While both are independently associated with cognitive decline, whether APOE ε4 dose modulates the hippocampal volume-cognition relationship longitudinally in sporadic Alzheimer's disease remains underexplored at adequate statistical power.<h4>Methods</h4>This study analyzed data from 2,417 Alzheimer's Disease Neuroimaging Initiative participants with complete APOE genotypes, intracranial volume-adjusted hippocampal volumes, and longitudinal cognitive assessments spanning a mean follow-up of 4.2 years and up to 19.3 years with an average of 4.9 visits per participant. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.