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) was launched in 2001 to investigate whether long-term use of naproxen (Aleve) or celecoxib (Celebrex) could decrease the risk of developing AD. The trial was based on the premise that because inflammation is known to be involved in the process of Alzheimer’s disease, anti-inflammatory drugs may help to prevent it. The NIH suspended this trial due to evidence that the NSAID naproxen was associated with increased incidence of cardiovascular and cerebrovascular events among participants. No adverse effects appeared during this trial for the COX-2 inhibitor celecoxib. However, heart safety concerns about this drug had been raised in other trials, and investigators did not believe that celecoxib’s potential benefits outweighed its risks.

Since 2004, the ADAPT investigators have continued to monitor the trial’s participants to see if these treatments had any effect in changing their risk for Alzheimer’s. In an update analysis of ADAPT data published in 2007, the researchers announced that neither naproxen nor celecoxib appear to reduce the risk for Alzheimer’s.

Heart-Protective Medications and Behaviors

The same lifestyle and medical choices that reduce risk factors for heart disease and diabetes are important for reducing the risk for Alzheimer’s disease. And, experts believe that treating high blood pressure and diabetes may help slow the progression of 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. While 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 Alzheimer’s disease rates vary 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, in patients with existing Alzheimer’s, weight loss is a strong indicator of mental decline.

Fats and Oils. Some studies 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.

The recommended dietary goal is to limit total fat intake to 25 - 35% of total daily calories. But not all fats are alike. Unhealthy fats include saturated fats (contained in animal products such as meat) and trans-fatty acids (contained in fast foods and commercially baked products). The American Heart Association recommends limiting saturated fat intake to less than 7% of total daily calories and trans-fatty acid intake to less than 1% of total daily calories.

It is best to replace saturated fats and trans-fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids are excellent sources of unsaturated fats. Plant sources of omega-3 fatty acids include canola oil, soybeans, flaxseed, and certain types of nuts such as walnuts. For fish sources, salmon, mackerel, sardines, lake trout, herring, and albacore tuna are especially high in marine omega-3 fatty acids. For heart health, and possibly brain health, experts recommend eating these types of fish at least twice a week.

Two types of omega-3 fatty acids are found in fish oils: Docosahexaenoic acid (DHA) and eicosapentaneoic acid (EPA). Researchers are particularly interested in the role that DHA may play in Alzheimer’s disease prevention. DHA has been linked to many brain cell functions, and appears to have particular importance for aging brains. Studies indicate that people who have higher blood levels of DHA have a much lower risk of developing dementia and Alzheimer’s disease.

Although evidence suggests that consuming DHA-rich foods later in life helps to increase DHA levels in the brain, it is unclear whether dietary supplements can provide similar benefits. A 2007 study indicated that omega-3 fatty acid supplements may help slow cognitive decline in some patients with very mild Alzheimer’s disease, but that the supplements have little effect for advanced stages of the disease. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to evaluate whether DHA supplements can slow the progression of cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease.

Mediterranean diet is an eating plan that has specific heart-health 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. Other studies also indicate the Mediterranean diet is associated with a lower risk for Alzheimer’s.

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

Fruits and Vegetables. According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. Blueberries, which are very rich in antioxidants, are of particular interest. A 2006 study of over 3,000 elderly adults found that consumption of vegetables (especially green leafy vegetables) helped reduce the rate of cognitive decline, but fruit intake had no effect.

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. Deficiencies in these vitamins can increase homocysteine levels, which some research associates with a higher risk for Alzheimer’s disease. Foods containing folate include avocados, bananas, oranges, asparagus, green leafy vegetables, and dried beans. In the United States and some other countries, grain and cereal products are fortified with folate. B12 is found only in animal, dairy, and fish products. B6 is found in a variety of foods, including fortified cereals, beans, meat, fish, and some fruits and vegetables.

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

Research is still inconclusive and conflicting about whether increased consumption of folate, through food or dietary supplements, can help prevent Alzheimer’s disease or slow its progression. A small 2006 study of healthy older adults, published in the New England Journal of Medicine, found that supplements containing folate, vitamin B12, and vitamin B6 did not help improve cognitive performance. A 2007 Lancet study indicated that folic acid supplements may help slow cognitive decline. People in the Lancet study took 800 mcg of folic acid daily, which is twice the recommended daily allowance of 400 mcg. However, this study was conducted in the Netherlands, where people tend to get less folate in their daily diets than in the United States.

Another 2007 study found that elderly people who consumed folate from both diet and supplement sources had a reduced risk for Alzheimer’s disease. Neither diet alone nor supplements alone affected Alzheimer’s risk; only the combination of the two produced an effect. The study also indicated that vitamins B6 and B12 do not affect Alzheimer’s risk.

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 of the evidence finding any benefits from other antioxidants comes from using a combination of antioxidant vitamins, such as vitamins C and E, but not from using them separately. However, there is no strong evidence of protection to date from using antioxidant supplements.

Other Health Behaviors

Physical Exercise. Studies indicate 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.

Mental Exercise. Cognitive training that includes exercises to stimulate memory, reasoning, and mental processing speed may help improve both mental ability and daily functioning. In an important 2006 study in the Journal of the American Mental Association, older community-dwelling adults who received cognitive training showed reductions in cognitive decline. In addition, they were better able to handle daily living tasks -- such as performing housework, managing money, and preparing meals -- than people who did not receive the training. The benefits of cognitive training lasted for up to 5 years afterwards. Other studies indicate that participating in intellectually engaging activity -- such as doing crossword puzzles or learning a new language -- may help reduce the risk of Alzheimer’s disease.

Social Interaction. Social interaction is also important for maintaining emotional health as well as keeping the mind active and energized. A 2007 study indicated that adults who are lonely have twice the risk of developing Alzheimer’s dementia as those who are not socially isolated.