Deborah A Levine1,2,3, Alden L Gross4, Emily M Briceño1,3,5, Nicholas Tilton1, Bruno J Giordani6,7, Jeremy B Sussman1,3,8, Rodney A Hayward1,3,8, James F Burke2,3,8, Stephanie Hingtgen1, Mitchell S V Elkind9,10, Jennifer J Manly9,11, Rebecca F Gottesman12, Darrell J Gaskin13, Stephen Sidney14, Ralph L Sacco15, Sarah E Tom9,10, Clinton B Wright16, Kristine Yaffe17,18,19, Andrzej T Galecki1,20. 1. Cognitive Health Services Research Program, Department of Internal Medicine, University of Michigan, Ann Arbor. 2. Department of Neurology and Stroke Program, University of Michigan, Ann Arbor. 3. Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor. 4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 5. Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor. 6. Department of Psychiatry, University of Michigan, Ann Arbor. 7. Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor. 8. VA Ann Arbor Healthcare System, Ann Arbor, Michigan. 9. Vagelos College of Physicians and Surgeons, Department of Neurology, Columbia University, New York, New York. 10. Mailman School of Public Health, Department of Epidemiology, Columbia University, New York, New York. 11. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York. 12. Department of Neurology, Johns Hopkins University, Baltimore, Maryland. 13. Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 14. Kaiser Permanente Northern California Division of Research, Oakland. 15. Department of Neurology, University of Miami, Miami, Florida. 16. Division of Clinical Research, National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland. 17. Department of Psychiatry, University of California, San Francisco. 18. Department of Neurology, University of California, San Francisco. 19. Department of Epidemiology, University of California, San Francisco. 20. Department of Biostatistics, University of Michigan, Ann Arbor.
Abstract
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 34 349 participants, 26 088 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 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 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.
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 34 349 participants, 26 088 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 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 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.
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