We can’t do much about our age or genetic profile, but scientists are working hard to understand a variety of other factors that may be involved in the disease. Some scientists are examining the biological bases for AD. This research might lead to the development of drugs that could protect against or block biological processes leading to cognitive decline and AD.
Other scientists are studying health, lifestyle, and environmental factors—such as exercise and diet or the control of chronic diseases like diabetes—that may play a role in preventing or slowing AD or cognitive decline. Recent research suggests that maintaining good overall health habits may help lower our chances of developing several serious diseases, including brain diseases such as AD. This area is of particular interest because it appears that there may be things that individuals can do themselves to hold off AD.
Several of these potential factors have been identified in animal studies and in epidemiologic studies (studies that compare the lifestyles, behaviors, and characteristics of groups of people). At present, these factors are only associated with changes in AD risk. Further research, especially clinical trials, will be needed to determine cause-and-effect—whether these factors really do help prevent cognitive decline or AD directly.
Understanding Scientific Findings in the News
It can be hard to know what to conclude about scientific study findings. Knowing how the study was conducted can help put the results into the right perspective. One main type of research is the epidemiologic study. These studies are observational—they gather information about people who are going about their daily lives. Study participants follow many behaviors and practices. It is difficult, therefore, to determine the exact benefits or risks of one particular behavior from among all the healthy or harmful things that may happen to participants or that they do. That is why, in epidemiologic studies of AD, scientists will say that a finding is “associated with” AD, or not. The epidemiologic evidence linking a behavior and AD is, at best, suggestive, but we do not know that the behavior by itself actually helps to cause or prevent AD. Other types of research—test-tube studies and studies in animals—add to the findings from epidemiologic studies. Scientists sometimes use these studies to control factors that might otherwise influence a research result. Controlling specific factors allows scientists to be more certain about why they get the results they do. It also allows them to describe their results more precisely. Of course, showing a cause-and-effect relationship in tissue samples or even in animal studies does not mean that the relationship will be the same in humans. Clinical trials—research studies in humans that rigorously test safety, side effects, and how well a medication or behavioral treatment works—are the gold standard for research. Clinical trials are used to determine whether a specific medication, device, or treatment actually prevents or delays AD. |
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Assessing Physical Activity
Accumulating evidence suggests that physical activity may be good for our brains as well as our hearts, waistlines, and ability to carry out activities of daily living. Epidemiologic studies have found associations between physical activity and improved cognitive skills or reduced AD risk. For example, investigators looked at the relationship of physical activity and AD risk in about 1,700 adults aged 65 years and older over a 6-year period. They found that the risk of AD was 35 to 40 percent lower in those who exercised for at least 15 minutes 3 or more times a week than in those who exercised fewer than 3 times a week.
Scientists have sought to confirm these associations in animal studies, hoping to clarify why physical activity might be related to reduced risk of cognitive decline and AD. For example, studies in older rats and mice have found that exercise increases the number of small blood vessels that supply blood to the brain and increases the number of connections between nerve cells. Other research has shown exercise to raise the level of specific brain-growth factors in an area of the brain that is particularly important to memory and learning.
Both epidemiologic and animal studies point to associations and help to explain them. However, epidemiologic studies can’t tell us whether a true cause-and-effect relationship exists between a particular factor and AD risk. For example, people who exercise tend to be healthier in other ways, such as having decreased rates of heart disease or diabetes. They may also have healthier lifestyles, such as eating a nutritious diet. This means that even if people who exercise are less likely to develop AD, we don’t know whether this is due to the exercise or the more healthful eating or other lifestyle differences that distinguish them from inactive people.
Likewise, animal studies can’t tell us whether an intervention will definitely work in humans. That’s why investigators conduct clinical trials—controlled studies involving humans. Clinical trials are the most reliable method for showing whether intervention strategies really can work to prevent or treat AD in people. This is because clinical trial participants are randomly assigned to receive or not receive a treatment (for example, exercise). Therefore, any differences between the groups should be due to the exercise program rather than other differences between the groups.
