disease
WLNS - Lansing, MI, USA
US researchers think they've figured out what is responsible for seizures suffered by Alzheimer's patients. Scientists found that an enzyme that contributes...
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New MRI Image Technique Predicts Early Onset Of Alzheimer's Disease
Medical News Today (press release) - UK
Using new MRI techniques to analyze tissue composition and structure in the brain, researchers from the University of Pennsylvania School of Medicine and the National Institute on Aging successfully detected mild cognitive disorder (MCI), a condition in which patients suffer mild memory problems and is often an early symptom of Alzheimer's disease (AD). Results of the research were published in a recent issue of Neurobiology of Aging."This is important because detecting this kind of brain abnormality in its early stages with these techniques could have pivotal importance for the early detection and management of AD," said lead author of the study Cristos Davatzikos, MD, Chief of the Biomedical Image Analysis Section in Penn's Department of Radiology. "The diagnostic power of this technique could work hand-in-hand with the new drugs currently under development that target the early stages of AD before irreversible brain tissue damage sets in."In the first-of-its-kind study, researchers created a unique picture of patients' brains by combining and analyzing MRI images measuring the density and volume of various different tissues and their spatial distribution within the brain. From these images patterns associated with MCI were detected. Using this technique, researchers were able to not only to detect, with 100 % accuracy, those patients in the study with cognitive impairment from those with normal cognitive function, but also those predicted, with 90 percent accuracy, those patients with increasing onset of MCI, thereby demonstrating the diagnostic power of the new tool...

CoMentis Receives FDA Clearance to Begin Human Clinical Trials for Its Disease-Modifying Alzheimer's Therapy: Highly Potent Beta-Secretase Inhibitor to Enter the Clinic
Market Wire (press release) - USA
SOUTH SAN FRANCISCO, CA--(Marketwire - June 18, 2007) - CoMentis, Inc., a privately held biopharmaceutical company, announced today it is initiating a Phase I first-in-man study of its proprietary, orally bioavailable, small-molecule beta-secretase inhibitor CTS-21166, which is being developed as a disease-modifying treatment for Alzheimer's disease (AD). In preclinical studies, CTS-21166 exhibits excellent efficacy, selectivity, brain penetration and pharmacologic activity. "This is a significant achievement for CoMentis and for Alzheimer's disease drug development," stated W. Scott Harkonen, M.D., President and Chief Executive Officer. "CTS-21166 is an entirely new approach to the treatment of AD because it is a disease-modifying agent targeting beta-secretase, a critical enzyme involved in the pathogenesis of Alzheimer's disease, and it has the potential to become the first-in-class therapeutic agent." The CoMentis initial Phase I trial in healthy volunteers is designed as a dose escalation study to measure the safety, tolerability and pharmacokinetics of CTS-21166 following intravenous administration. Forty-eight subjects will receive one of several different doses or placebo. The company expects to begin generating human clinical data by the end of 2007 and to begin Phase II studies in Alzheimer's patients in 2008. Beta-Secretase and Alzheimer's Disease: Drs. Jordan Tang and Arun Ghosh, two of the scientific founders of CoMentis, are pioneers in the field of aspartic proteases. Since publication of the first beta-secretase inhibitor in 2000, Dr. Tang has led the characterization of this enzyme's role in Alzheimer's disease and Dr. Ghosh has led the construct of drug candidates to inhibit its activity. The action of this enzyme on the amyloid precursor protein leads to the formation of plaques in the brain and is implicated in the development of Alzheimer's disease. Inhibition of beta-secretase reduces beta amyloid production and could slow the progression of Alzheimer's disease. CTS-21166 is the first of several highly selective and potent beta-secretase inhibitors being developed by CoMentis that are highly active in preclinical models of Alzheimer's disease. "This is the most exciting target today for intervention in the pathogenesis of Alzheimer's disease," said Dr. Tang, who holds the J.G. Puterbaugh Chair in Medical Research at the Oklahoma Medical Research Foundation. "Beta-secretase is involved at a very early stage in the disease, and if we could block the activity of this enzyme, we could prevent many of the harmful steps that follow and drastically reduce the impact of Alzheimer's disease." About CoMentis: CoMentis, Inc. has its headquarters in South San Francisco, with research operations in both South San Francisco and Oklahoma City. The company is engaged in the discovery and development of small-molecule drugs to treat diseases such as Alzheimer's disease, age-related macular degeneration (AMD) and cognitive disorders. The company has two fundamental technology platforms: (i) aspartic protease inhibitors, including beta-secretase inhibitors for Alzheimer's disease; and (ii) nicotinic acetylcholine receptor (nAChR) agonists and antagonists for the treatment of angiogenesis mediated diseases and cognitive disorders. Originally founded in 2004 as Athenagen, Inc., the company was re-named CoMentis following the August 2006 merger with Zapaq, Inc., which created a leading neurovascular disease franchise. Zapaq was founded in 2001 by Jordan Tang, Ph.D., of the Oklahoma Medical Research Foundation, and Arun Ghosh, Ph.D., now at Purdue University, both experts in the field of aspartic proteases. In 2000, Dr. Tang's groundbreaking discovery of beta-secretase, an aspartic protease which is a critical enzyme in beta amyloid production, was published in Proceedings of the National Academy of Sciences.

CPAP Improves Sleep in Patients With Alzheimer's Disease, Sleep-related Breathing Disorder: Presented at SLEEP
DG News - USA
WESTCHESTER, IL -- Patients with both Alzheimer disease and a sleep-related breathing disorder (SRBD) experience disrupted sleep, resulting in increased nocturnal awakenings and a decreased percentage of REM sleep.However, in another example of the effectiveness of continuous positive airway pressure (CPAP), CPAP has been found to reduce the amount of time spent awake during the night, increase the time spent in deeper levels of sleep, and improve oxygenation, according to research presented at the 21st Annual Meeting of the Associated Professional Sleep Societies (SLEEP).The study, conducted by Jana R. Cooke, MD, of the University of California at San Diego, focused on 48 adults, with an average age of 77.8 years, with Alzheimer disease and an SRBD. It was discovered that treating the sleep-related breathing disorder with CPAP resulted in these patients spending less time awake during the night as well as sleeping deeper."In general, improved sleep is associated with improvements in quality of life," said Cooke. "Clinicians should consider CPAP treatment for Alzheimer disease patients with a sleep-related breathing disorder, as the potential benefits may be significant."Scientific evidence shows that CPAP is the best treatment for obstructive sleep apnea (OSA). CPAP provides a steady stream of pressurized air to patients through a mask that they wear during sleep. This airflow keeps the airway open, preventing the pauses in breathing that characterize OSA and restoring normal oxygen levels. Source: American Academy of Sleep Medicine.

Breakdown of myelin may be the cause of Huntington's disease
News-Medical.net - Sydney, Australia
Last month, Dr. George Bartzokis, director of the UCLA Memory Disorders and Alzheimer's Disease Clinic, suggested in the journal Alzheimer's & Dementia that the breakdown of a type of myelin that develops late in life promotes the buildup of toxic amyloid plaques long associated with Alzheimer's disease. Myelin is the insulation that wraps around nerve axons in the brain. Now, in a new report currently online in the journal Neurochemical Research, Bartzokis turns his attention to Huntington's disease. Again, he suggests that a breakdown of myelin is the cause, but with a twist it is the myelin that develops early in the formation of the brain that breaks down prematurely and eventually leads to the disease's symptoms. Huntington's disease (HD) is a rare, inherited neurological disorder that ultimately deprives individuals of their ability to control their movement, behavior and thinking. It affects approximately 30,000 people in the U.S., with another 150,000 at risk. While it is known that HD is caused by a mutation in a gene called Huntingtin (Htt), the exact mechanism by which the Htt gene causes or contributes to neuronal cell death and HD symptoms remains unclear. Bartzokis research suggests it is Htt's affect on myelin that may prove to be the cause. The earliest parts of the developing brain include systems of neurons that control movement and behavior. These neurons have long axons finger-like projections that serve as the primary transmission lines of the nervous system covered with thick myelin sheaths. The sheaths are nourished by an ongoing supply of a protein called brain-derived neurotrophic factor, which travels down a neuron's axon. Bartzokis believes the Htt gene interferes with this nourishment-delivery system, resulting in a breakdown of the myelin that depends on it. That, in turn, disrupts cell signaling, which results in the neuron's death. The problem is compounded by the continual production of other cells that continue to make myelin. In HD, increasing numbers of these cells, called oligodendrocytes, are produced in an attempt to remyelinate axons whose myelin sheaths have broken down. This results in strikingly elevated numbers of oligodendrocytes years before the appearance of HD symptoms. Such elevation is detrimental because oligodendrocytes are rich with iron, which, while required for myelination, is also a well-known catalyst of free-radical-induced tissue damage. Iron accumulates during normal aging, and abnormal iron metabolism is believed to be involved in many human disorders. This is true for both highly prevalent, chronic disorders of aging, such as Alzheimer's and Parkinson's diseases, and acute disorders, such as stroke, where the extent of tissue damage is also related to iron levels. To spot myelin destruction, neuron death and iron accumulation in the brains of HD subjects, Bartzokis used two magnetic resonance imaging (MRI) machines operating at different field strengths. Measurements of myelin breakdown and iron content were taken from the brains of 11 HD subjects and compared to a control group of 27subjects. Bartzokis found that both the breakdown and the iron accumulation matched the typical progression of the disease from early to late myelinating regions. Thus, according to Bartzokis, earlier myelinated axons, such as the ones controlling movement, bear the brunt of damage from the mutant gene in the disease. And the early symptoms of Huntington's are problems with controlling movement, behavior and eventually thinking," he said. The implications of this are important, Bartzokis noted, since there is a decades-long period during which therapeutic interventions could modify the course of the disease, long before clinical evidence such as behavioral, cognitive and motor problems appear. Thus, it may be possible to develop medication that could be administered in the very early stages using non-invasive in vivo neuroimaging markers of both myelin breakdown and levels of iron. Source: http://www.ucla.edu/

Alzheimer's News in Brief (12 June 2007)

2007-06-12T09:50:00.000+03:00

Alzheimer's Disease Set to Explod. Prediction: 106 Million Alzheimer's Patients by 2050

WebMD USA, by Daniel J. DeNoon (11 June 2007) -- Today, 26.6 million people worldwide suffer Alzheimer's disease. In just over 40 years, that number will quadruple to more than 106 million patients -- and 43% of them will need full-time care in nursing homes. This grim prediction of the global burden of Alzheimer's disease comes from Johns Hopkins researcher Ron Brookmeyer, PhD, and colleagues. The researchers base their forecast on a complex computer model fed United Nations population projections and data on Alzheimer's disease. "We face a looming global epidemic of Alzheimer's disease as the world's population ages," Brookmeyer says in a news release. "By 2050, one in 85 people worldwide will have Alzheimer's disease." The only good news from the computer model is that if new ways are found to slow the disease, it would significantly reduce the global burden of Alzheimer's -- even if these new treatments had only modest effects. Delaying Alzheimer's onset by just one year would reduce the 2050 case load by 12 million patients. But not all breakthroughs are equal. If researchers succeed in slowing Alzheimer's progression as well as delaying onset, there would be only 9.2 million fewer cases by 2050 -- because people with the disease would survive longer. "The worldwide costs will be huge," Brookmeyer and colleagues warn. Currently, nearly half of the people with Alzheimer's disease live in Asia. That proportion is expected to grow to 59% by 2050, with nearly 64 million cases. Brookmeyer's reported the grim numbers to the Second Alzheimer's Association International Conference on Prevention of Dementia, held June 9-12 in Washington. The findings also appear in the Alzheimer's Association journal Alzheimer's & Dementia.

Myriad Genetics Presents Mathematical Comparison of Disease Modification Trial Designs at Alzheimer's Conference. Current Flurizan Phase 3 Study Design May Demonstrate Disease Modification

Salt Lake City, UT, Market Wire (11 June 2007) -- Myriad Genetics announced today that it presented a mathematical comparison of a "Staggered Start" and a "Randomized Withdrawal" clinical trial design with a "Natural History Staggered Start" clinical trial design at the Alzheimer's Association Prevention Conference held June 9 - 12, 2007, in Washington, D.C. The analysis demonstrates that the "Natural History Staggered Start" trial design currently being used in the Flurizan Phase 3 study can provide the same level of disease modification support as the cross-over trial designs, which are challenged by ethical concerns, dropout bias and complications. A disease modifying therapy for Alzheimer's disease (AD) is one that has an impact on the underlying pathology of the disease and thus slows the rate of a patient's decline over the course of long-term treatment. In contrast, the currently available AD medicines are believed to treat the symptoms of AD without impacting the underlying disease process or providing long lasting benefit. The development of robust methods to demonstrate disease modification in AD clinical trials has been a controversial issue in the field, and to date, there have been no studies that provide convincing evidence of disease modification in AD. Two clinical trial designs that could provide evidence for disease modification were originally proposed for AD studies over 10 years ago by Paul Leber, then the head of the Division of Neuropharmacological Drug Products of the FDA. These designs have come to be known as the "Randomized Withdrawal" and "Staggered Start" designs and are based on measuring clinical outcomes in a cross-over type study. In the randomized withdrawal design, patients are withdrawn from therapy after a defined period to determine whether the long-lasting benefit to the patient is maintained, demonstrating disease modification, or if the patient drops back to the level of patients on placebo for the duration of the study. In a staggered start design, one group of patients receives the active study drug for the entire study period, while a second group initially receives placebo and then later is given the active drug. If the second group fails to "catch up" in the level of performance of the first group, this is taken to be evidence for a disease modifying effect of the drug. Unfortunately, these designs are difficult to implement and have rarely been used in clinical trials as they are complicated by very long study durations, leading to high dropout rates that introduce biased results, as well as presenting ethical concerns unacceptable to patients and their families. A team of biostatisticians and mathematicians at Myriad, led by Suzanne Hendrix, Ph.D., Sasha Gutin, Ph.D., and Scott Horton, has proposed an alternative strategy designated the "Natural History Staggered Start" analysis, that compares the slopes of decline of drug treated patients with those of patients receiving placebo and corrects for the severity of disease at baseline. The mathematical analysis presented at the Alzheimer's Association AD Prevention Conference demonstrates that this trial analysis methodology is mathematically equivalent to the "Staggered Start" and "Randomized Withdrawal" designs and provides the same level of evidence of a disease-modifying drug effect in a clinical trial that is not subject to the above-mentioned complications, bias and ethical challenges of the previous designs. "We are excited about this persuasive mathematical comparison of clinical trial designs," said Adrian Hobden, PhD, President of Myriad Pharmaceuticals, Inc. "We believe that this mathematical proof, coupled with the Flurizan trial design may strengthen the Company's position with the FDA in favor of a disease modification label for Flurizan..."

