Possible protective factors

| January 1, 2007

Possible protective factors

Although no treatment is available to prevent or cure Alzheimer's, certain factors may lower your risk for it. For now, it's premature to recommend taking nonsteroidal anti-inflammatory drugs or statins to prevent Alzheimer's, but research is under way to test the effectiveness of these and other substances for preventing or delaying its onset.

Nonsteroidal anti-inflammatory drugs

Nine studies suggest that using pain relievers such as ibuprofen (Advil, Motrin, and others) or naproxen (Aleve) can lower the risk of developing Alzheimer's disease. These medications, called nonsteroidal anti-inflammatory drugs (NSAIDs), block enzymes that promote inflammation, pain, and fevers. Scientists suspect that NSAIDs protect against Alzheimer's by reducing brain inflammation that may occur during the disease's development. In addition, there is experimental evidence that ibuprofen decreases the production and accumulation of beta-amyloid.

People who reported taking ibuprofen and other nonaspirin NSAIDs lowered their risk of developing Alzheimer's by as much as 60% in a large 16-year study involving 1,828 participants, which was conducted by researchers at Johns Hopkins University and the National Institute on Aging.

But it's too early to recommend NSAIDs for Alzheimer's prevention. Because all nine studies mentioned were observational, their findings are not considered conclusive. In addition, NSAID medications have a variety of side effects; for example, frequent use of naproxen and celecoxib (Celebrex) may increase the risk of heart attack or stroke. Concern about safety led the National Institutes of Health to suspend enrollment in a large study evaluating the potential of these drugs to prevent Alzheimer's disease. However, the researchers are still following people who enrolled in the study before recruitment was suspended to learn whether the drugs can safely reduce the risk of Alzheimer's.

Statins

Several studies have found that statins, a commonly prescribed class of cholesterol-lowering drugs, may lower the risk for Alzheimer's disease. One 2000 study in the Archives of Neurology found that statins cut the risk of developing Alzheimer's disease by as much as 73%.

Such preliminary findings have paved the way for future research to test the use of statins in preventing or slowing the progression of Alzheimer's disease. A trial conducted as part of the Alzheimer's Disease Cooperative Study, with funding from the National Institute on Aging, is under way to determine whether statins can slow the progression of the disease among patients with mild to moderate Alzheimer's.

Alcohol consumption

Epidemiological studies have found evidence that moderate alcohol consumption reduces risk for Alzheimer's disease. A 2003 study in the Journal of the American Medical Association, for example, found that people over age 65 who drank up to one alcoholic beverage a day had about half the risk of Alzheimer's disease as nondrinkers. And a study reported in 2005 by researchers in New York found that resveratrol, a compound in red wine, broke down beta-amyloid in the laboratory — suggesting that red wine in particular may be protective. But further study is needed. In the meantime, experts do not recommend drinking alcohol to fend off Alzheimer's disease. If you do drink, limit your consumption to two drinks a day for men and one drink for women. Heavy drinkers in the JAMA study cited above had a 22% higher risk than the nondrinkers.

Education

Epidemiologists have found that a disproportionate number of people with Alzheimer's disease are poorly educated. The reason is unknown, but it raises two intriguing questions. Does education produce biological changes in the brain, actually stimulating neurons to grow and form more synapses? Or is it socioeconomic status, rather than educational level, that makes a difference?

If education causes beneficial changes in brain structure, it's possible that an educated person could lose a certain number of neurons without a noticeable change in mental ability, while an uneducated person who lost the same number would suffer mental deficits. In effect, education might delay the onset of symptoms.

Research supports this theory. Imaging studies of people with the same degree of Alzheimer's symptoms have shown that the most educated people had less brain activity and blood flow to the brain than the least educated people. In other words, it took more brain damage to cause symptoms in the people who'd had the most schooling. Autopsies of participants in an ongoing (longitudinal) study show that among people who had the same degree of brain damage from Alzheimer's, the most educated people experienced the least severe symptoms. Socioeconomic factors may be important, too. People who grow up in poverty are also likely to be poorly educated. But they might also have dietary deficiencies or exposures to more environmental toxins that would leave them vulnerable to Alzheimer's disease later in life. The interaction among these social, economic, and educational factors is complex, further muddying the waters.

Many researchers now believe that education level is less important in maintaining a healthy brain than the habit of staying mentally active as you age. A 2002 study reported an association between frequent participation in cognitively stimulating activities (such as reading, doing crossword puzzles, visiting museums) and a reduced risk for Alzheimer's.

Enriched environment

Taking the research on intellectually stimulating activities one step further, scientists have been looking at the notion of "environmental enrichment" — living in a place with a lot of interesting things to do — and how this might benefit the brain. Some intriguing findings have emerged from research involving laboratory mice. Researchers have found, for instance, that mice raised in cages with running wheels, colorful tunnels, and other toys exhibit better memory function than mice raised in bare cages. What's more, autopsy studies have revealed that the mice raised in enriched environments also have "enriched" brains, with more synapses per neuron and more branches extending from their neurons.

