title: Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies.
abstract: OBJECTIVE
  Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing-remitting MS (RRMS) treated with DMTs over 1 year.
  
  
  METHODS
  Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change.
  
  
  RESULTS
  Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability.
  
  
  CONCLUSIONS
  Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable.
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Kathrin S
authors.initials: KS
authors.lastname: Utz
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: De-Hyung
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lämmer
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Waschbisch
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.affiliation: Department of Psychology, Ludwig-Maximilians-Universität München, Leopoldstr. 13, 80802 München, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schenk
keywords: Paced Auditory Serial Addition Test; fingolimod; natalizumab; neuropsychological test; reliable change; repeated testing