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Longitudinal Assessment of Physical Activity and Cognitive Outcomes Among Women at Midlife

Gail A. Greendale, MD1Weijuan Han, MS1MeiHua Huang, DrPH1; et alDawn M. Upchurch, PhD2Carrie Karvonen-Gutierrez, MPH, PhD3Nancy E. Avis, PhD4Arun S. Karlamangla, PhD, MD1

JAMA Netw Open. 2021;4(3):e213227. doi:10.1001/jamanetworkopen.2021.3227

Key Points

Question  Is physical activity during midlife associated with better performance in cognitive measures over time?

Findings  This cohort study of 1718 women at midlife found that, with adjustment for socioeconomic characteristics, menopause symptoms, hormone therapy use, and presence of diabetes and hypertension, self-reported physical activity was not associated with measured cognitive performance in the domains of processing speed, verbal memory, or working memory.

Meaning  These findings suggest that the cognitive protection effect of physical activity observed in later life may be an artifact of reverse causation.


Importance  The increasing prevalence of cognitive decline, impairment, and dementia spurs intense interest in cognitive preservation strategies.

Objective  To explore the longitudinal association between physical activity (PA) and cognitive performance among women at midlife.

Design, Setting, and Participants  This cohort study is an analysis from the Study of Women’s Health Across the Nation. Enrollment occurred from 1996 through 1997, and follow-up extended into 2017. Included individuals were those who had undergone cognitive measures during the first 3 cognitive test visits and had at least 1 additional cognitive measurement. Stroke prior to baseline was an exclusion, and observations were censored for subsequent stroke. Data were analyzed from June 2018 through August 2019.

Exposures  Engaging in sport or exercise PA (self-reported).

Main Outcomes and Measures  The Symbol Digit Modalities Test (SDMT) was used to assess cognitive processing speed. The East Boston Memory Test-Delayed (EBMT-D) was used to measure verbal episodic memory. The digit span backwards (DSB) test was used to evaluate working memory.

Results  Among 1718 women with a median (range) observation time of 11.9 (0.60-13.5) years, the mean (SD) baseline age was 45.7 (2.5) years. From baseline through age 61 years, mean change in SDMT score was −0.20 annually (95% CI, −0.26 to −0.15; P < .001). After age 61 years, the mean change in SDMT was −0.51 yearly (95% CI, −0.54 to −0.41; P < .001). Beginning at age 58 years of the mean change in EBMT was −0.03 yearly (95% CI, −0.04 to −0.02; P < .001). Starting at age 61 years, mean (SD) change in DSB was −0.03 annually (95% CI, −0.04 to −0.01; P = .001). When adjusted for attrition and practice effect, PA was associated with higher concurrent SDMT and EBMT scores and a smaller decrease in SDMT score. For each unit increment in PA, there was a 0.36 increment in concurrent SDMT score (95% CI, 0.14 to 0.59; P = .002) and a 0.10 increment in concurrent EBMT score (95% CI, 0.05 to 0.15; P < .001). Greater PA was associated with a smaller annual mean decrease in SDMT score (0.06 yearly; 95% CI, 0.02 to 0.09; P = .001). After additional adjustment for demographic characteristics, menopause symptoms, hormone therapy use, and the presence of diabetes and hypertension, PA was not associated with trajectories (ie, levels or slopes) of any cognitive outcome.

Conclusions and Relevance  This cohort study found no association between greater PA levels and cognitive outcomes among women in midlife, unlike cohort studies that begin observations at later ages, which may be associated with confounding by reverse causation (ie, cognitive decline associated with an outcome of lower PA levels).