A 2005 study in Cell looked specifically at whether environmental enrichment might prevent Alzheimer's disease in mice bred to develop the disease. Sure enough, by the time they reached old age, the mice raised from birth in the cages with plenty of toys had far lower levels of beta-amyloid peptide and amyloid deposits in their brains — the physical signs of Alzheimer's disease — than mice raised in a bland environment. The researchers also noticed that environmental enrichment increased the expression (activity) of genes involved with memory, neuron growth, and the generation of blood vessels to the brain. This evidence suggests that an enriched environment can change the brain in ways that may preserve memory and prevent Alzheimer's disease.

As far as people are concerned, there may never be data available to quantify the health advantages of enriching one's days with good books to read, musical instruments to play, computers as learning tools, excursions to the theater, and travel to interesting destinations. But stimulating activities make for a full life, and they may keep your brain healthy, too.

Exercise

Exercise offers an impressive array of health benefits. It helps prevent heart disease and type 2 diabetes; lowers the risk for high blood pressure, colon cancer, and breast cancer; and helps relieve insomnia, anxiety, and depression. But that's not all. Several studies suggest that exercise might also help ward off Alzheimer's disease and other forms of dementia.

One study of 2,000 people, published in 2005 in Lancet Neurology, found that those who exercised during midlife for 20 to 30 minutes twice a week were at least 50% less likely to develop Alzheimer's disease or another dementia in the following decades than people who were sedentary. Earlier, a Canadian study involving 9,000 people over age 65 found that regular exercise cut the risk for cognitive impairment by 37%. Studies of seniors in the United States and the Netherlands have yielded similar results.

Just how exercise may prevent Alzheimer's disease is unclear, but research on mice offers a clue. A 2005 study in the Journal of Neuroscience reported that mice that used their treadmills most often not only proved better able to learn how to get around test mazes than others, but also had fewer deposits of beta-amyloid in their brains. And in the environmental enrichment study described previously, the lowest levels of beta-amyloid and amyloid deposits were found in the most active mice, who spent the most time running and climbing on the toys placed in their cages.

Diet

Just as some dietary fats can protect against cardiovascular disease and others can increase the risk, several studies suggest that the same is true for Alzheimer's disease. Diets that are high in damaging saturated fats and trans fats appear to increase the risk of Alzheimer's disease, whereas diets that are high in heart-healthy monounsaturated and polyunsaturated fats appear to decrease the risk. Saturated fats come mainly from meat and dairy, and trans fats from processed foods made with partially hydrogenated oils. Sources of healthy unsaturated fats include nuts, olive oil, canola oil, and fish.

A 2003 study in Archives of Neurology, for example, followed 815 cognitively normal people ages 65 and older for four years. By the end of the study, the people who ate the most saturated and trans fats were twice as likely to have Alzheimer's disease as the people who consumed the least. However, the people who ate the most mono- and polyunsaturated fats were 70% less likely to develop Alzheimer's than the people who ate the least of these healthy fats.

Several other studies have found a benefit specifically from eating fish that is rich in omega-3 fatty acids, a type of polyunsaturated fat. Salmon, mackerel, and sardines are good sources. One 2005 study in Neurology found that people who ate fatty fish more than twice a week had a 28% lower risk of dementia and a 41% lower risk specifically of Alzheimer's disease than people who ate fatty fish less than once a month. This study did not find a protective effect from eating lean fried fish.

Many unanswered questions about diet remain, however. It is unclear whether fish oil supplements are also beneficial. If fish does reduce the risk of various types of dementia, it could be because of its protective effect against cardiovascular disease. But fish may also benefit the brain directly. In a 2005 study reported in Neurobiology and Aging, researchers found that a diet supplemented with omega-3 fatty acids limited the accumulation of beta-amyloid in the brains of mice bred to develop Alzheimer's disease. Whether people would enjoy the same benefit remains to be seen, but in the meantime, it can't hurt to replace the unhealthy fats in your diet with healthy ones.

Estrogen

For many years, doctors believed that hormone therapy during and after menopause might protect women from Alzheimer's disease: A handful of studies suggested that women who took estrogen were less likely to develop this type of dementia than those who didn't take supplementary hormones. But a large clinical trial, the Women's Health Initiative Memory Study (WHIMS), challenged this longstanding dogma.

WHIMS researchers reported in 2003 that women who took combination estrogen-progestin therapy were twice as likely to develop dementia as women who did not use hormones. The following year, the researchers revealed that estrogen therapy by itself also increased the risk. This study and others also found that women as young as 50 who used estrogen therapy, with and without progestin, were more likely to have strokes, which can cause dementia. As a result of such findings, menopausal hormone therapies now carry warning labels stating that they increase the risk of dementia.

Despite the negative findings about hormone therapy as a preventive measure, some early evidence suggests that hormone therapy or estrogen-like medications may somewhat improve memory and other cognitive functions in women with Alzheimer's disease (see "Estrogen therapy").

Review Date: 2007-01-01

Harvard Medical School does not endorse products or services.