Associations of dementia polyexposure scores to Alzheimer's disease endophenotypes in a diverse population.

INTRODUCTION

Dementia clinical risk scores (CRSs) provide accessible tools for identifying individuals at risk for Alzheimer's disease (AD) and related dementias, yet their performance across diverse populations and relationships to AD endophenotypes remains unclear.

METHODS

We evaluated four CRSs, modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (mCAIDE), Washington Heights-Inwood Columbia Aging Project (WHICAP), Lifestyle for Brain Health (LIBRA), and Cognitive Dementia Risk (CogDRisk), in relation to cognitive impairment (CI) and AD endophenotypes, including tau phosphorylated at threonine 217 (pTau217)/amyloid beta 42 (Aβ42) positivity defined using a Youden index-derived cutoff for amyloid positron emission tomography (PET) positivity. Logistic and linear regression models stratified by self-reported race/ethnicity were used to assess the associations of CRS with endophenotypes and CI and to evaluate predictive performance.

RESULTS

CogDRisk showed the strongest and most consistent performance across endophenotypes, pTau217/Aβ42 positivity, and CI, with mCAIDE performing the worst and lacking associations with plasma biomarkers. Higher CRS were consistently associated with increased odds of dementia across all races/ethnicities.

CONCLUSIONS

CRSs capture AD-related risk across diverse populations and modestly reflect underlying biological endophenotypes, supporting their utility in community-based risk assessment.