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. 2024 Oct;30(11-12):1468-1478.
doi: 10.1177/13524585241256540. Epub 2024 Aug 28.

Cognitive progression independent of relapse in multiple sclerosis

Tom A Fuchs  1   2   3 , Menno M Schoonheim  1 , Robert Zivadinov  2   3   4 , Michael G Dwyer  2   3 , Elisa Colato  1 , Zachary Weinstock  2   3 , Bianca Weinstock-Guttman  2 , Eva Mm Strijbis  5 , Ralph Hb Benedict  2
Affiliations

Cognitive progression independent of relapse in multiple sclerosis

Tom A Fuchs et al. Mult Scler. 2024 Oct.

Abstract

Background: Substantial physical-disability worsening in relapsing-remitting multiple sclerosis (RRMS) occurs outside of clinically recorded relapse. This phenomenon, termed progression independent of relapse activity (PIRA), is yet to be established for cognitive decline.

Methods: Retrospective analysis of RRMS patients. Cognitive decline was defined using reliable-change-index cut-offs for each test (Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised, California Verbal Learning Test-II). Decline was classified as PIRA if the following conditions were met: no relapse observed between assessments nor within 9 months of cognitive decline.

Results: The study sample (n = 336) was 80.7% female with a mean (standard deviation (SD)) age, disease duration, and observation period of 43.1 (9.5), 10.8 (8.4), and 8.1 (3.1) years, respectively. A total of 169 (50.3%) subjects were cognitively impaired at baseline relative to age-, sex-, and education-matched HCs. Within subjects who experienced cognitive decline (n = 167), 89% experienced cognitive PIRA. A total of 141 (68.1%) cognitive decline events were observed independent of EDSS worsening. Cognitive PIRA was more likely to be observed with increased assessments (p < 0.001) and lower assessment density (p < 0.001), accounting for baseline clinical factors.

Conclusion: These results establish the concept of cognitive PIRA and further our understanding of progressive cognitive decline in RRMS.

Keywords: Multiple sclerosis; cognition; progression independent of relapse activity.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.A.F. serves on the editorial board of Frontiers in Neurology and receives research support from the European Committee for Treatment and Research in Multiple Sclerosis and consulting fees for Click Therapeutics. M.M.S. serves on the editorial board of Neurology and Frontiers in Neurology, receives research support from the Dutch MS Research Foundation, Eurostars-EUREKA, ARSEP, Amsterdam Neuroscience, MAGNIMS and ZonMW (Vidi grant, project number 09150172010056), and has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Celgene/Bristol Meyers Squibb, EIP, Sanofi, MedDay, and Merck. R.Z. received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Biogen, Sanofi, Filterlex, Mapi Pharma, and Janssen for speaking and consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, EMD Serono, Filterlex, CorEvitas, Protembis, and V-WAVE Medical. M.G.D. received grant support from Novartis, Bristol Myers Squibb, Mapi Pharma, Merck Serono, Keystone Heart Ltd., Protembis GmbH, and V-Wave Ltd., and consulting fees Bristol Myers Squibb, Merck Serono, and Keystone Heart Ltd. E.C. receives grant support from MAGNIMS and research support from EIP. Z.W. has nothing to disclose. E.M.M.S. serves on the editorial board of Frontiers in Neurology and receives research support from Stichting MS Research and ZonMS and received speaker fees from Merck and Novartis. Dr B.W.-G. received honoraria as a speaker and/or as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Genentech, Novartis, Celgene/BMS, Janssen, Labcorp, TG therapeutics, and Horizon. He received research funds from Biogen Idec, EMD Serono, Genzyme, Genentech, Sanofi, and Novartis. R.H.B.B. for research support from Bristol Meyers Squibb, National Institutes of Health, National Multiple Sclerosis Society Consultancy from Bristol Meyers Squibb, Novartis, Roche, and Sanofi, speaking from Bristol Meyers Squibb and EMD Serono, and royalties from Psychological Assessment Resources.

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