title: Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients.
abstract: The purpose of this work was to determine whether changes in cholesterol profiles after interferon-β (IFN-β)1a treatment initiation following the first demyelinating event suggestive of multiple sclerosis are associated with clinical and MRI outcomes over 4 years. A group of 131 patients (age: 27.9 ± 7.8 years, 63% female) with serial 3-monthly clinical and 12-monthly MRI follow-ups over 4 years were investigated. Serum cholesterol profiles, including total cholesterol (TC), HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C) were obtained at baseline, 1 month, 3 months, and every 6 months thereafter. IFN-β1a initiation caused rapid decreases in serum HDL-C, LDL-C, and TC within 1 month of IFN-β1a initiation (all P < 0.001) that returned slowly toward baseline. In predictive mixed model analyses, greater percent decreases in HDL-C after 3 months of IFN-β1a treatment initiation were associated with less brain atrophy over the 4 year time course, as assessed by percent brain volume change (P < 0.001), percent gray matter volume change (P < 0.001), and percent lateral ventricle volume change (P = 0.005). Decreases in cholesterol biomarkers following IFN-β1a treatment are associated with brain atrophy outcomes over 4 years. Pharmacological interventions targeting lipid homeostasis may be clinically beneficial for disrupting neurodegenerative processes.
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Uher
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY.
authors.forename: Kelly
authors.initials: K
authors.lastname: Fellows
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY.|MR Imaging Clinical Translational Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Department of Radiology, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.affiliation: Department of Statistics and Probability, University of Economics in Prague, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Sobisek
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.affiliation: Department of Radiology, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.affiliation: Department of Radiology, Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY.|Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) "S.Maria Nascente", Don Gnocchi Foundation, Milan, Italy.
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY Murali@Buffalo.Edu.|Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY.
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003711:Demyelinating Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D009410:Nerve Degeneration / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D002784:Cholesterol; D000068556:Interferon beta-1a
keywords: brain atrophy; cholesterol; magnetic resonance imaging