Multimodal Magnetic Resonance Imaging Study To Explore The Interplay Of White Matter Hyperintensities,Cerebral Networks,and Cognitive Impairment In Cerebral Small Vessel Disease

Background: Cerebral small vessel disease(SVD)is a major cause of vascular cognitive impairment in the elderly.The characteristic lesions,of which white matter hyperintensities(WMHs)and lacunes are the most prevalent,interfere with the trajectories of the white matter(WM)and may disrupt the connections between distributed brain regions involved in cognition.However,there is no consensus yet about the precise underlying neurobiological mechanism.Purpose: The purpose of this study was to investigate the relationships between WM tract integrity,structural connectome and cognitive functions in ischemic leukoaraiosis(ILA)subjects.To examine whether ILA and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population.Materials and Methods: A total of 89 patients with moderate to severe ILA(Fazekas score ? 3)and 90 healthy controls(HCs)underwent comprehensive neuropsychological examinations(including cognitive domains episodic memory,visuospatial ability,information processing speed,and executive function)and diffusion tensor imaging scans.The tract-based spatial statistics approach was employed to investigate the WM integrity.Graph theoretical analysis were further applied to construct the topological architecture of the structural connectome in ILA patients.Partial correlation analysis was used to investigate the relationships between WM tract integrity,structural network measures and cognitive performances in the ILA group.Results: In ILA patients,cognitive function in cognitive domains episodic memory,information processing speed,and executive function were significantly worse than HCs.Compared with HCs,the ILA patients showed decreased fractional anisotropy(FA)values in the corpus callosum,left external capsule,bilateral superior fronto-occipital fasciculus,and posterior thalamic radiation(P < 0.05,FDR-corrected).Moreover,the ILA group displayed increased characteristic path length(Lp)and decreased global network efficiency at the level of the whole brain relative to HCs,and reduced nodal efficiencies,predominantly in the frontal-subcortical and limbic system regions.In particular,these structural connectomic alterations and WM fibers disruptions were associated with cognitive impairment in ILA patients.The association between WM changes(i.e.,FA and mean diffusivity measures)and cognitive function was mediated by the structural connectivity measures(i.e.,local network efficiency and Lp).Conclusion: Cognitive impairment in ILA patients is related to microstructural disruption of multiple WM fibers and topological disorganization of structural networks,which have implications in understanding the relationships between WMHs,structural connectivity measures and the possible attendant cognitive impairment.