New test may help predict Alzheimer's disease

OCRegister - Orange County, CA, USA (11 June 2007 by Maggie Fox, Reuters, Washington, DC) -- New tests involving blood and brain scans can detect symptoms of Alzheimer's disease, and brief appraisals of real-life functioning can predict who is likely to develop it, researchers said on Sunday. The tests will be critical, experts told a meeting on Alzheimer's disease, because more than 26 million people now have the brain-wasting disease and this number will quadruple, to 106 million, by 2050. "By 2050, 1 in 85 persons worldwide will have Alzheimer's disease," said Ron Brookmeyer of Johns Hopkins University, who led the study on how many people have the disease. No drugs can significantly affect Alzheimer's disease, although four have a very modest impact if given early on. The disease is very difficult to detect until it has progressed from mild memory loss to clear impairment. Patients eventually lose all ability to care for themselves. Detecting the disease early can help patients and their families plan better for the future but can also help researchers develop drugs to treat and perhaps even prevent the disease. Anders Lonneborg and colleagues of DiaGenic, a biotech company based in Oslo, Norway, found a set of 96 genes that look different in the blood of Alzheimer's patients when compared to the same genes in healthy people. Their study of more than 100 older people, half from memory clinics and half from senior centers, found Alzheimer's accurately 85 percent of the time.
They identified genes related to the immune system, to inflammation and to cell division. The company has applied to regulators in the United States and Europe to approve the test, Lonneborg told a meeting of the Alzheimer's Association in Washington...

Biologic Agent from Elan/Wyeth Will Drive the Alzheimer's Disease Drug Market to More Than Triple by 2016, Reaching $8.8 Billion

Earthtimes.org: USA WALTHAM, Mass., (11 June 2007, by PRNewswire) -- Decision Resources, Inc., one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that Elan/Wyeth's bapineuzumab, the first biologic agent for the treatment of Alzheimer's disease, will drive the Alzheimer's disease drug market to more than triple by 2016, reaching $8.8 billion. According to the new Pharmacor report Alzheimer's Disease, bapineuzumab -- a monoclonal antibody that is poised to begin Phase III trials and is expected to launch by 2011 in the United States and Europe -- will account for more than $5 billion in sales in 2016. A second monoclonal antibody, Eli Lilly's LY-2062430, may also launch by 2016 and contribute to market expansion. The report finds that bapineuzumab, Neurochem's Alzhemed, and Myriad Genetics' Flurizan -- three disease-modifying therapies that will launch over the next several years -- will account for 82% of Alzheimer's disease drug sales in 2016. Bapineuzumab will garner 61% of sales, while Alzhemed and Flurizan will garner 13% and 8%, respectively. However, the report finds that significant safety concerns may limit the overall sales potential of bapineuzumab. "The launch of bapineuzumab will be the most important factor driving growth in the Alzheimer's disease drug market," said Nitasha Manchanda, Ph.D., analyst at Decision Resources. "Despite being priced considerably lower than monoclonal antibodies in other markets, we expect bapineuzumab to enter the market priced nearly eightfold higher than current small molecule therapies. Nevertheless, we anticipate significant uptake of this agent -- particularly in patients with mild Alzheimer's disease -- despite the safety concerns. Alzhemed and Flurizan, both in Phase III development, have shown modest efficacy in trials to date and are likely to offer a better safety profile than bapineuzumab."

'Natural Protection' To Reduce Spread Of Alzheimer's Disease Possible

Science Daily (press release) - USAScience Daily -- Although numerous drugs have been developed over the years to alleviate the symptoms of Alzheimer's disease, there is still no real cure to halt this progressive, neurodegenerative disorder that causes premature death of nerve cells in the deep brain nuclei, leading to dementia and death. A graduate student in biological chemistry at the Hebrew University of Jerusalem has, however, developed an approach that holds out promise of providing natural brain protection against the spread of this disease. For his work, Erez Podoly, a joint student of Dean of Science Prof. Hermona Soreq and the head of the Wolfson Center for Applied Structural Biology, Prof. Oded Livnah, has been named one of the winners of this year's Kaye Innovation Awards, which were presented on June 6 during the 70th meeting of the Hebrew University Board of Governors. Alzheimer's Disease afflicts 12 million people worldwide, and this figure is expected to almost double over the next 25 years, due to prolonged life expectancy. Alzheimer disease patients develop neurotoxic precipitates ("plaques"), composed of the amyloid beta (Aβ) peptide, which spread as fibrils in the brain and destroy nerve cells. (A peptide is short chain of amino acids).
The several drugs that have been developed for Alzheimer's disease serve to enhance neuronal function, suppress inflammation, block or reduce the generation of oxidative stress in the brain, or minimize cognitive damage. Unfortunately, however, it is still unknown as to how to halt the spread of the neurotoxic plaques.
Podoly, 34, a native New Yorker, and his colleagues set out to design a blocker for the neurotoxic effects of the Aβ peptide, using the Butyrylcholinesterase (BChE) protein, which was cloned and engineered in their lab. BChE's brain concentration increases with age, a fact overlooked so far, but which for Podoly and his colleagues seemed highly relevant to the progress of Alzheimer's. The researchers set out in their laboratory to see if they could chemically improve and intensify BChE's effect on the brain fibrils. The researchers were indeed able to show in the lab that BChE purified from human blood and short synthetic peptides of BChE were able to reduce fibril formation. However, supply limitations and health risks limit the value of blood serum-derived human BChE. Fortunately, a breakthrough was achieved when PharmAthene Inc., an American company, was able to produce engineered human BChE that was introduced into the milk of transgenic goats. Recently, in collaboration between the Hebrew University, Yissum -- the technology transfer company of the university -- and PharmAthene, Podoly and his colleagues have succeeded in demonstrating by several independent methods that the goat-derived BChE efficiently interacts with and reduces amyloid fibrils formation. They anticipate that recombinant human BChE produced in the milk of transgenic goats and/or synthetic peptides derived from BChE can become novel prophylactic or therapeutic agents for slowing the progression of senile plaque formations in the brain of Alzheimer's patients. Further research, leading to clinical tests on humans, is planned for the future. Note: This story has been adapted from a news release issued by The Hebrew University of Jerusalem.

Unexplained Late-life Weight Loss May Be Early Predictor Of Alzheimer's

Science Daily, USA (11 June 2007) - Unexplained weight loss late in life, when coupled with other biomarkers, may help to identify those at risk of Alzheimer's disease...

New findings show unexplained weight loss that precedes dementia by more than 10 years is associated with the severity of Alzheimer changes in the brain. Using data from the Nun Study, a prospective study of the causes of dementia in Catholic sisters, University of South Florida researcher James Mortimer, PhD, reported today that the most likely cause of the unexplained weight loss is the severity of the Alzheimer changes in the brain rather than an eating disorder or other condition associated with declining cognition. Dr. Mortimer presented the findings at the Alzheimer's Association International Conference on the Prevention of Dementia in Washington, DC. Although a previous study showed that individuals with lower weight for their height at the time of death had more Alzheimer brain changes at autopsy, this is the first study to show that lower weight up to 10 years earlier is specifically related to the severity of the disease. "While weight one year or less prior to death was related to the amount of cognitive decline, this association could be explained by the severity of the Alzheimer process in the brain seen at autopsy," said Dr. Mortimer, professor of epidemiology at the USF College of Public Health. "Given its very long duration prior to onset of dementia, it is likely that weight loss is specifically associated with the Alzheimer disease process and not to a restriction in food intake due to cognitive decline," he said. "There is considerable evidence that Alzheimer changes in the brain precede the first symptoms of this illness by decades." Unexplained weight loss late in life, when coupled with other biomarkers, may help to identify those at risk of Alzheimer's disease more than a decade in the future. Identification of individuals who are at high risk of Alzheimer's long before cognitive decline becomes evident will be critical to its prevention once agents become available to slow the disease, Dr. Mortimer said.
The Nun Study, begun in 1992, is a study of 678 Catholic sisters, initially 75 to 102 years of age, who are evaluated yearly and who agreed to brain donation at the time of death. The Nun Study is directed by Dr. David Snowdon of the University of Kentucky. Dr. Snowdon is a co-author of the presentation as is Dr. William Markesbery, director of the Sanders-Brown Center on Aging at the University of Kentucky. Dr. Yougui Wu, the third coauthor, is an assistant professor of epidemiology and biostatistics at the USF College of Public Health
The Nun Study is funded by a grant from the National Institute on Aging.

ABC 7 Medical: Alzheimer's Disease

WJLA, ABC7 Medical by Kathy Fowler (11 June 2007) - Washington, DC, USA: Tony Sudler, Alzheimer's Association: "We look for Alzheimer's disease as projecting to bankrupt both Medicaid and Medicare in the future if we cannot...

Anchor: Alzheimer's disease is being called this country's next public health crisis. The number of people sick with this devastating disease is expected to quadruple by 2050. experts worry it's an epidemic that could break the healthcare system. Medical reporter Kathy Fowler joins us with the story.

Researchers at Johns Hopkins project in 40 years more than 100 million people worldwide will have Alzheimer's. Tonight health experts are warning - this is a problem so big it could bankrupt the united states healthcare system.

Story:
Jerome Menefee's mother is 82 years old and in the late stages of Alzheimer's so he quit his job to become her 24 hour caregiver.

Jerome Menefee, caregiver: "When I was born I was two pounds 14 ounces in 1953, you know a preemie; i only survived because of her." He promised to take care of her the way she took care of him.... but it takes a physical and emotional toll.

Jerome Menefee: "it was exhausting... my health was suffering... if i get sick no one else is going to take care of her." Not to mention the financial burden.....

Jerome Menefee" i'm looking at the possibility of selling the house and then taking what's available after taxes into an annuity to give her another income stream and then i'll start over. "

Health experts say right now one in eight people over the age of 65 has Alzheimer's and one in two people get the disease over the age of 85.

That's not even considering the 78 million aging baby bommers.....

Tony Sudler, alzheimer's association: "we look for alzheimer's disease as projecting to bankrupt both medicaid and medicare in the future if we cannot figure out a way to slow the diseases down."

Scientists are scrambling to come up with better treatments and say this is exactly the wrong time for the government to cut research funding.

Dr. Sam Gandy, Farber Institute for Neurosciences: "Alzheimer's funding for the NIH fell for the first time in 30 years. so as the epidemic is upon us, it's becoming more and more difficult to retain good scientist in the field."
Kathy on set:

Scientists say they might be close - maybe three to five years away from developing medicines that can slow down and maybe even prevent alzheimer's.

In the meantime, doctors say everyone can protect their brains by exercising and reducing blood pressure and cholesterol. basically the same things that prevent heart disease can also prevent Alzheimer's.

Dimebon Shows Promise When Treating Alzheimer's Disease

Ecanadanow.com, 11 June 2007 -- Importantly, on every endpoint studied, the benefits of Dimebon over placebo at one year were stable or greater when compared to benefits at six months. Dimebon patients were stabilized over the one year study period, meaning that their level of function was preserved for a full year on all five endpoints. The endpoints spanned all of the most frequently studied aspects of Alzheimer's disease: cognition, overall clinical function, activities of daily living, and behavioral problems. Dimebon was well tolerated throughout the entire one-year treatment period.On the study's primary endpoint, the ADAS-cog, Dimebon caused an improvement over placebo of 6.9 points at one year (observed case analysis; p<0.0001). p="0.006)." p="0.006)." p="0.03)">

Heart Disease a Risk Factor for Alzheimer's

Alz.org press info by HealthDay News - SUNDAY, 10 June 2007 -- There's more evidence that cardiovascular problems help drive Alzheimer's disease, scientists say, and that treating the heart might help protect the brain. The findings "represent hope that interventions with well-known drugs can interfere with the disease's progression," said lead investigator Yan Deschaintre, a neurologist and research fellow at the University Regional Hospital Center in Lille, France. In fact, cognitive impairment, as measured by a standard test, stayed in the low end of the mild range over 36 months for Alzheimer's patients who got treatments for both the neurological disease and their cardiovascular problems, the researchers reported. In contrast, Alzheimer's patients with vascular trouble who did not receive these medications experienced declines in cognition that approached the severe level, Deschaintre's team found. They were slated to present the findings Sunday at the Alzheimer Association's International Conference on Prevention of Dementia, in Washington, D.C... The work done by Deschaintre's team is consistent "with what we've been hearing over the past three to five years" about vascular risk factors increasing the risk for Alzheimer's, Gandy said. The new study, "really nails that down by looking at the other side of the coin by establishing that treating vascular risk factors slows the progression of cognitive decline," he added. He suggested that physicians begin to take vascular risk factors seriously as they treat patients with Alzheimer's. The vascular risk factors for early Alzheimer's patients "certainly should be treated" because it "seems to slow progression," Gandy said. Another expert agreed. The Lille results "reinforce the treatment guidelines for these vascular conditions, such as hypertension and diabetes, and emphasize that Alzheimer's and demented patients should be treated, too," said Hugh C. Hendrie, a professor of psychiatry at the Indiana University Medical School and a scientist at its Center for Aging Research. However, Deschaintre and Hendrie both noted that physicians at times may not treat vascular risk factors in Alzheimer's patients, for a variety of reasons. For example, Alzheimer's disease often leaves patients apathetic, so they may neglect to tell their physicians about vascular symptoms, Hendrie said. And Deschaintre noted that, in the clinic where the research was done, patients with Alzheimer's were less likely than other patients to be treated for vascular risk factors. The reverse was true, as well -- patients with vascular dementia were more likely to be treated for heart risk factors, but not for Alzheimer's. But, "since the majority of patients have both Alzheimer's disease and cerebrovascular disease, and since patients with pure Alzheimer's do seem to benefit from treatment of vascular risk factors, the message is to treat both conditions rather than to focus only on one," he said. Hendrie remained cautious about the scientific impact of Deschaintre's study, however. He said results from a clinical epidemiological study, such as the Lille research, aren't as conclusive or compelling as those from randomized, controlled clinical trials. Two other studies scheduled for release at the Alzheimer's conference on Sunday also emphasized the role of the brain-body connection in cognitive impairment and dementia. Weight loss may signal the onset of Alzheimer's, and the rate of weight loss could be early warning of dementia severity, according to a new review of data from what's known as the Nun's Study. That effort followed health outcomes for a group of 537 non-demented Catholic sisters, aged 75 to 102, for 10 years. In the study, a team led by Dr. James Mortimer, a professor of epidemiology and biostatistics at the University of South Florida, Tampa, found that unexplained weight loss late in life was often linked to Alzheimer's neuropathology in the brain and not to any change in eating habits linked to Alzheimer's. Mortimer explained that, "early weight loss appears to result from the Alzheimer's disease process itself before that process leads to dementia. That's why it is a marker of impending dementia." In a third study, a team from the Mayo Clinic in Rochester, Minn., found an increased risk of mild cognitive impairment (MCI) or dementia among 70- to 89-year-olds who have had a carotid endarterectomy (surgical clearance of the carotid artery, which brings blood to the brain) or a stroke or "mini-stroke," also known as a transient ischemic attack (TIA). In the study, the team compared the medical histories of 295 people with MCI and 590 age and sex-matched controls. "Elderly subjects who have had a carotid endarterectomy or stroke or TIA are about two times more likely to have MCI," lead researcher Dr. Rosebud O. Roberts, a Mayo epidemiologist, said in a prepared statement.

