Sex Differences in Cognitive Decline among US Adults

Deborah A. Levine, Alden L. Gross, Emily M. Briceño, Nicholas Tilton, Bruno J. Giordani, Jeremy B. Sussman, Rodney A. Hayward, James F. Burke, Stephanie Hingtgen, Mitchell S.V. Elkind, Jennifer J. Manly, Rebecca F. Gottesman, Darrell J. Gaskin, Stephen Sidney, Ralph L. Sacco, Sarah E. Tom, Clinton B Wright, Kristine Yaffe, Andrzej T. Galecki

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women. Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk. Design, Setting, and Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020. Exposure: Sex. Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results: Among 34349 participants, 26088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P <.001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P <.001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P <.001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P <.001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P <.001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P =.61). Conclusions and Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia..

Original languageEnglish (US)
Article numbere210169
JournalJAMA Network Open
Issue number2
StatePublished - Feb 25 2021

ASJC Scopus subject areas

  • Medicine(all)


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