Alzheimer’s Prevention

Newspapers, magazines, the Internet, and TV seem to be full of stories about ways to stay healthy, eat right, and keep fit. Many people are concerned about staying healthy as they get older. Along with keeping their bodies healthy, they want to keep their minds sharp. They also want to avoid brain diseases, such as Alzheimer’s disease (AD), that occur more often in older people than in younger people.

Currently, AD has no known cure, but the results of recent research are raising hopes that someday it might be possible to delay the onset of AD, slow its progress, or even prevent it altogether. Delaying by even 5 years the time when AD symptoms begin could greatly reduce the number of people who have this devastating disease. The National Institute on Aging (NIA), part of the National Institutes of Health at the U.S. Department of Health and Human Services; other Government agencies; and private-sector groups support research that takes many different approaches to studying how to prevent or delay the disease.

Can We Prevent Complex Diseases Like AD?

Many diseases, such as diabetes, heart disease, and arthritis, are complex. They develop when genetic, environmental, and lifestyle factors interact to cause disease and/or make it worse. The importance of these factors may be different for different people.

AD is one of these complex diseases. It develops over many years and appears to be affected by a number of factors that may increase or decrease a person’s chances of developing the disease. These factors include genetic makeup, environment, life history, and current lifestyle. We can’t control some of these risk factors, but we can control others.

AD Risk Factors We Can’t Control

Age

Age is the most important known risk factor for AD. The risk of developing the disease doubles every 5 years after age 65. Several studies estimate that up to half of all people older than 85 have AD. These facts are significant because of the growing number of people 65 and older. A 2005 Census report estimates that the number of Americans 65 and older will more than double to about 72 million by 2030. Even more significant, the group with the highest risk of AD—those older than 85—is the fastest growing age group in the United States.

Genetics

Genetic risk is another factor that a person can’t control. Scientists have found genetic links to the two forms of AD—early-onset and late-onset. Early-onset AD is a rare form of the disease, affecting only about 5 percent of all people who have AD. It develops in people ages 30 to 60. In the 1980s and early 1990s, researchers found that mutations (permanent abnormal changes) in certain genes cause most cases of early-onset AD. If a parent has any of these genetic mutations, his or her child has a 50-50 chance of inheriting the mutated gene and developing early-onset AD.

Late-onset AD, the much more common form of the disease, develops after age 60. In 1992, researchers found that three forms, or alleles (ε), of a gene called apolipoprotein E (APOE) can influence the risk of late-onset AD:

  • APOE ε2, a rarely occurring form, may provide some protection against AD.
  • APOE ε3, the most common form, plays a neutral role, neither increasing nor decreasing risk.
  • APOE ε4, which occurs in about 40 percent of all people who develop late-onset AD and is present in about 25 to 30 percent of the population, increases risk by lowering the age of onset. Having this allele does not mean that a person will definitely develop AD; it only increases risk. Many people who develop AD do not have an APOE ε4 allele.

Researchers think that at least half a dozen other risk-factor genes exist for late-onset AD and are intensively searching for them. In 2007, they found another likely risk-factor gene called SORL1. When this gene is active at low levels or in an abnormal form, levels of harmful beta-amyloid increase in the brain. Beta-amyloid is a component of amyloid plaques, one of the hallmarks of AD. Interestingly, the SORL1 gene also was identified as a risk-factor gene for certain aspects of cognitive decline, suggesting that cognitive decline and AD may share at least one predisposing genetic factor.

Finding AD risk-factor genes is essential for understanding the very early biological steps that lead to the vast majority of AD cases and for developing drugs and other prevention and treatment strategies. Finding these genes also will help scientists develop better ways to identify people at risk of AD and determine how the genes may interact with other genes or with lifestyle or environmental factors to affect an individual’s AD risk.

The Search for AD Prevention Strategies

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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