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Practice effect in Symbol Digit Modalities Test in multiple sclerosis patients treated with natalizumab

Multiple Sclerosis and Related Disorders, Volume 10, November 2016, Pages 116–122



How practice effect influences cognitive testing measured by monthly Symbol Digit Modalities Test (SDMT) during natalizumab treatment, and what factors confound such effect.


Eighty patients were examined monthly with SDMT for 26.2stripin: si0007.gif8.4 months. After 26.0±8.1 months, SDMT was also performed with a rearranged key in 59 cases. Results of SDMTs with the rearranged and previous regular key were compared. We examined if gender, age, Extended Disability Status Scale (EDSS), relapses, and disability progression/improvement influence SDMT performed with the regular and the rearranged key, respectively. We also explored if natalizumab applied before regular monthly SDMT may influence practice effect and cognition.


SDMT performance improved by 1.2 points/test during the first six months and by 0.4 points/test thereafter. Rearranging the symbols of the key after 26.0±8.1 months returned SDMT scores to baseline indicating a practice effect. Such practice effect was more significant after longer testing period, but was not influenced by gender, age, relapses, disability progression and prior natalizumab treatment. Although the change from baseline to 2.5 years was significant in subgroups with EDSS 0–3, 3.5–5.5 and 6–7.5, this was higher in patients with EDSS 0–3 compared to 6–7.5.


Practice effect significantly contributes to continuous improvement in SDMT performance during natalizumab treatment: to test cognition, a change in key is required. Practice effect is less pronounced in patients with advanced disease. Cognition remains stable even in patients with progressive disease during more than 2 years of natalizumab treatment indicated by scores corresponding to baseline after changing the key.


  • Repeated monthly SDMT score continuously improves in MS patients.
  • A new key reverts the SDMT score to baseline indicating a practice effect.
  • Change of key is required with repeated use of SDMT in MS patients.
  • Practice effect was unrelated to age, relapses and pre-study natalizumab treatment.
  • Cognition measured by SDMT is stable on natalizumab treatment over two years.

Keywords: Symbol digit modalities test, Processing speed, Neuropsychological test, Cognition, Changed key, Extended disability status score.


a Department of Neurology, Odense University Hospital, Sdr. Boulevard 29, Odense 5000, Denmark

b Institute of Clinical Research, University of Southern Denmark, Denmark

Corresponding author.