Alzheimer’s prevention strategies

Unlike age and genetics, certain health and lifestyle factors associated with Alzheimer’s disease risk may be controlled. Scientists are exploring prevention strategies to determine whether or not things like exercise, diet, and “brain games” can help delay or prevent Alzheimer’s disease and age-related cognitive decline. They are also investigating how certain medical conditions, such as high cholesterol, high blood pressure, and diabetes, influence risk for cognitive impairment.

So far, studies have not demonstrated that, over the long term, health or lifestyle factors can prevent or slow Alzheimer’s disease or age-related cognitive decline. Similarly, clinical trial results do not support the use of any particular medication or dietary supplement to prevent these conditions.

Promising research in these areas is underway. The NIA supports more than 30 clinical trials, including many that are investigating possible ways to prevent or delay Alzheimer’s disease or age-related cognitive decline. Observational studies have associated factors such as physical activity, blood pressure, and diabetes control with changes in risk. More research is needed to determine whether these factors can in fact directly help prevent Alzheimer’s or cognitive decline.

Understanding scientific findings in the news

Results of medical research studies appear in the headlines every day, raising and dashing hopes that cures for devastating diseases are right around the corner. It can be hard to know what to think about these study findings. Knowing the type of study and how it was conducted can help put the results into perspective.

An epidemiological study is an observational study that looks for common factors that might explain why or how a disease occurs in a certain group of people. Scientists gather information about people who are going about their daily lives, then analyze the data to see which behaviors or environmental factors are linked to a disease or other outcome.

Epidemiological studies can’t tell us for sure that these factors actually cause or prevent the disease or health condition. Based on epidemiological studies of Alzheimer’s disease, scientists can report that a finding is or is not “associated with” Alzheimer’s, not whether it directly affects development or progression of the disease.

For example, some epidemiological studies have found that people who exercise are less likely than inactive people to develop Alzheimer’s disease. But, people who exercise tend to be healthier in other ways than those who do not exercise, such as having lower rates of heart disease or eating a nutritious diet. We don’t know if their lower Alzheimer’s risk results from exercise, healthier eating, reduced risk of other diseases, a combination of those factors, or something else. So, we don’t know if exercising—including how much and how often—will directly lower Alzheimer’s risk.

Scientists also use in vitro (test tube) studies and animal studies to learn about disease. pipette dripping liquid into a test tube. These types of studies control specific factors that might influence a research result. This approach allows researchers to be more certain about possible causes of a disease. However, showing a cause-and-effect relationship in tissue samples or animals does not mean that the relationship will be the same in humans.

Randomized clinical trials are the best way to test directly in people the safety, effectiveness, and side effects of a medication or other treatment. In this type of research, some participants are randomly assigned to receive the intervention being tested—say, medication or exercise—while others receive a placebo (such as an inactive pill or a control intervention). Any differences in outcome between the groups should result from the treatment rather than other differences between the participants.

Do exercise and physical activity protect the brain?

Exercise and other types of physical activity have many benefits. Studies show that they are good for our hearts, waistlines, and ability to carry out everyday activities. Epidemiological studies and some intervention studies suggest that physical exercise may also play a role in reducing risk for Alzheimer’s disease and age-related cognitive decline.

Animal studies point to why this might be so. Exercise increases both the number of small blood vessels that supply blood to the brain and the number of connections between nerve cells in older rats and mice. In addition, researchers have found that exercise raises the level of a nerve growth factor (a protein key to brain health) in an area of the brain that is important to memory and learning.

Researchers have also shown that exercise can stimulate the human brain’s ability to maintain old network connections and make new ones that are vital to healthy cognition. In a year-long study, 65 older people exercised daily, doing either an aerobic exercise program of walking for 40 minutes or a nonaerobic program of stretching and toning exercises. At the end of the trial, the walking group showed improved connectivity in the part of the brain engaged in daydreaming, envisioning the future, and recalling the past. The walking group also improved on execu­tive function, the ability to plan and organize tasks such as cooking a meal.

