Alzheimer's Club

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)

Labels: Cholesterol and AD

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...
See all stories on this topic

Labels: Alzheimer's media news

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...
See all stories on this topic

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 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 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.