title: The APOE ɛ4 allele affects complexity and functional connectivity of resting brain activity in healthy adults.
abstract: The apolipoprotein E (APOE) gene is associated with structural and functional brain changes. We have used multiscale entropy (MSE) analysis to detect changes in the complexity of resting blood oxygen level-dependent (BOLD) signals associated with aging and cognitive function. In this study, we further hypothesized that the APOE genotype may affect the complexity of spontaneous BOLD activity in younger and older adults, and such altered complexity may be associated with certain changes in functional connectivity. We conducted a resting-state functional magnetic resonance imaging experiment in a cohort of 100 younger adults (aged 20-39 years; mean 27.2 ± 4.3 years; male/female: 53/47) and 112 older adults (aged 60-79 years; mean 68.4 ± 6.5 years; male/female: 54/58), and applied voxelwise MSE analysis to assess the main effect of APOE genotype on resting-state BOLD complexity and connectivity. Although the main effect of APOE genotype on BOLD complexity was not observed in younger group, we observed that older APOE ɛ4 allele carriers had significant reductions in BOLD complexity in precuneus and posterior cingulate regions, relative to noncarriers. We also observed that reduced BOLD complexity in precuneus and posterior cingulate regions was associated with increased functional connectivity to the superior and inferior frontal gyrus in the older group. These results support the compensatory recruitment hypothesis in older APOE ɛ4 carriers, and confer the impact of the APOE genotype on the temporal dynamics of brain activity in older adults.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, School of Medicine National Yang-Ming University, Taipei, Taiwan; Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yang
authors.forename: Chu-Chung
authors.initials: CC
authors.lastname: Huang
authors.forename: Mu-En
authors.initials: ME
authors.lastname: Liu
authors.forename: Yin-Jay
authors.initials: YJ
authors.lastname: Liou
authors.forename: Chen-Jee
authors.initials: CJ
authors.lastname: Hong
authors.forename: Men-Tzung
authors.initials: MT
authors.lastname: Lo
authors.forename: Norden E
authors.initials: NE
authors.lastname: Huang
authors.forename: Chung-Kang
authors.initials: CK
authors.lastname: Peng
authors.forename: Ching-Po
authors.initials: CP
authors.lastname: Lin
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D012146:Rest / Q000502:physiology*; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; D010100:Oxygen
keywords: APOE; aging; blood oxygen level dependent; complexity; multiscale entropy