Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory.

Apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE epsilon4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition-memory performance between AD-symptom-free carriers (N=30) and non-carriers (N=30) of the APOE epsilon4 (age range: 49-79 years). We observed reduced right hippocampal volume in APOE epsilon4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE epsilon4 carriers made significantly more false alarms in the recognition-memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.