Reduced Global Efficiency and Random Network Features in Patients with Relapsing-Remitting Multiple Sclerosis with Cognitive Impairment

BACKGROUND AND PURPOSE: Graph theory uses structural similarity to analyze cortical structural connectivity. We used a voxel-based definition of cortical covariance networks to quantify and assess the relationship of network characteristics to cognition in a cohort of patients with relapsing-remitting MS with and without cognitive impairment. MATERIALS AND METHODS: We compared subject-specific structural gray matter network properties of 18 healthy controls, 25 patients with MS with cognitive impairment, and 55 patients with MS without cognitive impairment. Network parameters were compared, and predictive value for cognition was assessed, adjusting for confounders (sex, education, gray matter volume, network size and degree, and T1 and T2 lesion load). Backward stepwise multivariable regression quantified predictive factors for 5 neurocognitive domain test scores. RESULTS: Greater path length (r = ?0.28, P < .0057) and lower normalized path length (r = 0.36, P < .0004) demonstrated a correlation with average cognition when comparing healthy controls with patients with MS. Similarly, MS with cognitive impairment demonstrated a correlation between lower normalized path length (r = 0.40, P < .001) and reduced average cognition. Increased normalized path length was associated with better performance for processing (P < .001), learning (P < .001), and executive domain function (P = .0235), while reduced path length was associated with better executive (P = .0031) and visual domains. Normalized path length improved prediction for processing (R-2 = 43.6%, G(2) = 20.9; P < .0001) and learning (R-2 = 40.4%, G(2) = 26.1; P < .0001) over a null model comprising confounders. Similarly, higher normalized path length improved prediction of average z scores (G(2) = 21.3; P < .0001) and, combined with WM volume, explained 52% of average cognition variance. CONCLUSIONS: Patients with MS and cognitive impairment demonstrate more random network features and reduced global efficiency, impacting multiple cognitive domains. A model of normalized path length with normal-appearing white matter volume improved average cognitive z score prediction, explaining 52% of variance.