Description
The earliest observed deficits in Alzheimer’s Disease (AD) are in the sense of smell. To understand this, this study will examine the effect of the Apolipoprotein E Epsilon 4 (ApoE ε4) allele, a genetic risk factor for AD, and gender on functional connectivity (FC) of two olfactory memory regions; the hippocampus and the perirhinal cortex (PC). Archival data from 39 older adults above the age of 65 (19 male, 20 female) were used in this study. Participants were genotyped to detect the presence of the ε4 allele. 4 subjects who possessed the ApoE ε2 allele, a potential protective factor against AD development, were removed from the sample, leaving 35 older adults. There were 19 ε4 negative participants (9 male, 10 female) and 16 ε4 positive participants (9 male, 7 female). Participants completed an odor identification task and the Mattis Dementia Rating Scale (DRS) prior to MRI scans. Immediately prior to MRI scanning, participants were asked to smell and remember 16 odors. During a functional MRI scan, participants were presented with verbal labels and asked whether they remembered smelling the corresponding odor immediately prior to scanning. Seed-based FC analyses were performed using the left and right hippocampus and PC as regions of interest (ROI), producing time based beta-weights in each voxel for both ROIs during correct recognition. Odor identification performance, DRS score, odor memory hits and false positives, and age were compared between genders and ε4 statuses using independent t-tests. For each ROI, FC was entered into a regression equation with gender, ε4 status, and ApoE x gender interaction effects as independent variables. ApoE ε4 carriers showed increases in frontal FC with the MTL and decreases in FC between the MTL and parietal regions. Females showed widespread increases in MTL-cortical connectivity when compared to males. ε4 carrier females, however, showed widespread decreases in MTL-cortical connectivity, perhaps indicating that female ε4 carriers are at the greatest risk for AD development due to earlier disconnections between the MTL and cortical processing areas.
