ALTERED FUNCTIONAL CONNECTIVITY AND GLOBAL NETWORK PROPERTIES IN AMNESTIC MILD COGNITIVE IMPAIRMENT

Abstract

Background: Amnestic mild cognitive impairment (aMCI) patients demonstrate lower global network interactions. However, graph theory (GT) analysis has not been used to examine networks compromised by strong amyloid (A β) deposition, such as the default mode network (DMN). In addition, no study directly compared GT and functional connectivity (FC) analysis between healthy controls (HCS) and aMCI with respect to Aβ and APOE genotype. Based on the known structural and functional impairments in MCI, we hypothesize that FC and global network interactions are reduced in MCI and in subjects with Aβ load and e4 allele presence. Methods: We compared 24 HCS to 15 matched aMCI by resting-state fMRI. FC (within the DMN) and GT (whole-brain) analyses were performed with the toolbox CONN at p<0.05 (corrected). Three group comparisons were examined: HCS versus aMCI, PiB- versus PiB+ (i.e., significant global PiB load), and APOE+ (e4 carrier) versus APOE-. The DMN regions were: superior prefrontal cortex (sPFC), medial PFC (mPFC), ventral PFC (vPFC), anterior (aPFC), posterior cingulate cortex (PCC), lateral posterior parietal cortex (PPC), retrosplenial cortex (RSC), parahippocampal gyrus (PHG), cerebellar tonsils (CT), and inferior temporal cortex (ITC). For GT we looked at global- and local efficiency (LE), clustering coefficient (CC), and cost. Results: HCS demonstrated stronger FC between sPFC - RSC, left PPC - right sPFC, and mPFC - left sPFC. PiB+ subjects showed lower FC for: mPFC - CT, vPFC - aPFC, vPFC - left sPFC, aPFC - left sPFC, and left PPC - dACC. PiB+ showed stronger FC between left and right PHG, left PPC - RSC, and left PHG - aPFC. APOE- demonstrated higher FC between left PPC - dACC, vPFC - aPFC, left sPFC - left PPC, mPFC - right ITC, vPFC - RSC, and aPFC - ITC. HCS showed higher cost in the sPFC and PCC, and LE in the dorsolateral PFC. PiB- yield stronger LE and cost in temporal, visual, and frontal regions. APOE- exhibits higher LE and CC in temporal and visual areas. Conclusions: The spatial extent of FC reductions (especially in prefrontal-related connections) depends on the presence of Aβ and APOE. GT results suggest lower local network interactions and cost in MCI, as well as higher efficiency in PiB- and APOE-individuals.