Global Alterations of Whole Brain Structural Connectome in Parkinson’s Disease: A Meta-analysis

Abstract Recent graph-theoretical studies of Parkinson's disease (PD) have examined alterations in the global properties of the brain structural connectome; however, reported alterations are not consistent. The present study aimed to identify the most robust global metric alterations in PD via a meta-analysis. A comprehensive literature search was conducted for all available diffusion MRI structural connectome studies that compared global graph metrics between PD patients and healthy controls (HC). Hedges’ g effect sizes were calculated for each study and then pooled using a random-effects model in Comprehensive Meta-Analysis software, and the effects of potential moderator variables were tested. A total of 22 studies met the inclusion criteria for review. Of these, 16 studies reporting 10 global graph metrics (916 PD patients; 560 HC) were included in the meta-analysis. In the structural connectome of PD patients compared with HC, we found a significant decrease in clustering coefficient (g = -0.357, P = 0.005) and global efficiency (g = -0.359, P < 0.001), and a significant increase in characteristic path length (g = 0.250, P = 0.006). Dopaminergic medication, sex and age of patients were potential moderators of global brain network changes in PD. These findings provide evidence of decreased global segregation and integration of the structural connectome in PD, indicating a shift from a balanced small-world network to ‘weaker small-worldization’, which may provide useful markers of the pathophysiological mechanisms underlying PD.