New Evidence That Exercise Preserves Cognitive Function

Susan Jeffrey

July 19, 2011

July 19, 2011 (Paris, France) — Two new studies support the idea that regular exercise can cut the risk for subsequent cognitive decline and dementia risk.

The studies were published online today in the Archives of Internal Medicine to coincide with presentation here of one of the reports at the Alzheimer's Association International Conference 2011. Both will appear in the July 25 issue.

Women's Antioxidant Cardiovascular Study

In the first study, researchers used data from the Women's Antioxidant Cardiovascular Study (WACS), a cohort of women with prevalent vascular disease or 3 cardiovascular risk factors.

"It's important to stress that individuals with cardiovascular disease or risk factors have substantially higher rates of decline," said lead author Marie-Noël Vercambre, PhD, from the Foundation of Public Health, Mutuelle Generale de l'Education Nationale in Paris, who presented the results here.

Dr. Marie-Noël Vercambre

This high-risk population is rapidly growing as the population ages, but little is known about how cognition might be preserved in this group, she said.

In WACS, a randomized trial of vitamin supplementation for secondary prevention, recreational physical activity was assessed at baseline in 1995-1996 and then again every 2 years. Between December 1998 and July 2000, 2809 of the women were assessed by telephone using a cognitive testing battery that included 5 tests of global cognition, verbal memory, and category fluency.

The assessment battery was administered 3 additional times over the next 5.4 years. The investigators then used multivariable-adjusted general linear models for repeated measures to compare annual rates of cognitive score changes across levels of total physical activity, as well as energy expended in walking, that had been part of the WACS baseline assessment.

They report a significant trend toward decreasing rates of cognitive decline with increasing energy expenditure (P < .001). Compared with women in the bottom quintile of total physical activity, significant differences in the rates of cognitive decline were seen for those in the fourth (P = .04) and the fifth (P < .001) quintiles.

"This was equivalent to the difference in cognitive decline observed for women who were 5 to 7 years younger," the authors noted.

Specifically, regularly walking was "strongly related" to slower rates of cognitive decline, they note (P = .003 for trend). However, significant associations were seen only with the top quartile of walking, with a minimum of 30 minutes of walking daily. However, the benefit was not limited to vigorous exercise.

"In summary, we found a clear and strong association between greater physical activity and reduced cognitive decline in our population of women with vascular disease or coronary risk factors," Dr. Vercambre concluded. Daily activity, at least a 30-minute daily walk at a brisk pace, "appears to delay cognitive aging by 5 to 7 years."

Senior author Jae Hee Kang, ScD, assistant professor of medicine at Brigham and Women's Hospital in Boston, Massachusetts, pointed out that even among those women who only walked and never did vigorous activity, such as running, most showed significant cognitive preservation.

"It has been projected that if interventions could delay the onset of Alzheimer's disease, the most common type of dementia, by even 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050," Dr. Kang told Medscape Medical News. "Based on our findings, we believe that moderate physical activity may be a very promising intervention for cognitive preservation, for both healthy aging populations and those at higher risk of cognitive impairment and dementia due to cardiovascular disease or risk factors."

Health ABC Study

Dr. Laura E. Middleton

In a separate report, Laura E. Middleton, PhD, from the Heart and Stroke Foundation Center for Stroke Recovery at Sunnybrook Health Sciences Center, Toronto, Canada, and colleagues used data from the Health, Aging and Body Composition (Health ABC) Study to examine this same question.

In this paper, they looked at the relationship between exercise and incident cognitive impairment using activity energy expenditure (AEE), an objective measure. Physical activity questionnaires usually focus on moderate or vigorous activity related to exercise but don't capture other aspects of activity, such as moving around the house or even fidgeting, the authors note.

Dr. Middleton and colleagues calculated AEE as 90% of total energy expenditure, assessed over 2 weeks using doubly labeled water, minus resting metabolic rate, measured using indirect calorimetry, in 197 men and women (mean age, almost 75 years) who had no mobility or cognitive impairments at study baseline in 1998-1999.

Cognitive function in participants was measured by using the Modified Mini-Mental State Examination (MMSE) at baseline and then at 2 or 5 years. Cognitive impairment was defined as a decline of at least 1.0 standard deviation (9 points) between baseline and follow-up.

The authors report that after adjustment for baseline MMSE scores and a variety of other factors, including demographic characteristics, fat-free mass, sleep duration, self-reported health, and diabetes mellitus, adults in the highest sex-specific tertile of AEE had lower odds of incident cognitive impairment than those in the lowest tertile (odds ratio, 0.09; 95% confidence interval, 0.01 – 0.79).

"The highest tertile actually had a 90% reduction in the rate of incident cognitive impairment compared to the lowest tertile of activity energy expenditure," Dr. Middleton told Medscape Medical News. "Even that middle group had a 70% lower rate of incident cognitive impairment compared to that lowest group."

