Epidemiologic studies, animal studies, and clinical trials are all important in identifying potential factors that may contribute to or protect people from AD risk—separately or interactively with genetics. In the past several years, two areas of focus have emerged: lifestyle factors and the management of health conditions. Scientists also have continued their research interest in looking at estrogen and AD.
Lifestyle Factors and ADSeveral elements of a healthy lifestyle, including a nutritious diet, regular physical activity, not smoking, and strong social networks, can help people stay healthy as they grow older. An important reason for this benefit is that lifestyle choices strongly affect the risk of several chronic diseases, including heart disease, diabetes, and stroke, that commonly affect people as they age. Evidence is emerging that AD may share some of these risk factors. Findings from epidemiologic research, basic studies in animals, and limited clinical trials suggest that an array of lifestyle factors may influence the risk of developing age-related cognitive decline, aMCI, or even AD.
Epidemiologic studies correlate lifestyle factors with altered cognitive function. Epidemiology cannot, however, establish a cause-and-effect relationship. To directly examine cause and effect, NIA is sponsoring several clinical trials to test the questions raised by observational and animal studies and to specifically look at the effects of one lifestyle factor—physical activity and exercise—on cognitive function in older adults.
Additional clinical trials are critical to discern whether physical activity and exercise can, in fact, prevent or delay long-term cognitive decline or AD and, if so, to determine the type and amount of physical activity necessary.
Although the evidence to date suggests that physical activity and other lifestyle choices, such as mentally stimulating activity, a healthy diet, and social engagement, have positive effects on brain function and may reduce risks of cognitive decline and AD, results from definitive clinical trials will not be available for several years.
Even so, experts can recommend that older adults (and other age groups) participate in these activities. These low-risk, low-cost interventions have many proven benefits for overall healthy aging. For example, regular physical activity and a healthy diet help reduce the risk of age-related diseases and conditions, such as heart disease and type 2 diabetes. Social activities with friends and family and the pursuit of mentally stimulating activities help people feel engaged.
Health Conditions and ADA growing body of evidence suggests that the metabolic changes that occur in a variety of age-related chronic diseases, such as heart disease, stroke, high blood pressure, and type 2 diabetes, may contribute to the development of AD, affect the severity of AD, or cause vascular dementia (a loss of thinking and reasoning abilities caused by stroke or other forms of brain injury related to damage to the brain’s blood vessels). However, these relationships are complex. Several studies in the past year have attempted to untangle them.
As noted earlier, epidemiologic studies cannot determine cause-and-effect relationships even though they provide valuable information about associations between chronic diseases and aMCI or AD. As a result, NIA is supporting several clinical trials to see whether managing these conditions might reduce the risk of cognitive decline and dementia.
Clinical trials have examined whether two treatments—simvastatin (a cholesterol-lowering drug) and vitamin supplements that reduce homocysteine (an amino acid linked to heart disease and AD)—could slow the rate of cognitive decline in older adults with AD. These trials were recently completed, and the data are being analyzed.
Other clinical trials are underway to examine whether diabetes-related interventions can prevent or delay the progression of cognitive decline or AD:
Estrogen and ADProduction of estrogen, a hormone made by a woman’s ovaries, declines dramatically after the childbearing years. During the past 25 years, laboratory and animal research and human observational studies have suggested that estrogen may protect the brain. Experts have wondered whether using estrogen could reduce the risk of AD or slow its progression.
Clinical trials have shown that estrogen does not slow the progression of already-diagnosed AD and does not effectively treat or prevent the disease if treatment begins in later life. However, questions remain as to whether some forms of estrogen might help if started somewhat earlier than the older ages already tested. These questions are now being investigated.
The Framingham Heart Study, begun in 1948, is a long-term investigation of physical and environmental factors that influence the development of cardiovascular disease in healthy individuals. The study, funded by NHLBI, is still following the remaining members of the original study group, as well as the remaining members of a group of 5,000 people who were recruited in 1971 into the Framingham Offspring Study. Investigators are now working with the third generation of volunteers in this landmark epidemiologic study.
One of the distinguishing elements of the study has been “add-on” components funded by other NIH institutes, including NIA and NIMH. These add-on components have provided a cost-effective opportunity for scientists to examine additional issues using existing study populations.
The Framingham Study’s rich harvest of data has allowed researchers to explore many dimensions of the relationship between cardiovascular risk factors, cognitive health, and AD. The fact that it has been going on for so many years also gives scientists a unique opportunity to study certain aspects of an issue. For example, in describing the burden of any disease, scientists often refer to incidence, or the number of people who may develop the disease in a given time period, usually a year. However, some investigators have argued that “lifetime risk,” or the risk of developing a disease across the remaining estimated lifespan, may provide a more accurate measure of the possible burden to a population than incidence. They note that lifetime risk reflects risk across a longer period of time rather than does risk over a single year.
Framingham investigators at the Boston University School of Medicine conducted a lifetime risk analysis using many years of follow-up data from the original group of Framingham participants. This analysis, which was supported by NHLBI, NIA, and NINDS, focused on the lifetime risk of stroke and AD, two conditions of enormous public health concern.
Using 51 years of follow-up data, the analysis showed that the lifetime risk of stroke was 1 in 5 for a middle-aged woman and 1 in 6 for a middle-aged man. For AD, using 29 years of follow-up data, lifetime risk was 1 in 5 for a middle-aged woman but only 1 in 10 for a middle-aged man. The authors concluded that measures of age- and sex-specific lifetime risk indicate that a middle-aged person has a 1 in 3 chance of having a stroke or becoming demented. These rates have serious implications for the provision and cost of future health care services.
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