WASHINGTON, DC—Adequate levels of social and mental activity; a diet that includes fruit and vegetable juices, folic acid, and moderate alcohol consumption; and exercise were among lifestyle interventions linked to a reduction in cognitive decline, according to the results of studies presented at the Alzheimer’s Association International Conference on Prevention of Dementia. The following reports detail those and other related findings.

SOCIAL AND MENTAL ACTIVITY

Among 2,513 elderly Japanese-American men ages 71 to 92 who were followed since 1965 as part of the Honolulu-Asia Aging Study, decreased social activity from midlife to late life led to a significant increase in risk of dementia and smaller hippocampal volume, reported Jane S. Saczynski, PhD, and colleagues. Indicators of social connectivity assessed in 1968 (midlife) included marital status, living arrangement, group participation, social events with coworkers, and confiding in coworkers; when social activity was assessed in 1991 (late life), items pertaining to coworkers were replaced with contact with close friends and relatives. MRI was performed in 1996 on 480 participants. “Our findings suggest that interventions in late life need to consider that the dementing process may already be modifying social engagement,” said Dr. Saczynski, a fellow at the NIA in Bethesda, Maryland.

TWIN RISK

Having had a stroke, periodontal disease earlier in life, and fewer years of education constituted a pattern of risk factors that appears to explain why one monozygotic twin—and not the twin sibling—develops dementia. Margaret Gatz, PhD, a Professor at the University of Southern California, Los Angeles, and Foreign Adjunct Professor in Medical Epidemiology at the Karolinska Institute, Stockholm, and colleagues evaluated participants in the Study of Dementia in Swedish Twins, which followed 109 pairs of identical twins from the Swedish Twin Registry, in which one twin had dementia and the other did not.

The goal of the study was to find factors that allowed the prediction of “which is the demented twin in these twin pairs,” Dr. Gatz said. “In deciding which risk and protective factors to test, we were guided by both conceptual and practical considerations. The practical consideration is this: When the twins joined the Swedish Twin Registry in 1967, they filled out a lot of questionnaires about health, about lifestyle, and this gives us information [and] ways to measure potential risk and protective factors that occurred well before dementia onset. The person answering the questions had no bias about whether he or she was the demented twin; the downside to the availability of these data is that we are limited to what items were on that survey.”

Dr. Gatz said to test factors that had a theoretical basis, the researchers included level of education and people’s description of participating in leisure activities that might be mentally engaging. “We were also interested in how health status at a young age might affect brain development—differences that might already set people on a different life course from very early in life,” she said. “It’s been shown that differences in inflammatory load early in life can be associated with worse health trajectories later on, and differences in life span. The indicator that we had for exposure to infection or inflammatory burden was periodontal disease, which was measured in 1963. Another factor that might affect early brain development is nutrition, and for this reason we looked at adult height; other people have looked at limb length, but we didn’t have that information available.

“We also wanted a cardiovascular indicator, and we were able to link our information to the National Inpatient Discharge Registry; we identified people who had had stroke, and we also had in the questionnaires information about level of physical exercise, which, of course, is also thought about as a cardiovascular protective factor,” said Dr. Gatz.

“We found that three of these factors were statistically significant in predicting which was the demented twin: history of stroke, which increased risk sixfold; periodontal disease, which increased risk fourfold; and there was also a significant difference in level of education.” No differences were observed for the other variables, she noted.

“Importantly, these risks were not highly correlated,” Dr. Gatz said, “so in one twin pair, one might have higher mentally stimulating activities than the other but have no difference on any of the other factors. In another twin pair, one might have had a stroke, and the other not, and have no difference on the other activities. There’s no single factor that enabled differentiating the twin pairs, and if we take all of these factors together and ask, How well can we predict which is the demented twin? we also find ability to predict is different with different types of dementia.”

For example, in twin pairs where the individual with dementia was diagnosed with Alzheimer’s disease, only one third of the cases could be predicted; the one predictor that was significant was history of periodontal disease. However, Dr. Gatz reported better success in predicting other dementias. “We could correctly predict two thirds of the time which was the demented twin, and this was based on the factors I’ve already mentioned from the overall analysis: history of stroke, periodontal disease, years of education. There was also a significant difference in level of physical exercise, with the twin who was not demented reporting more physical exercise earlier in life, and the mentally stimulating leisure activities index also contributed significantly to the prediction,” she noted.

“The implication of these findings is that there are indeed exposures and experiences—lifestyle habits—that can influence risk of dementia; in particular, this would point to cardiovascular risk factors and to inflammatory load. And, importantly, good brain health, as suggested by these results in old age, reflects influences that began much earlier in the life span. At this point, these results give us some suggestions for moving ahead and testing all these things further but are quite suggestive and supportive in the idea of thinking of good brain health as a life span commitment,” Dr. Gatz concluded.

