Examining the Interactive Effect of Cardiovascular Risk Factors and APOE Genotype on Population Health Disparities in dementia risk

Abstract

AbstractBackgroundThere is a need to better understand the role of modifiable risk factors in the development of racial/ethnic health disparities in Alzheimer’s disease (AD). In particular, research is lacking on how clinical risk scores may interact with genetic liability for dementia in diverse populations. Here, we examined the influence of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (CAIDE) and APOE genotype on MCI/Dementia risk in non‐Latinx White (NLW), Black, and Latinx populations.MethodParticipants were from the National Alzheimer’s Coordinating Center Uniform Dataset who self‐reported as NLW (n = 15,296), Black (n = 2,136), or Latinx (n = 955) who were either cognitively normal or had a clinical diagnosis of MCI/Dementia at baseline (Table 1). CAIDE is comprised of age, gender, years of education, hypertension, obesity, and hypercholesteremia with scores ranging from 0‐14. Logistic regression models stratified by race/ethnicity were used to examine the association between CAIDE, APOE genotype, or their combination (9 categories combining favorable, intermediate, and unfavorable CAIDE scores with APOE e3/e3, e2+, and e4+) on MCI/dementia (Fig. 1‐2). Population differences were determined using Fisher’s z‐score method.ResultsAPOE e2+ was associated with reduced odds of MCI/dementia in NLW participants, while APOE e4+ was associated with increased risk in Latinx, Black, and NLW participants. Higher CAIDE scores were associated with increased risk of MCI/dementia in Latinx and NLW but were non‐significant in Black participants. The association of CAIDE on MCI/dementia in Black participants was significantly different from that in NLW and Latinx participants. Similarly, the effect of APOE e4+ on the risk of MCI/dementia was weaker in Latinx compared to NLW participants. In NLW, increasingly unfavorable modifiable risk profiles attenuated the protective effect of APOE e2+ and accentuated the deleterious impact of APOE e4+ on MCI/dementia. In Black participants, modifiable risk factors did not significantly affect the relationship between APOE genotype and MCI/dementia; in Latinx participants, there was only a moderate effect.ConclusionThe risk associated with APOE on MCI/Dementia is moderated by modifiable risk factors with suggestive population‐specific effects. Addressing health disparities will require risk scores that combine clinical, genetic, and social determinants of health and are applicable across diverse populations.