title: Structural network efficiency predicts conversion to dementia.
abstract: OBJECTIVE
  To examine whether structural network connectivity at baseline predicts incident all-cause dementia in a prospective hospital-based cohort of elderly participants with MRI evidence of small vessel disease (SVD).
  
  
  METHODS
  A total of 436 participants from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC), a prospective hospital-based cohort of elderly without dementia with cerebral SVD, were included in 2006. During follow-up (2011-2012), dementia was diagnosed. The structural network was constructed from baseline diffusion tensor imaging followed by deterministic tractography and measures of efficiency using graph theory were calculated. Cox proportional regression analyses were conducted.
  
  
  RESULTS
  During 5 years of follow-up, 32 patients developed dementia. MRI markers for SVD were strongly associated with network measures. Patients with dementia showed lower total network strength and global and local efficiency at baseline as compared with the group without dementia. Lower global network efficiency was independently associated with increased risk of incident all-cause dementia (hazard ratio 0.63, 95% confidence interval 0.42-0.96, p = 0.032); in contrast, individual SVD markers including lacunes, white matter hyperintensities volume, and atrophy were not independently associated.
  
  
  CONCLUSIONS
  These results support a role of network disruption playing a pivotal role in the genesis of dementia in SVD, and suggest network analysis of the connectivity of white matter has potential as a predictive marker in the disease.
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Anil M
authors.initials: AM
authors.lastname: Tuladhar
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Ingeborg W M
authors.initials: IW
authors.lastname: van Uden
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Loes C A
authors.initials: LC
authors.lastname: Rutten-Jacobs
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lawrence
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Helena
authors.initials: H
authors.lastname: van der Holst
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: van Norden
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Karlijn
authors.initials: K
authors.lastname: de Laat
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Ewoud
authors.initials: E
authors.lastname: van Dijk
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Jurgen A H R
authors.initials: JA
authors.lastname: Claassen
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Roy P C
authors.initials: RP
authors.lastname: Kessels
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands.
authors.forename: David G
authors.initials: DG
authors.lastname: Norris
authors.affiliation: From the Departments of Neurology (A.M.T., I.W.M.v.U., H.v.d.H., E.v.D., F.-E.d.L.), Geriatrics (J.A.H.R.C., R.P.C.K.), and Medical Psychology (R.P.C.K.), Radboudumc, and Centre for Cognitive Neuroimaging, Radboud University Nijmegen (A.M.T., D.G.N.), Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J., A.L., H.S.M.), University of Cambridge, UK; Department of Neurology (A.v.N.), Amphia ziekenhuis Breda; Department of Neurology (K.d.L.), HagaZiekenhuis Den Haag, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany; and MIRA Institute for Biomedical Technology and Technical Medicine (D.G.N.), University of Twente, Enschede, the Netherlands. frankerik.deleeuw@radboudumc.nl.
authors.forename: Frank-Erik
authors.initials: FE
authors.lastname: de Leeuw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D059345:Cerebral Small Vessel Diseases / Q000150:complications* / Q000175:diagnosis*; D015331:Cohort Studies; D003704:Dementia / Q000175:diagnosis* / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology*; D011237:Predictive Value of Tests; D011446:Prospective Studies