There was also a significant dose-response relationship between AEE and the incidence of cognitive impairment (P = .05 for trend over tertiles).

In an interview, Dr. Middleton pointed out that there are now a number of studies that have confirmed this relationship, but the vast majority of those have used self-report of physical activity, an approach that carries inherent errors. Those with preclinical dementia may have issues with accurately recalling exercise, for example, and even those who have no such problems tend to overreport how much they exercise.

The other issue with self-report is that it doesn't capture activity that is not actual exercise, such as housework, "and in older adults that type of activity makes up a fairly large portion of your total physical activity, especially in someone who doesn't do purposeful exercise."

When they did this comparison using only self-report, there was still a relationship, she notes, but it was much clearer using the objective evidence of total energy expenditure.

This also suggests a real role for the less intense activity captured by the AEE measure in preventing cognitive impairment, Dr. Middleton adds. "So it indicates that it's not only important to run, but it's also important to just move during the day."

"Our study provides new evidence that objectively measured total daily activity, as measured by energy expenditure, is associated with a reduced incidence of cognitive impairment in older adults," the authors conclude.

The relative contribution of overall activity vs vigorous or light activity should be the focus of future research, they add. "We are optimistic that even low-intensity activity of daily living may be protective against incident cognitive impairment."

Some of the same researchers on this report also presented data July 19 here at the meeting and simultaneously published them in Lancet Neurology: They reported a projected estimate based on published studies worldwide that half of the cases of Alzheimer's disease are potentially attributable to 7 risk factors. A sedentary lifestyle was 1 of these. They also estimated that a 10% to 25% reduction in these 7 risk factors could potentially prevent as many as 3 million cases of Alzheimer's disease worldwide and up to almost half a million cases in the United States alone.

At a press conference here, lead author on the Lancet Neurology report and coauthor on this current paper, Deborah Barnes, PhD, from the Department of Psychiatry at San Francisco Veterans Affairs Medical Center and the University of California San Francisco School of Medicine, said they estimate that the population attributable risk of a sedentary lifestyle is 13% worldwide, and higher than that in the United States, at about 21%. "So about 1 in 5 Alzheimer's cases are attributable to a sedentary lifestyle," she said.

It has been said that some people are more afraid of Alzheimer's disease than of death, Dr. Barnes told Medscape Medical News. "So in some ways I hope if the evidence keeps mounting about how bad it is to be sedentary, that one of those things will help motivate people to change behavior," she said. "But I think we need to start using behavioral change models, psychological models to figure out how to get people to change. We need to fund that research and then start implementing it, but I really think it will have to come from the government."

Informing Practice

In an editorial accompanying the Archives of Internal Medicine studies, Eric B. Larson, MD, MPH, Group Health Research Institute, Group Health Cooperative, in Seattle, Washington, says he believes the findings in these papers can "inform practice and the advice we give our aging patients.

"We can tell them that ongoing maintenance of physical activity is definitely worthwhile and likely of increasing benefit as they advance into old age," Dr. Larson writes. "For prevention at all ages, there is growing evidence that vascular risk likely plays a role and is, of course, modifiable."

Clinical research, he says, "should now be increasingly directed to the development of effective ways to change behavior to promote habitual physical activity, ideally throughout life but especially in middle and late life."

Other areas where better understanding may lead to "actionable discoveries" include the extent to which other risk factors might reduce late-life cognitive decline and dementia risk, the relationship of known risk to newly discovered growth factors, such as brain-derived neurotrophic factor, and the potential that widespread use of anticholinergic drugs, "an all too common 'environmental' exposure, might have more than transient effects on late-life cognition," he writes.

"Most urgent of all for research is to develop and test programs that promote ongoing physical activity, especially in late life," Dr. Larson concludes.

The study by Dr. Vercambre and colleagues was supported by grants from the National Institutes of Health. Dr. Vercambre's postdoctoral fellowship is supported by the Fondation Bettencourt-Schueller. Dr. Kang, a coauthor of the study, is the recipient of a Scientist Development Award from the American Heart Association. The authors have disclosed no relevant financial relationships. The study by Middleton and colleagues was supported by the National Institute on Aging as well as other agencies through grants to coauthors. The authors have disclosed no relevant financial relationships. Dr. Barnes has disclosed no relevant financial relationships. Dr. Larson is supported by a grant from the National Institute on Aging.

Arch Intern Med. Published online July 19, 2011. Abstract for Vecambre study Abstract for Middleton study

Lancet Neurol. Published online July 19, 2011.

Alzheimer's Association International Conference (AAIC) 2011: Abstract O3-06-05. Presented July 19, 2011.

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