title: Widespread cortical thinning characterizes patients with MS with mild cognitive impairment.
abstract: BACKGROUND
  Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white matter changes.
  
  
  METHODS
  A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer.
  
  
  RESULTS
  Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p < 0.001) and cognitively normal patients with RRMS (CN-RRMS) (p < 0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = -0.69, p < 0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between -0.20 and -0.65, p < 0.01). A correlation was found between T2-WM-LV and mean CTh (r = -0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment.
  
  
  CONCLUSIONS
  A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology.
authors.affiliation: Department of Neurosciences, University Hospital of Padova, Multiple Sclerosis Centre of Veneto Region, First Neurology Clinic, 35128 Padova, Italy. calabresem@hotmail.it
authors.forename: M
authors.initials: M
authors.lastname: Calabrese
authors.forename: F
authors.initials: F
authors.lastname: Rinaldi
authors.forename: I
authors.initials: I
authors.lastname: Mattisi
authors.forename: P
authors.initials: P
authors.lastname: Grossi
authors.forename: A
authors.initials: A
authors.lastname: Favaretto
authors.forename: M
authors.initials: M
authors.lastname: Atzori
authors.forename: V
authors.initials: V
authors.lastname: Bernardi
authors.forename: L
authors.initials: L
authors.lastname: Barachino
authors.forename: C
authors.initials: C
authors.lastname: Romualdi
authors.forename: L
authors.initials: L
authors.lastname: Rinaldi
authors.forename: P
authors.initials: P
authors.lastname: Perini
authors.forename: P
authors.initials: P
authors.lastname: Gallo
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001284:Atrophy / Q000473:pathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D015999:Multivariate Analysis; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012720:Severity of Illness Index