How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts

Anaïs Rouanet; Justina Avila-Rieger; Aline Dugravot; Jeremie Lespinasse; Rachel Stuckwisch; Richard Merrick; Emma Anderson; Leann Long; Catherine Helmer; Helène Jacqmin-Gadda; Carole Dufouil; Suzanne Judd; Jennifer Manly; Severine Sabia; Alden Gross; Cecile Proust-Lima

doi:10.1093/aje/kwab227

How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts

Anaïs Rouanet, Justina Avila-Rieger, Aline Dugravot, Jeremie Lespinasse, Rachel Stuckwisch, Richard Merrick, Emma Anderson, Leann Long, Catherine Helmer, Helène Jacqmin-Gadda, Carole Dufouil, Suzanne Judd, Jennifer Manly, Severine Sabia, Alden Gross, Cecile Proust-Lima

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

Abstract

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 subjectspecific estimands (mixed/joint models fitted by likelihood maximization) in 8 studies of aging: 6 populationbased studies (the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (1996-2009), Personnes Agees 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 f luency) 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.

Original language	English (US)
Pages (from-to)	441-452
Number of pages	12
Journal	American journal of epidemiology
Volume	191
Issue number	3
DOIs	https://doi.org/10.1093/aje/kwab227
State	Published - Mar 1 2022

Keywords

aging cohorts
cognition
death
dropout
longitudinal models
selection
sex/gender

ASJC Scopus subject areas

General Medicine

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10.1093/aje/kwab227

Cite this

Rouanet, A., Avila-Rieger, J., Dugravot, A., Lespinasse, J., Stuckwisch, R., Merrick, R., Anderson, E., Long, L., Helmer, C., Jacqmin-Gadda, H., Dufouil, C., Judd, S., Manly, J., Sabia, S., Gross, A., & Proust-Lima, C. (2022). How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts. American journal of epidemiology, 191(3), 441-452. https://doi.org/10.1093/aje/kwab227

Rouanet, A, Avila-Rieger, J, Dugravot, A, Lespinasse, J, Stuckwisch, R, Merrick, R, Anderson, E, Long, L, Helmer, C, Jacqmin-Gadda, H, Dufouil, C, Judd, S, Manly, J, Sabia, S, Gross, A & Proust-Lima, C 2022, 'How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts', American journal of epidemiology, vol. 191, no. 3, pp. 441-452. https://doi.org/10.1093/aje/kwab227

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abstract = "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 subjectspecific estimands (mixed/joint models fitted by likelihood maximization) in 8 studies of aging: 6 populationbased studies (the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (1996-2009), Personnes Agees 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 f luency) 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.",

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AU - Rouanet, Anaïs

AU - Avila-Rieger, Justina

AU - Dugravot, Aline

AU - Lespinasse, Jeremie

AU - Stuckwisch, Rachel

AU - Merrick, Richard

AU - Anderson, Emma

AU - Long, Leann

AU - Helmer, Catherine

AU - Jacqmin-Gadda, Helène

AU - Dufouil, Carole

AU - Judd, Suzanne

AU - Manly, Jennifer

AU - Sabia, Severine

AU - Gross, Alden

AU - Proust-Lima, Cecile

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How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts

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