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Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: A longitudinal retrospective 5-year study.
Mult Scler 2019; :1352458519881428MS

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.

Authors+Show Affiliations

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.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.Department of Pharmaceutical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.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.Novartis AG, Basel, Switzerland.Novartis AG, Basel, Switzerland.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.Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.Novartis AG, Basel, Switzerland.Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.Jacobs MS Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31610732

Citation

Jakimovski, Dejan, et al. "Serum Neurofilament Light Chain Level Associations With Clinical and Cognitive Performance in Multiple Sclerosis: a Longitudinal Retrospective 5-year Study." Multiple Sclerosis (Houndmills, Basingstoke, England), 2019, p. 1352458519881428.
Jakimovski D, Zivadinov R, Ramanthan M, et al. Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: A longitudinal retrospective 5-year study. Mult Scler. 2019.
Jakimovski, D., Zivadinov, R., Ramanthan, M., Hagemeier, J., Weinstock-Guttman, B., Tomic, D., ... Benedict, R. H. (2019). Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: A longitudinal retrospective 5-year study. Multiple Sclerosis (Houndmills, Basingstoke, England), p. 1352458519881428. doi:10.1177/1352458519881428.
Jakimovski D, et al. Serum Neurofilament Light Chain Level Associations With Clinical and Cognitive Performance in Multiple Sclerosis: a Longitudinal Retrospective 5-year Study. Mult Scler. 2019 Oct 15;1352458519881428. PubMed PMID: 31610732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: A longitudinal retrospective 5-year study. AU - Jakimovski,Dejan, AU - Zivadinov,Robert, AU - Ramanthan,Murali, AU - Hagemeier,Jesper, AU - Weinstock-Guttman,Bianca, AU - Tomic,Davorka, AU - Kropshofer,Harald, AU - Fuchs,Tom A, AU - Barro,Christian, AU - Leppert,David, AU - Yaldizli,Özgür, AU - Kuhle,Jens, AU - Benedict,Ralph Hb, Y1 - 2019/10/15/ PY - 2019/10/16/entrez KW - Multiple sclerosis (MS) KW - cognition KW - longitudinal KW - neurofilament light chain KW - processing speed SP - 1352458519881428 EP - 1352458519881428 JF - Multiple sclerosis (Houndmills, Basingstoke, England) JO - Mult. Scler. N2 - 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. SN - 1477-0970 UR - https://www.unboundmedicine.com/medline/citation/31610732/Serum_neurofilament_light_chain_level_associations_with_clinical_and_cognitive_performance_in_multiple_sclerosis:_A_longitudinal_retrospective_5-year_study L2 - http://journals.sagepub.com/doi/full/10.1177/1352458519881428?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -