Objective: We investigated the association between APOE e4 status and spatial navigation in patients with amnestic mild cognitive impairment (aMCI) and assessed the role of hippocampal volume in this association. Method: Participants were 74 patients with clinically confirmed aMCI (33 APOE e4 noncarriers, 26 heterozygous, and 15 homozygous e4 carriers). Body-centered (egocentric) and world-centered (allocentric) spatial navigation in a computerized human analogue of the Morris Water Maze was assessed. Brain MRI with subsequent automated hippocampal volumetry was included. Results: Groups were similar in neuropsychological profile. Controlling for age, sex, education, and free memory recall, the APOE e4 carriers performed more poorly on all spatial navigation subtasks (ps< .05). APOE e4 homozygotes performed worse than heterozygotes (p = .021). Right hippocampal volume accounted for the differences in allocentric and delayed subtasks (ps >.05), but not in the egocentric subtask (p < .001). Conclusions: Using an easy-to-use, computer-based tool to assess spatial navigation, we found spatial navigation deficits to worsen in a dose-dependent manner as a function of APOE e4 status. This was at least partially due to differences in right hippocampal volume.
