Apolipoprotein E genotype, gender and age modulate connectivity of the hippocampus in healthy adults

Important risk factors for Alzheimer's disease (AD) are ageing and the Apolipoprotein E (APOE) epsilon 4 allele, with female APOE epsilon 4 carriers having the greatest risk. In this study we investigated effects of AD risk factors on connectivity of the hippocampus, a structure that shows early AD related pathology. Resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 86 cognitively healthy subjects aged 30 to 78 years were analysed. Female APOE epsilon 4 carriers showed overall significantly reduced functional connectivity between the hippocampus and precuneus/posterior cingulate cortex (PCC) and a significant age-related decrease in connectivity of these regions. In females and APOE epsilon 4 carriers we found significantly reduced white matter integrity of the tract connecting the hippocampus and PCC with a significant positive correlation of white matter integrity and resting-state connectivity. Increased vulnerability of the connection between the hippocampus and PCC might be one reason for increased AD risk in female APOE epsilon 4 carriers. Interventions targeting hippocampal connectivity might be especially effective in this at risk population. (C) 2014 Elsevier Inc. All rights reserved.