Alzheimer's Club

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.