Alzheimer Related News Items

News as of 07/10/05

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Top Items

World First: Brain Cells Grown in Laboratory - Scientists have grown fully mature brain cells in a laboratory for the first time, using a technique that mimics the natural process of brain regeneration. It promises to open the door to new ways of treating and possibly curing debilitating brain diseases such as Parkinson’s, epilepsy and AD. The scientists said they were able to produce virtually unlimited quantities of brains cells, which could revolutionize transplant medicine as well as leading to new drugs to stimulate the regrowth of damaged nerves. Bjorn Scheffler, a neuroscientist at Florida University who made the breakthrough, said the procedure involved mimicking the natural process through which key stem cells in the brain orchestrate partial regeneration of the brain. “Our study shows for the first time the entire process that goes on in our brain for life. We can, in a dish, recapture the process in front of our eyes,” Dr Scheffler said. It was not the first time that scientists had shown stem cells can be manipulated in the lab to produce mature brain cells, he added. “But nobody has been capable of replicating the process from the very first step to the very last step - it’s unique to get the whole process happening before your eyes.” The study was done with mice but the scientists believe it is only a matter to time before they are able to reproduce the same process of development with human brain cells. The findings, in effect, show it is possible to construct an assembly line for manufacturing unlimited quantities of human brain cells, or neurons, Dr Scheffler said. “We can basically take these cells and freeze them until we need them. Then we thaw them, begin a cell-generating process and produce a ton of new neurons.” Professor Dennis Steindler, who led the Florida research team, said the strength of the technique lay in its ability to identify vital stem cells that have the power to grow into adult brain cells. “We’ve isolated for the first time what appears to be the true candidate stem cell,” Professor Steindler said. “There have been other candidates but, in this case, we used a special microscope that allows us to watch living cells over long periods of time. So we’ve actually witnessed the stem cell give rise to new neurons. We’ve watched it under a living microscope generate brand new neurons. Now we can make a lot of brain cells from just a very small number of these stem cells, which is great because we’d have to do that to repair neurological disease,” Professor Steindler said. Another possibility is to use the technique as a model of natural brain repair so that scientists can test potential drugs for stimulating the regrowth of damaged nerves. “We are already beginning the process of screening for compounds that will allow this to happen perhaps without sticking anything into our brains,” Professor Steindler said. “It’s been the goal of this field of stem cell biology and regenerative medicine to get us closer to being able to pop a pill in your mouth when you have a neurological disorder that has a specific action on your own indigenous stem cell population.” By Steve Connor, Science Editor Independent News UK 6/14/05 Proceedings of the National Academy of Sciences June 28, 2005 vol. 102: 9353-9358

Drugs

Ispronicline Joins Effort to Find AD Cure - There is a new kid on the block in the race to find a cure for AD and dementia. Ispronicline is now enrolling participants for a Phase II study after clinical studies in which elderly people taking Ispronicline performed better on memory and attention measures than those taking a placebo. This improved performance continued well beyond the time that Ispronicline was eliminated from the body, reported Geoffry C. Dunbar, M.D., and vice president of Targacept, Inc., the biopharmaceutical company making the drug. Targacept made their presentation on Ispronicline at the 8th World Congress of Biological Psychiatry in Vienna, Austria on 7/2/05. Dr. Dunbar’s presentation included results from the placebo-controlled clinical studies in which elderly subjects dosed with 80 mg or 50 mg of Ispronicline performed better on certain memory and attention measures than elderly subjects dosed with placebo. Targacept also reported that it has completed more than 50% of its target enrollment of 180 elderly subjects for its ongoing Phase 2 efficacy trial of Ispronicline in age associated memory impairment (AAMI). This clinical trial is designed as a double-blind, randomized comparison of two doses of Ispronicline to placebo over a 16-week treatment period. The trial is being conducted at 16 clinical sites in the United States. Targacept is also preparing for a Phase 2 study of Ispronicline in patients with mild to moderate AD. The AD study is scheduled to begin in the first half of 2006. In six completed clinical trials with a total of 200 subjects, Ispronicline has been well tolerated and has demonstrated cognitive-enhancing effects. SeniorJournal.com 7/6/05