Several other clinical trials are exploring further the effect of physical activity on the risk of Alzheimer’s and cognitive decline. Other NIA-supported research is examining whether exercise can delay the development of Alzheimer’s disease in people with MCI. Findings from these and other clinical trials will show more definitively whether exercise helps protect our brains from cognitive impairment.

Does diet matter?

A number of studies suggest that eating certain foods may help keep the brain healthy—and that others can be detrimental to cognitive health. A diet that includes lots of fruits, vegetables, and whole grains and is low in fat and added sugar can reduce the risk of many chronic diseases, including heart disease and type 2 diabetes. Researchers are looking at whether a healthy diet also can help preserve cognitive function or reduce the risk of Alzheimer’s.

Studies have found, for example, that a diet rich in vegetables, especially green leafy vegetables and cruciferous vegetables like broccoli, is associated with a reduced rate of cognitive decline. One epidemiological study reported that people who ate a “Mediterranean diet” had a 28 percent lower risk of developing MCI and a 48 percent lower risk of progressing from MCI to Alzheimer’s disease. A Mediterranean diet includes vegetables, legumes, fruits, cereals, fish, olive oil, mild to moderate amounts of alcohol, and low amounts of saturated fats, dairy products, meat, and poultry.

While some foods may stave off cognitive decline, other foods, such as saturated fats and refined carbohydrates (white sugar, for example), may pose a problem. In one study, scientists fed rats a “Western” diet high in fats and simple carbohydrates for 90 days. The results: rats fed this high-energy diet performed significantly worse on certain memory tests than rats fed a diet containing one-third the fat. Notably, the rats scored poorly on tests that involve the hippocampus, a part of the brain that plays a major role in learning and memory.

Some scientists have focused on DHA (docosahexaenoic acid), an omega-3 fatty acid found in salmon and certain other fish. Studies in mice specially bred to have features of Alzheimer’s disease found that DHA reduces beta-amyloid plaques, abnormal protein deposits in the brain that are a hallmark of Alzheimer’s. Although a clinical trial of DHA showed no impact on people with mild to moderate Alzheimer’s disease, it is possible that DHA supplements could be effective if started before cognitive symptoms appear.

These findings are of great interest and suggest possible areas for future study. The NIA supports clinical trials to examine the relationship between several dietary components and Alzheimer’s disease and cognitive decline.

What about vitamins and dietary supplements?

Can any vitamins or dietary supplements protect the brain from Alzheimer’s disease and cognitive decline? One area of research focuses on antioxidants, natural substances that appear to fight damage caused by molecules called free radicals. Other studies are looking at a compound called resveratrol.

As a person ages, free radicals can build up in nerve cells, causing damage that might contribute to Alzheimer’s. Some epidemiological and laboratory studies suggest that antioxidants from food or dietary supplements help prevent this oxidative damage— and lower the risk of Alzheimer’s disease—but other studies have shown no effect. Vitamin E, vitamin C, B vitamins, ginkgo biloba, and coenzyme Q have all been tested in clinical trials, but none has proven effective in preventing or slowing down Alzheimer’s disease.

Resveratrol, a compound found in red grapes as well as supplements, appears to have properties that may help protect the brain. Observational studies have shown that moderate consumption of red wine is associated with a lower incidence of Alzheimer’s disease, and animal studies have shown that resveratrol can reduce beta-amyloid deposits in the brain. Resveratrol also appears to affect the biological processes of aging-related diseases, including Alzheimer’s. An NIA-supported clinical trial will test the effects of resveratrol in people with Alzheimer’s disease.

What is the effect of other chronic diseases?

Age-related diseases and conditions—such as vascular disease, high blood pressure, heart disease, and type 2 diabetes—may increase the risk of Alzheimer’s and cognitive decline. Many studies are looking at whether this risk can be reduced by preventing or controlling these diseases and conditions through medication or changes in diet and exercise.

Much of the evidence about possible ties between vascular diseases and Alzheimer’s risk comes from observational studies. For example, high cholesterol levels and obesity during midlife—known risk factors for heart disease—have also been linked to increased risk of Alzheimer’s disease. High blood pressure may be another risk factor.

