title: Structural network efficiency is associated with cognitive impairment in small-vessel disease.
abstract: OBJECTIVE
  To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment.
  
  
  METHODS
  A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested.
  
  
  RESULTS
  Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed.
  
  
  CONCLUSIONS
  Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies.
authors.affiliation: From the Stroke & Dementia Research Centre (A.J.L., A.W.C., T.R.B.), St George's University of London; Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London; and Clinical Neurosciences (H.S.M.), University of Cambridge, UK. alawrenc@sgul.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: From the Stroke & Dementia Research Centre (A.J.L., A.W.C., T.R.B.), St George's University of London; Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London; and Clinical Neurosciences (H.S.M.), University of Cambridge, UK.
authors.forename: Ai Wern
authors.initials: AW
authors.lastname: Chung
authors.affiliation: From the Stroke & Dementia Research Centre (A.J.L., A.W.C., T.R.B.), St George's University of London; Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London; and Clinical Neurosciences (H.S.M.), University of Cambridge, UK.
authors.forename: Robin G
authors.initials: RG
authors.lastname: Morris
authors.affiliation: From the Stroke & Dementia Research Centre (A.J.L., A.W.C., T.R.B.), St George's University of London; Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London; and Clinical Neurosciences (H.S.M.), University of Cambridge, UK.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.affiliation: From the Stroke & Dementia Research Centre (A.J.L., A.W.C., T.R.B.), St George's University of London; Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London; and Clinical Neurosciences (H.S.M.), University of Cambridge, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Barrick
mesh_terms: D000368:Aged; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D059345:Cerebral Small Vessel Diseases / Q000150:complications / Q000473:pathology*; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D056344:Executive Function; D005260:Female; D006801:Humans; D049292:Leukoaraiosis / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology; D009483:Neuropsychological Tests; D012044:Regression Analysis; D012720:Severity of Illness Index; D013997:Time Factors