Background/Aims: Because of conflicting findings across studies, we sought to better determine the relationship between apolipoprotein E (APOE) genotype, hippocampal volume, and cognitive performance in nondemented older adults. Methods: Two groups ofolder adults, as determined by their APOE Ε4 allele status, received structural MRI and comprehensive neuropsychological testing on two occasions separated on average by 17 months. Results: Cross-sectional comparisons by APOE group revealed no differences in hippocampal volumes, although longitudinal percent reduction in hippocampal volume was significantly greater for those possessing the APOE Ε4 allele. Relationship between hippocampal volumes and memory performance was strongly impacted by diagnosis of mild cognitive impairment. Conclusions: APOE Ε4 allele appears to significantly impact rate of volume loss over time in the hippocampus in nondemented older adults, and detailed cognitive characterization of the sample is necessary to reliably interpret the relationship between cognition and brain structure.

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