Effective Treatment for Alzheimer's Disease - Research Paper Example

?Amy, D. M. Mar 30). How to outsmart alzheimer's --- new effort tries to fight disease with word, math games, even wii for exercise. Wall Street Journal, pp. D.1-D.1. Title: How to Outsmart Alzheimer's --- New Effort Tries to Fight Disease With Word, Math Games, Even Wii for Exercise Doctors frustrated by a lack of a cure, or even an effective treatment, for Alzheimer's disease are trying a new approach: preventing the disease altogether. A new project, the Cognitive Fitness and Innovative Therapies, or CFIT, is trying to keep people at risk for Alzheimer's intellectually and physically fit with quizzes and other cognitive challenges to see if onset of the disease can be delayed, perhaps indefinitely. The program, which is being advised by many famous names in Alzheimer's research and treatment, also promotes diet changes and maintaining a social life to try to slow cognitive decline and lower the risk for Alzheimer's. Kenneth S. Kosik, co-director of the Neuroscience Research Institute at the University of California, Santa Barbara, launched CFIT with a center in Santa Barbara last year. Dr. Kosik recommends that individuals start efforts to prevent the disease in their 50s. "By the time someone walks in my door with symptoms of the disease, it's too late" to stop it, says Dr. Kosik, who plans to open four CFIT centers in New York and California. The idea behind the new research is that lifestyle interventions may delay or prevent the disease before symptoms appear -- or slow the progression of Alzheimer's once they do manifest. The shift in thinking has been bolstered by public health efforts to prevent cognitive decline and delay or prevent Alzheimer's disease, which affects some 5.3 million Americans. A 2007 report by the Centers for Disease Control and Prevention and the Alzheimer's Association, a nonprofit group that funds research and supports advocacy and education, called for implementing findings on exercise and diet into actions people can do to maintain cognitive health. A CDC review of the scientific literature is expected to be released this year. The groups have been working together to gather data from individual states on the extent of cognitive impairment and meeting with state health officials to develop public campaigns to promote brain health. Scientists don't know exactly what causes Alzheimer's, a progressive brain disorder that accounts for the majority of dementia cases, although genetics and age likely play a role. There are only four drugs approved for the disease, but these just treat individual symptoms and don't stop the relentless course of the illness. New medicines are in testing but are likely to take years before they reach medical clinics. Even if someone is destined to get the disease, delaying its onset for even a few years could dramatically improve quality of life. It could also reduce the estimated 500,000 new cases diagnosed every year, according to the Alzheimer's Association. Many of the 50 people currently enrolled in the CFIT program have no clinical symptoms yet, but they know they have some sort of genetic risk of getting Alzheimer's disease. This usually means a first-degree relative who has Alzheimer's or either one or two copies of the ApoE gene, which is a risk factor of Alzheimer's. Participants, in their 50s to 80s in age, come at least once a week to CFIT, which resembles a community center. They undergo an initial evaluation to determine a baseline level of cognitive fitness, then are re-evaluated again after six months and a year. The center tailors a regimen for each individual based on a combination of physical exercise, diet, cognitive challenges, music therapy, and social interaction to try to stave off the disease. The CFIT center charges participants $4,000 a year, which it says is to cover the costs of maintaining the program. Dr. Kosik says he raised more than $1 million in private donations, which helps defray the program's costs and provides financial aid to one-quarter of the participants who can't afford the full price of the program. Participants follow an exercise regimen and a meal plan based on the Mediterranean diet, and control blood pressure and cholesterol. Since one of the risk factors for cognitive decline isn't having friends, there are social activities at the center, ranging from a Wii station where people can join in games to groups for singing and playing music. At CFIT, like other programs, people are encouraged to take on increasingly difficult brain challenges to improve cognitive function. Alzheimer's researchers over a decade ago got excited about the protective ability of cognitive activity, such as brain challenges or learning a new language, after early results from the so-called Nun Study. Started in 1986 and still going on, the study follows 678 nuns, ages 75 to 106, of the same religious congregation but living in various U.S. cities, including Milwaukee and St. Louis. In a report published in 1996 in the Journal of the American Medical Association, or JAMA, researchers reviewed the autobiographies found in the convent's archives of 93 of the women. Shortly before taking their religious vows, these women, then mainly in their early 20s, were asked to write a short autobiography, no more than 200 to 300 words, describing their families and the events that led them to join the convent. The researchers examined these same women 58 years later. They found that women whose essays were richer in the number and complexity