Genes & Genetic Issues

Little Distress From AD Gene Test - Conventional wisdom suggests the adult children of AD patients might react negatively to gene tests aimed at calculating their own risk for the brain- robbing disorder. But a new study finds that’s not the case. Researchers found that people who underwent genetic risk assessment for AD were satisfied and psychologically unharmed -- even when their results suggested they might be at high risk for the disease. The findings were presented 6/20/05 at the Alzheimer’s Association’s International Conference on the Prevention of Dementia, in Washington, D.C. In their study, researchers at Boston University School of Medicine randomly divided 162 adult children of AD patients into two groups. The people in one group were assessed for AD risk based on their age, family history and gender. Those in the second group were assessed based on age, family history, gender and for one form of the Apolipoprotein E (APOE) gene called Apoe4 -- a known risk marker for AD. One year after this assessment, the researchers found no significant differences in tests of anxiety and depression between the study participants who were told they were either positive or negative for the Apoe4 gene or those who did not receive disclosure. Overall, 95 percent of the study participants said they’d choose risk assessment again, and 82 percent said they’d recommend risk assessment to family or friends. By Robert Preidt HealthDay News 6/20/05

Caregivers

Behavior Approach Helps AD Patients Sleep - Behavioral techniques that are known to improve sleep in non-demented institutionalized older adults may benefit patients with AD who have nighttime insomnia, according to the findings of a small study. Dr. Susan M. McCurry and colleagues from the University of Washington, Seattle, examined whether a comprehensive sleep education program -- dubbed Nighttime Insomnia Treatment and Education for Alzheimer’s Disease (NITE-AD) -- could improve sleep in AD patients living at home with family caregivers. A total of 36 patients and their caregivers were included in the study. All subjects received handouts describing age- and dementia-related changes in sleep and principles of good sleep hygiene. Seventeen caregivers in the NITE-AD intervention group were given recommendations about developing a sleep hygiene program for AD patients. They also received training in behavior management skills. The patients in this group were instructed to walk daily for 30 minutes -- in practice, usually accompanied by a caregiver -- and to increase daily light exposure by 1 hour using a light box. The 19 subjects assigned to the other group just received general dementia education and caregiver support. Patients in the NITE-AD group spent an average of 36 minutes less time awake at night -- a 32-percent reduction from the start of the study -- and had 5.3 fewer nightly awakenings -- also a 32-percent reduction from the start of the study -- than control subjects, McCurry’s team reports. Depression levels were also significantly lower in NITE-AD patients and they had lower ratings of daytime sleepiness than control subjects after accounting for level of mental functioning. Treatment gains were maintained at six months. “Whether all components of the NITE-AD intervention are necessary to achieve treatment effects and whether the timing of walking and light therapy sessions are important to treatment outcome need to be evaluated, and strategies to enhance long-term treatment adherence should be identified,” the investigators note. Reuters Health 6/10/05 Journal of the American Geriatric Society, May 2005 vol 53, issue 5, 793-802

