APOE ɛ4 Influences Within and Between Network Functional Connectivity in Atypical Alzheimer Disease (P11-6.006)

Abstract

<h3>Objective:</h3> To assess functional connectivity in posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) and evaluate how within and between-network functional connectivity differs based on the apolipoprotein E (<i>APOE)</i> ɛ4 status. <h3>Background:</h3> <i>APOE</i> ɛ4 influences atrophy and tau deposition in patients with atypical Alzheimer’s disease (AD), with <i>APOE</i> ɛ4 carriers having greater predisposition to medial temporal involvement. This raises questions on whether the <i>APOE</i> genotype would influence memory network connectivity, a network mainly comprised of medial temporal structures. <h3>Design/Methods:</h3> One-hundred forty amyloid-positive PCA (n=58) and LPA (n=82) patients were recruited by the Neurodegenerative Research Group and underwent structural and resting state functional MRI. Spatially preprocessed data were analyzed to explore the default mode network (DMN), salience, language, visual and memory networks, using a region of interest approach in Conn toolbox. Bayesian hierarchical linear models (BHLM) adjusted for age and sex, assessed the influence of APOE ɛ4 on within and between-network connectivity. <h3>Results:</h3> We found reduced within-network connectivity in the memory and language networks in LPA, with an increase in salience network connectivity in PCA, in <i>APOE</i> ɛ4 carriers compared to non-carriers. <i>APOE</i> ɛ4 did not influence memory within-network connectivity in PCA. Between-network analysis showed evidence of reduced connectivity from the DMN in both groups, with reduced DMN-to-salience and DMN-to-language network connectivity in PCA <i>APOE</i> ɛ4 carriers, and reduced DMN-to-visual network connectivity in LPA <i>APOE</i> ɛ4 carriers. In addition, we found reduced connectivity from the visual-to-language and visual-to-salience networks in <i>APOE</i> ɛ4 carriers compared to non-carriers in both PCA and LPA. Both network-level and voxel-level findings concurred with the BHLM findings, specifically showing reductions in the within-network connectivity for the memory network in LPA <i>APOE</i> ɛ4 carriers. <h3>Conclusions:</h3> The <i>APOE</i> genotype influences brain connectivity, both within and between-networks, in atypical AD variants. However, there was evidence that the modulatory effects of <i>APOE</i> differ across phenotype. <b>Disclosure:</b> Dr. Singh has nothing to disclose. Mr. Martin has nothing to disclose. Dr. Graff-Radford has received personal compensation for serving as an employee of Mayo Clinic. Dr. Graff-Radford has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NINDS/NIH. Dr. Graff-Radford has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. The institution of Dr. Graff-Radford has received research support from NIH. The institution of Dr. Machulda has received research support from NIH. Minerva Carrasquillo has nothing to disclose. The institution of Dr. Taner has received research support from NIH. Dr. Josephs has nothing to disclose. Dr. Whitwell has nothing to disclose.