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Midlife Fitness Associated with Decreased Dementia Later in Life

Rukovets, Olga

doi: 10.1097/01.NT.0000429369.31764.75
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Researchers tracked nearly 20,000 patients for about 25 years, and found that those individuals with higher levels of fitness at midlife were 36 percent less likely to develop all-cause dementia than those with the lowest midlife fitness levels.

Just in case there aren't already enough good reasons to exercise, here's one more: dementia prevention. New research, published in the Feb. 5 edition of Annals of Internal Medicine, reports that midlife fitness levels were associated with risk of dementia later in life. The study tracked nearly 20,000 patients for about 25 years, and found that those individuals with higher levels of fitness at midlife were 36 percent less likely to develop all-cause dementia than those with the lowest midlife fitness levels.

Lead study author Laura DeFina, MD, interim chief scientific officer at the Cooper Institute in Dallas, told Neurology Today that the purpose of the study was to address questions raised by the NIH State-of-the-Science Conference on Preventing Alzheimer's Disease and Cognitive Decline, which took place in April 2010. At the conference, they determined that “the studies up till now did not have sufficient evidence to promote any particular lifestyle changes to prevent dementia. That was because there were small sample sizes in other studies, they didn't have solid definitions of the exposures, they didn't have consistent definition of dementia, and the follow-up period was short. We felt that with our epidemiologic population database, we really could address these concerns.”



Our hypothesis, said Dr. DeFina, was that people who have higher midlife fitness would have a lower risk of dementia later in life. “It was a very large population of individuals who were generally well at their clinic exam, and who were followed for a mean of 25 years, thus we also were able to address the duration of follow-up issue. Then, finally, because of the preventative medicine clinic at Cooper, the patients are very well phenotyped,” Dr. DeFina said. “We decided to address this question [of lifestyle changes to prevent dementia] in a manner that met all the missing issues in the Consensus Conference.”



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The prospective, observational cohort study looked at Medicare data from nearly 19,500 community-dwelling, nonelderly adults who had a baseline fitness examination. Median age at baseline was 49.8 years. Fitness levels were assessed using the modified Balke treadmill protocol — a test in which subjects increase their heart rate to 80-90 percent of the maximal rate during exercise on a treadmill — between 1971 and 2009, and incident all-cause dementia was recorded using Medicare Parts A and B claims data from 1999 to 2009. Medicare data were obtained from the Centers for Medicare & Medicaid Services for participants who were aged 65 years or older by 31 December 2009 and eligible for Medicare between January 1, 1999 and December 31, 2009.

“The Medicare data have been validated in defining a diagnosis of dementia in other studies,” Dr. DeFina said. There were 1659 cases of incident all-cause dementia during a median follow-up of 25 years. Participants in the highest quintile (quintile 5) of fitness level had a lower hazard of all-cause dementia than those in the lowest quintile (quintile 1). Higher fitness levels in midlife were associated with a lower adjusted hazard of dementia (hazard ratio for quintile 5 vs. quintile 1,0.64).

“You might ask, how does fitness directly relate to physical activity? Well, it's a great marker for what we call habitual physical activity or being a regular exerciser. When people report their physical activity, it is known to be fraught with error. Fitness is objectively measured — it's done on a treadmill and has been measured the same way for forty years,” Dr. DeFina said. This objective measurement is another strength of our study, she added.

In our final result, she said, “the highest fit group versus the lowest fit group, had a thirty-six percent lower chance of developing all-cause dementia in later life.”

The study was funded by The Cooper Institute; University of Texas Southwestern Medical Center; the National Heart, Lung, and Blood Institute; and American Heart Association.

Future research needs, Dr. DeFina said, are two-fold. First, “we would need to look more at the physical activity variable and figure out if there is a threshold above which you must exercise to get this benefit. Then, it's also important to address this question [of fitness levels and dementia] in other population groups.”

On a more basic science level, she added, although some of the benefits of fitness on the brain are clear, there are other associations we haven't yet identified. Trying to figure out “the why” would be another important step, she said.

