Alzheimer's Disease

Description

Prevention

Although there is no strong evidence that any lifestyle change can prevent Alzheimer's disease, studies are showing that certain behaviors may help protect against mental decline. In particular, medications and lifestyle choices that protect the heart may be of specific importance. Other preventive agents are under investigation, including antioxidant and anti-inflammatory therapies.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) as Prevention

Although recent data have not supported the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating Alzheimer's, research is continuing to explore whether these drugs may help to prevent the disease. A 2003 analysis of several studies indicated that the long-term use of NSAIDs may help to lower the risk of developing Alzheimer's disease, but more research needs to be conducted to confirm these results. Some studies have demonstrated that the NSAIDs most strongly associated for protection include ibuprofen (Advil, Motrin) and the prescription NSAIDs sulindac (Clinoril) and indomethacin (Indocin). These agents have properties that prevent beta amyloid accumulation in the brain. One important 2001 study suggested that taking them for two years or longer provided protection. (Protection was not significant for shorter durations.) Evidence further suggests that even low doses may be beneficial, which may help prevent bleeding and ulcers that commonly occur with long-term high-dose use. Aspirin may offer some protection but it is not as significant. The protective benefits of other NSAIDs, including naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and the newer COX-2 inhibitors also require research.

Heart-Protective Agents and Behaviors

The same lifestyle and medical choices that reduce risk factors for heart disease and diabetes may be important for reducing the risk for Alzheimer's disease. The following are some heart-protective medications that may also protect the brain.

Calcium-Channel Blockers and Other Anti-Hypertensive Agents. Some studies indicate that lowering high blood may reduce the risk of Alzheimer's disease in elderly patients with systolic hypertension. In one study, the calcium channel blocker nitrendipine was especially associated with protection. Studies are needed to determine if protection is derived from calcium channel blockers or if other blood-pressure lowering agents provide the same benefits. (Calcium-channel blockers are known to have nerve-protecting properties.)

Statins. Statins are common drugs used to lower cholesterol levels. Of considerable interest are a number of studies now reporting a significantly lower risk for Alzheimer's disease in people who were taking specific statins. Some evidence suggests they may even improve mental function in people without unhealthy cholesterol levels. Those showing promise include lovastatin (Mevacor), pravastatin (Pravachol), and atorvastatin (Lipitor). Such statins appear to reduce levels of beta-amyloid. Other statins have not been associated with an lower risk for Alzheimer's. In fact, some researchers are concerned that certain statins that cross the blood-brain barrier may actually worsen Alzheimer's in people who already have it.

Male and Female Hormone Replacement Therapies

Hormone Replacement Therapy. Hormone replacement therapy (HRT) has been studied for years for health effects after menopause, including its effect on mental decline. Results have been mixed. In a 2002 study of women over 80, a history of HRT used for longer than 10 years appeared to reduce the risk for Alzheimer's disease, but HRT did not protect women who took it for less than ten years. A number of studies, including a major 2003 analysis, have found no differences in mental performance and no protection from Alzheimer's disease in women taking HRT compared to non-users. This trial, called the Women's Health Initiative Memory Study (WHIMS), enrolled 4,500 women over 65 years of age. The fact that most women who take HRT tend to be healthier and better educated to begin with may bias study results that favor HRT. Well-conducted studies are under way to resolve this important issue. It should be noted that long-term use of HRT may pose some health risks, including breast cancer, stroke, heart attack, and blood clotting, which a woman at risk for Alzheimer's should discuss with her physician.

The WHIMS study showed that older postmenopausal women who took combination HRT (estrogen plus progestin) had twice the risk of developing dementia than similarly aged women who received placebo pills. In addition to increasing the risk for dementia, (including Alzheimer's disease), combination HRT failed to prevent the development of mild cognitive impairment. Based on these results, the researchers from the National Institute on Aging (NIA) recommended against prescribing combination hormone therapy to older women for maintaining or improving cognitive function. Although a 2000 study indicated that estrogen replacement therapy was not effective in treating dementia in women with Alzheimer's who had undergone hysterectomy, the NIA is continuing research to determine whether estrogen-only therapy can prevent or delay the onset of Alzheimer's disease.

Testosterone. Some testosterone converts to estrogen, which may be a factor in the lower risk for Alzheimer's disease in older men than in women. Animal studies have also suggested that testosterone might be helpful in reducing levels of beta amyloid. There is also some evidence that low testosterone levels may be a particular risk factor in men with the APOE4 gene. Some experts believe that giving testosterone to elderly men and combinations of testosterone and estrogen to older women may prove to be protective. Side effects of testosterone in women include increased body hair, acne, fluid retention, anxiety, and depression. Long term benefits or serious adverse effects are unknown.