of ideas expressed had significantly lower rates of Alzheimer's disease. From this and other subsequent studies came the notion that high levels of linguistic ability -- which involve processes the brain uses to retrieve information -- developed early in life might prevent dementia later on. Now, some scientists think these same abilities can be created or reinforced later in life too, and help lower risk of dementia. Jeannette Shackell, 85, a widow who lives in a retirement community in Santa Barbara, was referred to CFIT by a neurologist after having memory lapses such as trouble recalling the names of people who live in her community. Once a week, Ms. Shackell drives herself down the road to the center, where she plays cards and board games like Connect 4 and Mastermind, which require skills such as planning moves ahead in order to win. She plays Wii games to help her with her balance. And every other day, for 20 to 30 minutes on her computer at home, she uses a software program that gives her increasingly difficult brain challenges to keep her mind sharp. "I am much better at recalling names now," Ms. Shackell says. "When I go into another room, I remember why I went in." After a year coming to CFIT, Ms. Shackell has improved her cognitive-fitness scores, Dr. Kosik says. But he adds that it's too soon to know if the program is helping Ms. Shackell -- or any of the participants in CFIT -- delay the onset of Alzheimer's. Dr. Kosik says that getting people to adhere to cognitive health regimens isn't always easy, but one of the successes of the program is the high level of adherence to diet, fitness, and cognitive exercises. Most, but not all, of the participants maintained or improved their cognitive fitness test scores, but Dr. Kosik says these tests have limits. The group is still small, they started at different baseline levels, he says, and sometimes people do better on tests that they re-take because they remember the previous test. Dr. Kosik says CFIT is working to set up a control group of senior citizens at a local assisted-living facility who aren't participating in the program, to compare how they fare over time in terms of cognition and Alzheimer's diagnoses. Collier, G., & Telegram, &. G. S. (1995, Mar 20). Doctors to answer questions about alzheimer's. Telegram & Gazette, pp. C.1-C1. Doctors to answer questions about Alzheimer's: [ALL Edition] Alzheimer's disease "robs people of their humanity," said Dr. Marc Fisher, a neurologist at The Medical Center of Central Massachusetts. Because of that, Alzheimer's has become feared by older people who might get it, and by younger people who might have to care for family members with the disease. To help people better understand Alzheimer's disease, the Worcester District Medical Society will sponsor a "Dial-the-Doctor" program from 6 to 9 tonight. Callers can ask doctors knowledgeable about the disease questions by calling 767-7030. According to Fisher, the call-in will provide information on what the disease is, how doctors diagnose it, how it progresses, support groups that can help and ongoing research into testing and treatments. KNOW WHAT IT'S NOT For individualized medical advice and treatment, callers are encouraged to contact their own physicians. As important as Alzheimer's is, it's also important to know what it's not. "Everyone forgets things from time to time, goes into a room and forgets why they walk in there, where they put their keys," said Cynthia B. Passarelli, a neurologist with the Fallon Clinic. "When we get older, and it happens more often, people worry that it is a sign of something more ominous." Some things are; some are not. Forgetting a name, unless it's your own, isn't particularly worrisome; forgetting that the box at the end of the living room is called a TV set is. RISK FACTOR TEST According to Dr. Daniel Pollen, a neurologist at the University of Massachusetts Medical Center, there is now a way to test for a risk factor associated with Alzheimer's. "I wouldn't recommend it, however," Pollen said, until physicians have a treatment to offer. That could be down the road, said Pollen, author of "Hannah's Heirs," an account of family-inherited early-Alzheimer's. Researchers are looking at the role of estrogen in delaying the onset or progression of Alzheimer's in women. Drugs that have shown some benefit are already available, and others are in clinical trials. Cookson, C. (1999, Jul 10). Conquering alzheimer's: Researchers investigating one of the most feared human diseases are reporting real progress towards effective prevention and treatment, says clive cookson: Financial Times, pp. 14-14. Conquering Alzheimer's: Researchers investigating one of the most feared human diseases are reporting real progress towards effective prevention and treatment, says Clive Cookson: [London edition] Twenty years ago, Alzheimer's disease was an obscure form of dementia that few people ever talked about. Ten years ago, it seemed a terrifying and untreatable threat to everyone's old age. Today Alzheimer's is one of the most exciting areas of medical science, with researchers reporting real progress toward effective treatments. Talk of Alzheimer's becoming a preventable or even curable disease no longer seems absurd. The pharmaceutical industry is spending hundreds of millions of dollars a year on developing drugs to stop what is now an inexorable decline from forgetfulness to confusion, dementia and death for an estimated 10m to 20m Alzheimer's patients worldwide. A vivid sign of the new optimism came this week, with