Alzheimer's News in Brief (5 June 2007)

2007-06-06T09:50:00.000+03:00

Alzheimer's on the rise, even locally
Summit Daily News - Frisco, CO, USA (4 June 2007)
FRISCO - The latest report by the National Alzheimer's Association showed a 10 percent increase in Alzheimer's Disease cases, and Summit County is not immune to this surge.In fact, as the population here continues to age, more diagnoses will be made. According to this year's report, one in eight people age 65 and older have the disease and age is the biggest risk factor for it."We believe with the number of baby boomers who will soon be turning 65 that that number (those with Alzheimer's) will increase," said Christy Nelson, volunteer coordinator at the Summit County Community and Senior Center who coordinates the Memory Loss Support Group.The group, that is a partnership with the Colorado Chapter of Alzheimer's Association, is designed to help family, caregivers cope with stress, share tough moments, joys, tips and become educated on the latest research and information.Linda Trenbeath, of Silver Plume, is a facilitator for the support group who has a masters in psychology and personal knowledge of what caring for someone is Alzheimer's is like."It's a devastating disease that has a major impact on any family," she said.While the exact number of those in Summit, Clear Creek, Eagle, Gilpin and Lake counties with the disease is not known, it is known that about 6,500 residents are above the age of 65. The Colorado Chapter of the Alzheimer's Association estimates that 10 percent of these individuals have some form of dementia or suffer from memory loss and that number will likely grow.An estimated 5 million people in the U.S. have Alzheimer's and every 72 seconds someone develops it, according to the national association. By the year 2050, the number of those diagnosed could reach 16 million.Also, 59 percent of care for the nation's elderly falls to women family members between the ages of 45 and 65. As a result of their role as caregivers, they are known to experience greater stress levels and ignore personal health needs.The local support group is designed to help ease some of this stress. Any caregiver of someone with memory loss that could be from stroke or another health issue not just Alzheimer's is welcome at the local meeting. And, "no matter what stage of Alzheimer's they find themselves caregiving, this would be a group for them," Nelson said. Additionally, the support could help someone even if the person they are caring for doesn't live in the county, she added.The group does not consist of medical professionals, but they do offer resources for people with questions and those wanting to understand the difference between normal aging memory loss and the disease, Trenbeath said. A brochure is available and it is online at the National Alzheimer's Association website.Behaviors in patients are "very distinctive," she added. At the monthly group, caregivers help each other understand next steps and how to deal with the confusion, frustration, agitation and other emotions patients go through."They're all there to support each other in a common challenge," Trenbeath said."When you have someone you care about with memory loss, you really get isolated ... You get embarrassed, life is changed and you face difficult things," she later continued. "I encourage people to come. It helps them be less isolated and could improve their life and the life of the one they are caring for."

MU researchers find mechanisms that may unlock answers to Alzheimer's disease, Neurobiology of Lipids is in focus
EurekAlert (press release) - Washington, DC, USA
COLUMBIA, Mo. — Four million people in the United States and 15 to 20 million people worldwide are affected by Alzheimer’s disease. These numbers are likely to triple by 2050 due to the fact that 24 percent of the population will be more than 65 years old. In their attempt to combat the disease, two University of Missouri-Columbia professors have identified new mechanisms that could have major implications in the development of treatments for the disease. The National Institutes of Health recently awarded a $6 million grant to the Mizzou researchers to continue their study. Grace Sun and Gary Weisman, professors of biochemistry in the School of Medicine and the College of Agriculture, Food and Natural Resources, are entering the second phase of an $11 million project aimed at identifying the causes of Alzheimer’s disease. Previous studies have indicated toxic effects of a protein, the amyloid-beta peptide or “A-beta,” which accumulates in amyloid plaques in the brain of Alzheimer’s patients. Despite unknown mechanisms, increased production of this peptide may cause impairments of brain functions. “When the A-beta protein comes together inside the plaque, it will fold into an abnormal shape that is toxic to cells,” Sun said. “While we know this has some effect on brain function, we don’t know how toxic it is or at what stage the toxicity begins. In the past five years, we have started to understand how this disease works. With the new grant, we will be able to go forward and see if there are treatments that can modify the cellular response in the brain.” The abnormal A-beta impairs the synapse connections that occur among neurons. These synapses control the communication among the brain cells, including how memory is processed. Besides neurons, A-beta also attacks astrocytes and microglial cells. Astrocytes are an important cell type that provides nutrients to neurons. Microglia cells are immune cells activated for defense related functions. Effects of A-beta on astrocytes and microglia may create abnormal inflammatory responses that can harm neurons and other brain cells. The next phase of the study includes three projects. Sun will study mechanisms whereby A-beta affects phospholipases, a group of enzymes that, when activated, will destroy membranes in brain cells. Current evidence suggests that A-beta activates some of these enzymes. In the second project, Weisman will study mechanisms of inflammation in the brain and A-beta’s role in creating the inflammatory response. Weisman will explore the role of a group of receptors that control both the function of the enzyme that produces A-beta in brain cells and regulates inflammation. By suppressing this receptor’s function, Weisman hopes to identify new treatments that minimize A-beta production and inflammation. Gibson Wood, professor of pharmacology at the University of Minnesota, will lead the third project, which will study the role of cholesterol in the brain. Wood’s study will evaluate the effects of statin drugs, typically used to treat high cholesterol. Wood’s previous research showed that statins have other beneficial effects in addition to lowering cholesterol. His study will test if the drugs also combat the ill effects of A-beta and limit the progression of Alzheimer’s disease. Findings from the research program have been published in the Journal of Neuroinflammation, the Journal of Neuroscience and the Journal of Biological Chemistry. Funding for the study has come from the National Institute of Aging, part of the National Institutes of Health, and the University of Missouri-Columbia. “Without matching funds from MU and interdisciplinary collaboration, we would not be able to conduct this research,” Sun said. According to the National Institutes of Health, Alzheimer’s disease is the most common form of dementia among older adults and affects areas of the brain that control memory, judgment, behavior and intelligence. The disease was first discovered more than 100 years ago by a German physician, Dr. Alois Alzheimer, when he diagnosed a patient who died of a dementia-type illness at age 55.

Off-Label Use of Alzheimer's Disease Drugs Drives the Market for Mild Cognitive Impairment
American Digital Networks (press release) - Annapolis, MD, USA
WALTHAM, Mass., June 4 PRNewswire — Decision Resources, Inc., one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that because there are no therapies approved specifically for the treatment of mild cognitive impairment, off-label use of Alzheimer's disease drugs currently drives the market and will continue to dominate the market through 2016. The new Pharmacor report entitled Mild Cognitive Impairment finds that it is the lack of regulatory approval that forces mild cognitive impairment therapeutic options to be entirely off-label. "Off-label use restricts the number of patients who can receive such therapies, particularly in Europe where reimbursement is more tightly regulated," said Bethany Kiernan, Ph.D., analyst at Decision Resources. "As a result, drug-treatment rates for mild cognitive impairment are low. However, I expect that diagnosis and drug-treatment rates will increase significantly by 2016 because of the emergence of disease-modifying therapies for Alzheimer's disease and the launch of amyloid biomarkers." The report also finds that treatment options for mild cognitive impairment are limited in Japan. Currently, the only therapy available for mild cognitive impairment is Eisai/Pfizer's Aricept/Bracco's Memac. This lack of therapeutic options has contributed to low drug-treatment rates in this market. However, the launches of Shire/Janssen/Ortho-McNeil Neurologics' Reminyl/ Razadyne, Novartis' Exelon/Esteve/Biofutura's Prometax, and Merz's Azura/Grupo Grunenthal's Akatinol/Lundbeck's Ebixa/Forest Laboratories' Namenda beginning in 2010 will provide additional therapeutic options to Japanese mild cognitive impairment patients and prompt modest sales growth in this market.

About Mild Cognitive Impairment:
Mild cognitive impairment is a diagnosis given to individuals who have cognitive impairments beyond that expected for their age and education, but that do not interfere significantly with their daily activities. It is considered to be the boundary or transitional stage between normal aging and dementia.

Nursing home placement associated with accelerated cognitive decline in Alzheimer's disease
RxPG NEWS - Westchester, CA, USA
Key point: The authors considered the possibility that nursing home placement is simply a sign of increased severity of Alzheimer's disease. Yet, the nursing-home-related increase in cognitive decline was observed even after simultaneous control for cognitive and noncognitive indicators of dementia severity at the time of nursing home entry. On average, cognition declined at a gradually increasing rate for all participants. As level of day care use at study onset increased, the association of nursing home placement with accelerated cognitive decline substantially decreased. People using day care 3 to 4 days a week at the beginning of the study showed no increase in cognitive decline upon nursing home placement.

Major result: The findings suggest that the transition from the community to a nursing home is particularly difficult for people with Alzheimer's disease and that those planning for their care should consider the possibility that experience in adult day care programs may help prepare affected persons for institutional living. Patients who had prior adult day care services may be better able to adjust to the unfamiliar environment.

Blocking stress protein decreases Alzheimer's peptide in mice
EurekAlert (press release) - Washington, DC, USA St. Louis (4 June 2007) --
Scientists revealed in November 2006 that stress increases production in mice of a brain peptide critical to Alzheimer's disease. Now the same group has shown that blocking a different brain peptide slows the stress-induced increase, opening a new door to treatment. Researchers from Washington University School of Medicine in St. Louis report the results online this week in the Proceedings of the National Academy of Sciences. Studies of humans and animals have suggested that stress may increase risk of Alzheimer's disease, but the new research is among the first studies to elaborate the basic biomolecular mechanisms that may underlie this increased risk. The results build on earlier findings from coauthors John G. Csernansky, M.D., the Gregory B. Couch Professor of Psychiatry and professor of neurobiology, and Hongxin Dong, Ph.D., instructor in psychiatry. Using mice genetically modified to model human Alzheimer's disease, Csernansky and Dong showed that raising them under isolated conditions in smaller cages accelerated the deposition of brain plaques and declines in cognitive ability. Brain plaques are believed to be a primary cause of the memory loss and other mental damage inflicted by Alzheimer's disease. They are mostly comprised of a peptide known as amyloid beta, so researchers immediately suspected that stress was increasing amyloid beta levels. But because there are other factors that can accelerate plaque build-up, they needed to test the link. For that new test, scientists used a technique known as microdialysis to monitor amyloid beta levels in the brains of mice exposed to the same stressors: isolation and smaller cages. "Stress remarkably elevated soluble amyloid beta levels in the spaces between brain cells," says senior author David Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "But we didn't know based on those initial experiments if it was a chronic effect or a much more immediate effect. If it was more immediate, we thought we might be able to identify some of the brain molecules involved in increasing the levels." Lead author Jea-Eun Kang, a graduate student in the Holtzman lab, utilized a quicker way to cause stress: temporarily restrain mice from moving. Three hours of restraint led to a 30 percent increase in amyloid beta levels. The spike in amyloid beta encouraged researchers to start looking for molecules that might be enabling this rapid change. Stress hormones produced by the adrenal gland were natural suspects. In mice, that meant corticosterone, the mouse equivalent of the human hormone cortisol. But a large dose of corticosterone didn't cause a similar rapid change in amyloid beta levels. When they widened their search for molecules released in the mouse brain by stress, the scientists identified one called corticotropin-releasing factor (CRF), which is linked to increased levels of brain cell communication. In 2005, Holtzman, John Cirrito, Ph.D., a postdoctoral research associate in neurology and psychiatry, and colleagues showed that increased communication between brain cells also contributed to increased amyloid beta. When they directly placed CRF in the mouse brain, amyloid beta levels rose immediately. Mice given a CRF blocker and then stressed did not display increased amyloid beta. "There are very few known environmental risk factors for Alzheimer's disease," Holtzman notes. "Head trauma increases risk, higher education lowers it. Stress may be another environmental factor that increases risk." Holtzman, Csernansky and their colleagues are intrigued by the possibility that drugs that block CRF or reduce anxiety may provide a new way to decrease amyloid beta and eventually delay or prevent Alzheimer's disease. Holtzman and his colleagues are also continuing to explore connections between brain cell activity and amyloid beta levels.

Yin And Yang -- Balance Could Play Key Role In Progression Of ...
Medical News Today (4 June 2007) - UK
Researchers at Rensselaer Polytechnic Institute are challenging current thinking on the causes and prevention of Alzheimer's disease, offering a new hypothesis that could be the key to preventing this form of dementia. The researchers have found that a specific imbalance between two peptides may be the cause of the fatal neurological disease that affects more than five million people in the United States. "We have found that two peptides, AB42 and AB40, must be in balance for normal function," said Chunyu Wang, lead researcher and assistant professor of biology at Rensselaer. "They are like the Yin and Yang in Taiji, an ancient Chinese philosophy. When the peptides are produced in the correct proportions, the brain is healthy; but when that delicate balance is changed, pathological changes will occur in the brain and the person's memories become hazy, leading to eventual dementia." Wang expects that this imbalance could be the main factor in the progression of Alzheimer's disease. If correct, the addition of AB40 may stop the disease's development. Wang notes that further research is needed, but his preliminary results challenge the current mode of thinking about how these peptides contribute to the progression of the disease. The research will be published in the June edition of the Journal of Molecular Biology. Peptides are formed by the linking of different amino acids. The two peptides that Wang investigated were both Amyloid B-peptides (AB) - specifically those composed of 40 and 42 amino acids, called AB40 and AB42. These two peptides have been previously found in deposits, called senile plaques or amyloid plaques, in brains afflicted with Alzheimer-s disease. These plaques, mainly composed of AB42 fibrils, are a hallmark of Alzheimer-s disease. Prior research has uncovered that increased levels of AB42 become toxic to brain cells when individual molecules of AB42, or monomers, combine to form oligomer or fibril chains. This process is called aggregation. But the role of AB40, which is also found in senile plaques and generated from the same protein as AB42, has not been clearly established. Wang set out to determine what role this peptide played in the generation of AB42 aggregates. Wang used the advanced Nuclear Magnetic Resonance (NMR) machines within Rensselaer-s Center for Biotechnology and Interdisciplinary Studies to monitor the formation of harmful AB42 fibrils in the presence of different levels of AB40. NMR is an extremely powerful research tool capable of characterizing the three-dimensional structure and dynamics of biological molecules. Using NMR data, Wang found that as AB40 levels increased, the aggregation of AB42 fibrils sharply decreased, protecting benign AB42 monomers. "We have found that the ratio of AB40 to AB42 plays a key role in AB42 aggregation," Wang said. "The current mode of thinking in Alzheimer-s emphasizes the toxic role of AB42 but neglects the protective role of AB40. Combined with previous work on AB40 by many other groups, our data suggest that AB40 has an equally important, protective role in Alzheimer-s. Thus AB42, the bad molecule, and AB40, the good molecule, are like Yin and Yang in Taiji. The brain can only function normally when they are in balance." Wang-s experiments show that when there is 15 times more AB40 than AB42, the formation of AB42 fibrils is almost completely stopped. "This means that the introduction of AB40 to tip the peptide balance toward AB40 could potentially halt or slow down the progression of the Alzheimer-s in the human brain," Wang said. Wang plans to continue investigating how AB40 halts the formation of AB42 fibrils, and he already sees vast implications for this change in thinking about the progression of the disease. "This has the potential to become a simple therapy to prevent the formation of toxic AB42 species," he said. "I plan to continue my research on the role of AB40 and hope that we can test this theory on human neurons, animal models, and someday in clinical trials. One critical advantage of using AB40 for the prevention or therapy for Alzheimer-s is that AB40 is already known to be largely free of side effects at near physiological concentration."

