Physical Activity May Preserve Memory in Seniors

Damian McNamara

January 23, 2019

Adding to the growing body of evidence that physical activity has a positive impact on cognition, new research shows that these benefits may even extend to older adults with blood and brain biomarkers of Alzheimer's disease (AD) and other common age-related brain pathologies.

More total daily activity and better motor abilities were each associated with a boost in cognitive reserve, investigators report.

"Our research team measured levels of physical activity in study participants an average of 2 years prior to death and then examined their brain tissue after death and found that moving more may have a protective effect on the brain," principal investigator Aron S. Buchman, MD, of the Rush University Medical Center in Chicago, Illinois, said in a statement.

"People who moved more had better thinking and memory skills compared to those who didn't move much at all. We found movement may essentially provide a reserve to help maintain thinking and memory skills when there are signs of dementia present in the brain," he added.

The study was published online January 16 in Neurology.

Autopsy Data

"Lifestyle factors such as physical activity are being intensely studied as a means to maintain brain health and reduce Alzheimer disease dementia in our aging population," Buchman told Medscape Medical News.

To examine the potential associations between physical activity, AD, and other brain pathologies and cognition, the researchers studied 454 older adults who were participants in the Rush Memory and Aging Project (MAP).

Of these individuals, 191 had dementia, and 253 did not. For the study, all participants underwent comprehensive annual medical examinations and cognitive testing during a 20-year period. At death, autopsies were conducted on their brains.

"We studied 454 brain autopsies from decedents with cognitive function, total daily physical activity derived from multi-day recordings with an activity monitor, and a motor ability score that summarized 10 supervised motor performances obtained proximate to death," said Buchman.

"We previously reported that a higher level of total daily physical activity was related to lower risk of AD dementia and a slower rate of cognitive decline in older adults. Yet, the mechanisms underlying these associations are poorly understood," he added.

One possibility is that physical activity may alter the relationship between motor function and white matter changes in older adults.

"This raises the possibility that a more active lifestyle may modify the association of brain pathologies with cognition," the researchers note.

For the study, trained technicians administered 21 cognitive tests, and researchers calculated a composite global cognition score. The investigators also measured 10 motor abilities to create a global motor score.

Total daily physical activity, including all exercise and nonexercise activities, was measured continuously 24 hours per day for up to 10 days with an omnidirectional accelerometer worn on the nondominant wrist. The researchers averaged all daily activity counts for each 15-second epoch for the first 7 complete days of data.

Reduced Dementia Risk

The investigators recorded AD pathology on autopsy. Summary scores were determined for neuritic plaques, diffuse plaques, and neurofibrillary tangles.

They specifically looked for these AD markers in the hippocampus and the frontal, temporal, parietal, and entorhinal cortex. They also measured β-amyloid burden and density of tau tangles in these five brain regions.

Brain autopsies also allowed investigators to assess nine other common, age-related pathologies. These included nigral neuronal loss, Lewy body disease pathology, TAR DNA-binding protein 43 pathology, hippocampal sclerosis, macroscopic and microscopic cerebral infarcts, cerebral atherosclerosis and arteriosclerosis, and any cerebral amyloid angiopathy.

The investigators evaluated the association between total daily physical activity and cognition in linear regression analyses before and after adjusting for AD age-related brain pathologies, controlling for age, sex, and education.

At the final assessment prior to death, total daily physical activity levels ranged from 0.06 × 105 counts/day to 6.56 × 105 counts/day (mean, 1.55 × 105 counts/day; SD, 1.16 × 105 counts/day). The average age at death was 91 years.

Results showed that higher levels of daily physical activity and motor abilities were each independently associated with improvements in semantic memory, episodic memory, working memory, perceptual speed, and visuospatial abilities.

The investigators found that for every 1 SD increase in physical activity, the risk for dementia was reduced by 31%. In addition, for every increase in motor ability by 1 SD, participants were 55% less likely to develop dementia.

On autopsy, the investigators found an average of three brain pathologies in the participants. The vast majority — more than 95% — showed evidence of at least one brain pathology.

When the researchers replaced the AD pathology summary measure with the observations regarding β-amyloid burden and the density of tau tangles density, results were similar.

Overall, with the exception of atherosclerosis, the association of the other eight pathology indices with cognition did not change with level of physical activity or motor abilities.

Public Health Implications

Associations that emerged in the study may be a result of the fact that increased total daily activity improves cognition, or it may be the other way around, that poorer cognition/dementia may cause individuals to become less active, the researchers acknowledge.

To learn more, they conducted a series of sensitivity analyses. They sequentially excluded participants who tested in the lowest 5%, 10%, and 15% for global cognition. In each instance, total daily activity and motor abilities remained independently associated with cognition, "suggesting that poorer cognition did not account for the association of total daily activity and motor abilities with cognition proximate to death."

The study findings "suggest that a more active lifestyle may provide cognitive reserve or resilience for older adults," the investigators write.

"These findings may have important public health implications because they suggest that resilience factors such as more cognitive activities or physical activity might mitigate late-life cognitive impairment even in the absence of effective therapies to reduce AD and other common brain pathologies," they add.

In addition, the current study suggests that late-life cognitive activities are independently associated with better cognition and "seem to bypass indices of AD and other brain pathologies."

The mechanisms underlying the association between a more active lifestyle and better cognition among older adults remain unknown.

"Further studies are needed to identify the molecular mechanisms underlying this potential reserve," Bachman said.

Future research also is warranted to determine which physical interventions in late life contribute to the cognitive reserve indicated in this study.

Few Downsides

In an accompanying editorial, James A. Mortimer, PhD, College of Public Health, the University of South Florida, Tampa, and Yaakov Stern, PhD, the Department of Neurology, Columbia University, New York City, note that the study provides "evidence for beneficial effects of total daily physical activity on cognitive performance that is independent of a variety of brain lesions, including AD pathology."

"Because the data from this study are cross-sectional, causal inferences cannot be drawn," they note.

Like the investigators, Mortimer and Stern point out that the results may be due, at least in part, to reverse causality, such that lower cognitive function may lead to less physical activity.

Consistent with this view, unadjusted comparisons of physical activity in those who had dementia vs those who did not showed a significant reduction in physical activity among those with dementia.

"It is important to emphasize that this does not imply that physical activity does not increase reserve against cognitive decline, only that the effect may be more modest among those with better cognition," they note.

What is needed to establish causation are longitudinal studies of physical activity and cognition with brain imaging to document the influence of pathology on this association.

"Although important questions remain, currently available data suggest that promotion of an active lifestyle in late as well as early life that includes regular physical activity and exercise may be beneficial in reducing the risk of dementia, both through increases in reserve and reduction of Alzheimer neuropathology," they write.

"The fact that physical exercise and activity have few, if any, downsides make them an attractive target for the prevention of cognitive impairment and dementia," they state.

The study was supported by the National Institutes of Health, the Illinois Department of Health, and the Robert C. Borwell Endowment Fund. The authors and editorialists have disclosed no relevant financial relationships.

Neurology. Published online January 16, 2019. Abstract, Editorial

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