newspaper headlines about an experimental Alzheimer's vaccine. These stemmed from a paper in the scientific journal Nature by researchers working for Elan Pharmaceuticals, an Irish-American biotechnology company. They have shown that immunisation protects laboratory mice against the build-up of the "amyloid plaques" which, most scientists believe, destroy the brain of Alzheimer's patients. Ivan Lieberburg, Elan's head of research, says the company plans to start testing its AN-1792 vaccine on human volunteers later this year, followed by full-scale clinical trials and, if all goes well, marketing approval around 2005. There is scope for disappointment because the "mouse models" used to develop Alzheimer's drugs are far from perfect. The genetic engineering of mice to mimic the human disease in the mid-1990s removed one of the biggest obstacles to research, but the animals do not show all the symptoms of real patients. However, even if AN-1792 fails in human trials because it turns out to be unexpectedly toxic or because it does not work in people, scientists will learn a lot more about the causation of Alzheimer's disease. And researchers are developing many other novel approaches that might be more effective. The Pharmaceutical R&D Compendium, published by CMR International and Scrip, shows that the number of companies developing drugs for dementias rose from 52 in 1997 to 72 last year. They are aiming for a market that hardly exists today - current drugs such as Aricept from Pfizer and Exelon from Novartis do not affect the underlying degeneration though they give some patients a temporary respite by increasing levels of a chemical messenger that is severely depleted by the disease. But sales could be worth $6bn a year in the US alone when effective treatments become available, according to a recent forecast by Genetic Technology News, a specialist newsletter. It is most unlikely that one single blockbuster drug will emerge to capture the market, says Harry Cayton, executive director of the Alzheimer's Disease Society in the UK. Instead a range of treatments will target different forms of the disease. "Alzheimer's is a very complex disorder of the brain, resulting from a combination of genetic risks and environmental triggers," Mr Cayton says. "It is probably better to think of it as a range of diseases with varying causes and genetic factors." Alzheimer's brains show two abnormal features on post-mortem examination - plaques and tangles. Plaques are little lumps of an insoluble chemical called beta-amyloid protein (BAP). They accumulate from the breakdown of a parent molecule, amyloid precursor protein, which is present in the healthy brain, playing an unknown role. Tangles are insoluble fibres composed of break-down products from another protein, known as tau. Two schools of thought have been debating the relative significance of plaques and tangles with almost theological intensity for several years. The BAPtists promote the amyloid hypothesis: that plaques are a fundamental cause of Alzheimer's while tangles are a secondary phenomenon. The tauists, who have a smaller following, focus on the tangles and regard plaques as a side-effect. If it does nothing else, the trial of Elan's AN-1792 should resolve the dispute. "If the vaccine blocks the amyloid deposition and arrests the progress of the disease, then we have a preventative therapy for Alzheimer's," says Bill Thies, head of science and medicine at the US Alzheimer's Association. "If it blocks deposition without affecting the disease, people working on the amyloid hypothesis will have to look elsewhere." When given to young mice, the vaccine - a form of BAP - stopped any plaque building up. In older animals it reduced the amount of existing plaque. Elan scientists believe that the mice make antibodies against BAP; some of these get through the blood-brain barrier and target amyloid molecules for destruction by the immune system. Although Elan's immunisation strategy is unique, several large drug companies, including Novartis, Merck, SmithKline Beecham and others, are working intensively to develop more conventional medicines that patients could take by mouth to prevent plaque formation. For example Bristol-Myers Squibb is collaborating with Sibia, a Californian biotechnology company, on a pill to block the protease enzyme that breaks amyloid precursor protein down into BAP. Glaxo Wellcome is pursuing a different approach under its head of genetics, Allen Roses, who discovered the most important Alzheimer's gene (ApoE) in 1993. Dr Roses rejects the amyloid hypothesis. He says different forms of the ApoE gene determine people's susceptibility to Alzheimer's by the way they interact with tau protein. A research project with Duke University, where Dr Roses used to work, is under way to identify the key metabolic difference between the forms of ApoE and then find drugs to block the pathway that leads to Alzheimer's. "We will not get into the clinic as soon as the amyloid people but I'm convinced that we can prevent the disease," he says. More futuristic, but no longer in the province of science fiction, is the prospect of implanting healthy neurones to repair brains already damaged by Alzheimer's. Clinical trials have shown that cells derived from aborted foetuses can help people with Parkinson's, a brain disease that is much easier to treat than Alzheimer's, and research is now beginning to open up more acceptable sources of such cells. Evan Snyder, a neurologist at Harvard Medical School, is developing what might become