Effect of APOE ε4 Status on Intrinsic Network Connectivity in Cognitively Normal Elderly Subjects

Objective: To examine default mode and salience network functional connectivity as a function of APOE epsilon 4 status in a group of cognitively normal age-, sex-, and education-matched older adults. Design: Case-control study. Subjects: Fifty-six cognitively normal APOE epsilon 4 carriers and 56 age-, sex- and education-matched cognitively normal APOE epsilon 4 noncarriers. Main Outcome Measure: Alterations in in-phase default mode and salience network connectivity in APOE epsilon 4 carriers compared with APOE epsilon 4 noncarriers ranging from 63 to 91 years of age. Results: A posterior cingulate seed revealed decreased in-phase connectivity in regions of the posterior default mode network that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the epsilon 4 carriers relative to APOE epsilon 4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE epsilon 4 carriers vs noncarriers. There were no groupwise differences in brain anatomy. Conclusions: The observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE epsilon 4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.