Lifestyle, Diet May Help Stave Off Alzheimer’s

by Tom Valeo

September 25, 2008

Several Alzheimer’s drugs may be approved in a few years, but research suggests some simple lifestyle changes now may also help ward off the disease.

Clinical trials in progress suggest that several new treatments for Alzheimer’s may emerge from the pharmaceutical pipeline within a few years. They may not provide a “magic bullet” that will cure or prevent the disease, but preliminary results suggest they will help control the symptoms. But in the meantime, some simple lifestyle choices may help people stave off the disease, suggest several studies reported at the Alzheimer’s Association’s recent International Conference.

Some of the findings are obvious, but others are downright perplexing.

For example, staying married seems to be linked with a degree of protection from Alzheimer’s. Krister Hakansson of Sweden’s Karolinska Institute says his numbers point to a strong correlation, though he can only guess at the reason.

“The risk is doubled for people without a partner, and it’s tripled for those who live alone for a longer time,” he says. “Those who are widowed in midlife and never remarry face a sevenfold increase in their risk for Alzheimer’s disease.”

But for some, it can get even worse. ApoE, a gene located on chromosome 19, codes for proteins that carry cholesterol in the blood. One of the three variants, ApoE4, is the strongest genetic risk factor for Alzheimer’s. Those who carry one copy of the gene face a risk for late-onset Alzheimer’s three times greater than non-carriers. Those who carry two copies are 10 times as likely to develop the disease.

Hakansson found that widows and widowers who lose a spouse early in life and do not remarry and who also carry the gene for ApoE4 face a 25-fold increase in their risk for Alzheimer’s disease.

Hakansson bases his finding on relatively small numbers. Out of 1,432 people he studied, only 139—less than 10 percent—developed some degree of cognitive impairment, and only 48 developed Alzheimer’s. But the correlations he found within this sample were strong enough that he thought he had miscalculated.

“I couldn’t believe what I was seeing,” he says.

So how could losing a spouse, especially early in life, increase risk of dementia so many years later?

“Maybe traumatic loss early in life destabilizes the psychobiological system,” Hakansson suggests, although he admits he is only speculating.

Good news for ruminators

Another perplexing study, by Israeli researchers, suggests that rumination—the tendency to reflect obsessively about one’s problems—may decrease the risk of Alzheimer’s.

This is the opposite of what Ramit Ravona-Springer of Sheba Medical Center expected to find when she and her colleagues began their research using data from about 9,000 Israeli civil servants. Rumination is considered a neurotic tendency that increases stress, and many studies have linked stress to dementia.

“Personality traits can be risk factors for the incidence of dementia,” she says. “We expected rumination to increase the risk of dementia.”

Instead, dementia rates were 50 percent higher among those who said they seldom engaged in rumination.

“Ruminating over problem situations may be a form of cognitive activity,” Ravona-Springer says. “Intellectual activity in midlife has been demonstrated to confer protection [against dementia].”

Food for thought

If ruminating has a protective effect, researchers say it may be best done with a cup of coffee. Caffeine can reverse cognitive impairment, at least in aged mice, says Gary W. Arendash of the Byrd Alzheimer’s Institute in Tampa, Fla.

By giving the mice a caffeine dose equivalent to what a human would receive in five cups of coffee, Arendash lowered the level of toxic beta-amyloid in the animals’ brains, reduced brain inflammation and reversed cognitive impairment.

“After four to five weeks, these mice displayed memory ability equal to normal mice,” Arendash says. “Even the plaques of Alzheimer’s disease are reduced after two months of caffeine treatment in aged AD mice.”

He is now conducting a similar trial involving several dozen humans to see if their blood levels of beta-amyloid also drop. “With less soluble A-beta in the brain, neurons could function more normally,” he says.

Brain inflammation accompanies Alzheimer’s disease and inflicts its own form of damage, but resveratrol, the widely touted antioxidant found in red wine, suppresses the inflammation, Johannes C.M. Schlachetzki of the University of Freiburg and colleagues reported at the conference. However, the compound did not stimulate the brain’s microglial cells to remove toxic beta-amyloid from the brain, as the researchers had hoped.

Resveratrol also alleviates dysfunction in mitochondria, the power plants of cells, which precedes the symptoms of Alzheimer’s disease by decades in some patients, according to Gary E. Gibson of the Weill Medical College of Cornell University and his colleagues. They found that mice genetically engineered to produce human-type brain plaques formed fewer of them when given resveratrol. And a Korean group demonstrated that the antioxidative properties of resveratrol helped limit a toxic process induced in the brain of Alzheimer’s mice.

Another compound, ginkgo biloba, long used as an oral herbal treatment to enhance memory, seems to reduce the loss of brain volume in people 85 and older, according to a report by Jeffrey A. Kaye and colleagues at the Oregon Health and Science University.

Working it out

Meanwhile, a new report by Jack-Christopher Cossec and colleagues at the National Center for Scientific Research (CNRS) in France adds to the ongoing debate over statins’ effect on Alzheimer’s. Cholesterol appears to promote the production of toxic beta-amyloid 42, and the researchers found a 66 percent increase in beta-amyloid in cells overloaded with cholesterol. In cells depleted of the chemical, however, amyloid decreased 32 percent in cells.

Metabolic syndrome—an unhealthy combination of high blood pressure, high cholesterol, high triglycerides and high blood glucose—seems to increase the risk of dementia, says Matheus Roriz-Cruz and his colleagues at Federal University of Rio Grande do Sul State in Brazil. However, metabolic syndrome contributes to vascular disease, which constrains the flow of oxygen to the brain and promotes dementia. That might explain the correlation, he says.

That brings up the old standby, exercise, which does seem to provide protection against dementia, says Robyn A. Honea of the University of Kansas Medical Center.

She and her colleagues found that two brain areas linked to memory loss and Alzheimer’s shrink less among the physically fit. “This suggests that maintaining cardiorespiratory fitness may modify Alzheimer’s disease–related atrophy,” she says.

Nicola T. Lautenschlager of the University of Western Australia and colleagues also reported on a randomized clinical trial that showed that adults with memory problems who engaged in an additional 110 minutes of physical activity a week over six months improved their score on a test that measures cognitive impairment by 1.1 points, compared with those who remained sedentary. This improvement persisted when the exercisers were tested again at 12 months and 18 months after beginning the program.

“To our knowledge this is the first randomized, controlled trial to confirm a benefit of exercise on cognitive function in older adults with memory complaints,” the authors concluded in their report. “Adoption of similar programs in the community could represent an affordable and readily available intervention to decrease the burden of cognitive impairment in older people.”