Alzheimer's risk 'rises if oxygen supply hit'
Scotsman - Edinburgh, Scotland, UK (by Rhiannon Edward, 4 June 2007)
An incident of reduced oxygen to the brain caused by a stroke, heart attack, or even heavy snoring could make people more vulnerable to Alzheimer's disease, according to scientists. It can leave the patient more open to the gradual build-up of toxic chemicals which can cause Alzheimer's, a team at Leeds University said. This means a stroke victim may still be more at risk of developing Alzheimer's decades after they have made a full recovery. Professor Chris Peers, of the school of medicine, who led the research, said: "Our research is looking into what happens when oxygen levels in the brain are reduced by a number of factors, from long-term conditions like emphysema and angina, to sudden incidents such as a heart attack, stroke or head trauma. "Even though the patient may outwardly recover, the hidden cell damage may be irreversible. "It could even be an issue for people who snore heavily. It can be anything that stops the heart and lungs working together." Professor Susanne Sorensen, head of research at the Alzheimer's Society, said: "This is exciting because rather than focusing on neurons they looked at processes in the brain, which until now have not been researched in so much detail." Alzheimer's disease accounts for more than half of the 700,000 people in the UK with dementia, the university said. The number of people with dementia will more than double by 2050 because people are living longer, it is predicted. Alzheimer's is a fatal and incurable brain disease. Beyond the age of 65 the chances of developing it double every five years.

Alzheimer's News in Brief (10 April 2007)

2007-04-10T10:27:00.000+03:00

Alzheimer's study highlights programs
BusinessWeek - USA
Recent reports of an early breakthrough study on Alzheimer's disease in Japan brought attention to several Western companies dealing with similar ...

Memory Pharmaceuticals Completes Enrollment in Phase 2a MEM 1003 ...
Drug Newswire (press release) - Oakville, CT, USA
(NASDAQ:MEMY) today announced that it has completed enrollment in its Phase 2a trial of MEM 1003 in Alzheimer's disease. The Company expects to report ...

Diabetes may increase risk for Alzheimer's Disease

Insider Medicine - Kingston, Ontario, Canada

People with diabetes may be at greater risk of developing cognitive impairment- a transitional state to Alzheimer’s disease- say researchers in a report published in the Archives of Neurology. Type 2 diabetes is a metabolic disorder in which the body has trouble using its own insulin to control blood sugar. It is the most common type of diabetes, and is strongly linked to lifestyle factors such as obesity, high blood pressure, and poor diet. In the US, it is estimated that more than 21 million people have diabetes and twice as many are at high risk of developing the disease. Some earlier studies have found a significantly greater risk of mental impairment, and a greater risk of overall dementia and Alzheimer's disease, among people with diabetes. The findings, however, have not been consistent. Alzheimer’s disease affects approximately 4.5 million Americans, robbing them of their memory and leading to profound disability and eventually death.
To investigate the association between diabetes and mental impairment, researchers studied more than 900 healthy people over age 65. At 18-month intervals, the participants underwent an interview, a physical and neurological exam, and a variety of tests to measure learning, memory, reason and language skills. Of the participants, 24% had diabetes, 68% had high blood pressure, 33% had heart disease, and 15% had suffered a stroke. Over the six-year follow-up, about one-third developed mild mental impairment, and diabetes was found to be a significant risk factor. In fact, as much as 11% of mental deterioration was caused directly by diabetes. It is thought that poorly controlled diabetes may impair mental function by compromising the small vessels of the brain due to a build-up of plaques. As a result, small strokes may occur, producing ischemic damage that affects mental function. Lifestyle modifications, including weight management and blood pressure control, are important ways to reduce the risk of developing type 2 diabetes, and perhaps ultimately, Alzheimer’s disease.

Alzheimer's Association urges baby boomers to 'maintain your brain'
Delmarva Daily Times - MD, USA
Baby boomers are entering the age of highest risk for Alzheimer's disease. The focus of the Maintain Your Brain campaign calls attention to the fact that...

UT Southwestern Medical Center Alzheimer's disease forum to focus ...
Pegasus News - Dallas, TX, USA
The Friends of the Alzheimer’s Disease Center will hold its Spring Public Forum on April 24 at UT Southwestern Medical Center. The talk, “Neuropathology One Century After First Description of Alzheimer’s Disease,” will be given by Dr. Charles L. White, professor of pathology at UT Southwestern.
The 7 p.m. forum in the Simmons/Hamon Biomedical Research Buildings on UT Southwestern’s North Campus, 6000 Harry Hines Blvd., is open to the public at no charge. .. Dr. Alois Alzheimer, a German neuropathologist and psychiatrist, studied stained brain slices from a woman with severe dementia in 1906, and discovered the distinctive plaques and tangles characteristic of the disease that now bears his name.
Dr. White is director of the Winspear Family Special Center for Research on the Neuropathology of Alzheimer’s Disease... The Friends of the Alzheimer’s Disease Center was established in 1996 to provide financial support for Alzheimer’s research at the medical center. All of the group’s membership contributions go directly to support Alzheimer’s research at UT Southwestern. Since its founding, the group has raised more than $750,000 for grants to researchers. This year, for the first time, two grants will be given, with $50,000 each being awarded to Dr. White and Dr. Hanzhang Lu, assistant professor in the Advanced Imaging Research Center and in radiology and psychiatry...

'Cruising the high seas'
Napa Valley Register - Napa, CA, USA
Though it has a cruise theme, this will be a camping weekend for individuals with Alzheimer's disease or other forms of dementia...

Neuroptix Corp. Opens New Corporate Headquarters in Acton
Genetic Engineering News (press release) - New Rochelle, NY, USA
Neuroptix Corporation, a Massachusetts-based pioneer in the early detection of Alzheimer's disease, today announced that it has opened its corporate headquarters in Acton, Mass., as it ramps up development of its innovative technology for non-invasive diagnosis of Alzheimer's disease through laser eye scanning.
Paul Hartung, President and CEO of Neuroptix, said, "We are very pleased to announce expanded operations in our new facility, following our successful Series A funding and new hires of senior personnel, as we work to further develop our diagnostic platform for Alzheimer's disease toward commercialization." The new facility, leased to Neuroptix by Wedgewood Realty, is located at 20 Main Street in Acton, Mass.

Alzheimer's news alerts (20 March 2007)

2007-03-22T15:00:00.000+02:00

Imaging Exposes Alzheimer's-Like Plaque in the Human Brain
MedPage Today - Little Falls, NJ, USA
Explain to patients who ask that the diagnosis of Alzheimer's disease is made on the basis of clinical features of the disease, and can be confirmed only on...

Alzheimer's disease onset from inhaled anesthetics
SpiritIndia - New Delhi, New Delhi, India
A specific effect of these drugs on dementias like Alzheimer's disease, though suspected for many years, has only been recently supported by data...

Genetic Risk Factors For Alzheimer's Disease Examined
Medical News Today (press release) - UK
Cardiff University researchers have found evidence for new genes involved in the development of Alzheimer's disease. The study, to be published in the next...

Groups aid Alzheimer's caregivers
Poughkeepsie Journal - Poughkeepsie, NY, USA
People caring for loved ones with Alzheimer's disease or a related disorder face tremendous challenges, but it does not have to be a lonely experience...

SeniorBridge Excellence in Social Work Practice Award Announced
American Digital Networks (press release) - Annapolis, MD, USA
SeniorBridge services are especially beneficial to those with Alzheimer's disease and chronic or multiple illnesses. Headquartered in New York City...

Social workers honour Citizen series on Alzheimer's disease
Ottawa Citizen (subscription) - Ottawa, Ontario, Canada
A Citizen special project on Alzheimer's disease has received a second honour for excellence in journalism. The eastern branch of the Ontario Association of...

79-year-old has Alzheimer's Disease
KRGV - Westlaco, TX, USA
Liandro Garcia has Alzheimer's Disease. The 79-year-old's been missing since Sunday. He was last seen near his home on Manuel Perez Road in Rio Grande City...

Strawn Center offers Alzheimer's session
The Advocate - Newark, OH, USA
...You're invited to attend "Home Safety for People with Alzheimer's Disease," a free training and information session on Alzheimer's and other forms of...

Flower auction supports Alzheimer's
Capital News 9 - Albany, NY, USA
...held their second annual flower auction to raise money to support the services they provide to patients and families dealing with Alzheimer's disease...

BBC Says that "1.7m 'will have dementia by 2051'"

2007-03-16T10:27:00.000+02:00

Elderly people are more at risk
More than 1.7 million people in the UK will have dementia by 2051, costing billions of pounds each year, experts have forecast.
The grim projections are based on the most up-to-date evaluation of dementia.

Currently 700,000 - or one person in every 88 in the UK - has dementia, incurring a yearly cost of £17bn.

The government welcomed the London School of Economics and Institute of Psychiatry research, and said dementia care was already a priority.

This research highlights the desperate need for dementia to be made a national priority

'You are just left alone' Alzheimer's disease

The total number of people with dementia in the UK will increase to 940,110 by 2021, they predict.

By 2051 the figure will be 1,735,087 - an increase of 154% from now -, which will mean dementia will affect the lives of around one in three people either as a sufferer, or as a carer or relative.

This is mainly because of the UK's ageing population. However, conditions such as high cholesterol and blood pressure, and lack of exercise are also thought to increase the risk.

One in 20 people over 65 and one in five people over 80 has a form of dementia. Around two thirds of those affected have Alzheimer's disease.

There is no cure for dementia, and those with the condition need increasing care as the disease progresses.

My 89 year old mother is obviously suffering from Dementia and is getting worse by the week -Anthony Darby, London

The researchers' investigations reveal caring for one person with late-onset dementia costs an average of £25,472 per year.

Currently, the bulk of this cost is met by people with dementia and their families.

Two thirds of these people live at home - either alone or with friends or relatives.

They said there were "marked variations" in the levels of provision and spending across the UK, and that care and support is "delivered piecemeal and in an inefficient fashion."

With every second ticking by, dementia costs the UK £539 -Neil Hunt, Alzheimer's Society

Professor Martin Knapp, of the London School of Economics, one of the report's authors, said: "This research highlights the desperate need for dementia to be made a national priority.

"Current levels of services and support for people with dementia and carers are clearly inadequate.

"Dementia is one of the main causes of disability later in life ahead of cancer, cardiovascular disease and stroke, yet funding for dementia research is significantly lower than these other conditions.

"Even delaying the onset of dementia by five years would halve the number of related deaths, saving nearly 30,000 lives annually."

'Intolerable strain'

Neil Hunt, chief executive of the Alzheimer's Society, added: "With every second ticking by, dementia costs the UK £539. We can't afford to ignore the true cost of dementia to society as a whole.

"We must tackle this huge challenge head on."

"We need to invest in dementia services, research, support and training and use what money is being spent more effectively. Planning now will save lives and money in the future."

He added: "This new research shows that the government is failing to support people with dementia and their carers.

"Dementia will place an intolerable strain on our health and social care system unless the right services and support are in place."

Older people's tsar Professor Ian Philp, who is currently preparing new guidance for local health and social care bodies on early intervention and support for people with dementia, said: "This is a significant report that highlights the key issues around dementia and its economic impact."

Health Secretary Patricia Hewitt said: "We've already doubled the research that we're doing on Alzheimer's and just last week, we announced a new investment, for instance, in emergency respite care for carers of people with dementia, which is one of the things that carers particularly told us it was their top priority."

Two drugs companies - Pfizer and Eisai - are currently seeking a judical review with the aim of over-turning a National Institute of Health and Clinical Excellence (NICE) decision not to recommend the use of three drugs for patients in the early stages of Alzheimer's disease.

NICE ruled that donepezil, rivastigmine and galantamine should only be used to treat Alzheimer's once it has progressed to its moderate stages

Source: 1.7m 'will have dementia by 2051'. Professor Martin Knapp, London School of Economics - report author BBC.co.uk (27 Feb 2007)[FullText]

Technology Will Help Get People with Alzheimer's Safely Back Home

2007-03-14T13:09:00.000+02:00

The Police Department is adding GPS technology to its Never Alone: Safely Back Home program to help families of those with Alzheimer's disease or other special needs who may frequently wander away from home.

The Never Alone program has several components. According to Redlands Police Chief Jim Bueermann, the first component is the group of volunteers who look after people who may need help.

Bueermann referred to an instance when a volunteer called to check on an elderly woman and could not get in touch with her. The volunteer called the police who went to the woman's home where they found that she had fallen and broken her hip the night before.

The program also helps seniors with transportation. Volunteers make sure that their clients are able to get to medical appointments and go grocery shopping.

The Safely Back Home part of the program involves registering people with Alzheimer's or dementia and autistic children and others with special needs. Bueermann said the focus is on those who tend to wander.

By registering the person's information, police can access the information online from their patrol vehicles while out searching for the lost person.

According to police spokesman Carl Baker, in 2006 Redlands police responded to more than 130 reports of missing adults, roughly once every three days.

According to the Alzheimer's Association, six out of 10 people with Alzheimer's disease will wander sometime during the progression of the disease.

"If they are not found within 24 hours, half of those could suffer serious injury or death," Baker said.

When every minute is precious, it is often difficult to ascertain vital information from frantic family members or other caregivers, Baker said. Thus registering the person's information makes the process easier.

When caregivers register with the program, they will also be provided with information and resources to help them better protect their clients and families.

The GPS technology that has been added to the program, similar technology to that is in cell phones and cars, will help to quickly locate people who are prone to "wandering syndrome."

But Baker said there are many issues that need to be worked out regarding the GPS element of the program.

"We will not be monitoring the GPS but are looking at a way, for instance, to set up a Rvirtual fence' that would alert someone if the subject wanders out of a predetermined area," Baker said. "It would also be useful if we get a report that a subject is missing. If they have GPS we can locate that person electronically, cutting down on the manpower and, more importantly, search time since often time is of the essence in searching for people with medical needs."

Though there are some glitches with GPS, Bueermann said that it can help "tremendously" in finding people.

Source: Darcie Flansburg. Technology will help get people safely back home (24 Feb 2007) [FullText]

Amyloid Dogma on a Rise: Another Alzheimer's Drug to Tackle Amyloid?

