BACKGROUND: Hippocampal atrophy is implicated in the early onset of Alzheimer's disease (AD). It is closely associated with rapid cognitive decline and serves as a critical predictor for conversion from mild cognitive impairment (MCI) to AD. Consequently, with growing interest in utilizing hippocampal volume (HV) as an outcome measure in clinical trials, elucidating the neurobiological mechanisms underlying hippocampal atrophy is essential for early diagnosing AD and predicting its progression. OBJECTIVE: The risk of AD associated with the apolipoprotein E ε4 ( METHODS: This hospital-based prospective longitudinal study included 73 patients with aMCI. ΔHV, the major outcome measure, was assessed using magnetic resonance imaging performed at a baseline date and 2 years after the baseline evaluation. A two-way analysis of variance was conducted to examine the effects of the interaction between the RESULTS: A significant interaction was observed between CONCLUSIONS: We identified that the