Abstract

Introduction: Midlife diabetes is associated with an increased risk of dementia. Associations between late-life diabetes and dementia are less robust, potentially because late-life multisystem dysregulation from frailty—a strong predictor of dementia—could influence dementia expression. Given diabetes is more prevalent in old age, the contribution of diabetes to dementia may vary by age of diabetes assessment and frailty status. We quantified population attributable fractions (PAFs) of dementia, which account for exposure prevalence and strength of relative risks, by diabetes in midlife and late-life. We also investigated whether associations for late-life diabetes varied by frailty status. Hypothesis: Because diabetes prevalence rises with age and the strength of the relative risk of dementia tends to decrease, PAFs should be higher with older age of diabetes ascertainment, and larger among those without frailty. Methods: We conducted a prospective cohort analysis of data from the Atherosclerosis Risk in Communities Study. Dementia was ascertained from baseline (1987-89) to 2020. We quantified PAFs of incident dementia by age 80 and 90 from diabetes assessed at various age strata (aged 45-54 [n=7,731], 55-64 [n=12,273], 65-74 [n=6,660], and 75-84 [n=2,126] years). Among those aged 75-84, we stratified PAFs by frailty status (robust, pre-frail/frail). Results: Diabetes prevalence increased with age (Table). Diabetes was associated with large PAFs of dementia by age 80 in midlife through early late-life (Table) (e.g., PAF: 45-54, 7.9% [95% CI: 6.2-9.1%]; 65-74, 18.4% [95% CI: 14.1-22.0%]). PAFs of dementia by age 90 were of a smaller magnitude (Table) (e.g., PAF: 45-54, 6.5% [95% CI: 5.2-7.6%]; 65-74, 8.2% [95% CI: 6.2-9.9%]). PAFs were 8-fold larger among robust individuals relative to pre-frail/frail individuals (Table). Conclusions: Up to 18% of incident dementia was attributed to diabetes through age 74. Diabetes after age 74 might be associated with a large fraction of dementia among people without frailty.

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