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Coughlan, Gillian, Zhukovsky, Peter, Puthusseryppady, Vaisakh, Gillings, Rachel, Minihane, Anne-Marie 
ORCID: https://orcid.org/0000-0001-9042-4226, Cameron, Donnie ORCID: https://orcid.org/0000-0001-9841-6909 and Hornberger, Michael ORCID: https://orcid.org/0000-0002-2214-3788
(2020)
Functional connectivity between the entorhinal and posterior cingulate cortices underpins navigation discrepancies in at-risk Alzheimer’s disease.
Neurobiology of Aging, 90.
pp. 110-118.
ISSN 0197-4580
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Abstract
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.
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