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We aimed to investigate how disease-modifying therapies (DMTs) of varying efficacy are associated with long-term cognitive trajectories in MS, as measured by the Symbol Digit Modalities Test (SDMT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the data from Swedish population-based MS cohorts linked to the Swedish MS registry, we included individuals with relapsing-onset MS receiving DMT to evaluate longitudinal SDMT trajectories. From a cohort of 5467 treated individuals, several analytic subsets were defined for specific trajectory analyses. Mixed-effects models were used to examine changes in cognitive performance across treatment categories, including platform therapies, high-efficacy therapies overall, and specific high-efficacy agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SDMT scores increased during the first years of follow-up among individuals initiating high-efficacy DMT and subsequently declined, whereas changes in the platform group were smaller over time. Differences between groups were observed at years 3 and 4, with an estimated difference of approximately 2 points, which were not sustained at later follow-up. When compared with anti-CD20 therapies, natalizumab-treated individuals showed a greater early increase (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2212\u00a00.77, 95% CI \u2212\u00a01.26, \u2212\u00a00.27) and a more pronounced subsequent decline (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      0.38, 95% CI 0.21\u20130.55), with trajectories converging over time. Adjustment for repeated testing attenuated early increases in SDMT scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There was limited evidence for a sustained or clinically relevant short-term effect of high-efficacy DMTs on cognitive trajectories in MS. Differences between groups and changes over time are likely influenced by underlying patient characteristics and practice effects related to repeated testing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13860-8","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:15:33Z","timestamp":1779304533000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Trajectories of processing speed in multiple sclerosis across disease-modifying therapies"],"prefix":"10.1007","volume":"273","author":[{"given":"Jie","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hillert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-4749","authenticated-orcid":false,"given":"Anna Karin","family":"Hedstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"13860_CR1","first-page":"183","volume":"403","author":"D Jakimovski","year":"2024","unstructured":"Jakimovski D, Bittner S, Zivadinov R, Sarah A M, Ralph Hb B, Frauke Z, Bianca WG (2024) Mult Scler 403:183\u2013202","journal-title":"Mult Scler"},{"key":"13860_CR2","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.neurol.2018.03.006","volume":"174","author":"H Z\u00e9phir","year":"2018","unstructured":"Z\u00e9phir H (2018) Progress in understanding the pathophysiology of multiple sclerosis. 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He received unrestricted research support from Biogen, Bristol-Myers-Squibb, Merck KGaA,\u00a0Novartis, Roche and\u00a0Sanofi-Genzyme; TO received lecture\/advisory board honoraria, and unrestricted MS research grants from Biogen, Novartis, Sanofi and Merck; LA has nothing to disclose; AKH serves on the editorial board of MS Journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All studies received approval from the Regional Ethical Review Board at Karolinska Institute and were conducted in compliance with the ethical standards outlined in the 1964 Declaration of Helsinki and its subsequent amendments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard statement"}}],"article-number":"324"}}