title: Disruption of rich club organisation in cerebral small vessel disease.
abstract: Cerebral small vessel disease (SVD) is an important cause of vascular cognitive impairment. Recent studies have demonstrated that structural connectivity of brain networks in SVD is disrupted. However, little is known about the extent and location of the reduced connectivity in SVD. Here they investigate the rich club organisation-a set of highly connected and interconnected regions-and investigate whether there is preferential rich club disruption in SVD. Diffusion tensor imaging (DTI) and cognitive assessment were performed in a discovery sample of SVD patients (n = 115) and healthy control subjects (n = 50). Results were replicated in an independent dataset (49 SVD with confluent WMH cases and 108 SVD controls) with SVD patients having a similar SVD phenotype to that of the discovery cases. Rich club organisation was examined in structural networks derived from DTI followed by deterministic tractography. Structural networks in SVD patients were less dense with lower network strength and efficiency. Reduced connectivity was found in SVD, which was preferentially located in the connectivity between the rich club nodes rather than in the feeder and peripheral connections, a finding confirmed in both datasets. In discovery dataset, lower rich club connectivity was associated with lower scores on psychomotor speed (β = 0.29, P < 0.001) and executive functions (β = 0.20, P = 0.009). These results suggest that SVD is characterized by abnormal connectivity between rich club hubs in SVD and provide evidence that abnormal rich club organisation might contribute to the development of cognitive impairment in SVD. Hum Brain Mapp 38:1751-1766, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.|Centre for Cognitive Neuroimaging, Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Anil M
authors.initials: AM
authors.lastname: Tuladhar
authors.affiliation: Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lawrence
authors.affiliation: Centre for Cognitive Neuroimaging, Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.|Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Arendahls Wiese 199, Tor 3, Essen, D-45141, Germany.|MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: David G
authors.initials: DG
authors.lastname: Norris
authors.affiliation: St. George's University of London, Neuroscience Research Centre, Cardiovascular and Cell Sciences Research Institute, London, United Kingdom.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Barrick
authors.affiliation: Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.affiliation: Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Frank-Erik
authors.initials: FE
authors.lastname: de Leeuw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D059345:Cerebral Small Vessel Diseases / Q000150:complications* / Q000000981:diagnostic imaging*; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000209:etiology*; D063132:Connectome; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009434:Neural Pathways / Q000000981:diagnostic imaging*; D011597:Psychomotor Performance / Q000502:physiology; D012044:Regression Analysis; D012720:Severity of Illness Index
keywords: cerebral small vessel disease; diffusion tensor imaging; graph-theory; rich club organisation; structural networks