Sex differences in the association between age-related decline in blood pressure and decline in cognition: A prospective cohort study

medRxiv [Preprint]. 2025 Jan 9:2025.01.08.25320209. doi: 10.1101/2025.01.08.25320209.

Abstract

Background: Both high and declining blood pressure (BP) are associated with cognitive decline risk in older adults. In late-life, women have higher rates of hypertension, experience faster cognitive decline, and represent two-thirds of individuals with Alzheimer's disease dementia. However, sex differences in the association between BP decline and cognitive decline are unknown.

Methods: Data were analyzed from 4719 older adults without known baseline dementia (mean age = 76.7 [SD = 7.7] years; 74% women) enrolled in one of five US-based prospective community-based cohort studies, followed annually for up to 31 years (mean = 8.7 [SD = 5.7] years). A 19-test cognitive battery, yielding composite global and five domain-specific scores, and BP were assessed annually. Bivariate mixed-effects models simultaneously estimated change in BP and cognition, for the total group and by sex.

Findings: Systolic BP, diastolic BP, and cognition all declined over time (ps <0.01). Bivariate mixed-effect models revealed a sex difference in the correlation of decline in systolic BP and decline in global cognition (women: r = 0.26, 95%CI: 0.17 - 0.37; men: r = 0.01, 95%CI: -0.13 - 0.11), such that women exhibited a stronger correlation than men. Decline in systolic BP was related to decline in global and all five cognitive domains in women but none in men, with another sex difference identified in the working memory domain. An increase of diastolic BP was related to decline in working memory in men, and no other associations with diastolic BP were significant for either sex.

Interpretation: Systolic BP decline in late-life is related to decline in global and domain-specific cognition in women but not men, with sex differences in global cognition and the working memory domain. These findings suggest that in older women, declining systolic BP - a routinely-used clinical measure - may be an important marker of concurrent cognitive decline.

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  • Preprint