Reduction of Alzheimer's Disease and Lifestyle Changes

People may be able to reduce their risk of developing Alzheimer's disease, according to two recently published studies that are the latest in a long line of research. But does that hold for everyone? And by how much can you lower the risk? Here's a look at the facts. Alzheimer's afflicts 5.3 million Americans and that number is predicted to grow to nearly 8 million in the next 20 years, according to a 2009 report by the Alzheimer's Assn. Because the disease has no cure, medical researchers continue to focus on preventing or delaying the disease.

Two weeks ago, a paper in the journal Dementia and Geriatric Cognitive Disorders reported that people with even moderately elevated cholesterol in their 40s have twice the risk of developing Alzheimer's disease in their 60s, 70s and 80s, adding blood cholesterol to a variety of already-known risk factors for the disorder. High blood pressure, diabetes, obesity, smoking and high-fat diets have all been associated with increasing one's risk. Last week, a paper in the Journal of the American Medical Assn. reported that people eating a so-called Mediterranean diet and exercising regularly were at lower risk -- by as much as 50%. And in earlier studies, other lifestyle factors -- such as doing the daily crossword puzzle or other intellectually stimulating activities, maintaining an active social life and getting a college education -- have been associated with lowered Alzheimer's risk. The recent cholesterol study was large and long -- 9,844 Californians were followed for three decades -- and the data are striking. People with high cholesterol -- 240 or higher -- were 57% more likely to develop Alzheimer's disease. Those with borderline range cholesterol -- 200 to 239 -- were 23% more likely. Still, this is an association at best. No one can say that high cholesterol causes Alzheimer's disease: Other factors linked to it in some way could be to blame. Also not known is whether lowering cholesterol -- for instance by taking statin drugs -- would be protective. "An association is hypothesis-generating -- it allows us to begin looking at why that relationship might exist," says Dr. Jeffrey Cummings, director of the Mary S. Easton Center for Alzheimer's Disease Research at UCLA. One possible clue comes from animal studies: Neurobiological studies have found that high cholesterol in the blood may trigger more of the brain-clogging substance beta-amyloid protein.

The diet and exercise study reported last week was smaller and shorter. In it, 1,880 elderly New Yorkers were followed for an average of 5 1/2 years. It found exercise alone was linked to as much as a 50% reduced risk, diet alone by as much as 40%. This is not the first study to suggest that diet and physical activity may be protective. The Mediterranean-type diet "combines several foods and nutrients potentially protective against cognitive dysfunction or dementia, such as fish, monounsaturated fatty acids, vitamins B12 and folate, antioxidants (vitamin E, carotenoids, flavonoids), and moderate amounts of alcohol," the authors wrote. There have been very few studies that meet the gold standard of human trials, in which people would be randomly assigned to either receive an intervention or not, then followed into their senior years to see if they develop Alzheimer's. Of trials that have been completed, no clear preventive treatment has been identified.Some studies have found that in patients with hypertension, blood-pressure-lowering medications reduced the risk of Alzheimer's disease; others have found no effect. The same is true for cholesterol-lowering medications and diabetes management -- some studies found lower risk for Alzheimer's and others found no difference. Similarly, several clinical trials that have tested cholesterol-lowering statin drugs in elderly patients have failed to find lowered risk. But "it doesn't invalidate the cholesterol story," Cummings says. "What it does is suggest that by the time you get to the end of this lifelong process, it's too late to do a meaningful intervention. Increasingly, we see Alzheimer's disease as a result of a lifelong process as opposed to simply a late-onset brain disease." Scientists generally agree that keeping cardiovascular risk factors in check is good for the brain as well as the heart. "The damage that those factors cause on the vessels of the heart, for instance, are exactly the same kind of damage that's caused in the brain," says Lenore Launer, chief of neuroepidemiology at the National Institute on Aging in Bethesda, Md. "The vasculature is impaired in some way and then the neurons may die."But that is just part of the story. Certain naturally occurring neuroprotective substances are stimulated by physical activity, Cummings says. "So there are direct neurobiological effects of exercise that go beyond just better blood flow." These effects of lifestyle on Alzheimer's are not yet proven. But -- in contrast to long-term drug treatments -- there is virtually no downside to recommending them, experts say. Cummings says he often fields questions from families of his patients about what they can do to prevent the disease from happening to them. He recommends supplements of vitamins C and E and omega-3 fatty acids, exercise three times per week for 30 minutes and taking care of one's cardiovascular risk factors such as blood pressure and cholesterol. Even in people with genetic predisposition for developing Alzheimer's (those who carry the apolipoprotein E-e4 gene have a doubled risk), lifestyle changes can make a difference, Cummings says. "My experience is that people who know that they're at genetic risk take the environmental interventions much more seriously." Debra Cherry, executive vice president of the Alzheimer's Assn. California Southland Chapter, says that when she served on the Healthy Brain Initiative, a government workshop seeking evidence-based recommendations for reducing risk, the strongest case made was for aerobic activity. "I don't know if anyone will ever be able to do a randomized, controlled study, but the evidence is pretty strong that aerobic exercise protects again heart disease and brain disease," she says. "And there's very little risk to doing it