2007-03-12T12:59:00.000+02:00

Can Old Idea Produce Potent New Alzheimer's Drug?

Nearly five-million Americans are living with Alzheimer's disease. Drugs on the market can treat the symptoms -- but not one goes after what causes it. Now, researchers are on the brink of a huge breakthrough with a drug that targets the cause and could stop the disease in its tracks.
Frances Goldstein: "I like to paint -- a lot."

Jacobo, her husband of 45 years, loves watching her mind at work. Frances has Alzheimer's disease -- diagnosed eight years ago at age 56.

Jacobo Goldstein, Wife has Alzheimer's: "For the first nine months, I couldn't tell her the word Alzheimer's because I was afraid, you know, that she might go into tremendous shock."

Instead, Frances fought back. For three years, she's been in a study testing a drug that could change her prognosis. Current Alzheimer's drugs target the symptoms of the disease...like memory loss and emotional problems. Well this new drug is taking a more direct approach.

Paul Aisen, M.D., Alzheimer's Specialist: "This drug is attacking the cause of Alzheimer's disease. If it works, it will change the course of the disease and that will represent a real breakthrough."

The drug - called Alzhemed - attacks Amyloid Peptide - the molecule that causes Alzheimer's. In mice, watch as the drug clears the molecule from the brain.

Paul Aisen, M.D.: "I think it is tremendously significant."

An early study showed Alzhemed stabilized the disease in nearly half of patients. Now, more than 1,000 are being followed.

Paul Aisen, M.D.: "If the phase three study confirms that the drug is effective, we will have a way of slowing the progression of Alzheimer's disease for the first time."

Frances takes Alzhemed twice a day.

Jacobo Goldstein: "I don't know where we would be if it wasn't for this. We have no idea. I know what she does now. If we can stay the way we are, we would be forever grateful."

With hope in hand, Frances continues to make every day and every painting count.

To date, more than 600 patients have completed one year of treatment on the medication. The study is scheduled to be complete soon. More than 70 centers across the United States and Canada are taking part. Side effects of the drug have been minimal and primarily include mild gastrointestinal symptoms.

Source: New Drug Stops Alzheimer's In Tracks (20 Feb 2007) [FullText]

Alzheimer's Care Facility on Agenda

2007-03-10T12:38:00.000+02:00

By Chuck Schultz

Objections by some Orcutt homeowners to plans for a 14-bedroom house on Soloman Road, where seniors with Alzheimer's disease would be cared for, will be heard Tuesday by the Santa Barbara County Board of Supervisors.

Opponents contend the care facility proposed by Chuck and Margie Halsell shouldn't be allowed in an area characterized by ranchette homes, each on one acre or more and many with horse stables.

County staff planners who approved the project - and whose decision was unanimously upheld in December by the Planning Commission - note that special care homes for seniors are routinely permitted in residential areas, under both state law and county land-use regulations.

Jack Brady, who is appealing the commission's decision to the supervisors, said he and some of his neighbors worry the senior facility could fail financially and then be converted to some other use, such as a drug-rehabilitation center or a halfway house for paroled prisoners.

The site is along the south side of Solomon, adjacent to Song Lane.

“It's horse county,” observed Brady, who owns a home in the same block on Solomon. “I'd call this a commercial facility, but the state and county define it as a residential facility.”

Residents of the 61-home Westrails subdivision directly east of the Halsells' property are concerned, too, about what the big house might be used for in the future, said Terry Morgan, a homeowners association board member.

“We don't want it to end up being a drug rehabilitation facility,” he said.

Even the proposed senior facility “would be too commercialized in the middle of a residential development,” he contended.

Marcie Halsell said numerous design changes have been made in response to neighbors' concerns since the permit application was submitted to the county Planning and Development Department last year. Second floors were deleted from the plans for adding two wings onto the existing, two-story structure, and there won't be any second-floor windows facing toward the Westrails tract, as originally envisioned, she said.

The home is 4,463 square feet now, and has four bedrooms, but would be expanded to 7,940 square feet.

“This area is very suitable for” the proposed Alzheimer's facility, she added. “The state needs to encourage the opening of these homes.”

Improvements already made to the property include paving what was a dirt road to a width of 24 feet, installing a fire hydrant and adding an 80-foot-wide cul de sac where emergency vehicles can turn around.

“We've already improved the look and safety of the neighborhood,” Halsell said.

The supervisors will meet beginning at 9 a.m. at the Betteravia Government Center, 511 E. Lakeside Parkway in Santa Maria.

Also on their agenda Tuesday is an item relating to a controversial plan to extend Stubblefield Road in Orcutt so it connects to Black Oak Drive.

Against the wishes of some nearby residents, the supervisors in July approved a 160-foot extension of Stubblefield eastward from where it now dead ends.

Connecting it to Black Oak Road will make Stubblefield a thoroughfare for housing tracts such as Vintage Ranch and Mesa Verde, but opponents contend it will mean too much traffic through their neighborhoods and diminish their quality of life.

The extended road would pass through land slated to become a neighborhood park when the 725-home Rice Ranch project is built. So, the supervisors are being asked Tuesday to revise that project's “specific plan” to reflect the Stubblefield extension.

Source: Chuck Schultz. Alzheimer's care facility on agenda. lompocrecord.com (26 Feb 2007) [FullText] Chuck Schultz can be reached at cschultz[at]lompocrecord.com

Scrapbooks Help Jog Memories of Alzheimer's Patients

2007-03-08T12:33:00.000+02:00

by Anne Polta, West Central Tribune

WILLMAR, Minn. - The pages of Bethesda Pleasant View's scrapbooks capture a wealth of memories: birthdays, Halloween parties, daily happenings, residents past and present.

When Rachel Hacker hands one of the books to residents of the memory care unit, "they can sit and look at it for hours," she said.

It's one of the ways in which the staff of the memory care unit tries to preserve the happy times and foster a sense of belonging for residents whose minds have been robbed by Alzheimer's disease and other memory disorders.

"It really shows that even though Alzheimer's is a horrible disease, given the right stimulus it really can be beautiful," said Lynae Whitmore, the supervising nurse for the unit. "These people still have a quality of life, and it shows in these pictures."

Hacker, a certified nursing assistant, spent months - on her own time and mostly with her own money - compiling the scrapbooks.

She's close to completing the second book and is ready to start on a third.

Hacker developed an interest in scrapbooking through a cousin who owns Creative Memories. Inspired by the array of scrapbooking products that were available, she decided to complete a scrapbook that had been started for the memory care unit when it opened in late 2005.

Within a week she had the book filled and started on another.

"Every page is different," said Hacker as she leafed through the book.

On one page, decorative orange pumpkins share space with photos of the memory care residents having a Halloween party. On another, residents and staff hug and smile for the camera.

A recent donation in honor of Hacker's grandfather, Archie Bowman, who was a resident of Bethesda Pleasant View and died in October, allowed the memory care unit to buy a digital camera. It also created a fund to help pay for the scrapbooks and products that Hacker previously bought on her own.

Hacker updates the scrapbook once a month, often incorporating new ideas she picks up from scrapbooking retail products or workshops.

"I like doing it. I can sit at the same table for hours and get 20 pages done," she said.

As she became more involved in the project, Hacker began creating a page for each resident and customizing it to reflect their lives and interests - for instance, apples and blackboards for a resident who used to be a teacher, cut-outs of dogs for someone who's fond of dogs.

"We've been doing that every time a new resident comes in," Whitmore said. "Every one of them is unique and special."

Several families have asked for copies of the photos, she said. "Families love it."

Bethesda has worked to make its memory care unit less institutional and more home-like, and having photo albums "is just natural," Whitmore said.

People with Alzheimer's or related dementia disorders often disappear from family photographs because no one is taking their picture, she noted.

Yet these residents still enjoy being photographed, she said. "They like the attention. It's nice to capture the good days they have because they don't always have good days."

The staff also has found that paging through the scrapbook can be very calming for residents, especially during times of agitation.

"This book is very therapeutic for them," Whitmore said. "They recognize the people they're surrounded by. They recognize themselves. They like to look at the bright colors. It provides a sense of comfort to them."

The memories are beneficial for the staff as well.

Fourteen of the residents whose pictures appear in the scrapbooks have since died, Hacker said.

The photo albums are "a good memory for us of who has been here and who has passed away," she said.

The staff and residents of the memory care unit are close-knit and often form strong bonds, Whitmore said.

"It's just a family," she said. "These people are special. Just because they can't think right doesn't mean their life is over. They don't need to be pitied. There's a lot of love there. They have quality of life."

Information from: West Central Tribune, wctrib.com (26 Feb 2007) [FullText]

There is Help Available for Alzheimer's Caregivers

2007-03-04T12:28:00.000+02:00

By Carol Sipfle, executive director, Alzheimer's Association, Greater Iowa Chapter,
West Des Moines.

The recent disappearance of Robert Krivolavy focuses a spotlight on one of the common and potentially tragic outcomes of Alzheimer's-disease wandering. Six out of 10 people with Alzheimer's, or a related dementia, will wander away from homes, neighborhood stores, places of worship or while visiting friends.

The Alzheimer's Association urges anyone dealing with a diagnosis of this devastating disease to enroll in Safe Return, the only nationwide program dedicated to reuniting loved ones with the person who has wandered.

We provide around-the-clock assistance, no matter when or where the person is reported missing.

The Alzheimer's Association also offers tips for preventing wandering, improving safety at home and dealing with the many other symptoms and behaviors common with Alzheimer's. We provide crucial support and assistance to caregivers, as well as offering education programs on subjects from disease basics to legal and financial planning.

FullText at DesMoinesRegister.com, IA (24 Feb 2007)

2007-03-02T12:19:00.000+02:00

Looking into the past becomes gradually impossible for those suffering from Alzheimer's disease - family faces become those of strangers and names are forever forgotten.

You know the face, but not the name. You've misplaced your glasses. Because it's happening more frequently as you age, you may be wondering, "Is this how Alzheimer's starts?"

Forgetting names or losing car keys occasionally should be no cause for concern, said Dr. Ron Petersen, director of the Mayo Clinic Alzheimer's Disease Research Center and a member of the Alzheimer's Association Medical and Scientific Advisory Council. In addition, according to Harvard University research, the key genes affecting learning and mental function start declining after age 40.

As we age, "We have to pay more attention and concentrate more when we're learning new information and events," said Dr. Petersen. "If we spend more time and are more mindful when we learn someone's name to try to get it more firmly in our memory, we can do it."

The greatest known risk factor for Alzheimer's is increasing age. The likelihood of developing Alzheimer's approximately doubles every five years after age 65. After age 85, the risk reaches nearly 50 percent.

And as we age, most of us eventually notice some slowed thinking and problems remembering certain things. However, serious memory loss, confusion and other major changes in the way our minds work are not a normal part of aging.

Possible causes of memory problems include: depression; medication side effects; excess use of alcohol; thyroid problems; poor diet; vitamin deficiencies; certain infections; and Alzheimer's disease and related dementias. Anyone experiencing significant memory problems should see a doctor as soon as possible. Early diagnosis and intervention methods are improving dramatically, and treatment options and sources of support can improve quality of life.

In 1980, when the Alzheimer's Association was established, there were not any available treatments. Now, 26 years later, the Association has funded extensive research into finding more treatments that can alleviate Alzheimer's symptoms and investigation into finding the cause and a cure.

If a means of prevention is not found, the number of people affected in the United States may grow from 4.5 million to 16 million by 2050. Because 70 percent of those with Alzheimer's live at home, the impact of the illness extends to millions of family members, friends and caregivers.

Lighting the path for people affected by Alzheimer's is the Greater Maryland Chapter. The Chapter serves more than 85,000 families touched by this devastating disease and its regional office in Salisbury serves more than 8,500 families living on the Eastern Shore. Services include a 24/7 telephone helpline, support groups, Safe Return Program, Family Care Program and Respite Care. Educational programs include: Professional training programs; workshops and conferences; community awareness; family education; speaker's bureau; book and audiovisual loan; and newsletter.

Annual fundraising events help support Eastern Shore families who are facing the emotional, physical, and financial challenges of Alzheimer's, as well as, critical research efforts.

On Saturday, March 17, spirits will run high when the 8th annual St. Paddy's Day 5K event kicks off at 3 pm at the Salisbury Elks Lodge near the zoo. More than 300 participants are expected.

Source: Dee Myers. Serious memory loss and confusion are signs of possible Alzheimer's. (26 Feb 2007) [FullText]

Dee Myers is public Awareness/Development Coordinator for the Alzheimer's Association, Greater Maryland Chapter

Cholesterol May Play Part in Alzheimer's Disease

2007-02-28T11:58:00.000+02:00

But role of cholesterol in Alzheimer's disease still unclear, reports the Harvard Men’s Health Watch.

It sounds simple: The lower your cholesterol, the better your heart health. But a man’s heart and his head don’t always agree.

In fact, the relationships among cholesterol levels, psychological function, and neurologic disorders are complex and sometimes controversial, reports the March 2007 issue of Harvard Men’s Health Watch.

There are two major forms of dementia: vascular dementia and Alzheimer’s disease. Vascular dementia results when blood vessel damage deprives the brain of oxygen. Brain cells die as a result, and mental function suffers.

Some studies link high cholesterol levels to an increased risk of cognitive impairment, but others report the opposite. More research is needed to sort this out, but even now, investigations of HDL (good) cholesterol and mental function have consistently reported that high HDL levels appear to help preserve mental function in older people.

The connection between Alzheimer’s disease and cholesterol is even more complex. Scientists have learned much of the damage of Alzheimer’s comes from deposits of a sticky protein, called beta-amyloid, in vital areas of the brain.

In some studies, high cholesterol levels appear to accelerate the formation of beta-amyloid plaques. People with the genetic trait that increases the level of a particular cholesterol transport protein have a greatly increased risk of late-onset Alzheimer’s.

The urgent question is whether cholesterol-lowering drugs, such as statins, can reduce the risk of Alzheimer’s disease. In the most recent studies, people who took statins did not appear to be at lower risk for the disease. Additional research is under way.

For an in-depth information on the role of lipids in Alzheimer's disease and other neurodegenerative diseases, please see major subject journal Neurobiology of Lipids.