NIA supports clinical trials related to exercise and cognitive function. One completed trial used functional magnetic resonance imaging (MRI) tests to measure changes in brain activity in older adults before and after a 6-month program of brisk walking. Results showed that brain activity increased in specific brain regions as the participants’ cardiovascular fitness increased. A similar study showed that brain volume increased as a result of a walking program.
These findings strongly suggest a biological basis for the role of aerobic fitness in helping to maintain the health and cognitive functioning of adults as they age, at least in the short term. Currently, a trial is underway to look at the effects of a 1-year aerobic fitness training program on cognition and brain activity and structure in older adults. Other NIA-supported research is examining whether exercise can delay the development of AD in people with mild cognitive impairment (MCI).
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Exploring Dietary Factors
A number of studies suggest that how we eat may be linked to our risk of developing—or not developing—AD. This is another important area of current AD research. A nutritious diet—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, type 2 diabetes, and obesity. Animal studies, epidemiologic studies, and clinical trials are looking at whether a healthy diet also can help preserve cognitive function or even reduce AD risk.
Studies have examined foods that are rich in antioxidants and anti-inflammatory components to find out whether those foods affect age-related changes in the brain. One study found that curcumin, the main ingredient of turmeric (a spice used in curry), can suppress the build-up of harmful beta-amyloid in the brains of rodents. Another study, in AD transgenic mice (those that are specially bred to have features of AD), found that DHA (docosahexaenoic acid, a type of omega-3 fatty acid found in some fish) reduced the presence of beta-amyloid and plaques. Other research has shown that older dogs perform better on learning tasks when they eat a diet rich in antioxidants and live in an “enriched” environment with many opportunities to play and interact with others.
In addition, studies in rats and mice have shown that dietary supplementation with blueberries, strawberries, and cranberries can improve cognitive function, both during normal aging and in animals that have been bred to develop AD. Scientists are beginning to identify some of the chemicals responsible for these berries’ beneficial effects and think that the chemicals may act by neutralizing free radicals. This may reduce inflammation or stimulate neurons to protect themselves better against some of the adversities of aging and AD.
Several epidemiologic studies have shown an association between eating a diet rich in vegetables (especially green leafy vegetables and cruciferous vegetables like broccoli) and a reduced rate of cognitive decline. Researchers speculate that the beneficial effect may come from the antioxidant and folate content of the vegetables.
These results are interesting, but in their normal daily lives, people typically consume many different foods and nutrients. With this in mind, some investigators have conducted epidemiologic studies to examine a group’s entire dietary pattern. One of these studies showed a reduced risk of AD in those who ate the “Mediterranean diet”—a diet that includes many fruits, vegetables, and beans; moderate amounts of fish; low-to-moderate amounts of dairy foods; small amounts of meat and poultry; regular but moderate amounts of wine; and olive oil.
These kinds of findings are exciting and suggestive, but they are not definitive. To confirm them, NIA is supporting several clinical trials to examine the relationship between specific dietary components and cognitive decline and AD.
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Investigating Chronic Diseases
For some years now, scientists have been finding clues that damage to the vascular system (the body’s vast system of large and small blood vessels) may contribute to the development of AD or affect its severity. Several common chronic diseases that affect older people, including heart disease, stroke, and type 2 diabetes, also affect the body’s vascular system and have been tied to declines in cognitive function or increased AD risk. In addition, heart disease, high blood pressure, and diabetes to a large extent can be modified by diet, exercise, and other lifestyle changes. Therefore, scientists are keenly interested in learning whether reducing the risks of or controlling these conditions through lifestyle changes also may reduce the risks of cognitive decline or AD.
