Resting state network modularity along the prodromal late onset Alzheimer's disease continuum

Abstract

Alzheimer's disease is considered a disconnection syndrome, motivating the use of brain network measures to detect changes in whole-brain resting state functional connectivity (FC). We investigated changes in FC within and among resting state networks (RSN) across four different stages in the Alzheimer's disease continuum. FC changes were examined in two independent cohorts of individuals (84 and 58 individuals, respectively) each comprising control, subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia groups. For each participant, FC was computed as a matrix of Pearson correlations between pairs of time series from 278 gray matter brain regions. We determined significant differences in FC modular organization with two distinct approaches, network contingency analysis and multiresolution consensus clustering. Network contingency analysis identified RSN sub-blocks that differed significantly across clinical groups. Multiresolution consensus clustering identified differences in the stability of modules across multiple spatial scales. Significant modules were further tested for statistical association with memory and executive function cognitive domain scores. Across both analytic approaches and in both participant cohorts, the findings converged on a pattern of FC that varied systematically with diagnosis within the frontoparietal network (FP) and between the FP network and default mode network (DMN). Disturbances of modular organization were manifest as greater internal coherence of the FP network and stronger coupling between FP and DMN, resulting in less segregation of these two networks. Our findings suggest that the pattern of interactions within and between specific RSNs offers new insight into the functional disruption that occurs across the Alzheimer's disease spectrum.

Long Longitudinal Tract Lesion Contributes to the Progression of Alzheimer's Disease

“…Our findings of destruction in the IFOF, ILF, and SLF in the aMCI and AD groups were consistent with previous ROIbased and voxel-based DTI studies, which showed damage of the WM regions outside the medial temporal lobe (MTL) network in AD patients (34). Our results supported the hypothesis that AD had a disconnection process (38).…”

No relationship between fornix and cingulum degradation and within-network decreases in functional connectivity in prodromal Alzheimer’s disease

“…That finding of increased functional connectivity parallels the lack of segregation between the DMN and frontoparietal networks that have been revealed using a graph theory approach in AD, and to a lesser extent, MCI patients [41]. Graph theory investigations of the brain look at the shape of information transfer at a high level, i.e., the network/connectome level.…”

Functional neuroimaging in subjective cognitive decline: current status and a research path forward

“…However, many groups have also observed lower connectivity between these regions in individuals with SCD [18,[76][77][78][79]. Others have reported no difference from control [60], or intricate patterns of greater and lower functional connectivity in individuals with SCD [51][52][53][54][55], suggesting that a complex reorganization of processing responsibilities across network nodes may occur. Multifaceted patterns of increased and decreased connectivity between regions could reflect breakdown in processing within a subnetwork that shifts processing load to more intact components of the broader network.…”