Functional connectivity between the entorhinal and posterior cingulate cortices underpins navigation discrepancies in at-risk Alzheimer's disease

• DOI: 10.1016/j.neurobiolaging.2020.02.007
• Publication Date: 2020-02-19T07:36:22Z
• Authors: Gillian Coughlan; Peter Zhukovsky; Vaisakh Puthusser...; Rachel Gillings; Anne-Marie Minihane; Donnie Cameron; Michael Hornberger
• Keywords: Male; Risk; 0301 basic medicine; APOE genotype; Genotype; 150; 610; Path integration; Middle Aged; Preclinical Alzheimer's disease; Spatial navigation; Gyrus Cinguli; 3. Good health; Functional connectivity; Executive Function; 03 medical and health sciences; Apolipoproteins E; Cognition; Alzheimer Disease; Entorhinal Cortex; Humans; Female; Aged; Spatial Navigation

Navigation processes that are selectively mediated by functional activity in the entorhinal cortex may be a marker of preclinical Alzheimer's disease (AD). Here, we tested if a short path integration paradigm can detect the strongest genetic-risk phenotype of AD in large sample of apolipoprotein E (APOE)-genotyped individuals. We also examined the associations between APOE-mediated navigation process, subjective cognitive decline, and rest-stating network connectivity. Navigation discrepancies classified 77% the APOE-genotyped cohort into their respective low-risk ε3ε3 and high-risk ε3ε4 categories. When connectivity strength between entorhinal and the posterior cingulate cortices (also a functional correlate of strongest APOE-dependant behavioral characteristics) was considered, this classification accuracy increased to 85%. Our findings present a whole picture of at-genetic-risk AD, including select impairment in path integration, self-report cognitive decline, and altered network activity that is reminiscent of the pathological spread of preclinical AD disease. These findings may have important implications for the early detection of AD.