title: Brain reserve against physical disability progression over 5 years in multiple sclerosis.
abstract: The brain reserve hypothesis links larger maximal lifetime brain growth (MLBG, estimated with intracranial volume [ICV]) with lower risk for cognitive decline/dementia. We examined whether larger MLBG is also linked to less physical disability progression over 5 years in a prospective sample of treatment-naive patients with multiple sclerosis (MS).
  
  
  
  Physical disability was measured with the Expanded Disability Status Scale (EDSS) at baseline and 5-year follow-up in 52 treatment-naive Serbian patients with MS. MRI measured disease burden (cerebral atrophy, T2 lesion volume) and MLBG: a genetically determined, premorbid (established during adolescence, stable thereafter) patient characteristic estimated with ICV (adjusted for sex). Logistic regression tested whether MLBG (smaller vs larger) predicts disability progression (stable vs worsened) independently of disease burden.
  
  
  
  Disability progression was observed in 29 (55.8%) patients. Larger MLBG predicted lower risk for progression (odds ratio 0.13, 95% confidence interval 0.02-0.78), independently of disease burden. We also calculated absolute change in EDSS scores, and observed that patients with smaller MLBG showed worse EDSS change (0.91 ± 0.71) than patients with larger MLBG (0.42 ± 0.87).
  
  
  
  Larger MLBG was linked to lower risk for disability progression in patients with MS over 5 years, which is the first extension of the brain reserve hypothesis to physical disability. MLBG (ICV) represents a clinically available metric that may help gauge risk for future disability in patients with MS, which may advance the science and practice of early intervention. Potential avenues for future research are discussed.
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia. james.sumowski@mssm.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Sumowski
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Leavitt
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Meani
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Sarlota
authors.initials: S
authors.lastname: Mesaros
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Drulovic
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosa
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Habeck
authors.affiliation: From the Department of Neurology (J.F.S.), Icahn School of Medicine at Mount Sinai, New York, NY; Neuroimaging Research Unit, Division of Neuroscience (M.A.R., A.M., P.P., M.F.), and Department of Neurology (M.A.R., M.F.), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology (V.M.L., C.G.H.), Columbia University Medical Center, New York, NY; and Clinic of Neurology (S.M., J.D.), Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging* / Q000254:growth & development; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009929:Organ Size; D012306:Risk