Associations of dementia polyexposure scores to Alzheimer’s disease endophenotypes in diverse populations

INTRODUCTION: Dementia clinical risk scores (CRS) provide accessible tools for identifying individuals at risk for Alzheimer's disease (AD), yet their performance across diverse populations and relationships to AD endophenotypes remains unclear. METHODS: We evaluated four CRS, mCAIDE, WHICAP, LIBRA, and CogDRisk, in relation to cognitive impairment diagnoses and endophenotypes for AD, including plasma biomarkers, neuroimaging measures, and cognitive composite scores. Logistic and linear regression models stratified by self-reported race/ethnicity were used to assess the associations of CRS with diagnosis and their predictive performance, and associations with endophenotypes. RESULTS: Higher CRS were consistently associated with increased odds of dementia across all races/ethnicities. CogDRisk showed the strongest and most consistent performance across diagnostic and endophenotypic outcomes. The other three CRS performed similarly, with mCAIDE performing the worst and lacking associations with plasma biomarkers. CONCLUSIONS: CRS capture AD-related risk across diverse populations and modestly reflect underlying biological endophenotypes, supporting their utility in community-based risk assessment.