Cognitive Function Is Associated With Risk of Conversion to Secondary Progressive Multiple Sclerosis: A Cross-Sectional Study Publisher Pubmed



Mirmosayyeb O ; Mohammadi I ; Firouzabadi SR ; Vaheb S ; Panah MY ; Fuchs TA ; Weinstockguttman B ; Shaygannejad V
Source: PLOS ONE Published:2026

Abstract

Background Predicting conversion from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is critical for managing people with multiple sclerosis (PwMS). Cognitive function has been linked to disease progression in RRMS, yet its association with conversion to SPMS remains underexplored. This study aimed to assess this relationship using the newly developed DAAE score to calculate the risk of conversion to SPMS. Methods The risk of conversion over five years was assessed using the DAAE score (0–12), and the PwMS were categorized into very-low-to-low and medium-to-high risk groups. Cognitive function was assessed using the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), Paced Auditory Serial Addition Test (PASAT), and California Verbal Learning Test-Second Edition (CVLT-II). Pairwise correlations and hierarchical linear and logistic regression analyses were performed to examine the relationship between cognition and conversion risk. Results A total of 217 PwMS were included (very low to low = 185, medium to high = 32). The DAAE score was moderately correlated with SDMT and BVMT-R and weakly correlated with PASAT and CVLT-II. Multivariable linear regressions found SDMT (beta = −0.125, 95%CI: −0.155, −0.096, p-value < 0.001), BVMT-R (beta = −0.157, 95%CI: −0.200, −0.114, p-value < 0.001), PASAT (beta = −0.084, 95%CI: −0.111, −0.057, p-value < 0.001), and CVLT-II (beta = −0.088, 95%CI: −0.125, −0.050, p-value < 0.001) were independently associated with the risk of conversion. Among these, SDMT (beta = −0.093, 95% CI: −0.133 to −0.054, p-value < 0.001) was the most robust predictor of conversion risk. © 2026 Mirmosayyeb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.