title: White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis.
abstract: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind.
  
  
  
  The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients.
  
  
  
  Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS).
  
  
  
  A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance (R2= 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major.
  
  
  
  Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Centre, Amsterdam, The Netherlands/NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK k.meijer@vumc.nl.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Meijer
authors.affiliation: NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK/School of Psychology and Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, UK/School of Psychological Sciences, University of Manchester, Manchester, UK.
authors.forename: Nils
authors.initials: N
authors.lastname: Muhlert
authors.affiliation: Clinical Imaging Centre, Brighton and Sussex Medical School, Brighton, UK.
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.affiliation: NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK.
authors.forename: Varun
authors.initials: V
authors.lastname: Sethi
authors.affiliation: NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ron
authors.affiliation: NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK/NIHR University College London Hospitals Biomedical Research Centre, London, UK.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK/NIHR University College London Hospitals Biomedical Research Centre, London, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.affiliation: NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK/NIHR University College London Hospitals Biomedical Research Centre, London, UK.
authors.forename: Declan
authors.initials: D
authors.lastname: Chard
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jeroen Jg
authors.initials: JJ
authors.lastname: Geurts
authors.affiliation: NMR Research Unit, Queen Square MS Centre, University College London Institute of Neurology, London, UK/NIHR University College London Hospitals Biomedical Research Centre, London, UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications / Q000000981:diagnostic imaging* / Q000523:psychology; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications / Q000000981:diagnostic imaging* / Q000523:psychology; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000000981:diagnostic imaging* / Q000523:psychology; D009483:Neuropsychological Tests
keywords: DTI; MRI; Multiple sclerosis; cognition; myelination; secondary progressive