Dementia risk scores, apolipoprotein E, and risk of Alzheimer's disease: One size does not fit all

INTRODUCTION Evaluating the generalizability of dementia risk scores, primarily developed in non‐Latinx White (NLW) participants, and interactions with genetic risk factors in diverse populations is crucial for addressing health disparities. METHODS We analyzed the association of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) and modified CAIDE (mCAIDE) scores with dementia risk using logistic regression models stratified by race/ethnicity in National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), and assessed their interaction with apolipoprotein E (APOE). RESULTS Higher CAIDE scores were associated with an increased risk of dementia in Asian, Latinx, and NLW participants but not in Black participants. In contrast, higher mCAIDE scores were also associated with an increased risk of dementia in Black participants. Unfavorable mCAIDE risk profiles exacerbated the apolipoprotein E*ε4 (APOE*ε4) risk effect and attenuated the APOE*ε2 protective effect. DISCUSSION Our findings underscore the importance of evaluating the validity of dementia risk scores in diverse populations for their use in personalized medicine approaches to promote brain health. Highlights Dementia risk scores demonstrate race/ethnic‐specific effects on dementia risk. Unfavorable modifiable risk profiles moderate the effect of APOE on dementia risk. Dementia risk scores need to be validated in diverse populations.