Is the Symbol Digit Modalities Test a useful outcome in secondary progressive multiple sclerosis? Koch MW, Mostert J, Repovic P, Bowen JD, Uitdehaag B, Cutter G. Eur J Neurol. 2021 Jan 15. doi: 10.1111/ene.14732. Online ahead of print

Background: It is unclear which cognitive outcome measure is the most useful for clinical trials in multiple sclerosis. To investigate the usefulness of the symbol digit modalities test (SDMT) as a clinical outcome measure in secondary progressive multiple sclerosis (SPMS), we describe the frequency of worsening and improvement events in a large randomized controlled trial (RCT) dataset.

Methods: Using original trial data from the ASCEND trial (n=889), a recent large RCT in SPMS, we describe worsening and similarly defined improvement with and without three month confirmation on the SDMT in the whole trial cohort and unconfirmed worsening and improvement on the Paced Auditory Serial Addition Test (PASAT) in a smaller subset (n=107).

Results: Somewhat unexpectedly, SDMT scores steadily increased throughout the two years of follow up in this trial. There were overall few SDMT worsening events throughout the trial (generally fewer than 10% of participants), but improvement events steadily increased from around 50% of participants with improvement at 12 weeks to more than 70% at 84 weeks and beyond. PASAT scores followed a similar pattern.

Conclusions: In this well characterized clinical trial cohort, the SDMT does not reflect the steady cognitive decline that patients with SPMS experience. Both SDMT and PASAT scores improve throughout follow-up, possibly due to a practice effect. The SDMT may not be a useful outcome measure of disease progression in two year clinical trials in SPMS.

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  • Yes this is why well designed studies replace the key for the sdmt with long periods in between retesting to reduce the practice effect. In a study I think it was found changing the key completely eliminates it. Regardless of the effects prevalence (and it exists in any cognitive test), statistically significant differences in improvement can be shown, which would imply a meaningful cognitive benefit.

  • Sorry if this second comment seems like spam but I am primarily concerned with the cognitive aspects of MS. Does anyone know if the opera trials changed the keys between SDMT tests?

    • Sorry I did not mean to launch this post

      In Opera I and II which is relapsing MS there was an affect
      “New data on cognitive performance that examined 12-week and 24-week confirmed cognitive decline, defined as a loss of 4 our more points on the symbol digital modalities test (SMDT), was presented. Patients treated with ocrelizumab had a 38% and 39% (P < .001, P = .002) respective reduction in risk of cognitive decline compared to patients treated with interferon beta-1a during a 96-week treatment period".

  • For physical tests its easy to adapt even with disability as people are quite resilient. May I suggest an online tool for cognitive testing? Its really fun, especially the memory ones. Might be useful for an at-home study like the over and under.

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