Sex Differences In Cognitive Decline: A Pooled Cohort Analysis Of Aric, Cardia, Chs, Fos, Nomas

Background: Sex differences in dementia risk are unclear but some have found greater risk for women. We hypothesized that women have greater cognitive decline than men, after adjusting for potential confounders. Objective: Determine associations between sex and cognitive decline. Methods: We pooled data from 19,378 participants free of stroke and dementia (mean [SD] age 59.8 [10.4] years at first cognitive assessment), of whom 8,654 (44.7%) were men and 3,852 (19.9%) were black, from 5 longitudinal cohorts between 1971 and 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Linear mixed-effects models measured changes in each continuous cognitive outcome over time by sex, adjusted for demographics, education, vascular risk factors, and age*follow-up time, race*follow-up time, systolic blood pressure*follow-up time, and use of antihypertensive medication*follow-up time interaction terms. Cognitive outcomes were set to a t-score metric (mean 50, standard deviation [SD] 10) at a participant’s first cognitive assessment; a 1-point difference represents a 0.1 SD difference in the distribution of cognition across the 5 cohorts. Median follow-up was 12.4 (IQR: 5.9, 21.0) years. Results: Women had significantly higher baseline performance than men in global cognition, executive function, and memory (adjusted differences in intercepts, 2.09 to 2.15 points; all P<0.001) ( Figure ). Compared with men, women had significantly faster declines in global cognition, executive function, and memory (adjusted differences in slopes, 0.04 to 0.06 points per year faster; P <0.001) ( Figure ). Conclusion: These results are consistent with women having greater cognitive reserve but faster cognitive decline than men.