APOE ε4 and CVH Interaction on Brain Age and Brain PAD: A Study of Interactive Effects

This study explored the association between cerebrovascular health (CVH) score and brain age and brain PAD, considering the influence of APOE ε4 status. After stratifying by APOE ε4, the association between CVH score and brain age was stronger among APOE ε4 carriers (β [95% CI]: -0.030 [-0.037, -0.023]) than among APOE ε4 non-carriers (β [95% CI]: -0.028 [-0.032, -0.024]) for every 1-point increment in CVH score. Conversely, the association between CVH score and brain PAD was weaker among APOE ε4 carriers (β [95% CI]: -0.032 [-0.038, -0.026]) compared to older participants (β [95% CI]: -0.033 [-0.036, -0.029]). Furthermore, the association between CVH and brain age (or brain PAD) was weaker for low CVH (vs moderate CVH) and stronger for high CVH (vs moderate CVH) among APOE ε4 carriers compared to APOE ε4 non-carriers. These findings suggest that CVH (both continuous and categorical) and APOE ε4 have interactive effects on brain age and brain PAD when adjusting for age, sex, and education (P<0.10). However, when additional covariates were included in the model (Model 2), the interaction between CVH and APOE ε4 on these outcomes was no longer significant (P>0.10).