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.

Keywords: APOE; aging; blood oxygen level dependent; complexity; multiscale entropy.

Figure 1

Voxelwise comparison of reduced MSE of BOLD signals in APOE ɛ4 carries, relative to APOE ɛ4 noncarries among (a) the young adult group and (b) the older adult group. Only the older adult group showed significant main effect of APOE genotype after correction for multiple comparisons. No opposite effect of the APOE genotype on MSE of BOLD signals was found. The coordinates represent the location of peak intensity.

Figure 2

Difference of functional connectivity in older APOE ɛ4 carries and noncarriers between the seed region identified in the older adult group (see Table 3 and Fig. 1b) and all gray matter voxels.