title: Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis.
abstract: OBJECTIVE
  Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures.
  
  
  METHODS
  Forty patients with multiple sclerosis (relapsing-remitting,n= 16; progressive,n= 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.
  
  
  RESULTS
  Compared with controls, patients showed reduced memory (P< .001) and processing speed (P= .02) and smaller putamen (P< .001), globus pallidus (P= .002), and thalamic volumes (P< .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (P= .003) and globus pallidus (P= .003). In patients only, thalamus (P< .001) and putamen (P= .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (P= .03; trend for transverse relaxation rate,P= .10) were still related to cognition.
  
  
  CONCLUSIONS
  Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.
authors.affiliation: From the Departments of Psychiatry (E.F., J.A.K.).
authors.forename: E
authors.identifier: http://orcid.org/0000-0003-4154-0145
authors.initials: E
authors.lastname: Fujiwara
authors.affiliation: From the Departments of Psychiatry (E.F., J.A.K.).
authors.forename: J A
authors.identifier: http://orcid.org/0000-0003-3463-2412
authors.initials: JA
authors.lastname: Kmech
authors.affiliation: Computer Science (D.C.).
authors.forename: D
authors.identifier: http://orcid.org/0000-0003-1318-4868
authors.initials: D
authors.lastname: Cobzas
authors.affiliation: Biomedical Engineering (H.S., P.S., A.H.W.).
authors.forename: H
authors.identifier: http://orcid.org/0000-0003-3436-7831
authors.initials: H
authors.lastname: Sun
authors.affiliation: Biomedical Engineering (H.S., P.S., A.H.W.).
authors.forename: P
authors.identifier: http://orcid.org/0000-0002-8812-2234
authors.initials: P
authors.lastname: Seres
authors.affiliation: Medicine (G.B.), Division of Neurology, University of Alberta, Edmonton, Alberta, Canada.|Northern Alberta Multiple Sclerosis Clinic (G.B.), Edmonton, Alberta, Canada.
authors.forename: G
authors.identifier: http://orcid.org/0000-0002-4598-2672
authors.initials: G
authors.lastname: Blevins
authors.affiliation: Biomedical Engineering (H.S., P.S., A.H.W.) wilman@ualberta.ca.
authors.forename: A H
authors.identifier: http://orcid.org/0000-0002-2758-8110
authors.initials: AH
authors.lastname: Wilman
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: D007501:Iron