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. 2021 Feb 1;4(2):e210169.
doi: 10.1001/jamanetworkopen.2021.0169.

Sex Differences in Cognitive Decline Among US Adults

Deborah A Levine  1   2   3 , Alden L Gross  4 , Emily M Briceño  1   3   5 , Nicholas Tilton  1 , Bruno J Giordani  6   7 , Jeremy B Sussman  1   3   8 , Rodney A Hayward  1   3   8 , James F Burke  2   3   8 , Stephanie Hingtgen  1 , Mitchell S V Elkind  9   10 , Jennifer J Manly  9   11 , Rebecca F Gottesman  12 , Darrell J Gaskin  13 , Stephen Sidney  14 , Ralph L Sacco  15 , Sarah E Tom  9   10 , Clinton B Wright  16 , Kristine Yaffe  17   18   19 , Andrzej T Galecki  1   20
Affiliations

Sex Differences in Cognitive Decline Among US Adults

Deborah A Levine et al. JAMA Netw Open. .

Erratum in

  • Error in Methods.
    [No authors listed] [No authors listed] JAMA Netw Open. 2023 Mar 1;6(3):e234786. doi: 10.1001/jamanetworkopen.2023.4786. JAMA Netw Open. 2023. PMID: 36877526 Free PMC article. No abstract available.

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Levine reported receiving consulting fees and grants from the National Institutes of Health (NIH)/ National Institute on Aging (NIA) outside the submitted work. Dr Tilton reported receiving consulting fees and grants from NIH/NIA outside the submitted work. Dr Hayward reported receiving grants from the US Veterans Affairs Department during the conduct of the study. Dr Burke reported grants from the NIH outside the submitted work. Dr Gottesman reported receiving grants from American Academy of Neurology and previous editorial work at the journal Neurology outside the submitted work. Dr Gaskin reported receiving grants from the US Centers for Disease Control and Prevention during the conduct of the study and personal fees from Altarum and the Robert Wood Johnson Foundation outside the submitted work. Dr Sidney reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Sacco reported receiving grants from the NIH Northern Manhattan Study during the conduct of the study and grants from Florida Department of Health Florida Stroke Registry, grants from the NIH Miami Clinical Translational Science Institute, and compensation as editor-in-chief of the American Heart Association’s Stroke outside the submitted work. Dr Wright reported receiving grants from the NIH during the conduct of the study and royalty fees from UpToDate.com outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Derivation of Participant Cohort
BP indicates blood pressure. aCategories for missing data on covariates are not mutually exclusive. Missing data for covariates included glucose (261 participants), alcohol use (18 participants), body mass index (33 participants), waist circumference (109 participants), smoking (3 participants), physical activity (30 participants), low-density lipoprotein cholesterol (264 participants), antihypertensive medication use (25 participants), and education (179 participants). No participants were missing history of atrial fibrillation.
Figure 2.
Figure 2.. Projected Mean Changes in Global Cognition, Executive Function, and Memory Over Time by Sex
Participant-specific (conditional) projected values of cognition were calculated for a 70-year-old Black participant (woman vs man) with the following values of all covariates at or before first cognitive assessment: Northern Manhattan Study cohort, eighth grade or lower education, 0 alcoholic drinks per week, nonsmoking, body mass index of 27.1 (calculated as weight in kilograms divided by height in meters squared), waist circumference (96.0 cm), low-density lipoprotein cholesterol (123.8 mg/dL [to convert to millimoles per liter, multiply by 0.0259]) and glucose (97.3 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), no history of atrial fibrillation, no hypertension treatment, and a baseline systolic blood pressure (BP) of 150 mm Hg that increases by 1 mm each year. Random effects for this projection were set to zero. Linear mixed-effects models included time since first cognitive assessment and baseline values (measured before or at time of first cognitive assessment) of sex, age, race, cohort study, years of school, alcohol use, cigarette smoking, body mass index, waist circumference, physical activity, cumulative mean systolic BP, hypertension treatment, fasting glucose, low-density lipoprotein cholesterol, history of atrial fibrillation, age × follow-up time, sex × follow-up time, race × follow-up time, cumulative mean systolic BP × follow-up time, and hypertension treatment × follow-up time.
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References

    1. Alzheimer's Association . 2020 Alzheimer's Disease facts and figures. Alzheimers Dement. 2020;16(3):391-460. doi:10.1002/alz.12068 - DOI - PubMed
    1. Chêne G, Beiser A, Au R, et al. . Gender and incidence of dementia in the Framingham Heart Study from mid-adult life. Alzheimers Dement. 2015;11(3):310-320. doi:10.1016/j.jalz.2013.10.005 - DOI - PMC - PubMed
    1. Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA. Is the risk of developing Alzheimer’s disease greater for women than for men? Am J Epidemiol. 2001;153(2):132-136. doi:10.1093/aje/153.2.132 - DOI - PubMed
    1. Andersen K, Launer LJ, Dewey ME, et al. ; EURODEM Incidence Research Group . Gender differences in the incidence of AD and vascular dementia: the EURODEM Studies. Neurology. 1999;53(9):1992-1997. doi:10.1212/WNL.53.9.1992 - DOI - PubMed
    1. Edland SD, Rocca WA, Petersen RC, Cha RH, Kokmen E. Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, Minn. Arch Neurol. 2002;59(10):1589-1593. doi:10.1001/archneur.59.10.1589 - DOI - PubMed

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