We used GAM to analyze the relationship between hippocampal volume and age, stratified by APOE genotype. We aimed to identify the age at which volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly diverged from those of ε3/ε3 carriers (Figure 3). Our analysis confirmed a significant non‐linear relationship between hippocampal volume and age across APOE genotypes (p < 2.0 × 10−16), as expected. Hippocampal volume in ε4/ε4 carriers began to deviate significantly from the ε3/ε3 trajectory at age 61, showing an accelerated decline, while significant deviation for ε3/ε4 carriers occurred at age 69. Conversely, ε2/ε3 carriers show a slower rate of decline in hippocampal volume compared to ε3/ε3 carriers starting at age 76.
