Susan Jeffrey

July 12, 2010

July 12, 2010 (Honolulu, Hawaii) — A new analysis from the Framingham Study suggests moderate to heavy physical activity is associated with a reduced risk for dementia during more than 20 years of follow-up.

Compared with those with lower levels of activity, participants reporting moderate to heavy physical activity had a 45% lower risk for dementia over time.

"A reduced risk of dementia may be one of the additional health benefits that can actually be derived from maintaining at least moderate physical activity," lead author Zaldy Tan, MD, MPH, from the Brigham and Women's Hospital, VA Boston, and Harvard Medical School, in Massachusetts, concluded.

Dr. Zaldy Tan

Dr. Tan presented the results here at the Alzheimer's Association International Conference on Alzheimer's Disease 2010.

Divergent Findings

Previous findings from the Framingham original cohort have already shown moderate or high physical activity to be associated with a number of positive outcomes, including a reduced risk for stroke and cardiovascular disease, higher high-density lipoprotein cholesterol levels, a reduced risk for colon cancer, and lower overall rates of mortality, Dr. Tan noted.

"Interestingly, while there are many potentially modifiable risk factors that have been linked with Alzheimer's disease and dementia, physical activity seems to be one that is fairly consistent in being shown to be related to the risk of dementia," he said. A recent review showed that 20 of 24 population-based studies showed a link between physical activity and reduced risk for dementia or cognitive decline.

Still, Dr. Tan added, the evidence is not entirely consistent. "There are some studies that seem to show no relationship between physical activity and dementia," he said, including the Bronx Aging Study, the Religious Orders Study, and the Radiation Effects Research Foundation Study.

The present investigation then looked at this relationship in the Framingham Study original cohort — a longitudinal community-based sample of 5209 men and women living in Framingham, Massachusetts, that has been evaluated every 2 years since 1948 for cardiovascular risk factors. A dementia study began in 1975, with the administration of a battery of neuropsychological tests, and 3349 of the original participants free of dementia at that time were enrolled and subsequently assessed every 2 years.

In 1986 to 1987, a survey was introduced to calculate a daily physical activity index (PAI) based on estimated hours spent performing physical activity and weighting each activity by an assigned caloric equivalent. The study population for this current study, then, includes those participants who were both free of dementia in 1986 and 1987 and who had a PAI available, for a total of 1211 Framingham study participants.

Participants were asked to estimate the amount of time they spent in various activities, ranging from sleep and sedentary states; to slight physical activity, such as standing and walking; to moderate activity, including things like housework, climbing stairs, or light sports like golf or bowling; to heavy activity, including heavy household work or more intensive exercise such as jogging.

During a mean follow-up of 9.9 ± 5.5 years, ranging from 0 to 21 years, 242 participants developed dementia. Of these, 193 cases were Alzheimer's disease, defined according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition/National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria.

"What we found is that participants who spent at least 1 hour per day of moderate or heavy physical activity had a 45% lower risk of developing dementia," Dr. Tan said.

Risk for All-Cause Dementia With Moderate to Heavy Physical Activity vs Low Activity

Outcome Hazard Ratio 95% Confidence Interval P
All-Cause Dementia 0.55 0.37 - 0.81 .003

Furthermore, those with a PAI in the lowest quintile had a 45% higher risk for dementia vs the highest quintile.

Risk for All-Cause Dementia for Highest Quintile of PAI vs Lowest

Outcome Hazard Ratio 95% Confidence Interval P
All-Cause Dementia 1.45 1.06 - 1.98 .021

Kaplain-Meier curves showed that the difference between groups could be seen as early as at 2 years of follow-up, and the curves continued to separate over time.

Similar results were seen when the researchers looked at the risk for Alzheimer's disease alone, but the association was no longer statistically significant, Dr. Tan said. Adjustment for apolipoprotein E4 status did not change the relationship, he added.

However, stratification by sex showed that the beneficial effect of exercise was largely seen in men. Still, he said, "I don't think the gender differences mean that females do not benefit from exercise." Although there are several possible explanations, he added, "I suspect the finding may be just due to the fact that females of the generation recruited for the original cohort perhaps did not have as many occupational and social activities as men did at that time."

Physical activity is a potential preventive factor that would likely take years to manifest its effect, "so the fact that we've followed them for over 20 years, this is something that suggests that long-term physical activity actually works," Dr. Tan noted. The mechanism is not clear, he added, but reduction of cardiovascular risk factors such as hypertension, or the release of neurotrophic factors, are possible effects.

Stronger Evidence

William Thies, PhD, chief medical and scientific officer at the Alzheimer's Association National Headquarters in Chicago, Illinois, acted as moderator of the press conference here. He pointed out that a National Institutes of Health State of the Science Conference in April this year concluded that the literature on potential preventive factors was lacking in many respects.

Dr. William Thies

"So we selected papers this morning really to respond to that at least partially, by picking papers that come from some of the biggest studies in the United States that have been responsible for defining many of the risk factors for other diseases," Dr. Thies said.

The strength of this paper in particular is that, "it comes from a really big, really good, historically dependable study" — the Framingham Study.

"The part of it that's a little hard to interpret is they got a sort of a dose-response curve, but they got their major effects at the highest levels of exercise. That doesn't necessarily agree with what's happened in other studies in other diseases as well, so I think that's something we should look at carefully," Dr. Thies told Medscape Medical News. "Because if you really look at the hazards, the only real hazard of exercise is overuse injuries, so you'd want to be a little careful of recommending everybody over 70 starts running marathons."

In addition, self-report is "notoriously error-prone really for anything — diet, exercise, alcohol intake."

Still, he said, "From a personal standpoint, there's no doubt that exercise results in public health good. There's no possibility that recommending exercise can be a bad thing, and I'm perfectly comfortable with that being one of our primary recommendations."

The Framingham Heart Study is funded by the National Heart, Lung, and Blood Institute; the National Institute on Aging; and the National Institute of Neurological Diseases and Stroke. The authors have disclosed no relevant financial relationships.

Alzheimer's Association International Conference on Alzheimer's Disease 2010: Abstract 01-01-03. Presented July 11, 2010.

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