title: Subcortical atrophy and cognition: sex effects in multiple sclerosis.
abstract: OBJECTIVE
  Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS.
  
  
  METHODS
  Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains. Stepwise linear regression was used to predict average cognition in the patient group.
  
  
  RESULTS
  Most deep GM volumes were reduced in patients, with larger effects on average in men (-11%) than in women (-6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R(2) = 0.31), while lesion volume was not a significant predictor in the model.
  
  
  CONCLUSIONS
  Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS.
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands. m.schoonheim@vumc.nl
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.forename: Veronica
authors.initials: V
authors.lastname: Popescu
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Rueda Lopes
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Wiebenga
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.forename: Linda
authors.initials: L
authors.lastname: Douw
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000328:Adult; D001284:Atrophy; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D012737:Sex Factors; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology