Concordance of Intrinsic Brain Connectivity Measures Is Disrupted in Alzheimer's Disease

Background: Recently, a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to evaluate the concordance between different rs-fMRI metrics has been proposed and has not been investigated in Alzheimer's disease (AD). Methods: 3T rs-fMRI data were obtained from healthy young controls (YC, n = 26), healthy senior controls (SC, n = 29), and AD patients (n = 35). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were analyzed, followed by the calculation of their concordance using Kendall's W for each brain voxel across time. Group differences in the concordance were compared globally, within seven intrinsic brain networks, and on a voxel-by-voxel basis with covariates of age, sex, head motion, and gray matter volume. Results: The global concordance was lowest in AD among the three groups, with similar differences for the single metrics. When comparing AD to SC, reductions of concordance were detected in each of the investigated networks apart from the limbic network. For SC in comparison to YC, lower global concordance without any network-level difference was observed. Voxel-wise analyses revealed lower concordance in the right middle temporal gyrus in AD compared to SC and lower concordance in the left middle frontal gyrus in SC compared to YC. Lower fALFF were observed in the right angular gyrus in AD in comparison to SC, but ReHo and DC showed no group differences. Conclusions: The concordance of resting-state measures differentiates AD from healthy aging and may represent a novel imaging marker in AD. Impact statement The usefulness of a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to assess the concordance between different rs-fMRI metrics has been demonstrated in mental disorders such as depression and schizophrenia. Our study, to the best of our knowledge, is the first to confirm a decreased concordance in Alzheimer's disease (AD) patients compared to healthy young and senior individuals on global, network, and voxel-wise levels, which moreover seems to be sensitive in differentiating age-related from AD-related functional brain changes. Our findings suggest that the concordance of rs-fMRI metrics may be useful as a candidate biomarker for neurodegenerative disorders such as AD.