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TAKING AIM AT ALZHEIMER'SNew drugs and diagnostic toolsForgetting about something left cooking on the stove or misplacing car keys is normal absentmindedness. Forgetting how to turn on the stove and what the keys are for is more likely to be Alzheimer's. Alzheimer's Disease (AD) is a degenerative brain disorder that afflicts 4 million Americans. Although it has been clinically recognized since 1907, researchers still know little about what causes AD or how to stop its debilitating effects. However, recent developments have shed new light on the disease and offer hope for early diagnosis and treatment as well as prevention. Because the risk of developing AD increases markedly with age (1 in 10 people over age 65, and nearly half of the population over 85, are believed to suffer from it), incidence of the disease is expected to balloon in the next two decades as baby boomers pass into their golden years. With costs to society now estimated by the Alzheimer's Assn. at $100 billion a year, the push to find a cure or, at the very least, cost-effective therapies, is intense. ''There has been a tremendous burst of research activity lately,'' due primarily to all the people who will be affected and the enormous strain the disease will impose on our health-care system if no solution is found, says Dr. Neil Buckholtz, head of the Office of Alzheimer's Disease Research at the National Institute on Aging. And the research has been fruitful. First, there is a new drug available to treat the memory loss associated with AD. Arisept, developed by Japanese drugmaker Eisai and distributed in the U.S. by Pfizer, received approval from the Food & Drug Administration last November. Like Warner Lambert's Cognex (approved in 1993 and the only other AD drug on the market), Arisept works to increase the amount of the neurotransmitter acetylcholine in the brain. Acetylcholine is essential to maintaining communications between the brain cells responsible for memory and is typically in short supply when someone has AD. Arisept is seen as a breakthrough because it requires only one dosage per day and has fewer side effects than Cognex, which must be taken four times a day. ''This is a plus for people with impaired memory,'' says Dr. Charles S. DeCarli, director of the Alzheimer's Disease Center at the University of Kansas. Arisept doesn't cause liver damage, a complication associated with Cognex. Another acetylcholine-boosting drug called Exelon, from Sandoz Pharmaceuticals, is in the final stages of FDA approval and could be on the market by 1998. Researchers also have discovered that nicotine, the active ingredient in cigarettes, stimulates the production of acetylcholine. While smoking would do AD patients far more harm than good, there have been efforts to avoid the negative effects by isolating nicotinelike substances. This would enhance the release of acetylcholine, diminishing the memory defects associated with the disease. Sibia Neurosciences of San Diego is currently testing such a product and hopes to submit it for FDA approval before the end of next year. DYING CELLS. However, increasing the amount of acetylcholine in the brain will only slow the progression of AD, not reverse it. Acetylcholine is scarce in AD patients because the brain cells that release it are essentially shriveling up and dying. What's needed is a way to stop the degenerative process. To that end, estrogen therapies hold some promise. According to a small-scale study conducted last year by the Veterans Affairs Dept. and the University of Washington, women with AD who were given estrogen for two months showed significant improvements in memory and attention, which diminished when they stopped taking it. And epidemiological research indicates that women who have estrogen-replacement therapy after menopause are less likely to develop AD. Although researchers are still unclear about how estrogen acts on the brain, they speculate that the hormone stimulates new cell growth. Antioxidants, agents that fight harmful substances that damage cells, also may have a restraining effect. Test-tube studies have shown that antioxidants such as vitamin E stop the brain cell erosion that is symptomatic of AD. And a recently completed nationwide clinical study with vitamin E and an antioxidant-like generic drug, deprenyl, normally used for Parkinson's Disease, looks encouraging. Although the results are under review, sources familiar with the research say that antioxidants appear to protect against AD. Another provocative finding last year was the so-called Kentucky nun study. Researchers at the University of Kentucky examined the early writings of more than 90 nuns in a long-term investigation of cognitive function. They found that those whose writings demonstrated poor linguistic abilities were much more likely to get AD. There is also recent evidence that lack of education is linked to an increased risk of AD. Dr. Buckholtz says that one of many hypotheses to explain these results is that higher intellect and education appear to give a person a greater ''reserve'' in terms of brain cells, so ''it takes a greater reduction to see AD's effects.'' But Dr. Rachelle Doody, clinical director of Alzheimer's Disease Research Center affiliated with Baylor College of Medicine, warns against complacency: ''Just because you've got two PhDs doesn't mean you're not going to get AD. People of any intellect, education, and lifestyle can and do get this disease.'' In terms of diagnosis, there are two new developments. One stems from groundbreaking genetic research announced in 1993. A Duke University team of scientists led by Dr. Allen Roses found that a gene that is responsible for a common protein can affect a person's susceptibility to AD. The gene, known as apolipoprotein E, or ApoE, comes in three varieties--E2, E3, and E4. Inheriting E2 seems to protect a person from AD, while having a copy of E4 markedly increases the risk of developing the disease. As a result, Athena Neurosciences of San Francisco introduced the first AD-specific diagnostic test last year. It screens for the E4 gene and uses spinal fluid to gauge levels of two biochemicals that tend to be elevated in AD patients. GLUCOSE LEVELS. The other new diagnostic tool is the result of recent advances in computerized scanning technology. SPECT (single photon emission computed tomography) offers a noninvasive way to trace blood circulation and glucose metabolism in the brain. Dead areas or regions in the brain that aren't actively taking up blood and utilizing glucose for energy are signs of AD. ''These tests are useful, but they won't provide confirmation of the disease,'' says Dr. Buckholtz. To date, the only definitive test for AD requires sampling brain tissue to assess cell damage, which is too dangerous to be practical. So clinicians rely on medical and neuropsychological tests (often to rule out other causes of dementia like strokes, thyroid disorders, and nutritional deficiencies) to come up with a diagnosis of ''probable'' AD, which can only be confirmed by autopsy after the patient dies. A diagnosis of probable AD is 80% to 90% accurate and allows people to start appropriate therapies. Finally, to help in the creation and assessment of future Alzheimer's tests and treatments, researchers at the University of Minnesota genetically engineered a mouse last year that manifests both the behavioral symptoms and brain-cell damage characteristic of AD. Because the mouse is closer to the human model, scientists say that it will be a much more effective specimen than ordinary mice in laboratory investigations. So when it comes to researching AD, hope lies in building a better mouse, not a better mousetrap. ADVICE: Caregivers need support, too. Seeking help from various groups can prevent burnout
By Kate Murphy
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Updated June 15, 1997 by bwwebmaster
Copyright 1997, by The McGraw-Hill Companies Inc. All rights reserved.
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