title: Relationship between gray matter volume and cognitive learning in CIS patients on disease-modifying treatment.
abstract: BACKGROUND
  Repeated administration of Paced Auditory Serial Addition Test (PASAT) results in a considerable learning effect in short- or long-term follow-up studies. However, the relationship between PASAT learning and changes in magnetic resonance imaging (MRI) parameters is yet to be investigated.
  
  
  OBJECTIVE
  The aim of this study is to determine if change in brain MRI metrics predicts evolution of PASAT in high functioning clinically isolated syndrome (CIS) patients on disease-modifying treatment (DMT).
  
  
  METHODS
  This prospective 48-month observational study examined 128 CIS patients treated with 30 μg of intramuscular interferon beta-1a once a week. The correlation between PASAT and MRI measures was assessed at baseline, at 6 months and then annually over the 48-month follow up. Linear mixed model analysis adjusted for age, gender, education and DMT was used to model the temporal association between MRI measures and PASAT performance.
  
  
  RESULTS
  MRI revealed 2.5% gray matter (GM) volume loss and 4.3 point increase in PASAT score over 48 months. MS patients evidenced significantly greater PASAT score absolute change, had lower loss of GM volume (p=.008) but not significant change in cortical (p=.061), white matter (p=.086) or whole brain volumes (p=.879).
  
  
  CONCLUSIONS
  The present study reveals a significant relationship between higher PASAT learning effect and less GM atrophy in CIS patients on DMT. These findings suggest that change in PASAT associated more with GM than WM pathology, and that treatment strategies oriented toward GM volume preservation may play an important role in prevention of cognitive deterioration in CIS patients.
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic; Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Uher
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Ralph H B
authors.initials: RH
authors.lastname: Benedict
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA; IRCCS "S.Maria Nascente", Don Gnocchi Foundation, Milan, Italy.
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Jana Blahova
authors.initials: JB
authors.lastname: Dusankova
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Deepa P
authors.initials: DP
authors.lastname: Ramasamy
authors.affiliation: Department of Radiology Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.affiliation: Department of Radiology Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.affiliation: Department of Radiology Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA; MR Imaging Clinical Translational Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address: rzivadinov@bnac.net.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
mesh_terms: D000328:Adult; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003071:Cognition / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology*; D009483:Neuropsychological Tests; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016899:Interferon-beta; D000068556:Interferon beta-1a
keywords: Clinically isolated syndrom; Cognition; Gray matter; Learning effect; MRI; Multiple sclerosis