Functional Connectivity in Hippocampal Sub‐Regions as a Function of Age, Sex, and ApoE e4 Status

Abstract

BackgroundOlfactory disturbances, thought to be related to preclinical neuropathology and functional decline of the medial temporal lobe, are a reliable predictor of later Alzheimer’s Disease (AD) onset (Murphy, 2019). This study focused on the relationship between hippocampal functional connectivity, olfaction, and risk factors for AD by studying the sub‐regions of the hippocampus independently.MethodFunctional and structural MRIs were obtained at 3T from 29 non‐demented older adults, genotyped for ApoE allele status. Archival functional data collected during correct recognition of verbal labels for odors presented prior to scanning were analyzed. Seed‐to‐voxel FC was calculated for six regions of interest (ROIs), including the dorsal and ventral dentate gyrus (dDG and vDG), subiculum, and CA fields 1‐3. The relationship between FC and age, ApoE, and sex was assessed using multiple linear regression.ResultIn the left vDG, decreased FC with the precuneus was observed in e4 positive older adults, while anterior cingulate gyrus FC increases were associated with the interaction of age, gender, and ApoE e4 status. In the right vDG, the presence of an ApoE e4 allele and increasing age were associated with decreased FC with the right anterior precuneus and increased FC with the right posterior precuneus, whereas there was a negative interaction effect between ApoE e4 and age in the posterior precuneus and a positive interaction effect in the anterior precuneus.ConclusionDifferential FC with the anterior precuneus, involved in self‐referential processing, and posterior precuneus, normally involved in successful memory retrieval, suggests that early risk factors result in greater reliance on posterior parietal processing, with the interaction effect implying that genetic risk and increasing age may result in FC patterns reflective of precuneus connectivity in preclinical AD (Cavanna & Trimble, 2006; Klaassens et al., 2017). The vDG may be of special importance because it is associated with odor memory processing (Kesner, 2018). Further research should focus on hippocampal sub‐region FC during olfactory processing.Supported by NIH grant # AG062006‐04 to CM. Special thanks to Aaron Jacobson, Lori Haase, Erin Green, MiRan Wang, and Vincent Rupp for data collection efforts.