Fassier · The journals of gerontology. Series A, Biological sciences and medical sciences 2022 · Prospective cohort study · n=7252

Vigorous Physical Activity and Cognitive Trajectory Later in Life: Prospective Association and Interaction by Apolipoprotein E e4 in the Nurses' Health Study.

Cited 13 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective longitudinal cohort study

PubMed 34125204 · doi:10.1093/gerona/glab169 · record verified 2026-08-30

What was done

Nurses' Health Study participants reported leisure-time physical activity biennially starting in 1986. Between 1995–2001 and 2008, 7,252 women aged 70 and older underwent up to four repeated cognitive assessments over 6 years via telephone, covering six tasks averaged into z-scores. Latent process mixed models identified three cognitive trajectories: high-stable, medium-stable, and decline. Multinomial logistic regressions assessed the prospective association between midlife vigorous physical activity (measured at least 9 years prior) and late-life cognitive trajectory, testing for interaction with APOE-e4 carrier status, using the high-stable trajectory as the reference.

What was found

Compared to the lowest tertile (≤0.9 MET-hours/wk), the highest tertile of vigorous physical activity (≥5.9 MET-hours/wk) was significantly associated with a lower likelihood of the medium-stable trajectory in global cognitive score (OR 0.72, 95% CI [0.63, 0.82]), verbal memory (OR 0.78, 95% CI [0.68, 0.89]), and telephone interview of cognitive status score (OR 0.81, 95% CI [0.70, 0.94]). Vigorous activity was also associated with a lower likelihood of decline in category fluency (OR 0.72, 95% CI [0.56, 0.92]). The association with global score trajectory was nominally stronger among APOE-e4 carriers (OR 0.60, 95% CI [0.39, 0.92]) than noncarriers (OR 0.82, 95% CI [0.59, 1.16]), with p-interaction = .07.

Why it matters

This prospective cohort study indicates that midlife vigorous exercise may help preserve cognitive trajectories in older adulthood, with potentially pronounced benefits among genetic carriers of the APOE-e4 risk allele.

Limits

Physical activity was self-reported by questionnaire. Cognitive testing was limited to telephone assessments. The cohort consisted exclusively of predominantly white female nurses, which may limit generalizability to men and more diverse populations. Unmeasured confounding remains possible given the observational design.

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