title: DT MRI microstructural cortical lesion damage does not explain cognitive impairment in MS.
abstract: OBJECTIVE
  We combined double inversion recovery (DIR) and diffusion tensor (DT) magnetic resonance imaging (MRI) to quantify the severity of cortical lesion (CL) microstructural tissue abnormalities in a large cohort of relapse-onset multiple sclerosis (MS) patients and its contribution to cognitive dysfunction.
  
  
  METHODS
  DIR, DT, dual-echo, and three-dimensional (3D) T1-weighted scans were acquired from 149 MS patients and 40 controls. Cognitively impaired (CI) patients had ⩾2 abnormal neuropsychological tests. Diffusivity values in CLs, cortex, white matter (WM) lesions, and normal-appearing (NA) WM were assessed. Predictors of cognitive impairment were identified using a random forest analysis.
  
  
  RESULTS
  Compared to controls, MS patients had lower normalized brain volume (NBV), gray matter volume (GMV), WM volume, lower fractional anisotropy (FA), and higher mean diffusivity in cortex and normal-appearing white matter (NAWM). A total of 44 (29.5%) patients were CI. Compared to cognitively preserved (CP), CI patients had higher T2WM lesion volume (LV), lower NBV and GMV, and more severe diffusivity abnormalities in WM lesions, cortex, and NAWM. CL measures did not differ between CI and CP patients. Cortex FA, age, disease duration, T2WM LV, and GMV best predicted MS-related cognitive impairment (C-statistic = 0.88).
  
  
  CONCLUSIONS
  "Diffuse" GM and NAWM damage and WM lesions, rather than intrinsic CL damage, contribute to cognitive impairment in MS.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy/Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosa
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pagani
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Morelli
authors.affiliation: Biostatistics Unit, IRCCS-Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy/Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Fiammetta
authors.initials: F
authors.lastname: Pirro
authors.affiliation: Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy/Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy/Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000000981:diagnostic imaging*; D011446:Prospective Studies; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
keywords: MRI; Multiple sclerosis; cognitive impairment; cortical lesions; diffusion tensor