• Highlights
• Introduction
• Causes
• Risk Factors
• Prevention
• Symptoms
• Diagnosis
• Medications
• Stages
• Resources
• References

Alzheimer's disease

Description

An in-depth report on the causes, diagnosis, and treatment of Alzheimer's disease.

Prevention

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

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) as Prevention

In 2004, the National Institutes of Health (NIH) halted a large clinical trial that was investigating the use of anti-inflammatory drugs in preventing Alzheimer's disease. While prior data had confirmed that NSAIDs were not effective in treating AD, research continued to explore these drugs' potential preventive benefits.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) investigated whether long-term use of naproxen (Aleve) or celecoxib (Celebrex) could decrease the risk of developing AD. The NIH suspended this trial due to evidence that the NSAID naproxen was associated with increased incidence of cardiovascular and cerebrovascular events among participants. (The evidence is not uniform; other research has not implicated naproxen as a cardiovascular risk.) No adverse effects appeared during this trial for the COX-2 inhibitor celecoxib. However, safety concerns about this drug had been raised in other trials. Investigators did not believe that celecoxib's potential benefits outweighed its risks.

Heart-Protective Medications 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.

Blood Pressure Drugs. Because high blood pressure is associated with increased risk of Alzheimer’s, researchers have been studying whether blood pressure medication can reduce this risk. In a 2006 study of patients who took high blood pressure drugs, researchers found that potassium-sparing diuretics reduced the risk of developing Alzheimer’s by 70%. Beta-blockers and certain calcium channel blockers also helped to a lesser extent. ACE inhibitors appeared to offer no protection.

Statins. Statins are common drugs used to lower cholesterol levels. In past years, a number of studies reported a significantly lower risk for Alzheimer's disease in patients who took statins. However, newer studies have failed to prove that statins can help prevent Alzheimer's disease. In these recent studies, large numbers of elderly people had their dementia evaluated at baseline and then monitored over several years. The results indicated that statin use did not predict onset of AD.  In the meantime, the NIH is conducting a clinical trial to investigate whether simvastatin can slow the progression of AD.

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. 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. The 2003 trial, called the Women's Health Initiative Memory Study (WHIMS), enrolled 4,500 women over 65 years of age. 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. The NIA continued to research whether estrogen-only therapy could prevent or delay the onset of Alzheimer's disease. Results released in 2004 indicated that women ages 65 years and older who took estrogen-only HRT had a slightly increased risk of developing dementia.

Testosterone. Some testosterone converts to estrogen, which may be why older men appear to have a lower risk for Alzheimer's disease than older women. Animal studies have suggested that testosterone may help reduce 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 higher doses and its effect on cancer-cell growth is unknown. Some evidence indicates that high levels may increase cancer 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 researching how diet can help in prevention. 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. 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 that suggest 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 U.S.
• A study in the Netherlands reported an association between dementia and diets high in total fat, saturated fat, and cholesterol.
• A number of studies suggest that a high-fat high-calorie diet in people who carry the ApoE4 gene may confer a particularly high risk. For example, in one 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.

Fish oil contains omega-3 fatty acids. These fatty acids are found in fish such as salmon, halibut, swordfish, and mackerel. In one study, eating oily fish at least once a week was associated with a lower risk for Alzheimer's disease. Studies indicate that a particular type of omega-3 fatty acid, called docosahexaenoic acid (DHA), may especially help protect the aging brain.

The Mediterranean diet is an eating plan that has shown heart-healthy benefits. It is rich in fiber and nutrients, including omega-3 fatty acids and antioxidant vitamins. The diet emphasizes fish, fruits, vegetables, and monounsaturated “good” fats, particularly olive and canola oils. A 2006 study suggested that the Mediterranean diet may also be good for the brain. In the study, patients who strictly followed the diet had a 40% lower risk of developing Alzheimer’s disease than patients who ate a conventional American diet.

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 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. Blueberries are of particular interest.

Alcohol. Some studies have suggested that moderate intake of alcohol (one or two drinks a day) 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. In any case, heavy alcohol consumption offers no protection and is dangerous.

Folate and Vitamin B12. Some studies suggest that deficiencies of vitamins B6, B12, and folate (folic acid) may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associates with a higher risk for Alzheimer's disease. Folate is added to cereal products. Other 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. The daily recommended allowance of folic acid is 400 mcg. Some experts recommend that people take at least this amount to reduce the risk of Alzheimer's.

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. Other studies suggest that vitamin E protects only those who carried the apoE4 gene. Most evidence on any benefits from other antioxidants come from a combination of antioxidant vitamins, such as vitamins C and E, but not the use of them separately. However, no strong evidence to date has found any protection from antioxidant supplements.

Other Health Behaviors

Exercise. Studies report that exercise may help prevent the development of Alzheimer’s disease and other forms of dementia. A 2006 study found that older adults (65 years and older) who exercised three times a week reduced their risk for Alzheimer’s by about 40%. Exercise in the study included walking, hiking, aerobics, calisthenics, swimming, water aerobics, weight training and stretching.

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

• Review Date: 5/22/2006
• Reviewed By: Harvey Simon, M.D., Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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