One NIH clinical trial is looking at how lowering blood pressure to or below current recommended levels may affect cognitive decline and the development of MCI and Alzheimer’s disease. Participants are older adults with high systolic blood pressure who have a history of heart disease or stroke, or are at risk for those conditions.

Diabetes is another disease that has been linked to Alzheimer’s. Previous research suggests that abnormal insulin production (insulin is the hormone involved in diabetes) contributes to Alzheimer’s-related brain changes. Can restoring normal insulin function in the brain provide cognitive benefits?

The results so far are mixed. One large NIH-funded clinical trial compared intensive glucose-lowering treatment with standard treatment in nearly 3,000 older adults with diabetes. After 40 months, the two groups showed no significant difference in cognitive function. But pilot testing of an insulin nasal spray has shown promising results. A clinical trial is testing this potential treatment in older adults with MCI or mild to moderate Alzheimer’s disease to see if it can improve memory and daily functioning.

Additional studies and clinical trials are looking at cardiovascular and diabetes medications to see if they might prevent Alzheimer’s disease. These therapies include aspirin, medications used to treat high blood pressure and other heart conditions, and the diabetes drugs metformin and pioglitazone.

Is keeping your brain active important?

Staying cognitively active throughout life—via social engage­ment or intellectual stimulation—is associated with a lower risk of Alzheimer’s disease. Several observational studies link continued cognitive health with social engagement through work, volunteering, or living with someone. Mentally stimulating activities such as reading books and magazines, going to lectures, and playing games are also linked to keeping the mind sharp.

In a large study of healthy older people, researchers found a relationship between more frequent social activity and better cognitive function. It is not clear whether improved cognition resulted from the social interaction itself or from related factors, such as increased intellectual stimulation, that generally accompany social interaction. Other studies are exploring these relationships.

Intellectually stimulating activities may also reduce the risk of Alzheimer’s, studies show. One large observational study looked at the impact of ordinary activities like listening to the radio, reading newspapers, playing puzzle games, and visiting museums. Investigators asked more than 700 older nuns, priests, and religious brothers to describe the amount of time they spent doing these activities. After 4 years, the risk of developing Alzheimer’s disease was 47 percent lower, on average, for those who did the activities most often than for those who did them least frequently.

A more recent study showed that people with less education who engaged in activities like reading, doing crossword puzzles, and writing letters performed as well on memory tests as their better-educated peers. Having fewer years of education has been associated with a higher risk of dementia. More research is needed to see if everyday cognitive activities can reduce the risk of cognitive decline in people with less education.

Formal cognitive training also seems to have cognitive benefits. In the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, for example, healthy adults 65 and older participated in 10 sessions of memory training, reasoning training, or processing-speed training. The sessions improved participants’ mental skills in the area in which they were trained. These improvements persisted 10 years after the training was complete.

Another approach is testing the impact of formal cognitive training, with and without aerobic exercise. For example, an NIA-funded clinical trial is investigating the effectiveness of cognitive training, alone and combined with aerobic exercise, in people with MCI to see if it can prevent or delay Alzheimer’s disease. Other trials are underway in healthy older adults to see if exercise and/or cognitive training (for example, a demanding video game) can delay or prevent age-related cognitive decline.

Other types of formal cognitive training are being studied in healthy older adults to explore their impact on age-related cognitive decline. Types of training being tested in NIA-funded trials include learning digital photography or quilting and volunteering at local schools.

How might an active brain prevent Alzheimer’s?

The reasons for the apparent link between social engagement or intellectual stimulation and Alzheimer’s risk aren’t entirely clear, but scientists offer these possibilities:

  • Such activities may protect the brain by establishing “cognitive reserve,” the brain’s ability to operate effectively even when it is damaged or some brain function is disrupted.
  • These activities may help the brain become more adaptable in some mental functions, so it can compensate for declines in other functions.
  • People who engage in these activities may have other lifestyle factors that protect them against Alzheimer’s disease.
  • Less engagement with other people or in intellectu­ally stimulating activities could be the result of very early effects of Alzheimer’s rather than its cause.


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