Source: Cholesterol May Play Part in Alzheimer's Disease. Toronto Daily News (25 Feb 2007) [FullText]

Alzheimer's News in Brief (26 February 2007)

2007-02-26T15:00:00.000+02:00

Ken Howard needed no research for Alzheimer's role in new TV movie
Gary Post Tribune - Gary, IN, USA
LOS ANGELES--Ken Howard required no research to play a man in the early stages of Alzheimer's disease. ''I did all my homework for this role years ago,'' he...
See all stories on this topic

MetLife Foundation Announces Major Awards to Scientists for ...
Insurance News Net - Harrisburg, PA, USA
The winners of the MetLife Foundation Awards for Medical Research in Alzheimer's Disease were announced in Washington, DC today...
See all stories on this topic

New Alzheimer's target a Notch above the rest?
DrugResearcher.com - Montpellier, France
Scientists have discovered a new potential target for Alzheimer's drugs that could reduce symptoms of the disease without interfering with...
See all stories on this topic

Man, 91, With Alzheimer's Disease Missing
WESH.com - Winter Park, FL,USA
He has Alzheimer's disease but currently isn't taking medication. Authorities said he has a heavy Polish accent and can be aggressive because of his...
See all stories on this topic

Serious memory loss and confusion are signs of possible Alzheimer's
Delmarva Daily Times - MD, USA
Forgetting names or losing car keys occasionally should be no cause for concern, said Dr. Ron Petersen, director of the Mayo Clinic Alzheimer's Disease...
See all stories on this topic

Role of Cholesterol in Alzheimer's Disease Unclear
Kansas City infoZine - Kansas City, MO, USA
There are two major forms of dementia: vascular dementia and Alzheimer's disease. Vascular dementia results when blood vessel damage deprives the brain of...
See all stories on this topic

TorreyPines Therapeutics and Eisai Co., Ltd. Extend Alzheimer's ...
PipelineReview.com (press release) - Barcelona, Spain
This collaboration, focusing on the discovery of novel, small molecules to treat Alzheimer's disease, is TorreyPines second discovery collaboration with...
See all stories on this topic

The Other Dementia
San Francisco Chronicle - San Francisco, CA, USA
"I do a lot of crying," says Dawn's mother, Emmogene, who lives in Antioch, cares for a husband with early Alzheimer's disease and regularly attends UCSF's...
See all stories on this topic

MetLife Foundation Announces Major Awards to Scientists for Research on AD

2007-02-26T12:09:00.000+02:00

The winners of the MetLife Foundation Awards for Medical Research in Alzheimer's Disease were announced in Washington, D.C. today. Awards were made at a special scientific briefing and luncheon, to David M. Holtzman, M.D. of the Washington University School of Medicine in St. Louis, for his pioneering work in molecular biology examining the early stages of Alzheimer's, and Berislav V. Zlokovic, M.D., Ph.D. of the University of Rochester Medical Center in Rochester, New York, for his research defining the impact that blood flow plays in Alzheimer's disease.

Since 1986, major awards have been made to scientists who have demonstrated significant contributions to the understanding of Alzheimer's disease. At the heart of the awards program is a strong belief in the importance of basic research, with an emphasis on providing scientists with the opportunity to liberally pursue ideas. Each of the winners will receive a $50,000 personal award, in addition to a $200,000 research award to each of their institutions, to further their research.

"Alzheimer's is an issue of national importance. The disease is not only financially devastating to many families, but it also robs them of the person they once knew," said C. Robert Henrikson, Chairman, President and Chief Executive Officer of MetLife, Inc. "The impact of Alzheimer's on families, society, and the economy is why MetLife has been committed for over 20 years to the search for a cure."

An estimated 4.5 million Americans have Alzheimer's disease, a number that has more than doubled since 1980, and will continue to grow - by 2050 the number of individuals with Alzheimer's could range from 11.3 million to 16 million. Increasing age is the greatest risk factor for developing Alzheimer's; one in 10 individuals over 65 and nearly half of those over 85 are affected. National direct and indirect annual costs of caring for individuals with Alzheimer's disease are at least $100 billion, according to estimates used by the Alzheimer's Association and the National Institute on Aging. Alzheimer's disease costs American business $61 billion a year, according to a report commissioned by the Alzheimer's Association. Of that figure, $24.6 billion covers Alzheimer health care and $36.5 billion covers costs related to caregiving.

"The scientists we honor today are making a significant contribution to our future, by helping us better understand a disease that has an impact on so many Americans," said Sibyl Jacobson, president, MetLife Foundation. "Their hard work and dedication give us hope for the future."

Richard Hodes, M.D., director of the National Institute on Aging at the National Institutes of Health, delivered the keynote speech during the luncheon. The author of more than 200 research papers and a leading immunologist, Dr. Hodes has devoted his tenure as Director of the National Institute on Aging to improving the health and quality of life for older people and their families. He is a graduate of Yale University and received his M.D. from Harvard Medical School.

The awards program began with a research briefing, where the award recipients discussed their work. The briefing was moderated by Robert N. Butler, M.D., president and chief executive officer of the International Longevity Center - USA, and Professor of Geriatrics, Mount Sinai Medical Center in New York City, and chair of the MetLife Foundation's Research Committee. He is also the founding director of the National Institute on Aging of the National Institutes of Health.

About the Award for Medical Research Winners

Dr. Holtzman is the Andrew B. and Gretchen P. Jones Professor of Neurology and Molecular Biology & Pharmacology at Washington University School of Medicine in St. Louis, and Head of the Department of Neurology. He is also associate director of the Alzheimer's Disease Research Center at Washington University. Dr. Holtzman and the Washington University School of Medicine in St. Louis were awarded a "promising work" grant from MetLife Foundation in 2002.

Dr. Holtzman and his team recently completed landmark studies in three areas of inquiry, significantly advancing our understanding of the biology of Alzheimer's disease. The first centered on the ability of antibodies directed against amyloid-beta to decrease plaque formation in the brains of mice. Dr. Holtzman's tests of the antibody resulted in a decrease in amyloid formation in the brain and improved memory function in mice within 24 to 72 hours. A human form of this antibody is now being tested. His second area of accomplishment has been in the search for physical traits that indicate whether a person is developing amyloid plaques and will ultimately suffer dementia. The third is in the development of novel methods of assessing the formation and clearance of amyloid-beta in the central nervous systems of both animals and humans. Dr. Holtzman has also been honored with the Potamkin Prize from the American Academy of Neurology, the MERIT award from the National Institute on Aging, and the Zenith Award from the Alzheimer's Association.

Dr. Zlokovic, who is known internationally for his work on stroke as well as Alzheimer's, focuses on the crucial role of blood vessels and has shown that blood circulation plays a key role in ridding the brain of the toxic amyloid beta that attacks the brains of Alzheimer's patients. For over a decade, Dr. Zlokovic has focused his attention on the transport of amyloid beta protein in the blood that flows through the brain. He suspected that the accumulation of amyloid beta in the brain might have to do with an abnormality in a patient's ability to clear the protein through the membrane that controls the passage of substances to and from the central nervous system.

Dr. Zlokovic and his team has identified much of the molecular machinery that allows amyloid beta to sidestep the body's safeguards and enter the brain, and he has discovered the molecules that falter when the toxic protein accumulates in the brain. He has shown that a breakdown in these mechanisms may lead to the symptoms displayed in Alzheimer's and other disorders associated with accumulations of amyloid-beta in the brain or blood vessels. As a result of this work, Dr. Zlokovic has demonstrated several strategies for preventing or lowering amyloid-beta accumulation and preventing reentry from the blood stream. Dr. Zlokovic is the Dean's Professor and Professor of Neurosurgery & Neurology at the University of Rochester Medical Center. He is also director of the university's Frank P. Smith Laboratories for Neurosurgical Research and associate chairman for Neurosurgery. He holds a MERIT award from the National Institute on Aging.

Source: MetLife Foundation Announces Major Awards to Scientists for Research in Alzheimer's Disease. Business Wire (23 Feb 2007) [FullText]

TorreyPines Therapeutics and Eisai Co., Ltd. Extend Alzheimer's Disease

2007-02-24T12:14:00.000+02:00

Announced the extension of an exclusive collaboration agreement between TorreyPines and Eisai Co., Ltd. that began in February 2005.

LA JOLLA, CA, USA TorreyPines Therapeutics, Inc. (NASDAQ: TPTX) today announced the extension of an exclusive collaboration agreement between TorreyPines and Eisai Co., Ltd. that began in February 2005. This collaboration, focusing on the discovery of novel, small molecules to treat Alzheimer’s disease, is TorreyPines’ second discovery collaboration with Eisai. In a separate series of agreements, dating back to 2001, Eisai and TorreyPines are collaborating in a genetics program to discover Alzheimer’s disease targets using whole-genome family-based association screening.

The goal of the small molecule program is to discover novel Alzheimer’s disease modifying compounds based on the study of the mechanism of the disease’s pathogenesis. Under the original agreement, Eisai has exclusive rights of first negotiation and refusal for validated compounds that are discovered through the research. TorreyPines and Eisai may enter into development agreements involving the validated compounds.

“We are excited about extending this agreement with Eisai, a leader in Alzheimer’s disease research and treatment,” said Neil Kurtz, M.D., President and Chief Executive Officer of TorreyPines. “We look forward to advancing the small molecule program further with Eisai’s support, as well as to continuing to work with them on our initial research collaboration to identify genetically-validated pharmaceutical targets for Alzheimer’s disease.”

About TorreyPines Therapeutics, Inc.

TorreyPines Therapeutics is a clinical stage biopharmaceutical company that discovers and develops small molecule drugs to treat diseases and disorders of the central nervous system (CNS). Led by an accomplished management team, TorreyPines is leveraging novel drug targets and technologies to potentially deliver new CNS therapies for chronic pain, including migraine and neuropathic pain; and cognitive disorders, including cognitive impairment associated with schizophrenia and Alzheimer’s disease. TorreyPines’ common stock is traded on The NASDAQ Global Stock Market under the symbol "TPTX." For detailed company information, including copies of this and other press releases, please visit TorreyPines’website at www.torreypinestherapeutics.com...

Source: TorreyPines Therapeutics, Inc [FullText]

Juices Warding Off Alzheimer's Disease

2007-02-22T12:23:00.000+02:00

Alzheimer's And Juice

Drinking fruit or vegetable juice may be better for you than you think. New research shows it may delay the onset of Alzheimer's disease.

Seattle researchers followed nearly 2,000 adults including for 10 years. They found drinking fruit or vegetable juice more than three times a week cuts the risk of developing Alzheimer's by 76 percent compared to drinking it less than once a week.

And having juice once or twice a week reduced the risk by 16 percent.

"The theory is that the brain accumulates damage due to oxidation as we age, and if you can protect the brain from that damage you can protect the person from Alzheimer's disease and other causes of dementia," said Dr. Eric Larson of Group Health Cooperative.

Antioxidants fight that process. And there are more in juice than in the actual fruit or vegetable.

"It's everything, the core the outside, seeds, and everything is put into it," said Dr. Larson.

Researchers saw the protective benefits from any type of juice.

The study also found there are more antioxidants in juice than in vitamin C and E supplements.

Source: Juices Warding Off Alzheimer's Disease. MFTV.com (21 Feb 2007) [FullText]

Funds Cut For Growing Brain Disease: Alzheimer's incidence expected to grow but research not in budget

2007-02-18T12:45:00.000+02:00

Alzheimer's incidence expected to grow but research not in budget

The incurable brain disease affecting more than 60,000 South Carolinians warrants more attention than it's getting on the local, state and national levels, national experts told an Orangeburg audience last week.

Without a cure, the incidence of Alzheimer's disease in the state is expected to increase by 49 percent by the year 2025, with more than 75 percent of these individuals expected to receive in-home care by an elderly spouse or adult child, according to Kate Gordon, National Alzheimer's Association associate director of grassroots advocacy.

"There are a high number of people with Alzheimer's, about 50 percent, living in nursing homes, but we know that families take on the greatest burden of care," Gordon said, speaking at Victory Tabernacle Deliverance Temple Wednesday.

The situation with federal funding for Alzheimer's research and care programs is discouraging, she said. Research funding has been on a steady decline since 2003, and funds for key Alzheimer's care program, including the 24/7 Contact Center, Safe Return and the Alzheimer's State Matching Grants Program, have been eliminated in the president's 2008 budget proposal to Congress, she said.

The FDA has over 20 drugs "in the pipeline" for Alzheimer's prevention or treatment, but money to move them forward has been declining steadily over the last 15 years, which dashes NAA's hopes for a cure within the next five to 10 years.

The reductions decrease services available for families, and Gordon encouraged such families to communicate with elected officials about what is needed.

The national association will hold its 19th Annual Public Policy Forum March 18-20.

Via "Virtual Visits," on-line users can write their personal Alzheimer's stories and voice their opinions against proposed budget cuts. State advocates will send the letters to the appropriate elected officials in Washington, D.C.

With baby-boomers approaching the highest risk age, 65, the numbers with Alzheimers will explode, Gordon said. A cure would decrease the burden on the country's overall health care system.

Alzheimer's is not "just a quiet, behind-closed-doors family issue," she said. "It's touching an entire community," said Gordon, stressing the need for caregivers.

Striking a population under 60, early-onset Alzheimer's disease is challenging for doctors specializing in older patients to diagnose, Gordon said. Ineligible for Medicare, early-onset victims don't have the resources of older patients, which offers an extra challenge to communities trying to offer services.

Hospice Care of Tri-county's Orangeburg office serves Orangeburg, Bamberg, Calhoun and Barnwell counties and a portion of Aiken County. Jerri Zeigler, community education coordinator with Hospice Care, is working to create an Alzheimer's support group with meetings likely rotating between her office and Morningside Assisted Living Center.

"My husband's grandmother died a few years ago with the disease, so it's very important to me to have a support group," she said. "I know how important it is to the community."

Hospice care can offer a critical link for those in the late, terminal stages of the disease. "People don't see hospice as a service for people with Alzheimer's disease because it's not widely known that it is a terminal disease," she said.

Family members and other caregivers experiencing burn-out can take advantage of respite care and other services that hospice provides, said Janice Harris, community education coordinator at Hospice Care of Tri-County's Columbia office. The respite program provides care for up to five days and can be used every three months, according to Zeigler.. She said the office has also helped individuals with light, taxes and other bills.

Harris, who has cared for four of her own family members with Alzheimer's, said she speaks at senior centers about how to detect the early stages of the disease. Memory loss and language problems are among the 10 warning signs of the disease.

Harris also does a 'Caring for the Caregiver' program and education programs on maintaining the brain, staying healthy, and understanding the challenging behaviors of those with Alzheimer's in nursing facilities and homes..

In book, "When Roles Reverse: A Guide To Parenting Your Parents," author Jim Comer identifies issues in families that need attention and helps them develop an action plan.

Among the 50 questions Comer said families must ask to save time, money and tears are: Who will be the primary caregiver or share responsibility when a parent becomes ill or incapacitated? What specific plans has the family made for a sudden parental illness or emergency? T

"Have a family discussion in a relaxed atmosphere, not in the middle of a holiday celebration, birthday or anniversary. These questions deserve a time slot of their own. If a family is geographically dispersed, ... arrange for a conference call," Comer says in his book.

Gordon is particularly excited about the creation of a local support group which she said will empower the community to fight Alzheimer's more effectively.

Because there is no cure, NAA advocates families getting involved in the fight for a world without the brain disease.

"People are suffering in our communities, and we need help," Gordon said.

