APOE and Alzheimer disease: Our key novel findings include: (1) lifestyle-reserve risk score alone had the highest predictive power for EF decline, (2) APOE moderated the association between M-CRS and EF performance and decline where only adults in the APOE ε4− group were significantly influenced by higher modifiable risk scores, (3) further AD-GRS genetic stratification in APOE ε4− provided a more precise illustration of older adults with the highest risk profile for EF decline.