an all-purpose source of brain cells for transplantation. His laboratory recently cloned human neural stem cells - immature cells that can develop into any more specialised brain cells. Several years' work on animal models of human diseases will be required before the stem cells are ready for clinical trials. But Dr Snyder offers the hope eventually of re-seeding the brain with progenitor cells that would mature into whatever neurones the brain needed. That could in principle treat almost any brain disease. Cellular repair kits for damaged brains are unlikely to be available before 2020. Over the next 10 years, the main emphasis will be on prevention, combined with accurate diagnostic tests. People who are at high risk of developing Alzheimer's through adverse genetics or are showing very early symptoms will be able to stop the plaques and tangles destroying their personalities. Although new drugs will have the most dramatic protective effect, scientists also see scope for enlisting some well-known existing substances in the fight against Alzheimer's. Large-scale epidemiological studies suggest that some benefit can be gained by taking the female sex hormone oestrogen, the anti-oxidant vitamin E and various anti-inflammatory medicines. For example, oestrogen is believed to stimulate the formation of more connections between brain cells. These associations will be tested more rigorously in clinical trials over the next few years. "At the least, we should be able to delay the onset of Alzheimer's, just as cardiovascular drugs can delay the onset of heart disease today," says Dr Thies. Demographic analysis shows that a five year delay in the average age at which Alzheimer's sets in would reduce the number of cases by half, because people would die of other causes. Fischman, J. (2006, Feb 20). An anti-alzheimer's workout. Physical Fitness May Slow Brain Atrophy In People with Early Alzheimer's Disease A new study shows that exercise may help slow brain shrinkage in people with early Alzheimer's disease. In the study, people with early Alzheimer's who were less physically fit had four times more brain shrinkage than normal older adults. One of the authors of the study, published last month in the journal Neurology, is Jeffrey Burns, who directs the Alzheimer and Memory Program at the University of Kansas School ofMedicine in Kansas City, KS. While brains shrink with normal aging, the rate is doubled in people with Alzheimer's disease, Burns says. The study included 57 people over the age of 60 in the early stages of Alzheimer's. The participants' physical fitness was assessed by measuring peak oxygen demand while on a treadmill. Brain shrinkage was estimated by MRI scans. The study also showed that participants who were more physically fit did not do significantly better on tests for mental performance. Burns says the study may have had too few patients to show an effect in the analysis. He adds that the work is only a starting point for exploring whether exercise and physical fitness can slow the progression of Alzheimer's and that the study cannot prove an effect because the participants were evaluated only once rather than repeatedly over time. According to previous studies and the AARP, exercise can help the brain in a number of ways, including improving concentration and attention, reducing gray-matter loss, promoting neurogenesis, enhancing blood flow and strengthening synapses Jeffrey, S. (1998). Regular exercise may help prevent alzheimer's: Higher education and vocational levels also seen as protective: Study. Medical Post, 34(19), 18-18. Regular exercise may help prevent Alzheimer's: higher education and vocational levels also seen as protective: study An active lifestyle may stave off Alzheimer's disease. Using a case-control design, researchers have found an apparent protective effect of a lifetime of regular exercise against the development of the disease. "We believe the findings are suggestive that exercise is protective, and certainly protective in this group of individuals that we think are representative of the public at large," said Dr. Arthur Smith, a fellow in neurology at Case Western Reserve University in Cleveland. The Cleveland group has previously reported that Alzheimer's patients appear to have fewer activities before developing disease than control subjects, and higher educational and vocational levels have also been shown to be protective. They looked at responses to a validated life-history questionnaire in 126 cases and 247 controls, on their participation in various activities, including jogging, biking, golf, weight training, racquetball, ice skating, tennis and swimming, over a 39-year period between the ages of 20 and 59 years. Controls responded for themselves, and responses for cases were taken from a surrogate, generally the caregiver, spouse or children. Aerobic output An exercise score, taking into account the level of effort and aerobic output of each activity, but blinded to Alzheimer's disease status, was calculated and multiplied by the number of hours per month spent doing the activity. When they matched exercise scores with case and control disease status, they discovered subjects who had the highest amount of exercise had the least occurrence of Alzheimer's disease. They then controlled for factors such as year of birth, education and gender, he said. "After controlling for those confounding variables, there was still a statistically significant difference between the exercise patterns of cases and controls," Dr. Smith said. Read More