Abstract
INTRODUCTION: Neighborhood environments are important social determinants of cognitive health, yet the potential mechanisms underlying neighborhood environments and dementia risk remain poorly understood. This study investigates whether cardiometabolic risk mediates the association between neighborhood disorder and subsequent dementia risk. METHODS: This cohort study analyzed data from the Health and Retirement Study (HRS, 2006-2020), a nationally representative sample of community-dwelling adults aged 51 years or older. Dementia status was identified using the validated Langa-Weir classification algorithm. Neighborhood disorder was assessed with an interviewer-reported checklist. Cardiometabolic risk was quantified as a composite score derived from seven biomarkers across inflammatory, cardiovascular, and metabolic systems. Inverse probability-weighted Cox proportional hazards models were employed to examine the association between neighborhood disorder and time to dementia. Mediation analyses were performed to assess the mediating effects of cardiometabolic risk. Data were collected in 2006-2020 and analyzed in 2025. RESULTS: Among the 9,426 participants, 1,747 (18.5%) developed dementia over a 14-year follow-up. After adjustment for covariates, living in disordered neighborhoods was associated with a higher risk of dementia (Hazard Ratio (HR): 1.37; 95% CI: 1.08-1.74) and cognitive impairment no dementia (CIND, HR: 1.50; 95% CI: 1.22-1.85). Cardiometabolic risk mediated 16.2% of the association between neighborhood disorder and dementia, and 19.3% of the association with CIND. CONCLUSIONS: Neighborhood disorder could be a significant risk factor for dementia, and this relationship is partially mediated by cardiometabolic health. Community initiatives that address neighborhood stressors and cardiometabolic risk may reduce dementia risk and support healthy aging in place.