Dejan Jakimovski1, Robert Zivadinov2, Murali Ramanthan3, Jesper Hagemeier4, Bianca Weinstock-Guttman5, Davorka Tomic6, Harald Kropshofer6, Tom A Fuchs4, Christian Barro7, David Leppert6, Özgür Yaldizli7, Jens Kuhle7, Ralph Hb Benedict5. 1. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA/Jacobs MS Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 2. Jacobs MS Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA/Center for Biomedical Imaging at Clinical Translational Science Institute, Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 3. Department of Pharmaceutical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 4. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 5. Jacobs MS Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 6. Novartis AG, Basel, Switzerland. 7. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Abstract
BACKGROUND: A limited number of studies investigated associations between serum neurofilament light chain (sNfL) and cognition in persons with multiple sclerosis (PwMS). OBJECTIVE: To assess cross-sectional and longitudinal associations between sNfL levels, clinical, and cognitive performance in PwMS and age-matched healthy controls (HCs). MATERIALS: One hundred twenty-seven PwMS (85 relapsing-remitting MS/42 progressive MS), 20 clinically isolated syndrome patients, and 52 HCs were followed for 5 years. sNfL levels were measured using the single-molecule array (Simoa) assay and quantified in picograms per milliliter. Expanded Disability Status Scale (EDSS), walking, and manual dexterity tests were obtained. At follow-up, Brief International Cognitive Assessment for MS (BICAMS) was utilized. Cognitively impaired (CI) status was derived using HC-based z-scores. Age-, sex-, and education-adjusted analysis of covariance (ANCOVA) and regression models were used. Multiple comparison-adjusted values of q < 0.05 were considered significant. RESULTS: In PwMS, sNfL levels were cross-sectionally associated with walking speed (r = 0.235, q = 0.036), manual dexterity (r = 0.337, q = 0.002), and cognitive processing speed (CPS; r =-0.265, q = 0.012). Baseline sNfL levels predicted 5-year EDSS scores (r = 0.25, q = 0.012), dexterity (r = 0.224, q = 0.033), and CPS (r =-0.205, q = 0.049). CI patients had higher sNfL levels (27.2 vs. 20.6, p = 0.016) and greater absolute longitudinal sNfL increase when compared with non-CI patients (4.8 vs. 0.7, p = 0.04). CONCLUSION: Higher sNfL levels are associated with poorer current and future clinical and cognitive performance.
BACKGROUND: A limited number of studies investigated associations between serum neurofilament light chain (sNfL) and cognition in persons with multiple sclerosis (PwMS). OBJECTIVE: To assess cross-sectional and longitudinal associations between sNfL levels, clinical, and cognitive performance in PwMS and age-matched healthy controls (HCs). MATERIALS: One hundred twenty-seven PwMS (85 relapsing-remitting MS/42 progressive MS), 20 clinically isolated syndromepatients, and 52 HCs were followed for 5 years. sNfL levels were measured using the single-molecule array (Simoa) assay and quantified in picograms per milliliter. Expanded Disability Status Scale (EDSS), walking, and manual dexterity tests were obtained. At follow-up, Brief International Cognitive Assessment for MS (BICAMS) was utilized. Cognitively impaired (CI) status was derived using HC-based z-scores. Age-, sex-, and education-adjusted analysis of covariance (ANCOVA) and regression models were used. Multiple comparison-adjusted values of q < 0.05 were considered significant. RESULTS: In PwMS, sNfL levels were cross-sectionally associated with walking speed (r = 0.235, q = 0.036), manual dexterity (r = 0.337, q = 0.002), and cognitive processing speed (CPS; r =-0.265, q = 0.012). Baseline sNfL levels predicted 5-year EDSS scores (r = 0.25, q = 0.012), dexterity (r = 0.224, q = 0.033), and CPS (r =-0.205, q = 0.049). CI patients had higher sNfL levels (27.2 vs. 20.6, p = 0.016) and greater absolute longitudinal sNfL increase when compared with non-CI patients (4.8 vs. 0.7, p = 0.04). CONCLUSION: Higher sNfL levels are associated with poorer current and future clinical and cognitive performance.
Authors: Dejan Jakimovski; Ralph H B Benedict; Bianca Weinstock-Guttman; Osman Ozel; Tom A Fuchs; Norah Lincoff; Niels Bergsland; Michael G Dwyer; Robert Zivadinov Journal: J Neurol Date: 2021-02-15 Impact factor: 4.849
Authors: Kira Ashton; Tom A Fuchs; Devon Oship; Robert Zivadinov; Dejan Jakimovski; Niels Bergsland; Deepa P Ramasamy; Caila Vaughn; Bianca Weinstock-Guttman; Ralph H B Benedict; Michael G Dwyer Journal: J Neurol Date: 2020-08-04 Impact factor: 4.849
Authors: Eleonora Tavazzi; Dejan Jakimovski; Jens Kuhle; Jesper Hagemeier; Osman Ozel; Murali Ramanathan; Christian Barro; Niels Bergsland; Davorka Tomic; Harald Kropshofer; David Leppert; Zuzanna Michalak; Norah Lincoff; Michael G Dwyer; Ralph H B Benedict; Bianca Weinstock-Guttman; Robert Zivadinov Journal: Neurol Neuroimmunol Neuroinflamm Date: 2020-05-18
Authors: Maija Saraste; Svetlana Bezukladova; Markus Matilainen; Jouni Tuisku; Eero Rissanen; Marcus Sucksdorff; Sini Laaksonen; Anna Vuorimaa; Jens Kuhle; David Leppert; Laura Airas Journal: Neurol Neuroimmunol Neuroinflamm Date: 2020-12-08
Authors: Jasmeer P Chhatwal; Aaron P Schultz; Yifan Dang; Beth Ostaszewski; Lei Liu; Hyun-Sik Yang; Keith A Johnson; Reisa A Sperling; Dennis J Selkoe Journal: Nat Commun Date: 2020-11-27 Impact factor: 14.919