Source: Dionne Gleaton, T&D Staff Writer. Alzheimer's incidence expected to grow but research not in budget (19 Feb 2007) [FullText]

T&D Staff Writer Dionne Gleaton can be reached by e-mail at dgleaton [at] timesanddemocrat.com

Another NIH Grant to Battle Amyloid Oligomers, Claims Plaques are Not Pathological

2007-02-16T12:52:00.000+02:00

A completely new approach to the study of Alzheimer's disease, initiated by a professor at the University of California, Santa Barbara, may solve a critical piece in the puzzle of the disease. This tragic neurological illness progressively erases memory in its millions of victims. The key to the new approach is understanding the way certain proteins in the brain fold, or rather "misfold."

Michael Bowers, a professor in the Department of Chemistry and Biochemistry, developed this project, which is being funded by the National Institutes of Health. Bowers's laboratory will receive $1.3 million of the total $9 million project grant, plus biological samples worth an additional $500,000. The grant covers a five-year period. Four institutions are involved.

Bowers is using specialized chemical research methods and applying them to biology. His research will depend upon the study of rare peptides, or strings of amino acids, that are difficult to produce. These will be provided by co-investigator David Teplow, a professor at UCLA's David Geffen School of Medicine, who has been involved in Alzheimer's research for over 10 years. Joan-Emma Shea, also a professor in UCSB's Department of Chemistry and Biochemistry, heads the theoretical modeling aspect of the project.

"Until about five or six years ago, everyone assumed that the large amyloid plaques, or neurofibrillary tangles, that were found in the brains of Alzheimer's victims were the cause of the disease," said Bowers. "However, recent scientific discoveries indicate that these large, insoluble aggregates might merely be markers of the disease ---- they do not cause the disease. Rather, smaller soluble oligomers, or peptide complexes, are now felt to be the causative agents, and I find that very interesting."

He explained that now the hunt is on for the "small stuff." Because of their expertise in certain chemical methodologies, Bowers and his research group are able to track down the molecular level changes that lead to development of the disease.

The process of aggregation of proteins that cause the plaque begins in a way that Bowers has begun to clarify. The goal is to find non-toxic drugs that will interrupt the aggregation process. "If we can do that, we can stop the disease," said Bowers. "However, once you start losing neurons, things become very difficult, because the body doesn't readily replace them due to their very large size. If we could find a marker, early on, to indicate when the patient first has the disease, then the new drug or drugs that we hope to develop could prevent further damage."

Bowers described his approach as a whole new way to determine the structure and composition of the Abeta 42 peptide and its oligomers that are primarily responsible for Alzheimer's disease. The research team is analyzing the way this peptide folds, causing it to aggregate and disrupt neuronal function.

"In biology, structure and function are tightly coupled," said Bowers. "When it became clear that small soluble oligomers were most probably the toxic agents, I realized our ion mobility methods could contribute, since we could measure the oligomer distribution and shapes of these peptides for the first time."

Three years of preliminary work convinced the National Institutes of Health to provide funding. "In the last several months, I believe we have uncovered the identity and shape of the primary toxic oligomer," said Bowers. "Our results are consistent with findings on transgenic mice, recently published in the journal Nature, indicating that soluble oligomers with masses matching those we have identified have been extracted from the brains of the diseased animals."

The transgenic mice that Bowers refers to are laboratory mice that have had the gene that creates the Abeta 42 precursor protein spliced into their genome. This process has been shown experimentally to produce memory loss in the animals.

The key aspect of ion mobility is its ability to measure accurate cross sections of complex aggregations of proteins and obtain information on their three-dimensional shape. When coupled with mass spectrometry, electrospray ionization, and high-level molecular modeling, it becomes a very powerful technique.

The experiment starts with electrospray ionization, a method of spraying the solution containing the peptides of interest into fine droplets and then letting the droplets evaporate. Following evaporation, mass spectrometry is employed to determine the mass or weight of the species that were in the solution, and from that to determine the composition. Finally ion mobility is used to show the shape of the Abeta 42 peptide and its oligomers.

"Our experimental and theoretical methods allow us to investigate structure, aggregation, and energetics in a variety of protein systems," said Bowers. "In addition, we are able to explore correlations between solution and gas phase protein structures, learning that in many critical cases, these structures are very similar."

The experimental methodology for the Alzheimer's study was developed at UCSB 15 years ago, in studies involving "buckyballs." Buckyball is the nickname for the versatile carbon molecule known as C60, which scientists named "buckminsterfullerene" after American architect R. Buckminster Fuller, who designed geodesic domes in a soccer-ball shape. "Our ion mobility and mass spectrometry methods provide a new way to attack the molecular basis of neurological diseases that has not been explored until now," said Bowers.

Bowers and his group are currently investigating proteins involved in the study of several neurological diseases. Besides Alzheimer's disease, they are studying Parkinson's disease and the various transmissible spongiform encephalopathies or "prion" diseases. In this latter case Bowers is receiving funding from the British government to find an ante-mortem test for the bovine prion disease usually called "mad cow" disease. The same test, if successful, should also work on deer and elk; an epidemic in the Midwestern United States now affects these animals.

Besides Teplow and Shea, co-investigators on the Alzheimer's project include Gal Bitan, assistant professor at UCLA's David Geffen School of Medicine; Eugene Stanley, physics professor at Boston University; and, George Benedek, physics professor at MIT.

Source: Innovative Alzheimer's Research May Solve Critical Piece In Disease's Puzzle. Science Daily (15 Feb 07) [FullText] Note: This story has been adapted from a news release issued by University of California - Santa Barbara.

Know the Symptoms of Alzheimer's Disease

2007-02-14T12:56:00.000+02:00

What you don't know about Alzheimer's disease could hurt you. That's why it's important to seek medical attention if you experience any of these warning signs:

Increasing and persistent forgetfulness.

Difficulty performing familiar tasks.

Problems with finding the right words to express your thoughts.

Disorientation with time and place.

Poor or impaired judgment.

Problems with abstract thinking.

Putting everyday items in illogical places.

Changes in mood, behavior or personality.

Forgetfulness and confusion can also be caused by diabetes, thyroid disease, depression, drug interaction and vitamin deficiencies. These symptoms may also indicate the presence of another form of dementia.

If you have Alzheimer's or another form of dementia, the sooner you're evaluated and diagnosed, the more options you're likely to have in improving your symptoms.

Although Alzheimer's is a progressive disease with no known cure, drugs may temporarily slow the progression of the disease or improve symptoms. An early diagnosis may give you the opportunity to be involved in making important legal, financial, social and medical decisions that will affect you and your family.

Source: Mayo Foundation for Medical Education and Research

Scientists Say Amyloid and TAU Partner To Destroy Nerve Cells

2007-02-12T10:40:00.000+02:00

Scientists at the University of Virginia have identified what appears to be a major missing link in the process that destroys nerve cells in Alzheimer’s disease, an incurable disease that slowly destroys memory and cognitive abilities.

In Alzheimer’s disease, two kinds of abnormal structures accumulate in the brain: amyloid plaques and neurofibrillary tangles. The plaques contain fibrils that are made from protein fragments called “beta-amyloid peptides.” The tangles also are fibrous, but they are made from a different substance, a protein called “tau.” In the new U.Va. study, the researchers found a deadly connection between beta-amyloid and tau, one that occurs before they form plaques and tangles, respectively.

According to George Bloom, the senior author of the study and a professor of biology and cell biology at U.Va., this connection causes the swiftest, most sensitive and most dramatic toxic effect of beta-amyloid found so far. What makes it most remarkable, though, is that it requires a form of amyloid that represents the building blocks of plaques, so called “pre-fibrillar beta-amyloid,” and it only happens in cells that contain tau. Even though they account for just ~10 percent of the cells in the brain, nerve cells are the major source of tau, which likely explains why they are specifically attacked in Alzheimer’s disease.

The researchers used cultured mammalian cells that either did or did not make tau to study how cells respond to beta-amyloid. They found that pre-fibrillar, but not fibrillar beta-amyloid works together with tau to break apart microtubules — highways along which “synapse” replacement parts move rapidly in the nerve cell from where they are made to where they are needed. Synapses are connections between nerve cells, and in the brain they are the structural basis of memory and cognition. When nerve cells in the brain lose their microtubules they also lose the ability to replace worn out synapse parts, and synapses therefore disappear. The loss of synapses, and consequent loss of memories and cognitive ski lls, cannot be reversed, and can lead directly to nerve cell de ath.

“We think we’ve found one of the seminal cell biological events in the pathogenesis of Alzheimer’s and if we can figure out all of the steps in the process and understand each player at every step, it will represent many potential new drug targets for Alzheimer’s therapy,” Bloom said. “Our paper defines one of the earliest events that causes neurons to die in both early-onset familial Alzheimer’s and late-onset Alzheimer’s disease. We believe this is the first evidence for the long elusive ‘missing link’ between amyloid and tau in Alzheimer’s disease.”

“This is a very significant finding that greatly improves our understanding of the mechanisms within the cell that ultimately lead to Alzheimer’s disease,” said Lester Binder, professor of cell and molecular biology at Northwestern University and a leading researcher on Alzheimer’s. Binder said he has already incorporated the U.Va. study into classes he teaches on the pathogenesis of Alzheimer’s disease and dementia.

The study’s first author and lead investigator is Michelle King, a U.Va. research assistant professor of biology. Other investigators include Bloom, Ho-Man Kan and Alev Erisir of U.Va., Peter W. Baas of Drexel University and Charles G. Glabe of the University of California at Irvine.

Source: (10 Feb 2006) Alzheimer's Disease : Missing link in process leading to Alzheimer's disease. SpiritIndia [FullText]

Probing Question: Can Alzheimer's disease be prevented?

2007-02-10T10:37:00.000+02:00

By Melissa Beattie-Moss, Research Penn State

Most of us have had the experience of forgetting where we've parked our car or have struggled to recall an acquaintance's name. But once we hit our 50s, said James R. Connor, these incidents might cause us to worry that we're showing early signs of Alzheimer's disease.

Fortunately, that's not usually the case, says Connor, professor of neurosurgery in Penn State's College of Medicine, Penn State Milton S. Hershey Medical Center. "If forgetting something now and then was a good indicator of dementia, we'd all be in trouble," he added with a laugh.

This dreaded condition was first classified as a disease 100 years ago by German psychiatrist Alois Alzheimer and is the "leading cause of dementia in the elderly," explained Connor. In fact, four million Americans now suffer from this progressive disease, including up to 50 percent of seniors over age 85 and up to 15 percent of those over 65.

The aging of baby boomers will swell those numbers in the coming years. "At the present time, Alzheimer's disease (AD) costs the nation $100 billion a year, with an average $174,000 lifetime cost per patient," Connor said. "By the year 2050, there will be an estimated 14 million Americans with the disease. The human and economic toll is devastating, so it's imperative that we learn more about prevention, early diagnosis and treatment."

Is it possible to prevent Alzheimer's? For those who already have signs of persistent memory decline, there are some neurosurgical procedures and therapeutic drugs available that may help slow the disease's ravages, Connor noted. But for the millions of "worried well," science has not yet found any definitive ways to prevent the disease.

Although recent research suggests that genes may play a role in contracting the disease, "the No. 1 risk factor for Alzheimer's is aging," said Connor. "You have to live long enough to develop this disease," which researchers believe to be caused, in part, by a sticky protein called "amyloid plaque" that accumulates on brain cells, disrupting the transmission of their signals. "Neurofibrillary tangles" -- protein threads that strangle and eventually kill nerve cells -- are also present in the brains of AD patients. "If we have a computer with cables that are broken and tangled, it won't work right, and it's the same with our brains," added Connor.

Scientists speculate that the protein coatings and tangles within the brain could be the body's inflammatory response to long-term toxin exposure, as well as damage from "free radicals," unstable molecules that attack and harm the body's cells by stealing their electrons through a process called oxidation.

Although some studies suggest that anti-inflammatory drugs (including common painkillers such as ibuprofen and naproxen) may help to dissolve amyloid plaques, "we need to proceed with caution in this area," Connor believes. One paradox of the disease, he says, is that "there may be a positive function to the plaques. They may be the body's way of sealing off leaky blood vessels in the brain."

Many researchers believe that metals (chiefly iron, copper and zinc) may play a role in Alzheimer's, since these substances are abundant within the folds of plaque in diseased brains. When free radicals bump into metal atoms in the body, they unleash a chain reaction that can wreak havoc on healthy cells, prematurely aging them and potentially leading to a variety of serious health conditions. MRIs and autopsies of patients with advanced Alzheimer's often reveal massive iron accumulation, Connor noted.

Although excess metals may damage the brain, he adds, another paradox is that small amounts of these micronutrients are absolutely essential to healthy brain function.

Research on the exact link between metals and memory processing is inconclusive at this point. "Is there too much copper or too little in the brains of AD patients? Studies are unclear," Connor remarked. So, too, is the role of zinc, he added. Though there's high zinc content in the healthy hippocampus -- the part of the brain responsible for short-term memory -- the jury is still out on the connection, so there's no reason to recommend zinc supplements at this point. Too much might cause a problem as well. It's all about the right balance.

Nor should one completely avoid dietary iron or copper, suggested Connor, although some physicians recommend "decreasing your iron burden" through occasional blood donation, particularly for men and post-menopausal women, who are at higher risk for accumulating iron and for developing neurodegenerative diseases.

Other recommendations made by some physicians (particularly for patients noticing subtle cognitive decline) include taking antioxidants such as vitamins E and C, going for chelation therapy and making dietary changes.

"Remember," said Connor, "that if you flip the statistics, at least half of those over 85 don't have Alzheimer's. In addition to studying those with the disease, we're also studying seniors with good short-term memories, looking for predictors of healthy neurocognitive aging."

Full Text at Psychorg.com

Study Finds Loneliness May Increase Alzheimer's Risk

2007-02-08T10:45:00.000+02:00

Chicago, IL (AHN)-A new study published in the February issue of the Journal Archives of General Psychiatry finds that loneliness may increase the risk of developing Alzheimer's disease later in life.

For the study, researchers at Rush University Medical Center in Chicago examined 823 participants, at an average age of 81, over a period of four years. Using a scale from 1 (lowest) to 5 (highest), researchers assessed the participants' level of loneliness at the start of the study and each subsequent year after over a period of 4 years. Participants were also screened for signs of dementia by testing a range of cognitive functions.

According to the study, the mean loneliness score at the start of the study was 2.3 on a scale of 1 to 5. Over the course of the study, seventy-six people developed Alzheimer's disease, with researchers determining that each point of increase on the loneliness score was associated with about a 51 percent increased risk of developing Alzheimer's.

While, the actual physiological mechanism linking loneliness and Alzheimer's remains unclear, researchers found that people who described themselves as most lonely were twice as likely to develop Alzheimer's as the ones who described themselves as least lonely.

But, the researchers' say that it is unlikely that Alzheimer's actually causes the loneliness, with the study authors writing, "In human beings, loneliness has been associated with impaired social skills. Thus, neural systems underlying social behavior might be less elaborated in lonely persons and, as a result, be less able to compensate for other neural systems compromised by age-related neuropathy."

