TY - JOUR
T1 - Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm
AU - Cole PhD, James H.
AU - Raffel MD, Joel
AU - Friede PhD, Tim
AU - Eshaghi MD, PhD, Arman
AU - Brownlee PhD, FRACP, Wallace J.
AU - Chard MD, PhD, Declan
AU - de Stefano MD, PhD, Nicola
AU - Enzinger MD, Christian
AU - Pirpamer MSc, Lukas
AU - Filippi MD, FEAN, Massimo
AU - Gasperini MD, Claudio
AU - Rocca MD, Maria Assunta
AU - Rovira MD, Alex
AU - Ruggieri MD, Serena
AU - Sastre-Garriga MD, PhD, Jaume
AU - Stromillo MD, PhD, Maria Laura
AU - Uitdehaag MD, PhD, Bernard M. J.
AU - Vrenken PhD, Hugo
AU - Barkhof MD PhD, Frederik
AU - Nicholas MD, PhD, Richard
AU - Ciccarelli PhD, FRCP, Olga
N1 - Funding Information: J.C. is funded by a UKRI/MRC Innovation Fellowship. O.C., R.N., F.B., and D.C. acknowledge the National Institute for Health Research University College London Hospitals Biomedical Research Centre. R.N. acknowledges the National Institute for Health Research Imperial College London Hospitals Biomedical Research Centre. A.E. received the McDonald Fellowship from Multiple Sclerosis International Federation (MSIF, http://www.msif.org) and ECTRIMS-MAGNIMS fellowship. The study received funding from the UK Multiple Sclerosis Society, the National Institute for Health Research University College London Hospitals, and Imperial College Healthcare Biomedical Research Centre. Publisher Copyright: © 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Objective: During the natural course of multiple sclerosis (MS), the brain is exposed to aging as well as disease effects. Brain aging can be modeled statistically; the so-called “brain-age” paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression, and future outcomes. Methods: In a longitudinal, multicenter sample of 3,565 magnetic resonance imaging (MRI) scans, in 1,204 patients with MS and clinically isolated syndrome (CIS) and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured “brain-predicted age” using T1-weighted MRI. We compared brain-PAD among patients with MS and patients with CIS and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. Results: Patients with MS had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years; 95% confidence interval [CI] = 8.5–12.1] versus 4.3 years; 95% CI = 2.1 to 6.4; p < 0.001). The highest brain-PADs were in secondary-progressive MS (+13.3 years; 95% CI = 11.3–15.3). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02; 95% CI = 1.01–1.03; p < 0.001); although normalized brain volume was a stronger predictor. Greater annualized brain-PAD increases were associated with greater annualized EDSS score (r = 0.26; p < 0.001). Interpretation: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, “brain-age” could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrollment. ANN NEUROL 2020 ANN NEUROL 2020;88:93–105.
AB - Objective: During the natural course of multiple sclerosis (MS), the brain is exposed to aging as well as disease effects. Brain aging can be modeled statistically; the so-called “brain-age” paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression, and future outcomes. Methods: In a longitudinal, multicenter sample of 3,565 magnetic resonance imaging (MRI) scans, in 1,204 patients with MS and clinically isolated syndrome (CIS) and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured “brain-predicted age” using T1-weighted MRI. We compared brain-PAD among patients with MS and patients with CIS and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. Results: Patients with MS had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years; 95% confidence interval [CI] = 8.5–12.1] versus 4.3 years; 95% CI = 2.1 to 6.4; p < 0.001). The highest brain-PADs were in secondary-progressive MS (+13.3 years; 95% CI = 11.3–15.3). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02; 95% CI = 1.01–1.03; p < 0.001); although normalized brain volume was a stronger predictor. Greater annualized brain-PAD increases were associated with greater annualized EDSS score (r = 0.26; p < 0.001). Interpretation: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, “brain-age” could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrollment. ANN NEUROL 2020 ANN NEUROL 2020;88:93–105.
UR - http://www.scopus.com/inward/record.url?scp=85084050634&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ana.25746
DO - https://doi.org/10.1002/ana.25746
M3 - Article
C2 - 32285956
SN - 0364-5134
VL - 88
SP - 93
EP - 105
JO - Annals of neurology
JF - Annals of neurology
IS - 1
ER -