Much of the evidence so far about possible relationships between vascular diseases and cognitive decline or AD risk comes from epidemiologic studies. To clarify and build on these findings, scientists have conducted a variety of studies, including test tube, animal, and additional epidemiologic studies. NIA is supporting several clinical trials, including a trial to test the effect of lowering blood pressure and blood cholesterol levels on cognition in people with diabetes. Several other trials are examining whether intensive diabetes treatment can reduce cognitive decline. Researchers are also looking at increased stiffness of blood vessels with age as another potential treatment target.
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Examining Social Engagement and Intellectually Stimulating Activities
Observations of nursing home residents and older people living in the community have suggested a link between social engagement and cognitive abilities. Having many friends and acquaintances and participating in many social activities also is associated with reduced cognitive decline and decreased risk of dementia in older adults. For example, the NIA-funded Chicago Health and Aging Project showed that more social networks and a higher level of social engagement were associated with a higher level of cognitive function at the beginning of the study. These factors also were related to a reduced rate of cognitive decline over time.
Studies have also shown that keeping the brain active is associated with reduced AD risk. In the Religious Orders Study, for example, investigators periodically asked more than 700 participants—older nuns, priests, and religious brothers—to describe the amount of time they spent in seven information-processing activities. These activities included listening to the radio, reading newspapers, playing puzzle games, and going to museums. After following the participants for 4 years, the investigators found that the risk of developing AD was 47 percent lower, on average, for those who did the activities most often than for those who did them least frequently.
Other studies have shown similar results. In addition, a growing body of research suggests that, even in the presence of AD plaques, the more formal education a person has, the better his or her memory and learning abilities.
Another NIA-funded study supports the value of lifelong learning and mentally stimulating activity. It showed that during early and middle adulthood, cognitively healthy older people had engaged in more mentally stimulating activities and spent more hours doing them than did those who ultimately developed AD. Other studies have shown that people who are bilingual or multilingual seem to develop AD at a later age than do people who only speak one language.
The reasons for this apparent link between social engagement or intellectual stimulation and AD risk aren’t entirely clear, but scientists suggest four possibilities:
- Such activities may protect the brain in some way, perhaps by establishing “cognitive reserve.” (Cognitive reserve is the brain’s ability to operate effectively even when some function is disrupted or the amount of damage that the brain can sustain before changes in cognition are evident.)
- These activities may help the brain become more adaptable and flexible in some areas of mental function so that it can compensate for declines in other areas.
- People who engage in these activities may have other lifestyle factors that protect them against developing AD.
- Less engagement with other people or in intellectually stimulating activities could be the result of very early effects of the disease rather than its cause.
The only way to really evaluate some of these possibilities is to test them in a controlled way in clinical trials. Several clinical trials have examined whether memory training and similar types of mental skills training can actually improve the cognitive abilities of healthy older adults and people with mild AD. In the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, for example, certified trainers provided 10 sessions of memory training, reasoning training, or processing-speed training to healthy adults 65 years old and older. The sessions improved participants’ mental skills in the area in which they were trained. Even better, these improvements persisted for up to 5 years after the training was completed.
The Cognitive and Emotional Health Project The National Institute on Aging (NIA) is part of the Federal Government’s National Institutes of Health, at the U.S. Department of Health and Human Services. NIA has primary responsibility for research on AD and age-related declines in mental skills (also called cognitive skills), such as remembering, learning, thinking, decision making, and language. This responsibility is part of a larger mission to understand the nature of aging and find ways to help people stay physically, emotionally, and cognitively healthy for as long as possible. Several years ago, NIA, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke launched the Cognitive and Emotional Health Project (http://trans.nih.gov/CEHP). This project has begun to identify and describe what we know about the diverse factors that may affect the emotional health and cognitive abilities of adults. Research on the most promising factors is being carried out to determine whether any of them will result in strategies that can help people remain mentally and emotionally vibrant as they age. The hope is that successful strategies will also add to our knowledge about what can be done to reduce the likelihood of developing neurodegenerative diseases such as AD. |
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