Source: Julie Farby. Study Finds Loneliness May Increase Risk Of Alzheimer's Disease. allheadlinenews.com (6 Feb 2007) [FullText]

Physicians do not always practice what drug watchdog preaches

2007-02-05T10:49:00.000+02:00

The UK government's drug watchdog NICE has received a lot of publicity recently after publishing guidelines restricting the prescription of certain cognitive enhancers for Alzheimer's disease for reasons of cost. However, a recent survey of 181 neurologists by Datamonitor indicates that the NICE cost-benefit methodology may not reflect how the drug is actually used in the clinical setting.

'Content Cognitive enhancers do not treat the cause of Alzheimer's, rather they seek to prevent the cognitive decline associated with it, and fall into two categories: acetycholinesterase inhibitors (AChEIs) including Aricept (donepezil), Exelon (rivastigmine) and Razadyne (galantamine), or the NMDA antagonist memantine, which is branded as Namenda and Ebixa in the US and Europe respectively.

Source: PBR Staff Writer. Alzheimer's disease: physicians do not always practice what NICE preaches (5 Feb 2007) [FullText]

Stepping out against Alzheimer's disease

2007-01-30T11:06:00.000+02:00

By Mark Brett

When diagnosed with Alzheimer's disease a year ago, Yvonne Letestu believed her life was over.

Just prior to receiving that devastating news from her doctor, friends and family had been noticing that she was becoming absent minded--forgetting little things here and there.

And they weren't the only ones.
"I knew something was wrong," said Letestu, who is currently living at the Village by the Station. "But I was only I was 55 years old. I was devastated, I cried for days and days thinking that my whole world was going to come to an end."
However having just moved to Penticton from her home in Saskatchewan where she had spent almost all of her life, she was fortunate to meet Laurie Myres of the Penticton branch of the Alzheimer's Society of B.C.

"I began going to the Alzheimer's support group meetings and I could really relate to the other people there and what they were going through," said Letestu, who was among the 150 people who took part in Sunday's Investors Group Walk for Memories fundraiser for the society. "Because I was the youngest the people were very sympathetic and very supportive.

"And Laurie has been just awesome, she has done things with me and for me and has helped me understand that it is a disease that not just older people get, it can happen to anybody. It is just one of those things you have no control over."
As well she has a lot of support, in terms of emotional, spiritual and financial assistance from her immediate family which has substantially reduced her stress of daily life.

"I'm very blessed that way," said Letestu. "What I've realized is that we have to do the best we can with what we've got and use the time we have in our life not to be bitter but to become an example of what we can do."
She is now doing so well she is able to help other residents of the Village as a small way of giving back.

According to Myres a large part of Letestu's progress is a result of the early diagnosis.

"That is very important because the medication strives to hold the person at the level they are currently at so you want to plateau at the highest level that you can," she said. "Now, her attitude is wonderful, she has picked herself up and gone forward to have the best possible life."

Letestu agreed: "For the future - and I know there is no cure for this - my goal is to live life the best I can and do the best I can for myself and my family. To be an example that when you're having difficulties and these things are thrown at you, you make the best of them that you can."

Source: Mark Brett. Stepping out against Alzheimer's disease. PentictonHerald.ca (29 Jan 2007) [FullText]

Alzheimer's Victim Family Story: Thanks to Aricept, the Family was Given Time to Come to Terms with this Dreadful Disease

2006-10-27T00:10:00.000+02:00

Geoff Older sits with his wife Sheila at St Thomas' Nursing Home
IN MARCH 2007, Geoff Older and his wife Sheila will have been married for 49 years. Their anniversary should be a happy occasion, when they can look back over the time they have spent together.

But the reality will be quite different. Sadly, Mrs Older is the victim of a terrible disease that has not only robbed her of her memories, but her husband of his wife.

After years of warning signs, Mrs Older, 72, was diagnosed with Alzheimer's disease in 2000, and Mr Older became her carer.

For two-and-a-half years, Mrs Older was prescribed Aricept - a drug which helps to slow down the development of the worst symptoms of the disease.

The National Institute for Clinical Excellence (NICE), the Government's watchdog, has now decided Aricept should no longer be prescribed to sufferers with early Alzheimer's.

Following the announcement, Mr Older, 71, of Holy Barn Close, Kempshott, Basingstoke, decided to speak to The Gazette about the difference the drug made to his family, and his anger and disappointment at the NICE decision.

He said: "I have very strong feelings about NICE. The people who sit on the committee are not the people who have to deal with dementia patients and their carers.

"They acknowledge that the drugs work, but the view they seem to have taken is what's the point in prolonging these people's lives'?"

Mrs Older is now in the very late stages of Alzheimer's and is no longer able to speak, feed or wash herself and does not recognise anybody.

She no longer takes the drug and has moved to St Thomas' Nursing Home in Basingstoke. But Mr Older said that, thanks to Aricept, the family was given time to come to terms with this dreadful disease.

He said: "This drug works and I have experienced it first-hand because it enabled my wife to stay at home for another two-and-a-half years.

This drug works and I have experienced it first-hand because it enabled my wife to stay at home for another two-and-a-half years
Geoff Older

"In 2003, she was taking the drug and attending Thrive, a charity based at Mortimer, which uses gardening to help people with disabilities. She won first prize in a flower show."

He added: "They say it costs £2.50 a day to treat a sufferer, but what NICE doesn't realise is that it is really treating two people - the patient and their carer - by allowing them to live a more normal life.

"If they don't start treating people until the moderate to advanced stage of the disease, that time will be lost. You can't reverse the disease and you can never get that time back."

Speaking movingly about his wife, he said: "She was always such a proud lady. She looked after our home and raised our two children.

"She was a very talented dog judge, breeder and handler, and in 1992 had a top golden retriever bitch at Crufts.

"Looking back, she began to show signs of the disease in the late '90s - she would go shopping and forget she had taken the car and walk home."

He added: "Sheila is not the only one to suffer. It affects me badly on some occasions as well. Until you experience it first-hand, you can never know what it is like."

Mr Older, who is a committee member of the Basingstoke and District branch of the Alzheimer's Society, now hopes to further increase awareness of the disease.

He said: "What people don't realise is that dementia is the second biggest killer in the UK after heart disease. There are 550,000 sufferers and, as the population ages, it will grow worse.

"Anybody could get this terrible disease and it goes beyond memory loss. It does not take prisoners.

"I know we can't do anything for Sheila now, but we had that extra time with her. NICE has taken that away from other families."

Source: Emily-Ann Elliott. ‘Drug gave my wife precious extra time’ This Is Basingstoke, UK (23 Oct 2006) [FullText]

$52 Million To Lead Alzheimer's Disease Study Received By UCSD

2006-10-25T15:30:00.000+02:00

"Leon Thal, Director of the Shiley-Marcos Alzheimer's Disease Research Center at UCSD, heads 70-site consortium funded by National Institutes of Health

The Alzheimer's Disease Cooperative Study (ADCS), a federally established consortium directed by Leon Thal, M.D., Director of the Shiley-Marcos Alzheimer's Disease Research Center at the University of California, San Diego (UCSD) School of Medicine, will receive $52 million over six years to conduct several new clinical trials on Alzheimer's disease, the National Institutes of Health (NIH) announced 17 October 2006. The award is the third renewal of a cooperative agreement between the NIH's National Institute on Aging (NIA) and UC San Diego, which coordinates the consortium of nearly 70 research sites in the United States and Canada.

Thal, Professor and Chair of the Department of Neurosciences at the UCSD School of Medicine, has led the ADCS since its inception in 1991.

"We are very excited to have the ability to test new therapies that may slow the rate of progression of this devastating disease," said Thal. "Given the rapid acquisition of knowledge in the field of Alzheimer's disease, we all remain hopeful that an effective treatment will be found within the next decade."

The purpose of the NIA award is to test drugs for their effectiveness in slowing down the progression or treating the symptoms of AD, as well as to investigate new methods for conducting dementia research.

"We have been able to bring together a larger universe of people studying therapies for Alzheimer's, and I think the group of studies we have developed for this phase of the study reflects new thinking in how to approach the disease," said Thal.

In the next six years funded by this award, researchers will focus on possible therapies aimed at affecting the peptide beta amyloid and the tau protein. Douglas R. Galasko, M.D., a physician scientist with the UCSD Shiley-Marcos ADRC, was one of the early scientists who determined that beta amyloid and tau could be measured in spinal fluid and were useful markers for Alzheimer's. It remains to be seen, however, whether plaques and tangles actually cause the disease or are byproducts of Alzheimer's... "

Source: $52 Million To Lead Alzheimer's Disease Study Received By UCSD. Medical News Today (22 Oct 2006) [Fulltext]

Clinical Trials: What you Should Know

2006-10-24T00:34:00.000+02:00

Dear Savvy Senior:
Can you tell me about clinical trials and how to go about finding one? My husband (who's 62) was just diagnosed with early stages of Alzheimer's disease and we are interested in trying anything that may be able to help him. What can you tell me? -- Clinical Candidate

Dear Candidate:

More and more older patients are volunteering for clinical trials to gain access to the latest, and possibly greatest, but not yet on the market treatments for all types of serious illnesses. Here's what you should know.

Savvy Tip: Clinical Trials

A "clinical trial" is the scientific term for a test or research study of a drug, device or medical procedure using people. These tests are done to learn whether a new treatment is safe and if it works. But, keep in mind that these new treatments are also unproven ones, so there may be risks too. Also note that all clinical trials have certain eligibility criteria (age, gender, health status, etc.) that you must meet in order to be accepted, and before taking part in a trial, you'll be asked to sign an informed consent agreement. You can also leave a study at any time you choose. To learn more or to locate an Alzheimer's disease clinical trial near you, visit the Alzheimer's Disease Education and Referral Center at www.nia.nih.gov/alzheimers and click on "Clinical Trials" or call (800) 438-4380.

Things to Know

Before you decide to participate in a clinical trial (of any kind), schedule an appointment with the study's medical team and ask lots of questions. Here are a few to help get you started.

What is the purpose of the study? (You may be surprised to know that many drug or procedural trials are not designed to find a "cure" but to achieve more modest goals, such as to slow down the progression of a disease.)

Is the trial you are considering best for your situation?

What advantages does the trial's experimental treatment offer over existing treatments?

What are the risks? (Some treatments can have side effects that are unpleasant, serious and even life-threatening.)

What kinds of tests and treatments does the study involve, and how often and where they are performed?

Is the experimental treatment in the study being compared with a standard treatment or a placebo? (If you get the placebo, you'll be getting no treatment at all.)

Who's paying for the study? Will you have any costs, and if so, will your insurance plan or Medicare cover the rest? (Sponsors of trials generally pay most of the costs, but not always. Also note that federally funded trials are regulated by the government and insure strict safety guidelines.)

hat if something goes wrong during or after the trial and you need extra medical care? Who pays?

Can you stay on the treatment after the study is completed? If so, who will pay for the treatment?

Find a Study

To learn about the many different types of clinical trials near you, try these resources:

National Institutes of Health: They offer the premier Web resource for locating federally and privately supported clinical studies on a wide range of diseases and conditions. See clinicaltrials.gov.

National Cancer Institute: Provides cancer specific clinical trials. Go to cancertrials.nci.nih.gov or call (800) 422-6237.

National Center for Complementary and Alternative Medicine: To find alternative medicine trials visit www.nccam.nih.gov or call (888) 644-6226.

International Federation of Pharmaceutical Manufacturers & Associations: To locate drug company trials, see ifpma.org.

Source: Clinical Trials: What you Should Know suburbanchicagonews.com (23 Octob 2006) [FullText]

Computer-based 'games' enhance mental function in patients with Alzheimer's

2006-10-23T00:10:00.000+02:00

Computer-based tasks aimed at increasing mental activity and enhancing mental function can improve cognition in patients with Alzheimer's disease, serving as an effective addition to medications commonly used to treat the disease. Researchers found that the internet-accessible computer activities were even more successful than classic exercises of mental stimulation commonly used with dementia patients. The findings, from the Fundació ACE, Institut Català de Neurociències Aplicades in Barcelona, Spain, and the University of Pittsburgh School of Medicine, are published in the October issue of the Journal of Neurology, Neurosurgery and Psychiatry.

"The interactive multimedia internet-based system, in combination with the standard pharmacological treatment of Alzheimer's disease, provides for better cognitive function in these patients, demonstrating that they are capable of benefiting from cognitive stimulation, even after the disease has advanced," said Mr. Lluís Tárraga, lead investigator of the study and developer of the IMIS tool.

"This study shows that tasks aimed at increasing or maintaining mental function have a place in treating Alzheimer's alongside pharmacotherapy," said Oscar Lopez, M.D., professor of neurology at the University of Pittsburgh School of Medicine, and a co-author on the study. "While further study is needed, it is encouraging to find that an internet-based program can work for cognitive stimulation, making it easily available and accessible to many people."

The study, conducted at an adult daycare center and referral clinic for community-dwelling persons with dementia in Barcelona, enrolled 46 people who were diagnosed with Alzheimer's disease. All were being treated with cholinesterase inhibitors, the most common pharmacological treatment for Alzheimer's, for at least one year prior to enrolling in the study; all participants remained on the drug for the duration of the study.

Participants were randomized to one of three groups. The first received no cognitive intervention; these participants lived at home and did not participate in the daily activities at the daycare center. The second group participated in an Integrated Psychostimulation Program (IPP), which was a daily program that included 2.5 to 3.5 hours of cognitive stimulation tasks, musical therapy, arts and crafts, physical activity and programs that reinforced instrumental activities of daily living. The third group participated in IPP as well, and used an interactive multimedia internet-based system (IMIS) which allowed them to carry out a variety of different cognitive stimulation tasks at varying levels of difficulty throughout the day. IMIS sessions (20 minutes each) were held three times a week for 24 weeks.

At baseline and after 12 and 24 weeks of treatment, participants were assessed using standard measures of cognitive function and performance including the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and the Mini-Mental State Examination (MMSE). After 12 weeks of treatment, the group that received both IPP and IMIS had improved outcome scores on both tests as compared to control; these improvements were maintained at 24 weeks. The group that received only IPP, showed improvement over the control group at 12 weeks, but the effects diminished by 24 weeks.

"While Alzheimer's disease is a progressive degenerative condition, studies have shown that in the early stages, the brain is still able to learn and change. This indicates that increasing brain activity, especially in regards to memory and cognition, may help stave off cognitive loss in people with Alzheimer's," said James T. Becker, Ph.D., professor of psychiatry, neurology and psychology at the University of Pittsburgh, and a co-author on the study.

Acknowledgement: The study was funded through an unrestricted grant from Fundació ACE, Institut Català de Neurociències Aplicades. Co-authors of the study include Mercè Boada, Gemma Modinos, Ana Espinosa, Susana Diego, América Morera, Marina Guitart and Jaume Balcells from Institut Català de Neurociències Aplicades.

Contact: Gloria Kreps, KrepsGA@upmc.edu (412) 647-3555, Fax: (412) 624-3184#
Source: Eurekalert.org