Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

BACKGROUND

Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient.

OBJECTIVE

To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting.

METHODS

This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed.

RESULTS

332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized β = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized β = -0.14, p = 0.028) in a linear regression model.

CONCLUSIONS

PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Zivadinov has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Janssen, Protembis, Filterlex and Novartis for speaking and consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Protembis, CorEvitas and V-WAVE Medical. Niels Bergsland and Dejan Jakimovski have nothing to disclose. Myassar Zarif, Samuel Hunter, Stephen Newman, Tom Fuchs and Mary Ann Picone have not declared any conflict of interest. Bianca Weinstock-Guttman received honoraria as a speaker and/or as a consultant for Biogen Idec, Sanofi &Genzyme, Genentech, Novartis, BMS, Bayer, Horizon and Janssen. Dr Weinstock-Guttman received research funds from Biogen Idec, Genentech and Novartis. Lorena Lorefice received honoraria for consultancy and speaking from Biogen, Novartis, Sanofi, Genzyme, Merck and Bristol Myers Squibb. Menno Schoonheim: 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. Sarah A. Morrow, in the last 3 years, has served as an advisory board member or received consulting fees from Biogen Idec; BMS/Celgene; EMDSerono; Novartis; Roche; Sanofi. She has participated in a speaker’s bureau for Biogen Idec; BMS/Celgene; EMDSerono; Novartis; Roche; Sanofi. She has received research support from Biogen Idec; EMDSerono, Novartis, Roche; Sanofi Genzyme. She has participated as a site investigator in clinical trials sponsored by Bristol Myers Squibb/Celgene; EMDSerono; Novartis; Roche; Sanofi. Gabriel Pardo received grants (to the institution) from Biogen, EMD Serono, Roche/Genentech, Sanofi Genzyme, Novartis, Abbvie, and BMS; consultant and/or speaker bureau for Biogen, EMD Serono, Roche/Genentech, Sanofi Genzyme, Novartis, Janssen, BMS, TG Therapeutics, PRIME Education, and MSAA. Mark Gudesblatt received honoraria from Biogen and Genentech. Jacqueline Nicholas received research grants from Biogen, Novartis, PCORI, Genentech, University of Buffalo, EMD Serono; Consulting for EMD Serono, Genentech, Greenwich Biosciences, Novartis, TG Therapeutics and Sanofi; Speaking honoraria for BMS, EMD Serono, Horizon, TG Therapeutics. Andrew Smith received honorariums from EMD Serono and Sanofi Genzyme for speaking bureau and combination for Genzyme for an advisory board. Mahmoud A. AbdelRazek received consultant fees from Bristol Myers Squibb. Wachy Vongchucherd, Jon Riolo and Diego Silva are employees of Bristol Myers Squibb. Michael G. Dwyer has received personal compensation from Bristol Myers Squibb and Filterlex for consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Protembis, CorEvitas and V-WAVE Medical. Ralph HB. Benedict has received consultation or speaking fees from Bristol Myer Squibb, Biogen, Merck, EMD Serono, Roche, Immune Therapeutics, Novartis, and Sanofi-Genzyme.