Comorbid diabetes and hypertension in early adulthood predict neurodegeneration in midlife: insights across racial/ethnic groups using a blood‐based biomarker of dementia risk

Abstract INTRODUCTION Cardiometabolic conditions have been linked to increased dementia risk, but their influence on early neurodegenerative processes – and whether it differs by race/ethnicity – remains unclear. We examined whether early‐adulthood diabetes and/or hypertension predicted midlife serum neurofilament light chain (sNfL), a neurodegeneration biomarker, and whether associations differed among White, Black, and Hispanic adults. METHODS Data from 4173 participants in the National Longitudinal Study of Adolescent to Adult Health study were analyzed. Diabetes and hypertension were assessed at Waves 4 (lagged effects) and 5 (concurrent effects); sNfL was measured at Wave 5. Regression models tested associations overall and by race/ethnicity. RESULTS Comorbid hypertension and diabetes consistently predicted higher sNfL across waves, while single conditions showed minimal effects. Wave 4 comorbidity had stronger associations than Wave 5, suggesting early dysregulation has a greater neurobiological impact. Racial/ethnic stratification revealed few differences, with isolated divergences among Hispanic participants. DISCUSSION Cardiometabolic conditions shape neurological health decades before old age, underscoring targets for prevention and health equity.