Mattia Rosso1,2, Brian C Healy1,2,3, Shrishti Saxena1,2, Anu Paul1,2, Kjetil Bjornevik4, Jens Kuhle5, Pascal Benkert6, David Leppert5, Charles Guttmann1,2, Rohit Bakshi1,2,7, Howard L Weiner1,2,7, Tanuja Chitnis1,2,7. 1. Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 2. Ann Romney Center for Neurologic Diseases, Harvard Medical School, Boston, MA. 3. Biostatistics Center, Massachusetts General Hospital, Boston, MA. 4. Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA. 5. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 6. Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 7. Brigham Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Abstract
BACKGROUND AND PURPOSE: Serum neurofilament light (sNfL) has been studied as a biomarker of disease activity in multiple sclerosis (MS). Several factors, including age, can influence its dynamics, and several studies have shown that sNfL increases with age in controls. Our objective was to explore the relationship of sNfL and age at different MS disease stages, including remission and after a gadolinium-enhancing (Gad+) lesion. METHODS: We included 94 patients with MS with annual sNfL measurements performed with a single-molecule array assay. We used multivariable linear mixed-effects models with random intercept to test the association between age and sNfL during remission and after a Gad+ lesion (ie, within 90 days after the Gad+ lesion). The model was adjusted for medication use and sex. RESULTS: We report a positive association between sNfL level and age during remission (adjusted estimate = 1.18% yearly increase, 95% CI = .34-2.03%, P = .008). In contrast, a negative interaction between age and Gad+ lesion status was observed (adjusted estimate = -1.73%, 95% CI = -2.85 to -.58%, P = .004). CONCLUSION: We propose that younger patients experience a greater elevation in sNfL than older patients in response to Gad+ lesions. Our study provides potential insights into the effects of aging on neuroinflammation in MS.
BACKGROUND AND PURPOSE: Serum neurofilament light (sNfL) has been studied as a biomarker of disease activity in multiple sclerosis (MS). Several factors, including age, can influence its dynamics, and several studies have shown that sNfL increases with age in controls. Our objective was to explore the relationship of sNfL and age at different MS disease stages, including remission and after a gadolinium-enhancing (Gad+) lesion. METHODS: We included 94 patients with MS with annual sNfL measurements performed with a single-molecule array assay. We used multivariable linear mixed-effects models with random intercept to test the association between age and sNfL during remission and after a Gad+ lesion (ie, within 90 days after the Gad+ lesion). The model was adjusted for medication use and sex. RESULTS: We report a positive association between sNfL level and age during remission (adjusted estimate = 1.18% yearly increase, 95% CI = .34-2.03%, P = .008). In contrast, a negative interaction between age and Gad+ lesion status was observed (adjusted estimate = -1.73%, 95% CI = -2.85 to -.58%, P = .004). CONCLUSION: We propose that younger patients experience a greater elevation in sNfL than older patients in response to Gad+ lesions. Our study provides potential insights into the effects of aging on neuroinflammation in MS.
Authors: Hrishikesh Lokhande; Mattia Rosso; Shahamat Tauhid; Renxin Chu; Brian C Healy; Shrishti Saxena; Christian Barro; Anu Paul; Mariann Polgar-Turcsanyi; Mark Anderson; Bonnie I Glanz; Harald Kropshofer; Cristina Granziera; David Leppert; Ludwig Kappos; Jens Kuhle; Howard L Weiner; Rohit Bakshi; Tanuja Chitnis Journal: Mult Scler J Exp Transl Clin Date: 2022-01-10
Authors: Christopher Harp; Gian-Andrea Thanei; Xiaoming Jia; Jens Kuhle; David Leppert; Sabine Schaedelin; Pascal Benkert; H-Christian von Büdingen; Robert Hendricks; Ann Herman Journal: Ann Clin Transl Neurol Date: 2022-03-01 Impact factor: 4.511