title: Multi-parametric structural magnetic resonance imaging in relation to cognitive dysfunction in long-standing multiple sclerosis.
abstract: BACKGROUND
  Cognitive deficits are common in multiple sclerosis. Most previous studies investigating the imaging substrate of cognitive deficits in multiple sclerosis included patients with relatively short disease durations and were limited to one modality/brain region.
  
  
  OBJECTIVE
  To identify the strongest neuroimaging predictors for cognitive dysfunction in a large cohort of patients with long-standing multiple sclerosis.
  
  
  METHODS
  Extensive neuropsychological testing and multimodal 3.0T MRI was performed in 202 patients with multiple sclerosis and 52 controls. Cognitive scores were compared between groups using Z-scores. Whole-brain, white matter, grey matter, deep grey matter and lesion volumes; cortical thickness, (juxta)cortical and cerebellar lesions; and extent and severity of diffuse white matter damage were measured. Stepwise linear regression was used to identify the strongest predictors for cognitive dysfunction.
  
  
  RESULTS
  All cognitive domains were affected in patients. Patients showed extensive atrophy, focal pathology and damage in up to 75% of the investigated white matter. Associations between imaging markers and average cognition were two times stronger in cognitively impaired patients than in cognitively preserved patients. The final model for average cognition consisted of deep grey matter DGMV volume and fractional anisotropy severity (adjusted R²=0.490; p<0.001).
  
  
  CONCLUSIONS
  From all imaging markers, deep grey matter atrophy and diffuse white matter damage emerged as the strongest predictors for cognitive dysfunction in long-standing multiple sclerosis.
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands/Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands m.daams@vumc.nl.
authors.forename: Marita
authors.initials: M
authors.lastname: Daams
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Martijn D
authors.initials: MD
authors.lastname: Steenwijk
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Lisanne J
authors.initials: LJ
authors.lastname: Balk
authors.affiliation: Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Prejaas K
authors.initials: PK
authors.lastname: Tewarie
authors.affiliation: Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Killestein
authors.affiliation: Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Centre, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000328:Adult; D001284:Atrophy; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging*; D009413:Nerve Fibers, Myelinated; D066127:White Matter / Q000000981:diagnostic imaging
keywords: Multiple sclerosis; cognition; magnetic resonance imaging