Testing

Study Finds AD Predictor - A subtle change in a memory-making brain region seems to predict who will get AD nine years before symptoms appear, scientists reported 6/19/05. The finding is part of a wave of research aimed at early detection of dementia. Researchers scanned the brains of middle-age and older people while they were still healthy. They discovered that lower energy usage in a part of the brain called the hippocampus correctly signaled who would get AD or a related memory impairment 85% of the time. “We found the earliest predictor,” said the lead researcher, Lisa Mosconi of New York University School of Medicine. “The hippocampus seems to be the very first region to be affected.” But it is too soon to offer scans that could predict AD. The discovery must be confirmed. Also, there are serious ethical questions about how soon people should know that AD is approaching when nothing yet can be done to forestall the disease. Still, the discovery may provide leads to scientists searching for therapies to at least delay the onset of the degenerative brain disease. Mosconi’s study is the first to rigorously examine people’s brains before symptoms appear. Her team scanned 53 healthy people and tracked them for up to 24 years. Six so far have developed AD and 19 developed an AD precursor called mild cognitive impairment. Those people showed less glucose metabolism in the hippocampus than people who were still healthy. Glucose, a form of sugar, is the brain’s main fuel. Scans known as PET, or positron emission tomography, show images of how brains use glucose. Other research supports the hippocampus’ early role in the disease. To prove if these early indicators are real, the National Institute on Aging, with financial help from the pharmaceutical industry and Alzheimer’s Association, is beginning a $60-million study to scan the brains of 800 older Americans and try to pin down AD earliest biological changes. That AD begins developing so early means even young people should adopt a brain-healthy lifestyle, such as staying socially active, said Dr. Mark Sager of the Wisconsin Registry for AD Prevention. “What we’re hoping is that 55 is not too late,” he said. By Lauran Neergaard AP 6/20/05

Word Tests Give 10-year Warning on AD - Simple memory tests can indicate up to a decade in advance which seniors are likely to get AD, Toronto-based researchers have found. Perfor-mance on one of these tests -- which involved trying to memorize a list of 15 words and repeat back as many as possible after a short delay -- was found to be closely linked to later incidence of AD, a brain-destroying disease. A normal recall for those aged 60 to 75 would be 10 or 11 words, said Mary Tierney, director of geriatric research at Sunnybrook and Women’s College Health Sciences Centre and lead researcher of the study. Acceptable recall for those over 75 might be in the range of eight or nine words. Since age and education are factored into the equation, Dr. Tierney could not give a precise point at which the numbers become worrisome. But she did say that much lower results, in the range of four words, could be a sign of problems to come. Dr. Tierney said 6/13/05 that previous research had shown short-term predictions were possible, up to roughly two years, but that no one had found such an early indicator. She admitted that the results surprised the whole team. “These were people, either 65 and older, who were functioning in society,” she said. “We could tell in that group, that combination of normal and those with mild impairment, 10 years before they actually developed the disease, their level of risk of getting it.” Although the disease currently has no cure, taking the test may eliminate a fear that plagues many seniors. “Many people worry that they have a memory problem when in fact they don’t,” Dr. Tierney said. “It also would provide that level of reassurance. But for those who have genuine concerns, or their families do, it provides more knowledge that . . . their complaints are real.” In the event that AD is found likely, she said, people may choose to take steps to ward it off as long as possible. “If we can identify 10 years before, when people actually are functioning, [when] they don’t actually have the disease, we can look at intervention strategies,” she said. “We do know from other large studies that those people who were more physically active throughout their adult life, and more mentally active, in fact had a later-age onset of AD. So maybe it doesn’t stop the disease but it actually delays its onset, which is very important. If you’re 75 and you can actually delay the onset of AD until you’re 80 or 85, that’s very significant.” Dr. Tierney’s work was based on large-sample testing done as part of the Canadian Study of Health and Aging. A study of thousands of people done in three parts over 10 years generated the data Dr. Tierney used for her research. By Oliver Moore Globe and Mail 6/14/05 Neurology 2005; 64:1853-1859

