title: APOE-ε4 Allele Altered the Rest-Stimulus Interactions in Healthy Middle-Aged Adults.
abstract: The apolipoprotein E-ε4 allele is a well-known genetic risk factor for late-onset Alzheimer's disease, which also impacts the cognitive functions and brain network connectivity in healthy middle-aged adults without dementia. Previous studies mainly focused on the effects of apolipoprotein E-ε4 allele on single index using task or resting-state fMRI. However, how these evoked and spontaneous BOLD indices interact with each other remains largely unknown. Therefore, we evaluated the 'rest-stimulus interaction' between working-memory activation and resting-state connectivity in middle-aged apolipoprotein E-ε4 carriers (n=9) and non-carriers (n=8). Four n-back task scans (n = 0, 1, 2, 3) and one resting-state scan were acquired at a 3T clinical MRI scanner. The working-memory beta maps of low-, moderate-, and high-memory loads and resting-state connectivity maps of default mode, executive control, and hippocampal networks were derived and compared between groups. Apolipoprotein E-ε4 carriers presented declined working-memory activation in the high-memory load across whole brain regions and reduced hippocampal connectivity compared with non-carriers. In addition, disrupted rest-stimulus interactions were found in the right anterior insula and bilateral parahippocampal regions for middle-aged adults with apolipoprotein E-ε4 allele. The rest-stimulus interaction improved the detectability of network integrity changes in apolipoprotein E-ε4 carriers, demonstrating the disrupted intrinsic connectivity within the executive-functional regions and the modulated memory-encoding capability within hippocampus-related regions.
authors.affiliation: Department of Radiology, Taipei Medical University-Shuang-Ho Hospital, New Taipei City, Taiwan; Brain and Consciousness Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Feng-Xian
authors.initials: FX
authors.lastname: Yan
authors.affiliation: Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan; Brain and Consciousness Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Changwei W
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Graduate Institute of Medical Mechatronics, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chao
authors.affiliation: Department of Radiology, Taipei Medical University-Shuang-Ho Hospital, New Taipei City, Taiwan; Brain and Consciousness Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Radiology, Taipei Medical University-Shuang-Ho Hospital, New Taipei City, Taiwan; Brain and Consciousness Research Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Tseng
mesh_terms: D000328:Adult; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001519:Behavior; D003710:Demography; D005260:Female; D006262:Health; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D009483:Neuropsychological Tests; D012146:Rest / Q000502:physiology*
chemical_list: D053327:Apolipoprotein E4