Sensitivity analyses across diagnostic strata, after outlier exclusion, and in multi-visit subsamples confirmed the robustness of hippocampal volume effects.<h4>Discussion/conclusion</h4>These findings demonstrate that APOE ε4 genotype significantly modulates the longitudinal relationship between hippocampal volume and cognitive decline, supporting the integration of APOE genotype and structural hippocampal imaging for refined individual risk stratification in Alzheimer's disease. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.