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Cole, JH; Raffel, J; Friede, T; Eshaghi, A; Brownlee, WJ; Chard, D; De Stefano, N; Enzinger, C; Pirpamer, L; Filippi, M; Gasperini, C; Rocca, MA; Rovira, A; Ruggieri, S; Sastre-Garriga, J; Stromillo, ML; Uitdehaag, BMJ; Vrenken, H; Barkhof, F; Nicholas, R; Ciccarelli, O; MAGNIMS study group.
Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm.
Ann Neurol. 2020; 88(1):93-105
Doi: 10.1002/ana.25746
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- Co-Autor*innen der Med Uni Graz
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Enzinger Christian
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Pirpamer Lukas
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- Abstract:
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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.
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.
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).
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.
© 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
- Find related publications in this database (using NLM MeSH Indexing)
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Adolescent -
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Adult -
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Aged -
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Aging - pathology
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Atrophy - diagnostic imaging
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Atrophy - pathology
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Brain - diagnostic imaging
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Brain - pathology
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Demyelinating Diseases - diagnostic imaging
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Demyelinating Diseases - pathology
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Disability Evaluation -
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Disease Progression -
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Female -
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Humans -
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Longitudinal Studies -
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Male -
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Middle Aged -
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Multiple Sclerosis - diagnostic imaging
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Multiple Sclerosis - pathology
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Young Adult -