POLYPHENOLS

Polyphenols in fruit and vegetable juices may delay onset of Alzheimer’s disease, reported Amy Borenstein, PhD, MPH, Professor of Epidemiology and Biostatistics at the University of South Florida, Tampa. Of 1,836 older Japanese-American men and women from the Kame Project in Seattle—in which participants were dementia-free at study onset between 1992 and 1994 and followed for up to nine years—the results of a semiquantitative food frequency questionnaire found that those who drank fruit or vegetable juices at least three times a week had a 75% reduced risk of developing Alzheimer’s disease compared with participants who drank these juices less than once a week. No benefit was seen from dietary or supplemental vitamin E, C, or betacarotene. Of those studied, 170 cases of dementia were diagnosed, 81 of whom met the criteria for probable Alzheimer’s disease.

“One of the questions you may ask is, If people who drink juices often have a four times lower risk of developing Alzheimer’s disease, could it be because there is a difference between juice drinkers and non–juice drinkers, in terms of their other characteristics?” Dr. Borenstein said. “For example, juice drinkers may be more healthy; they may exercise more; they may be more highly educated; so we’ve controlled for these things … and the main finding became actually stronger.”

Because the questionnaire asked about any fruit and vegetable juice consumption, specific juices could not be identified. A trial in which people are randomized to drink different kinds of juices is needed to determine for how long juices should be consumed and whether risk is reduced over time, she concluded.

FOLIC ACID SUPPLEMENTATION

Jane Durga, PhD, of Wageningen University, the Netherlands, presented the effect of folic acid supplementation on cognitive function in older adults. In a double-blind trial, 818 men and postmenopausal women ages 50 to 70 were randomized to receive 800 µg/day folic acid—approximately twice the US recommended daily allowance—as an oral supplement or placebo for three years. At screening, participants’ baseline plasma concentration of homocysteine was at least 13 mmol/L; and of vitamin B₁₂, at least 200 pmol/L. Outcome measures were five cognitive domains scored on a standardized test.

Dr. Durga said the participants were selected “because they had slightly elevated levels of homocysteine. Assuming that homocysteine is a causal risk factor, we would hope that these people would show the greatest benefit of folic acid supplementation.” Most participants scored well on the Mini-Mental State Examination; only seven scored below 24.

After three years, serum folate levels increased fivefold in the study group compared with the placebo group, and plasma total homocysteine concentrations decreased by 26% compared with homocysteine concentrations in the placebo group. “Memory, simple speed, and information processing speed significantly improved,” Dr. Durga said. When treatment effect was divided by age, after adjustment for gender, education, and treatment, “people on folic acid scored as if they were five years younger and, for the simple and information processing speed, it was two years.”

She concluded, “The most important point I want to make is that there is not enough evidence to suggest that those with age-related cognitive decline will eventually develop dementia, so although this does prevent age-related cognitive decline, whether it’s the magic bullet for dementia prevention or therapy still remains to be determined.”

INHERITED RISK?

The adult children of persons with Alzheimer’s disease have an increased prevalence of the apolipoprotein E (APOE) ε4 allele, making them a high-risk group for developing Alzheimer’s disease, according to Mark A. Sager, MD. Dr. Sager, Director of the Wisconsin Alzheimer’s Institute, University of Wisconsin-Madison, and his colleagues studied 471 adult children of persons with Alzheimer’s disease. The participants, ages 40 to 65, underwent neuropsychological testing, APOE genotyping, and health assessments. The mean age of cohort members was 53; 71% were women; and 45% had an APOE ε4 allele. Preliminary results showed that when age, education, and gender were controlled for, higher levels of homocysteine were associated with lower verbal memory scores. Exercise and moderate alcohol consumption were positively correlated with performance on several cognitive measures.

“Our finding that the neurocognitive performance of APOE ε4 carriers and noncarriers is not different at baseline suggests that this is an ideal population to follow longitudinally as cognitive changes develop in future years,” Dr. Sager said. “The finding that lifestyle and vascular risk factors are correlated with baseline cognitive performance raises the question about their influence on the future risk of developing Alzheimer’s disease.”

EXERCISE INTERVENTION

Hideaki Soya, PhD, of the University of Tsukuba in Japan, assessed the effect of two types of exercise intervention on cognitive function. One hour of exercise was offered up to six times a month in a community-based program, and a home-based program included 10 to 60 minutes of exercise daily. To encourage compliance, the program was designed to be simple, enjoyable, and of mild intensity. Calisthenics, or “Furfuri-Guppa,” were combined with singing a song. Memory function, peak torque of leg extension, aerobic capacity, reaction time, and daily energy expenditure were measured in 265 participants with either normal cognitive function or mild cognitive impairment.

After one year, 70% of subjects showed significant improvement in memory function, as measured on the 5-Cog Test. A significant correlation was found between the memory function score and energy expenditure through Furfuri-Guppa. “It is of particular interest that the rate of memory improvement was greater in participants with mild cognitive impairment than in cognitively normal subjects,” Dr. Soya said. “Our program may have the potential to delay cognitive decline and improve the physical fitness of elderly people, including people with mild cognitive impairment.”

NR

—Debra Hughes

Return to table of contents