MRI Can Identify AD, Other Dementia - Researchers say an MRI technology called arterial spin labeling can distinguish between AD and frontotemporal dementia (FTD), another common form of cognitive decline that’s often confused with AD. Investigators at the San Francisco VA Medical Center (SFVAMC) used arterial spin labeling to measure blood flow in the brains of people with AD and FTD. The study was presented 6/18/05 at the Alzheimer’s Association International Conference on Prevention of Dementia in Washington, D.C. “Blood flow indicates brain activation. So the area with less blood flow is the area affected by disease,” study leader Norbert Schuff, a principal investigator at SFVAMC and an associate professor of radiology at the University of California, San Francisco, said in a prepared statement. Arterial spin labeling successfully distinguished between FTD patients, AD patients and people with no dementia. FTD, the second most common dementia after AD, affects the front part of the brain. AD mainly affects other brain areas, such as the temporal lobe and hippocampus. People in the early stages of both diseases display similar symptoms. “Progression of frontotemporal dementia is usually faster than AD, and the underlying pathology is different, so it is important to know the difference,” Schuff said. Currently, positron emission tomography (PET) and single proton emission computerized tomography (SPECT) can be used to measure brain blood flow. But these techniques require that patients be injected with radioactive tracers. They are also expensive, can take up to half a day to perform, and are not widely available. “So if you can acquire blood flow information with MRI, that would be very beneficial. MRI is totally noninvasive, making it much safer for patients. It’s more widely available, it’s cheaper, and arterial spin labeling can be done in 10 minutes together with a conventional MRI scan,” Schuff said. By Robert Preidt HealthDay News 6/18/05

Marshfield Clinic Researchers Have Begun Searching for Genetic and Environmental Links to AD as a First Step Toward Developing Diagnostic Markers to Identify People at Risk Before They Develop the Disease - Researchers will study the DNA of AD patients from its database of more than 18,000 voluntarily- donated DNA samples. The Marshfield Clinic Research Foundation ( MCRF ) created the database as part of its landmark Personalized Medicine Research Project ( PMRP ). Marshfield Clinic also has a complete electronic medical record on each of the individuals to be studied. “We know exactly the medication they have been taking and what diseases they have been diagnosed for. We also know some environmental factors,” said Principal Investigator Nader Ghebranious, Ph.D., director of the Molecular Diagnostics Laboratory, Marshfield Laboratories. “Now we can do genetic analysis and examine the DNA together with phenotypes and relevant environmental factors.” “It’s exciting because we’re not looking at just environmental risk factors, or just genetics, but the two together,” said Marshfield Clinic Epidemiologist Catherine McCarty, Ph.D., principal investigator of the Personalized Medicine Research Project and co-investigator of the AD study. “We are the first that I know of to look at the interaction between genetics and environment on the risk of disease.” The study requires 150 people with AD and about 300 people of similar age who do not have the disease. “Association studies like this require us to match people who have the illness with those who do not,” Ghebranious said. Because the disease is extremely complex, researchers believe that more than one genetic anomaly and perhaps environmental factor leads to AD. Marshfield Clinic researchers are studying four specific genes and their connection to the disease process. A person with even the most probable genetic link, APOE4, a gene variant of the protein APOE that functions in the transport of cholesterol and phospholipids, is estimated to have five times higher risk of developing AD. A second gene, Cytochrome P46, which modifies cholesterol, may be associated with AD and the way the body removes cholesterol from the brain. The other two genes, Oxidized LDL receptor 1 and Angiotensin 1-converting enzyme, are tied to the way the brain cells bind to APOE and reduce buildup of harmful proteins, known as plaques, in the brain, respectively. Environmental factors likely contribute to AD as well. Two specific potentially protecting factors - cigarette smoking and use of cholesterol-lowering drugs called statins - will be considered in this study. “There are controversial findings in previous studies on smoking,” Ghebranious said. “Some earlier research has suggested nicotine decreases the brain plaque associated with AD. Results of a new mouse study point to the opposite conclusion. More studies are needed.” The Marshfield Clinic study is unique because other researchers do not have access to complete medical histories as researchers at Marshfield Clinic do, Ghebranious said. Having the history of medications people have taken, their illnesses and health status are important to linking genetics, environment and resulting disease. The study, funded by donors to Marshfield Clinic, is expected to take two years to complete. PR 5/6/05

