biostudies-literatureRouanet AUS National Institutes of HealthBritish Heart FoundationAgence Nationale de la RechercheUS National Institute on AgingNIA NIH HHSMedical Research CouncilNINDS NIH HHSUS National Institute of Neurological Disorders and Stroke441-452https://www.ebi.ac.uk/biostudies/studies/S-EPMC9214252biostudies-literatureUnknown191(3)The association between sex/gender and aging-related cognitive decline remains poorly understood because of inconsistencies in findings. Such heterogeneity could be attributable to the cognitive functions studied and study population characteristics, but also to differential selection by dropout and death between men and women. We aimed to evaluate the impact of selection by dropout and death on the association between sex/gender and cognitive decline. We first compared the statistical methods most frequently used for longitudinal data, targeting either population estimands (marginal models fitted by generalized estimating equations) or subject-specific estimands (mixed/joint models fitted by likelihood maximization) in 8 studies of aging: 6 population-based studies (the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (1996-2009), Personnes Âgées QUID (PAQUID; 1988-2014), the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (2003-2016), the Three-City Study (Bordeaux only; 1999-2016), the Washington Heights-Inwood Community Aging Project (WHICAP; 1992-2017), and the Whitehall II Study (2007-2016)) and 2 clinic-based studies (the Alzheimer's Disease Neuroimaging Initiative (ADNI; 2004-2017) and a nationwide French cohort study, MEMENTO (2011-2016)). We illustrate differences in the estimands of the association between sex/gender and cognitive decline in selected examples and highlight the critical role of differential selection by dropout and death. Using the same estimand, we then contrast the sex/gender-cognitive decline associations across cohorts and cognitive measures suggesting a residual differential sex/gender association depending on the targeted cognitive measure (memory or animal fluency) and the initial cohort selection. We recommend focusing on subject-specific estimands in the living population for assessing sex/gender differences while handling differential selection over time.American journal of epidemiologyHow Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts.PMC9214252U01 NS041588RF1AG062553MR/P014437/1MR/S011676/1ANR-18-CE36-0004-01R01AG056486R13 AG064971R01 AG056486NIH-NIA/R13AG064971RG/16/11/32334R01 AG056477S011676R01AG056477K01AG050699MR/R024227/1R024227RF1 AG062553K01 AG050699Stuckwisch RLong LProust-Lima CHelmer CGross ADugravot ALespinasse JJacqmin-Gadda HManly JAvila-Rieger JJudd SMerrick RAnderson ESabia SRouanet ADufouil CfalseHow Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts.The association between sex/gender and aging-related cognitive decline remains poorly understood because of inconsistencies in findings. Such heterogeneity could be attributable to the cognitive functions studied and study population characteristics, but also to differential selection by dropout and death between men and women. We aimed to evaluate the impact of selection by dropout and death on the association between sex/gender and cognitive decline. We first compared the statistical methods most frequently used for longitudinal data, targeting either population estimands (marginal models fitted by generalized estimating equations) or subject-specific estimands (mixed/joint models fitted by likelihood maximization) in 8 studies of aging: 6 population-based studies (the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (1996-2009), Personnes Âgées QUID (PAQUID; 1988-2014), the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (2003-2016), the Three-City Study (Bordeaux only; 1999-2016), the Washington Heights-Inwood Community Aging Project (WHICAP; 1992-2017), and the Whitehall II Study (2007-2016)) and 2 clinic-based studies (the Alzheimer's Disease Neuroimaging Initiative (ADNI; 2004-2017) and a nationwide French cohort study, MEMENTO (2011-2016)). We illustrate differences in the estimands of the association between sex/gender and cognitive decline in selected examples and highlight the critical role of differential selection by dropout and death. Using the same estimand, we then contrast the sex/gender-cognitive decline associations across cohorts and cognitive measures suggesting a residual differential sex/gender association depending on the targeted cognitive measure (memory or animal fluency) and the initial cohort selection. We recommend focusing on subject-specific estimands in the living population for assessing sex/gender differences while handling differential selection over time.2022-01-01T00:00:00Z2022 Feb2024-11-12T22:48:03.582Z2024-11-12T22:48:03.582ZS-EPMC92142523452111110.1093/aje/kwab227