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This study represents a “critical step forward in research on the role of physical fitness on dementia risk,” Jason Hassenstab, PhD, assistant professor of neurology and psychology at the Washington University in St. Louis, said. “To have this type of quantitative measure of fitness in 20,000 patients is truly remarkable, and makes the results of an approximately 36 percent reduction in dementia among the fittest patients compared to the least fit even more convincing.”

Jeff Burns, MD, associate professor of neurology at Kansas University Medical Center, told Neurology Today, agreed. But, he noted, one of the study's limitations is that it looks at fitness and not exercise. “Fitness is a measure of how ‘fit’ somebody is, or how much work they can do at a point in time, and there are a lot of factors that influence that.” Exercise is just one of those factors, he continued, which the authors do a good job of discussing, “but people interpreting these studies may not understand that fitness is not equal to exercise. Other factors like genetics can influence fitness.”

So what does the association mean? “It may mean people who are more active and exercise might therefore have a higher fitness level, and thus have a lower risk of developing dementia. But it may also mean that there are some genetic, cardiac, or pulmonary factors related to fitness that are driving the outcome that healthier people in general will have better [dementia] outcomes in the long term.”

There are still lingering questions, Dr. Burns said. “What we still don't know is if we use exercise to boost fitness, does it result in better long-term brain outcomes and dementia prevention? These are additional data to suggest that exercise to boost fitness will possibly prevent dementia, but we still need more direct evidence.”

Large studies looking at exercise specifically and large, randomized control trials to understand the role of exercise in the brain and in long term outcomes related to the brain are necessary, Dr. Burns told Neurology Today. But, Dr. Hassenstab added, “it is unlikely that a randomized-controlled trial with exercise versus no exercise that could adequately answer the question of whether physical fitness could ‘cause’ a reduction in dementia symptoms is even feasible.”

Dr. Hassenstab said he had very few criticisms of the study, all of which were addressed by the authors in their paper. “First, the rate of dementia in the patients was rather low compared to established rates, especially at older age ranges…which may hamper the generalizability of the findings. Related to this, the patients were also middle to upper class, and likely highly educated. As the authors point out, it is unclear if these results would be the same in less educated and lower income populations.”

Since the diagnosis of dementia was based on Medicare data, he added, “which the authors correctly acknowledge is subject to some considerable variability, it could be that only the most severe cases of dementia were captured by Medicare data, and only patients who lived long enough to develop severe dementia are included.”

Finally, as noted by the authors, this is an observational study, and no statements about causality could be made, he said. Overall,“the strengths of this study far outweigh the minor weaknesses, and I congratulate them on an outstanding paper that confirms that increasing physical fitness is almost universally beneficial for most of us, and it's one of the few things regarding our personal health, along with diet and sleep habits, that we have direct control over,” Dr. Hassenstab told Neurology Today.



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What can clinicians do with these data? Most doctors in general get very little training on how to write an exercise prescription, Dr. DeFina said. It's hard to fit exercise counseling into an already short and busy visit, she acknowledged, but she noted that there's really good literature to suggest that if doctors encourage their patients, presuming they're safe to exercise, there's more adherence to the regimen.

“I would encourage doctors to consider familiarizing themselves with the ‘Physical Activity Guidelines for Americans’ [from the President's Council on Fitness, Sports & Nutrition] as well as the ‘Exercise Is Medicine’ link on the website from the American College of Sports Medicine. Both of those are geared at making the exercise conversation easier, and more practical.”

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•. DeFina LF, Willis BL, Berry JD, et al.The association between midlife cardiorespiratory fitness levels and later-life dementia: A cohort study. Ann Intern Med 2013;158(3):162–168.
    •. NIH State-of-the-Science Conference Preventing Alzheimer's Disease and Cognitive Decline:
      •. Physical Activity Guidelines for Americans, from the President's Council on Fitness, Sports & Nutrition:
        •. From the American College of Sports Medicine:
          •. Neurology Today's archives on exercise and cognitive status:
            © 2013 American Academy of Neurology