Prevention

Nourish Your Brain and Stave Off AD - Exercise your brain. Nourish it well. And the earlier you start, the better. That's the best advice doctors can yet offer to ward off AD. The goal: build up what’s called a “cognitive reserve.” Your brain is like a muscle - use it or lose it. Brain scans show that when people use their brains in unusual ways, more blood flows into different neural regions and new connections form. A healthy brain isn’t just an intellectual one. Social stimulation is crucial, too. Don’t sit in front of the television. So do stress and anxiety. People who have what’s called chronic distress - extreme worriers - are twice as likely to develop some form of dementia. Getting physical is crucial also. Bad memory is linked to heart disease and diabetes, because clogged arteries slow blood flow in the brain. And don’t forget diet. The same foods that are heart-healthy are brain-healthy, so avoid artery-clogging saturated fat and try for omega-3 fatty acids, found in fish and nuts. Taking large amounts of folic acid improved the memory of older adults, Dutch scientists reported 6/20/05 in the first study to show a vitamin pill might slow the mental decline of ageing. The research adds to mounting evidence that a diet higher in folate, a B vitamin found in grains and certain dark-coloured fruits and vegetables, is important for a variety of diseases. As people age, some decline in brain function is inevitable. The Dutch study tested whether otherwise healthy people could slow that brain drain by taking double the recommended daily US dose of folic acid - the amount in two pounds of strawberries. “PA” Scotsman.com 6/21/05

Other Items

Small Study Targets AD Brain Plaque with IVIg Cocktail - A very small, short-term study may lead to a new approach to treating AD. Researchers found that an experimental treatment called IVIg (intravenous immunoglobulin) improved mental function in AD patients. IVIg is a “cocktail” of antibodies derived from donated human blood. Its antibodies include those that fight beta-amyloid, a key ingredient in the brain plaque associated with AD. The news does not amount to a new treatment, say the researchers, who included Marc Weksler, MD, of Cornell University’s medical school. These results clearly justify further examination in a larger study, says Weksler, in a news release. “However, our evidence does not recommend IVIg as a current treatment for AD.” The study was presented in Washington, at the Alzheimer’s Association’s International Conference on Prevention of Dementia. The study included eight people with mild to moderate AD. They received infusions of IVIg for six months. Participants took cognitive tests before and after the six-month treatment. They either received infusions once a week, once every two weeks, or once a month. After each infusion, patients’ blood samples showed higher levels of antibodies that target beta-amyloid. The antibody increase reflected the dose of IVIg, say Weksler and colleagues. Successive treatments brought increases in beta- amyloid antibodies in the weekly or every-other-week groups, but not in the monthly group. That may reflect the shorter life of such antibodies in people with AD, say the researchers. In addition, samples of spinal fluid taken from patients showed a drop in beta-amyloid. On average, beta-amyloid in the fluid dropped 45%, more than previously observed, says a news release. Scores on mental tests either held steady or improved for the participants during the study. Until more research is done on more patients it’s impossible to tell the true effect of IVIg on AD progression. By Miranda Hitti WebMD Medical News 6/20/05

New Strategy for Protecting Brain Against AD: Enhancing the Innate Immune System - The human body has its own defense against brain aging: the innate immune system, which helps to clean the brain of amyloid-beta waste products. However, UCLA researchers discovered that some patients with AD have an immune defect making it difficult to clean away these wastes. This may lead to over-saturation of the brain with amyloid beta, which form amyloid plaques, the definitive hallmark of AD. The findings could lead to a new approach in diagnosing and treating AD by helping to diagnose and correct this immune defect. This is the first time that researchers have discovered that the innate -- or more primitive -- part of the immune system may play a role in the development of AD. Using blood samples, investigators found that in healthy people, cells belonging to the innate immune system called macrophages, cleared amyloid-beta in a test tube test developed at UCLA. However, the macrophages of some AD patients could not adequately perform this cleaning job. “Macrophages are the janitors of the innate immune system, gobbling up waste products in the brain and throughout the body,” said Dr. Milan Fiala, first author and UCLA researcher. Fiala notes that there may be a problem either with the macrophages not effectively binding to amyloid beta or a problem in the absorption or uptake, which is called “phagocytosis.” “If further study shows that this defective macrophage function is present in most AD patients, new hormonal or immune-boosting approaches may offer new approaches to treating the disease,” adds Fiala. Researchers add that this new approach differs from the amyloid-beta immunization method, which utilizes another part of the immune system called the adaptive immune system. According to Fiala, the immunization approach has resulted in amyloid-beta clearance in the lab in an animal model, but in a human clinical trial led to brain inflammation in a subset of patients. In future studies, investigators plan to regulate the innate immune system by natural substances such as hormones, and natural products such as curcumin (from the curry powder). Currently in their lab, Fiala and Dr. George Bernard who is a professor in the UCLA Department of Oral Biology and Medicine, are testing the effectiveness of a naturally occurring hormone, called insulin-like growth factor I, in conjunction with a research team from the MP Biomedicals LLC Company. PR 6/10/05 Journal of Alzheimer's Disease 7(3): 221-232 (July 2005)

