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The following is a summary of “Measuring cognitive change in secondary progressive MS: an analysis of the ASCEND cognition substudy,” published in the April 2025 issue of Journal of Neurology by Leavitt et al. 

Researchers conducted a retrospective study on cognitive impairment in multiple sclerosis (MS), highlighting the need for accurate measurement of cognitive change in clinical trials. 

They quantified the change in cognitive scores, clinical metrics of physical disability, and neuroradiological metrics using data from a phase-3 randomized controlled trial of natalizumab in secondary progressive MS (SPMS). Adults with SPMS for ≥2 years and expanded disability status scale (EDSS) scores from 3 to 6.5 were randomized to receive natalizumab or placebo for 96 weeks. Change in symbol digit modalities Test (SDMT), paced auditory serial addition test (PASAT), selective reminding test (SRT), brief visuospatial memory test (BVMT-R), 2 subjective cognitive measures, beck depression inventory (BDI-FS), Timed 25-foot Walk Test, Nine Hole Peg Test, brain volume, and T2 lesion volume were evaluated. 

The results showed no significant differences in cognitive change between treatment arms. SDMT and PASAT scores improved over 96 weeks: mean SDMT scores increased by 4.5 points (SD 9.3), and mean PASAT scores increased by 2.4 points (SD 9.4). Verbal and visuospatial memory tests showed no consistent change. All MRI measures showed decreased brain volumes. NHPT scores worsened slightly, while T25FW scores worsened steadily. 

Investigators observed improvements in SDMT and PASAT performance regardless of treatment arm. These results supported the need for cognitive outcomes that overcome practice and learning effects to accurately quantify change. 

Source: link.springer.com/article/10.1007/s00415-025-13066-4