Higher Fat-Related Body Composition Measurement and Lower Resting-State Inter-Network Functional Connectivity of APOE ε4 Carrier in Mild Cognitive Impairment Patients With Aβ Deposition

Objective We aimed to evaluate the impact of interaction between APOE ε4 carrier status and body composition measurements on in-tra-and inter-regional functional connectivity (FC) in mild cognitive impairment (MCI) patients with Aβ deposition. Methods MCI patients with and without APOE ε4 allele (carrier, n=86; non-carrier, n=95) underwent neuropsychological battery, rest-ing-state functional magnetic resonance imaging scans, positron emission tomography scans with [¹⁸F]flutemetamol, and bioelectrical impedance analysis for measuring body composition. We employed a priori defined regions of interest to investigate the intra-and internetwork FC profiles of default mode network (DMN), central executive network (CEN), and salience network. Results There was a significant interaction of APOE ε4 carrier status with body fat mass index, visceral fat area, and waist-hip circum-ference ratio for inter-network FC between DMN and CEN, contributing higher fat-related body composition measurements in the APOE ε4 carrier with lower DMN-CEN FC. Conclusion The present results highlight the detrimental effect of APOE ε4 carrier status on the associations between the fat-related body composition measurements and FC in the MCI patients with Aβ accumulation.