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Introduction: Prior studies suggest that 15-20% of adults will develop dementia after midlife. However, current lifetime risk estimates are based on limited dementia ascertainment, potentially resulting in underestimation. Methods: We conducted a prospective cohort analysis using data from the Atherosclerosis Risk in Communities Study (ARIC) (baseline 1990-1992). We used non-parametric cumulative incidence function estimation to calculate lifetime risk of dementia while accounting for the competing risk of death, overall and stratified by demographics and APOE ε 4 status. Dementia was ascertained until December 31, 2019 by: (1) cognitive testing at study visits, with diagnoses generated using a standardized computer algorithm and confirmed by a panel of experts; (2) semiannual telephone cognitive testing and Clinical Dementia Rating interviews with informants; and (3) ICD codes from hospital records and death certificates. Results: We included 13,358 participants (mean age: 57 years; 25% of Black race; 55% female sex; 31% carried at least one APOE ε 4 allele). Over a median follow-up of 24 (IQR: 20, 29) years, there were 2,812 incident cases of dementia. At age 55, the lifetime risk of dementia (up to age 95) was 43% (Fig A) . Adults with two copies of the APOE ε 4 allele had substantially higher lifetime risk (61%) of dementia compared to those with one copy (48%) and those none (40%), with differences beginning at age ~70 years (Fig B) . Lifetime risk was higher in women and Black adults (Fig C-D) . Conclusion: More than 4 in 10 adults will develop dementia after midlife. Comprehensive capture of dementia in the ARIC study results in lifetime risk estimate substantially exceeding prior research.
Fang et al. (Tue,) studied this question.