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.

Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm / Cole, Jh; Raffel, J; Friede, T; Eshaghi, A; Brownlee, Wj; Chard, D; De Stefano Md, 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. - In: ANNALS OF NEUROLOGY. - ISSN 0364-5134. - 88:1(2020), pp. 93-105. [10.1002/ana.25746]

Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm

Gasperini C;Ruggieri S;Ciccarelli O
2020

Abstract

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.
2020
Adolescent; Adult; Aged; Aging; Atrophy; Brain; Demyelinating Diseases; Disability Evaluation; Disease Progression; Female; Humans; Longitudinal Studies; Male; Middle Aged; Multiple Sclerosis; Young Adult
01 Pubblicazione su rivista::01a Articolo in rivista
Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm / Cole, Jh; Raffel, J; Friede, T; Eshaghi, A; Brownlee, Wj; Chard, D; De Stefano Md, 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. - In: ANNALS OF NEUROLOGY. - ISSN 0364-5134. - 88:1(2020), pp. 93-105. [10.1002/ana.25746]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1473121
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