DHEA. Dehydroepiandrosterone (DHEA) is a male-like hormone in the body that declines with age. Some evidence suggests that it may help reduce mental decline in older women, but not in older men. Studies are under way. The hormone may, however, reduce HDL (the so-called good cholesterol) when taken in doses higher than 50 mg and its effect on cancer-cell growth is unknown, with some evidence indicating that high levels may increase the risk. In any case, DHEA is not regulated and brands vary widely in their content.

Dietary Factors

Because of differences in Alzheimer's disease rates among different populations, investigators are looking at dietary factors for protection. Caloric intake itself may play a role in brain health. In one study on animals, restricting calories below normal (but above starvation levels) helped prevent age-related nerve degeneration. It should be pointed out, however, that in patients with existing Alzheimer's, weight loss is a strong indicator of mental decline.

Fats and Oils. The following are some studies suggesting an association between fat and Alzheimer's disease.

• In China and Nigeria, where fat intake is low, the risk of developing Alzheimer's is 1% at age of 65 compared to 5% in the US.
• A study in the Netherlands reported an association between dementia and diets high in total fat, saturated fat, and cholesterol.
• A number of studies are now suggesting that a high-fat high-calorie diet in people who carry the ApoE4 gene may confer a particularly high risk. For example, in one 2000 US study, adults who carried the ApoE4 gene and whose diet consisted of 40% fat calories had 29 times the risk for Alzheimer's compared to non-ApoE4 carriers on the same high-fat diet.

It should be noted that fish oil, which contains omega-3 fatty acids, in particular the compound docosahexaenoic acid (DHA), may help protect the aging brain. In a 2002 eating fish at least once a week was associated with a lower risk for Alzheimer's disease. (In the same study, eating meat had no effect one way or the other.) These fatty acids are found in oily fish such as salmon, halibut, swordfish, and mackerel. People can also obtain DHA in supplements.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with IBD (inflammatory bowel disease).

The recommended dietary goal is to limit total fat intake to 30% or fewer calories from fat. Everyone should avoid saturated fats found in animal products) and trans-fatty acids (found in fast foods and commercial baked goods). People should also eat fish twice a week and choose polyunsaturated and monounsaturated oils (canola and olive oil).

Dark-Colored Fruits and Vegetables. According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. Of interest was a 1999 study on animals, in which extracts taken from blueberries and strawberries actually reversed age-related decline in brain function. Blueberries were the most effective. Dark-colored fruits and vegetables are recommended in any case for good health.

Soy. Soy has estrogen-like properties and animal studies suggest it may might be protective against Alzheimer's disease, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggest that the same estrogen-like effects of soy may actually pose a risk for greater mental among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.

Alcohol. Some studies have suggested that moderate intake of alcohol (one or two drinks a day) of any kind may protect the aging brain, possibly by releasing acetylcholine, the chemical in the brain that is deficient in Alzheimer's disease. Not all studies have been positive. One, for example, suggested that wine may have some protective properties for noncarriers of ApoE4 but actually increase the risk for carriers of the gene. In any case, heavy alcohol consumption offers no protection and is dangerous.

Caffeine. One study reported that women over 80 with a lifetime history of coffee intake had better performance on tests of mental function. (Coffee drinking in men and non-caffeinated drinking in either gender had no effect.)

Folate and Vitamin B12. Some studies suggest that deficiencies of vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Both vitamins are added to cereal products Foods containing folate include avocados, bananas, oranges, asparagus, green leafy vegetables, and dried beans. B12 is found only in animal products. (Oily fish are very high in B12 and also have other nerve-protective properties.). People who are folate deficient may need supplements of folate (natural form) or folic acid (its synthetic from), which is twice as potent at folate. Some experts recommend 400 mcg of folic acid to reduce homocysteine, although one study suggested 800 mcg (.8 mg) a day is necessary to reduce homocysteine levels.

Click the icon to see an image of vitamin B12 sources.

Click the icon to see an image of folate sources.

Antioxidant Supplements. Much research on Alzheimer's disease has indicated that oxidation (release of damaging unstable particles) may play an important role in the disease process. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. Most evidence on any benefits from other antioxidants come from a combination of the antioxidants, such as vitamins C and E and coenzyme Q-10 (but not the use of them separately). However, no strong evidence to date has found any protection from antioxidant supplements.

Other Health Behaviors

Exercise. Aerobic exercise (such as walking or jogging) is very important for helping to protect against mental decline during aging. A number of studies are reporting that regular exercise may protect specifically against Alzheimer's as well other forms of mental deterioration and dementia. And the more exercise, the better.

Social Behaviors and Stress Reduction. Lifelong learning, social engagements, and stress reduction are all useful in keeping the mind active and energized.