2263-P: Independent Association of Social Determinants of Health Score and Risk of Mild Cognitive Impairment and Dementia among People with Type 2 Diabetes: Findings from the All of Us Research Program

Introduction and Objective: Social determinants of health (SDOH) are key drivers of outcomes in type 2 diabetes (T2D). We examined the association between a composite SDOH score and incident mild cognitive impairment (MCI) and dementia, accounting for genetic risk and conventional risk factors. Methods: We analyzed data from 13,429 dementia-free adults with T2D in the All of Us Research Program. SDOH encompassed race and 21 indicators across five domains including: economic stability, education access and quality, health and health care, neighborhood and built environment, and social and community context. Weighted, standardized SDOH-MCI/dementia scores were derived via elastic-net penalized models. Cox regressions were used to assess the association between SDOH score and MCI and dementia, respectively, adjusting for age, diabetes duration, sex, race, anti-diabetes/hypertension medications, lipid-lowering medications, and Alzheimer’s disease-polygenic risk score. Linearity was evaluated using restricted cubic splines. Results: Over a median follow-up of 3 years, 488 participants developed MCI and 131 developed dementia. Each 1-SD increase in the SDOH score was associated with 24% or 73% higher risk of MCI (Hazard ratio: 1.24, 1.73) and dementia (1.12-1.37, 1.48-2.02, respectively). Compared with the lowest SDOH tertile, highest and moderate tertiles of SODH score was significantly associated with increased risk of MCI 1.17 (0.91-1.50) and 1.61 (1.27-2.03) and dementia 1.67 (0.95-2.95) and 4.90 (2.92-8.22) (both p-trend e-5). In addition, male participants were associated with a lower risk of incident MCI compared to female (HR: 0.68, 0.56-0.82). Spline analyses indicated linearity for MCI and dementia. Conclusion: In a large, diverse U.S. cohort of adults with T2D, higher SDOH risk scores were independently associated with greater risk of MCI and dementia. Incorporating SDOH score may enhance cognitive risk stratification among people with T2D. Disclosure Y. Lu: None. D. Li: None. Y. Yoshida: None. Funding American Diabetes Association (7-23-JDFWH-10), National Institute of General Medical Sciences of the National Institutes of Health (1P20GM152305), Administrative Supplement of the Louisiana Clinical & Translational Science Center (U54 GM104940).