Longitudinal Assessment of Multiple Sclerosis with the Brain‐Age Paradigm

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...

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Published in:Annals of neurology Vol. 88; no. 1; pp. 93 - 105
Main Authors: Cole PhD, James H., Raffel MD, Joel, Friede PhD, Tim, Eshaghi MD, PhD, Arman, Brownlee PhD, FRACP, Wallace J., Chard MD, PhD, Declan, De Stefano MD, PhD, Nicola, Enzinger MD, Christian, Pirpamer MSc, Lukas, Filippi MD, FEAN, Massimo, Gasperini MD, Claudio, Rocca MD, Maria Assunta, Rovira MD, Alex, Ruggieri MD, Serena, Sastre‐Garriga MD, PhD, Jaume, Stromillo MD, PhD, Maria Laura, Uitdehaag MD, PhD, Bernard M. J., Vrenken PhD, Hugo, Barkhof MD PhD, Frederik, Nicholas MD, PhD, Richard, Ciccarelli PhD, FRCP, Olga
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01.07.2020
Wiley Subscription Services, Inc
Subjects:
Adolescent
Adult
Age
Aged
Aging
Aging (natural)
Aging - pathology
Atrophy
Atrophy - diagnostic imaging
Atrophy - pathology
Biomarkers
Brain
Brain - diagnostic imaging
Brain - pathology
Confidence intervals
Demyelinating Diseases - diagnostic imaging
Demyelinating Diseases - pathology
Disability Evaluation
Disease control
Disease Progression
Female
Humans
Longitudinal Studies
Magnetic resonance imaging
Male
Middle Aged
Multiple sclerosis
Multiple Sclerosis - diagnostic imaging
Multiple Sclerosis - pathology
Neuroimaging
Young Adult
ISSN:0364-5134, 1531-8249, 1531-8249
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Summary: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
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ISSN:0364-5134
1531-8249
1531-8249
DOI:10.1002/ana.25746