Global Rearrangement of Degree Centrality Reflects Cognitive Impairment and Fatigue in Multiple Sclerosis

Abstract

AbstractBackground and ObjectivesThe aim of this secondary data analysis was to determine whether multiple sclerosis (MS) is associated with changes in global degree rank order disruption index (kD), a graph theory-based functional connectivity measure representing shift in overall distribution of nodal degree centrality. Additionally, we tested the relationship betweenkDand MS symptoms (cognitive and motor impairment, fatigue, and global disability).MethodsGlobalkDwas computed in a pre-existing cross-sectional fMRI dataset and compared between patients with MS (PwMS) and healthy controls (HCs). Group differentiation was tested against other known biomarkers in MS (regional degree centrality, structural MRI with volumetry, diffusion-weighted imaging, lesion mapping) using receiver operating characteristic and logistic regression analysis. Associations betweenkDand cognitive processing speed (Symbol Digit Modalities Test), fatigue (Fatigue Scale for Motor and Cognitive Functions), gait (Timed Up and Go Test), and disability (Expanded Disability Status Scale [EDSS]) were evaluated using Spearman correlation coefficient and ordinal regression adjusted for structural imaging, age, sex, and disease duration.ResultsAnalysis included 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years). GlobalkDwas lower in PwMS (median −0.30, inter-quartile range [IQR] 0.55) than in HCs (median −0.06, IQR 0.54;p= 0.009, Mann-Whitney U test).kDyielded acceptable differentiation between groups (area under curve 0.64), but did not improve such differentiation on top of structural imaging. BothkDand regional degree in medial prefrontal cortex (MPFC) were correlated with cognitive decline (kD: Spearman’sρ= 0.32,p= 0.019; MPFC:ρ= −0.45,p= 0.001,n= 55), whilekDwas also correlated with fatigue (ρ= −0.34,p= 0.010,n= 56), but not with EDSS (ρ= −0.06, p = 0.674,n= 56) or gait (ρ= −0.18,p= 0.211,n= 52).kDsignificantly explained cognitive impairment (χ2= 4.49,p= 0.034) and fatigue (χ2= 7.18,p= 0.007).DiscussionOur data provide evidence thatkDis a potential biomarker of cognitive decline and fatigue. Further cross-validations are required to assess its generalizability.