Richard W Browne1, Dejan Jakimovski2, Nicole Ziliotto3, Jens Kuhle4, Francesco Bernardi3, Bianca Weinstock-Guttman5, Robert Zivadinov6, Murali Ramanathan7. 1. Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address: rwbrowne@buffalo.edu. 2. 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 Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. 4. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 5. Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY, USA. 6. 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 Neurology, University at Buffalo, State University of New York, Buffalo, NY, USA. 7. Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA; Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Abstract
BACKGROUND: Fatigue is a frequent symptom in multiple sclerosis (MS). The role of cholesterol and lipids in MS fatigue has not been investigated. OBJECTIVE: To investigate the associations of cholesterol biomarkers and serum neurofilament light chain (sNfL) with fatigue in relapsing-remitting MS. METHODS: This cross-sectional study included 75 relapsing-remitting MS patients (69% female, mean age ± SD: 49.6 ± 11 years and median Expanded Disability Status Scale score: 2.0). Fatigue, disability, and depression were assessed with Fatigue Severity Scale (FSS), Expanded Disability Status Scale, and the Beck Depression Index-Fast Screen, respectively. sNfL was measured using single-molecule array technology. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and an apolipoprotein panel data were obtained. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), chemokine (C-C motif) ligand 5 (CCL5 or RANTES), and CCL18 levels were measured to assess inflammation. RESULTS: The mean FSS was 4.27 ± 1.73, and 57% had severe fatigue status (SFS, FSS ≥ 4.0). In regression analyses adjusted for age, sex, disability, and depression, lower FSS and SFS were associated with greater HDL-C (P = .006 for FSS, and P = .016 for SFS) and lower TC to HDL-C ratio (P = .011 for FSS, and P = .009 for SFS). Apolipoprotein A-II was also associated with FSS (P = .022). sNfL, CCL5, CCL18, sICAM-1, and sVCAM-1 levels were not associated with fatigue after adjusting for disability and depression. CONCLUSIONS: TC to HDL-C ratio is associated with MS fatigue. Our results implicate a potential role for the HDL-C pathway in MS fatigue and could provide possible targets for the treatment of MS fatigue.
BACKGROUND:Fatigue is a frequent symptom in multiple sclerosis (MS). The role of cholesterol and lipids in MS fatigue has not been investigated. OBJECTIVE: To investigate the associations of cholesterol biomarkers and serum neurofilament light chain (sNfL) with fatigue in relapsing-remitting MS. METHODS: This cross-sectional study included 75 relapsing-remitting MS patients (69% female, mean age ± SD: 49.6 ± 11 years and median Expanded Disability Status Scale score: 2.0). Fatigue, disability, and depression were assessed with Fatigue Severity Scale (FSS), Expanded Disability Status Scale, and the Beck Depression Index-Fast Screen, respectively. sNfL was measured using single-molecule array technology. Plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and an apolipoprotein panel data were obtained. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), chemokine (C-C motif) ligand 5 (CCL5 or RANTES), and CCL18 levels were measured to assess inflammation. RESULTS: The mean FSS was 4.27 ± 1.73, and 57% had severe fatigue status (SFS, FSS ≥ 4.0). In regression analyses adjusted for age, sex, disability, and depression, lower FSS and SFS were associated with greater HDL-C (P = .006 for FSS, and P = .016 for SFS) and lower TC to HDL-C ratio (P = .011 for FSS, and P = .009 for SFS). Apolipoprotein A-II was also associated with FSS (P = .022). sNfL, CCL5, CCL18, sICAM-1, and sVCAM-1 levels were not associated with fatigue after adjusting for disability and depression. CONCLUSIONS:TC to HDL-C ratio is associated with MS fatigue. Our results implicate a potential role for the HDL-C pathway in MS fatigue and could provide possible targets for the treatment of MS fatigue.
Authors: Maria L Elkjaer; Arkadiusz Nawrocki; Tim Kacprowski; Pernille Lassen; Anja Hviid Simonsen; Romain Marignier; Tobias Sejbaek; Helle H Nielsen; Lene Wermuth; Alyaa Yakut Rashid; Peter Høgh; Finn Sellebjerg; Richard Reynolds; Jan Baumbach; Martin R Larsen; Zsolt Illes Journal: Sci Rep Date: 2021-02-18 Impact factor: 4.379