The influence of genetic risk on dementia can be shaped by social environments. Following older adults without dementia at baseline for 12 years in two large cohorts—Health and Retirement Study (HRS) and English Longitudinal Study of Ageing (ELSA), we examine how APOE alleles interact with social adversity to determine dementia risk. A social adversity index is constructed based on five domains of social determinants of health outlined in the Healthy People 2030: education access, economic stability, healthcare quality, neighborhood environment, and social context. Participants are classified as having low (APOE-?2), intermediate (APOE-?3/?3), or high (APOE-?4) genetic risk of dementia. Dementia is ascertained via clinical diagnosis, cognitive testing, or validated caregiver report. Genetic effects are most pronounced among individuals with social advantage. In contrast, those experiencing high social adversity have elevated dementia risk regardless of genotype. Notably, individuals with high genetic risk but social advantage have lower dementia risks than those with low genetic risk but high social adversity. Addressing social adversity may reduce dementia risk across genotypes and enhance equity in dementia prevention.
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