» Articles » PMID: 33630089

Sex Differences in Cognitive Decline Among US Adults

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.

Citing Articles

Aging activates escape of the silent X chromosome in the female mouse hippocampus.

Gadek M, Shaw C, Abdulai-Saiku S, Saloner R, Marino F, Wang D Sci Adv. 2025; 11(10):eads8169.

PMID: 40043106 PMC: 11881916. DOI: 10.1126/sciadv.ads8169.


Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults.

Acharya V, Fan K, Snitz B, Ganguli M, DeKosky S, Lopez O Alzheimers Dement. 2025; 21(3):e14461.

PMID: 40042063 PMC: 11880917. DOI: 10.1002/alz.14461.


Tau pathology is associated with postsynaptic metabotropic glutamate receptor 5 (mGluR5) in early Alzheimer's disease in a sex-specific manner.

Wang Y, Wang J, Chen X, Lin Z, You Z, He K Alzheimers Dement. 2025; 21(2):e70004.

PMID: 39998900 PMC: 11853735. DOI: 10.1002/alz.70004.


Sex differences in the association of Alzheimer's disease biomarkers and cognition in a multicenter memory clinic study.

Boccalini C, Peretti D, Scheffler M, Mu L, Griffa A, Testart N Alzheimers Res Ther. 2025; 17(1):46.

PMID: 39966925 PMC: 11837373. DOI: 10.1186/s13195-025-01684-z.


Greater BMI across the lifespan is associated with better midlife cognition: The Bogalusa Heart Study.

Gwizdala K, Bazzano L, Carmichael O, Newton Jr R Sci Rep. 2025; 15(1):5336.

PMID: 39948186 PMC: 11825684. DOI: 10.1038/s41598-025-89363-9.


References
1.
Ji H, Kim A, Ebinger J, Niiranen T, Claggett B, Merz C . Sex Differences in Blood Pressure Trajectories Over the Life Course. JAMA Cardiol. 2020; 5(3):19-26. PMC: 6990675. DOI: 10.1001/jamacardio.2019.5306. View

2.
Gennatas E, Avants B, Wolf D, Satterthwaite T, Ruparel K, Ciric R . Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood. J Neurosci. 2017; 37(20):5065-5073. PMC: 5444192. DOI: 10.1523/JNEUROSCI.3550-16.2017. View

3.
Levine D, Gross A, Briceno E, Tilton N, Kabeto M, Hingtgen S . Association Between Blood Pressure and Later-Life Cognition Among Black and White Individuals. JAMA Neurol. 2020; 77(7):810-819. PMC: 7154952. DOI: 10.1001/jamaneurol.2020.0568. View

4.
Feinleib M, Kannel W, Garrison R, MCNAMARA P, CASTELLI W . The Framingham Offspring Study. Design and preliminary data. Prev Med. 1975; 4(4):518-25. DOI: 10.1016/0091-7435(75)90037-7. View

5.
Hachinski V, Iadecola C, Petersen R, Breteler M, Nyenhuis D, Black S . National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006; 37(9):2220-41. DOI: 10.1161/01.STR.0000237236.88823.47. View