Functional connectivity is altered by APOE4 carrier status in cognitively healthy older adults

Abstract

AbstractBackgroundResting‐state connectivity allows for investigating brain network changes in pathologic states of aging, such as Alzheimer’s Disease (AD). Recently, brain network changes have been associated with AD‐related risk factors in asymptomatic individuals. We explored how brain network connectivity is affected by one such risk factor, apolipoprotein e4 (APOE4) carrier status.MethodsIn a sample of cognitively healthy older adults (n=102), we acquired demographic information, APOE4 carrier status, and resting‐state fMRI scans. Individuals were designated as “APOE4 carrier” by the presence of at least one APOE4 allele. No APOE2 carriers were included in the analyses. Using independent component analysis approaches for both individual de‐noising and group‐level analysis, we identified key brain networks traditionally associated with AD‐related decline. Utilizing nonparametric permutation inference, we tested for differences in connectivity to these networks based on APOE4 carrier status.ResultsWe identified multiple networks with altered functional connectivity across groups, including networks associated with AD‐related decline. One key region, the anterior cingulate cortex, showed differences in connectivity with multiple resting state networks. Functional connectivity in these networks was decreased in APOE4 carriers compared to non‐carriers.ConclusionWe highlight changes in functional connectivity dependent upon genetic risk. Our results add to a growing body of evidence that APOE4 carrier status, along with other risk factors for AD, alter large‐scale functional networks. Additional characterization of the interaction of APOE4 status and other AD‐related biomarkers on functional connectivity is warranted.