No Link to Midlife Exercise and Cognitive Outcomes?

Erik Greb

April 07, 2021

Higher levels of physical activity at midlife are not linked to more positive cognitive outcomes, new research suggests.

Results from a cohort study of more than 1700 women showed no significant association between midlife activity and concurrent cognitive performance or with subsequent cognitive decline.

The findings diverge from those of previous research that suggested a cognitive benefit of exercise at midlife. However, most of those studies examined outcomes at one point in time and did not include a long follow-up, the current investigators note.

"We were not surprised by [our] results," lead author Gail A. Greendale, MD, professor of medicine and obstetrics/gynecology at the University of California, Los Angeles, told Medscape Medical News.

"We were aware that reverse causation could be playing a role in the prior studies of physical activity and cognition in older persons," Greendale added.

The findings were published online March 31 in JAMA Network Open.

No Definitive Answer

Although many randomized controlled trials have examined whether physical activity can maintain or improve cognition in older adults, that question has not yet been answered definitively, the researchers note.

Fewer studies have examined the benefit of exercise on cognition in midlife. Two meta-analyses of clinical trials that lasted at least 6 months provided no evidence physical activity prevents cognitive decline.

To look closer at these issues, the researchers examined data from the longitudinal Study of Women's Health Across the Nation (SWAN). It included 3302 women aged 42 to 52 years from 1996 through 1997. Follow-up began in 1998 and cognitive testing was completed in 2017.

Participants regularly underwent the Symbol Digit Modalities Test (SDMT), which evaluates cognitive processing speed and attention; the East Boston Memory Test (EBMT), which measures verbal episodic memory; and the Digit Span Backwards test (DSB), which assesses working memory. The current investigators examined participants' results beginning with the third cognitive test to minimize practice effects.

The self-reported Kaiser Physical Activity Survey was also used to gauge physical activity. The KPAS categorizes activity as household and caregiving, sport and exercise, or daily living. The researchers chose the sport and exercise category as the primary exposure for the analysis.

They assessed 1718 of the women, of whom 50.6% were white, 26.6% were Black, 12.2% were Japanese, and 10.5% were Chinese. The mean age at baseline was 45.7 years.

Participants' mean SDMT and DSB scores were approximately in the middle of their respective ranges. Mean baseline EBMT score was 10.3 out of a maximum of 12. Mean baseline sport and exercise score was 2.79 out of a maximum of 5.

Stress and Cognition

In initial analysis, sport and exercise levels were positively associated with concurrent SDMT score and annual change. However, after adjusting for demographic characteristics and factors related to menopause, this association was no longer statistically significant.

Sport and exercise level was positively associated in the initial analysis with current EBMT score, but not with change in EBMT score. After adjusting for demographic characteristics and menopause-related factors, this association was also no longer statistically significant.

Level of sport and exercise was not associated with DSB score or annual decline in this score in the initial analysis. After controlling for demographic characteristics and menopause-related factors, there was no significant link between age and decrease in DSB score.

"Our study agrees with one of the few longitudinal studies of physical activity and cognition, the Whitehall II study," said Greendale.

That study showed no association between midlife physical activity and cognitive performance. However, starting at age 70, participants with higher levels of physical activity did show better cognitive scores.

The only two factors in the current analysis related to a worsening of cognitive performance over time were anxiety and the inability to pay for basic needs such as food and rent.

"It is plausible that stress, as occurs with financial hardship or anxiety, impairs ability to concentrate on cognitive tasks," said Greendale. "It is also possible that stress hormones like cortisol damage brain function or tissue if they are chronically elevated."

She noted that the study findings are not generalizable to men.

In the future, the investigators plan to examine other potential factors that could increase or decrease rate of cognitive decline.

More than One Reason to Exercise

In an accompanying editorial, Arthur F. Kramer, PhD, director of the Center for Cognitive and Brain Health at Northeastern University, Boston, Massachusetts, writes that the new analysis "should be understood within the context of our increasingly digital world, in which physical activity and exercise continue to decrease alongside an increase in sedentary behavior across the lifespan."

These behaviors are associated with heart disease, stroke, and diabetes, he adds.

One advantage of studies at midlife, such as the current study, is its ability to avoid problems of reverse causation, Kramer writes. Studies that begin when participants are in late life make it difficult to distinguish the association of exercise with cognition from the association of cognition with exercise.

Other advantages of the new research, Kramer notes, were the diversity of the participants, the abundance of measurements over a long follow-up duration, and a thorough self-reported measure of physical activity. However, future studies could be improved by complementing self-reported measures of activity with continuous measures made by smartphones or other devices — and by incorporating brain imaging measures and blood biomarkers.

Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer's Association, said the study increases neurologists' understanding of the complex interaction of exercise and cognition.

"A growing body of evidence suggests that a combination of physical activity and other behavioral interventions, such as eating a balanced diet, may be more effective in reducing risk for cognitive decline. It is important that healthcare providers continue to encourage heart-healthy behaviors across the life course, as they are beneficial to our overall health and wellness," said Snyder.

She noted that, despite their value, the conclusions that can be drawn from observational studies are limited.

"More research is needed in an intervention-based trial where researchers can more accurately measure changes and benefits to memory," said Snyder.

She reported that the Alzheimer's Association is leading the U.S. POINTER clinical trial, which will assess the effect of multicomponent lifestyle interventions on reducing risk of cognitive decline in older Americans at risk of dementia.

The Study of Women's Health Across the Nation (SWAN) received funding from the National Institute on Aging, the National Institute of Nursing Research, and the National Institutes of Health Office of Research on Women's Health. Greendale, Kramer, and Snyder have disclosed no relevant financial relationships.

JAMA Netw Open. Published online March 31, 2021. Full text, Editorial

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