title: Cognitive function did not improve after initiation of natalizumab treatment in relapsing-remitting multiple sclerosis. A prospective one-year dual control group study.
abstract: BACKGROUND
  Cognitive impairment in multiple sclerosis (MS) is common and has severe implications. Natalizumab (NZ) has documented effects on relapse rate and radiological disease activity in relapsing-remitting MS (RRMS) but studies regarding its specific effects on cognitive functioning are few. Previous studies have reported improvement, however, often lacking relevant control groups. The objective of the present study was to evaluate the cognitive effects of NZ treatment, compared to patients on stable first-line treatment and healthy control subjects.
  
  
  METHODS
  MS patients starting NZ (MS-NZ), MS controls with stable interferon beta therapy (MS-C) and healthy control subjects (HC) were evaluated twice with one year interval, using a cognitive test battery covering six cognitive domains. The effects of NZ on levels of self-reported depression, fatigue, daytime sleepiness and perceived health were also examined.
  
  
  RESULTS
  MS patients (MS-NZ and MS-C) had significantly lower baseline cognitive performance compared to HC (global score, p=0.002), but there were no significant differences between MS-NZ and MS-C. At follow-up, both MS-NZ and MS-C had improved significantly in four and five cognitive domains, respectively, and in global score (p=0.013 and p<0.001, respectively). HC improved significantly in three cognitive domains but not in global score. A regression analysis including baseline cognitive z-score and z-score change showed that participants with lower baseline scores had a significantly greater improvement, compared to those with better initial performance (p=0.021). There were no significant changes in depression, fatigue, daytime sleepiness or perceived health in MS-NZ or MS-C.
  
  
  CONCLUSIONS
  Initiation of NZ therapy did not result in true cognitive improvement over one year. Presumably, the increased test performance in both MS groups was artificial and due to retest effects that were stronger in patients with lower baseline performance. Adequate control groups are essential when evaluating cognitive functioning in intervention trials among RRMS patients.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: mathias.sundgren@ki.se.
authors.forename: M
authors.initials: M
authors.lastname: Sundgren
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Institute of Gerontology, School of Health and Welfare, Jönköping University, Jönköping, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Wahlin
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tom
authors.initials: T
authors.lastname: Brismar
mesh_terms: D000328:Adult; D003071:Cognition / Q000187:drug effects*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000523:psychology*; D000069442:Natalizumab / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012044:Regression Analysis; D057566:Self Report; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta