Decreased Inter-Hemispheric Functional Connectivity in Cognitively Intact Elderly APOE ε4 Carriers: A Preliminary Study

The apolipoprotein E (APOE) epsilon 4 allele is the best-known genetic risk factor for developing sporadic Alzheimer's disease (AD). According to neuroimaging studies, the APOE epsilon 4 allele is associated with localized altered brain function. However, in long-range circuitry, APOE epsilon 4 allele-related alterations in functional communication between hemispheres have rarely been directly investigated. We examined the alteration of resting-state functional connectivity (RSFC) between interhemispheric homotopic regions in cognitively intact, elderly APOE epsilon 4 carriers. The voxel-mirrored homotopic connectivity method was used to assess the inter-hemispheric RSFC. The current study included 13 cognitively intact, elderly APOE epsilon 4 carriers (with at least one copy of APOE epsilon 4 allele) and 22 well-matched epsilon 3 homozygotes. Comparisons between the two groups were conducted, and subsequently, the correlation between the differential inter-hemispheric RSFC and cognitive ability was analyzed. Compared with epsilon 3 homozygotes, APOE epsilon 4 carriers showed decreased inter-hemispheric RSFC in the bilateral medial temporal lobe (MTL) and orbital frontal cortex (OFC). Moreover, in APOE epsilon 4 carriers, the inter-hemispheric RSFC of the MTL correlated with the Wechsler Memory Scale-Logical Memory (WMS-LM) (immediate and delayed performance, r = 0.64, p < 0.05; r = 0.65, p < 0.05, respectively), and the inter-hemispheric RSFC of the OFC correlated with the WMS-LM delayed performance (r = 0.71, p < 0.05). In our study, the presence of the APOE epsilon 4 allele was linked with decreased inter-hemispheric RSFC, which was attributed to memory performance in carriers.