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- Title
Evaluation of Selective Survival and Sex/Gender Differences in Dementia Incidence Using a Simulation Model.
- Authors
Shaw, Crystal; Hayes-Larson, Eleanor; Glymour, M. Maria; Dufouil, Carole; Hohman, Timothy J.; Whitmer, Rachel A.; Kobayashi, Lindsay C.; Brookmeyer, Ron; Mayeda, Elizabeth Rose
- Abstract
Key Points: Question: Can selective survival plausibly explain reported sex/gender differences in dementia incidence? Findings: In this decision analytical model of 100 000 simulated adults aged 50 years and without dementia at baseline, sex/gender differences in dementia incidence consistent with literature (ie, 15%-20% elevated risk for women aged ≥85 years) were only observed in the presence of moderate to strong effects of selective survival characteristics that differed by sex/gender. Meaning: These findings suggest that selective survival may contribute to sex/gender differences in dementia incidence but do not preclude the potential for additional contributions from biological mechanisms. This decision analytical model assesses the potential role of selective survival in sex/gender differences in dementia incidence. Importance: Dementia research is susceptible to bias arising from selective survival, a process that results in individuals with certain characteristics disproportionately surviving to old age. Spurious associations between risk factors and dementia may be induced when factors associated with longer survival also influence dementia incidence. Objective: To assess the role of selective survival in explaining reported sex/gender differences in dementia incidence. Design, Setting, and Participants: This decision analytical model used a simulated cohort of US participants aged 50 years and without dementia at baseline followed up for incident dementia through age 95 years. Selective survival was induced by a selection characteristic (eg, childhood social disadvantage or Alzheimer genetic risk) that influenced both mortality and dementia incidence at varying magnitudes. Data analysis was performed from April 2018 to May 2020. Exposure: Sex/gender, conceptualized as the combination of biological sex and social consequences of gender. Main Outcomes and Measures: Dementia incidence rate ratios (IRRs) for women compared with men. In all simulations, it was assumed that there would be no true effect of sex/gender on dementia incidence; all observed sex/gender differences were due to selective survival. Results: At baseline, the simulation included 100 000 participants aged 50 years (51 000 [51%] women, mirroring the 1919-1921 US birth cohort of non-Latino White individuals at age 50 years); distributions of the selection characteristic were standard normal (mean [SD], 0.0 [1.0]). Observed sex/gender differences in dementia incidence in individuals aged 85 years or older ranged from insignificant (IRR, 1.00; 95% CI, 0.91-1.11) to consistent with sex/gender differences (20% higher risk for women [IRR, 1.20; 95% CI, 1.08-1.32]) reported in an extant study. Simulations in which bias was large enough to explain prior findings required moderate to large differential effects of selective survival (eg, hazard ratio for selection characteristic on mortality at least 2.0 among men, no effect among women). Conclusions and Relevance: These results suggest that selective survival may contribute to observed sex/gender differences in dementia incidence but do not preclude potential contributions of sex/gender-specific mechanisms. Further research on plausibility of selection characteristics with outcomes of the magnitude required for selective survival to explain sex/gender differences in dementia incidence and sex/gender-specific mechanisms represent an opportunity to understand prevention and treatment of dementia.
- Subjects
UNITED States; SURVIVAL; CONFIDENCE intervals; MATHEMATICAL models; MORTALITY; LIFE expectancy; DISEASE incidence; COGNITION; SEX distribution; DEMENTIA; THEORY; RESEARCH funding; ODDS ratio; DATA analysis software
- Publication
JAMA Network Open, 2021, Vol 4, Issue 3, pe211001
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2021.1001