Increased fMRI Activity with Age in Left Temporal Lobe of Familial Alzheimer's Disease Mutation Carriers

Abstract

regard to APOE-related volumetric changes in mild cognitive impairment (MCI) and normal aging. The MTL is the earliest site of AD pathology, and autopsy studies have demonstrated that MTL pathophysiological changes occur in AD prodromal stages. Thus, we examined for APOE genotypic differences in cortical thickness in normally aging and MCI individuals in the following MTL structures: hippocampus, entorhinal cortex, fusiform gyrus, and parahippocampal gyrus. Methods: Fifty-nine nondemented participants were divided into demographically similar groups based on cognitive status (MCI: n 1⁄4 28; NC: n 1⁄4 29). APOE genotyping was conducted and Freesurfer-derived volumetric and cortical thickness values of MTL structures were compared across groups. Results: Despite no differences in hippocampal volumes or cortical thickness, participants possessing the e4 allele demonstrated significantly decreased thickness of the fusiform gyrus (p 1⁄4 .01), entorhinal cortex (p1⁄4 .002), and parahippocampal gyrus (p1⁄4 .04) relative to those without the e4 allele. Additionally, findings were considerably stronger in the right versus left hemisphere for all significant cortical thickness volumes (all pvalues < .01). Further, APOE-e4 status was predictive of MTL substructure thickness after adjusting for age, stroke risk, and hippocampal volumes. Conclusions: Possession of the APOE-e4 allele was strongly associated with cortical thickness of MTL substructures within our sample of nondemented older adults. Findings were independent of MCI status, hippocampal volumes, and stroke risk, suggesting that, even in the context of normal aging, possession of the APOE-e4 allele is associated with subtle alterations in cortical thickness in MTL structures implicated in the pathogenesis of AD. Interestingly, results revealed hemispheric differences by regional cortical thickness of MTL structures, suggesting a possible right hemisphere predilection for neurobiological changes associated with the APOE-e4 allele.