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

Robert Zivadinov; Niels Bergsland; Dejan Jakimovski; Bianca Weinstock-Guttman; Lorena Lorefice; Menno M Schoonheim; Sarah A Morrow; Mary Ann Picone; Gabriel Pardo; Myassar Zarif; Mark Gudesblatt; Jacqueline A Nicholas; Andrew Smith; Samuel Hunter; Stephen Newman; Mahmoud A AbdelRazek; Ina Hoti; Jon Riolo; Diego Silva; Tom A Fuchs; Michael G Dwyer; Ralph Hb Benedict

doi:10.1016/j.nicl.2024.103609

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

Neuroimage Clin. 2024 Apr 27:42:103609. doi: 10.1016/j.nicl.2024.103609. Online ahead of print.

Authors

Robert Zivadinov¹, Niels Bergsland², Dejan Jakimovski², Bianca Weinstock-Guttman³, Lorena Lorefice⁴, Menno M Schoonheim⁵, Sarah A Morrow⁶, Mary Ann Picone⁷, Gabriel Pardo⁸, Myassar Zarif⁹, Mark Gudesblatt⁹, Jacqueline A Nicholas¹⁰, Andrew Smith¹⁰, Samuel Hunter¹¹, Stephen Newman¹², Mahmoud A AbdelRazek¹³, Ina Hoti¹⁴, Jon Riolo¹⁵, Diego Silva¹⁵, Tom A Fuchs⁵, Michael G Dwyer¹⁶, Ralph Hb Benedict³

Affiliations

¹ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, United States; Center for Biomedical Imaging at Clinical and Translational Science Institute, University of Buffalo, State University of New York, NY, United States. Electronic address: rzivadinov@bnac.net.
² Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, United States.
³ Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York and Kaleida Health, BGH, Buffalo, NY, United States.
⁴ Department of Medical Sciences and Public Health, Multiple Sclerosis Center, Binaghi Hospital, ASL Cagliari, University of Cagliari, Cagliari, Italy.
⁵ MS Center Amsterdam, Anatomy & Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
⁶ Schulich School of Medicine and Dentistry, London Health Sciences Centre, University Hospital, London, Ontario, CA, Canada; Department of Clinical Neurological Sciences, Hotchkiss Brain Institute, University of Calgary, Canada.
⁷ Holy Name Medical Center, Teaneck, NJ, United States.
⁸ Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
⁹ South Shore Neurologic Associates NYU Langone, Patchogue, NY, United States.
¹⁰ OhioHealth MS Center, Riverside Methodist Hospital, Columbus, OH, United States.
¹¹ Advanced Neurosciences Institute, Franklin, TN, United States.
¹² Island Neurological Association, Plainview, NY, United States.
¹³ Mount Auburn Hospital, Harvard Medical School, United States; Atrium Health Neurosciences Institute, Wake Forest University School of Medicine, United States.
¹⁴ Mount Auburn Hospital, Harvard Medical School, United States.
¹⁵ Bristol Myers Squibb, Summit, NJ, United States.
¹⁶ Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, NY, United States; Center for Biomedical Imaging at Clinical and Translational Science Institute, University of Buffalo, State University of New York, NY, United States.

Abstract

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.