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
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 - 10.1002/ana.25746
DO - 10.1002/ana.25746
M3 - Article
C2 - 32285956
AN - SCOPUS:85084050634
VL - 88
SP - 93
EP - 105
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 1
ER -