Are we ready to define cognitive worsening in MS? How different cutoffs detect future cognitive worsening after six years of follow-up

Background: Although cognitive evaluation has been incorporated in recent MS clinical trials, the definition of cognitive progression is not clear and recent data are questioning the 4-point cutoff using the SDMT at the individual level. We aimed to evaluate the behavior of cognitive performance over time using different cutoffs. Methods: Cognitive performance over six years was analyzed in a cohort of 42 relapsing-remitting MS patients and 30 controls using verbal/visual memory and information processing speed tests. Fixed cutoffs were: 10% and 20% change (all tests) and a 4- and 8-point change (SDMT). The relative cutoff established by regression-based models was a 1SD change.Results: The distributions of worsening, stability, and improvement showed low concordance rates across the cutoffs (p < 0.001 for most comparisons). Most patients classified with worsening initially using fixed cutoffs had subsequent improvement in all cognitive tests, yielding a low sensitivity to predict later cognitive worsening. Using the relative cutoff, the proportion of patients with subsequent improvement was noticeably smaller.Conclusions: Fixed cutoffs classify a high proportion of patients with cognitive improvement. Most patients categorized with worsening initially presented subsequent improvement. Instead, the relative cutoff generally had a better performance. These data raise concerns about how we are defining cognitive worsening so far, especially at the individual level.

Automated summary

This study analyzed the cognitive performance of 42 RRMS patients and 30 controls over six years. Different cutoffs were used to evaluate the behavior of cognitive progression. The results showed that fixed cutoffs led to misclassification of many patients as having cognitive worsening, while the relative cutoff performed better.