Celebrity Photos Prompt Memory Study Breakthrough - Scientists have isolated single neurons responsible for holding the memory of an image, in what they called an unprece-dented finding that could be used as a building block in the study of how memory works. Professor Christof Koch of the California Institute of Technology, one of the scientists involved in the study, said pictures of celebrities like Halle Berry in her skin-tight leather suit from the movie “Catwoman” and former “Friends” television star Jennifer Aniston were used in their experiment because they are so widely recognizable. Working with researchers at the University of California, Los Angeles, they tested eight patients with epilepsy by implanting electrodes in the brain. They then determined which neurons were stimulated when shown pictures of celebrities, buildings and other familiar images. The single brain cells could also apparently differentiate similar images. When a new person was substituted in the catsuit, there was no response from the cell that had earlier responded to Berry. The study has serious implications for learning about the way memories are retained, scientists said. For years, researchers have known that images initially excite many neurons in the brain, but they did not know that collective memories can be stored in a single, isolated cell. Koch said practical implications are few for now, but he likened the knowledge discovery to a starting point from which to understand how the brain’s memory functions. Dr. Eric Braverman, director of PATH Medical in New York and author of “Edge Effect,” a specialist in memory study not involved with the experiment, said the finding might have a significant impact on research into illnesses like AD and dementia. He said, for example, that if a single cell is responsible for a memory and that image is impaired, then perhaps that single cell can be treated or maybe even replaced. Reuters Health 6/23/05 Nature

435, 1102-1107 (23 June 2005)

Paying for AD - From Op-Ed piece by Sam Gandy in The Washington Times 7/7/05. The promise of this scientific research cannot be realized, however, unless the federal government provides more funding for the clinical trials and technology needed to confirm all the initial research results and actually get the science into the national health-care system. That sounds like another of the myriad pitches for more federal spending that people in Washington must hear all of the time. But there are three powerful reasons to actually increase spending for AD research. The first is that spending a little money now saves a lot of money later, as was pointed out in “Fighting AD, saving tax dollars,” a June 16 editorial in The Washington Times. This is truly a ‘pay now, or pay later’ dilemma. Delaying the onset of AD could, within five years, save Medicaid $10 billion annually, the same amount that Congress is currently trying to wrench out of Medicaid programs over five years. It could save the Medicare program $51 billion a year. AD is unique. It costs taxpayers three times as much to treat an AD patient as any other patient under Medicare. Preventing AD is simply good health-care economics. An investment of millions will save the government billions. The second reason is that if we don’t stop this disease, the federal health-care system may be crushed in its path. The aging of the boomer generation will add tens of millions of people who will be living longer and joining the ranks of AD patients. Our health-care system, in its current state, will not be able to care for them. The third reason is one of simple human compassion. I see personally the devastation of this disease, not only on patients, but on their friends and family members who have to deal with the gradual progression and the financial, emotional and social toll it takes on all of them. If we can do something to ease that burden, then we should. It is as simple as that. I hope Congress will respond. Dr. Sam Gandy is director of the Farber Institute for Neurosciences at Thomas Jefferson University. He is a professor of neurology, psychiatry and biochemistry and molecular pharmacology at Jefferson Medical College, and chairman of the Alzheimer Association’s National Medical and Scientific Advisory Council.

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