Social determinants of health and risk of dementia in people with and without type 2 diabetes - findings from two large national-scale cohorts.

INTRODUCTION: Explore association between a weighted social determinants of health (SDOH) score and incident dementia in adults with and without type 2 diabetes (T2D). METHODS: Among 10,071 UK Biobank adults with T2D and 11,780 euglycemic individuals, SDOH indicators were weighted using elastic net and categorized as favorable, medium, or unfavorable. Sex- and T2D-stratified associations with incident dementia were estimated using multivariable Cox models and validated in All of Us. RESULTS: Over 14 years of follow-up in UKB, 247 T2D and 149 euglycemic participants developed dementia. In T2D, higher SDOH score was significantly associated with increased risk of all-cause dementia. Comparing unfavorable vs. favorable SDOH, hazard ratios (HRs) were 2.4 (95% CI: 1.7-3.6) overall, 1.7 (1.1-2.6) in men, and 5.4 (2.0-13.9) in women (Sex-interaction p 0.009). In euglycemic, corresponding HRs were 2.4 (1.4-3.8) overall, 2.4 (1.3-4.3) in men, 2.9 (0.9-8.9) in women. Stratified by SDOH category, T2D (vs. euglycemia) was significantly associated with higher dementia risk in the unfavorable/medium SDOH group: 2.9 (1.8-4.6) in all,1.7 (0.8-3.6) in men, and 3.1 (1.1-8.7) in women. CONCLUSIONS: Adverse SDOH was associated with higher dementia risk, with stronger T2D-related risk among medium/unfavorable SDOH groups, especially in women with T2D.