Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm
Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm
复制标题
DOI：
10.1002/ana.25746
复制
发表时间：
2020-05-06
影响因子：
11.2
通讯作者：
Ciccarelli, Olga
中科院分区：
文献类型：
--
作者：
Cole, James H.;Raffel, Joel;Ciccarelli, Olga
目的在多发性硬化（MS）的自然病程中，大脑暴露于衰老以及疾病的影响。大脑老化可以用统计学建模，即所谓的“大脑年龄”范式。在这里，我们评估了大脑预测的年龄差异是否方法在一项纵向、多中心的3，565例磁共振成像（MRI）扫描样本中，对1，204例MS和临床孤立综合征（CIS）患者和150例健康对照者进行研究（平均随访时间：患者3.41年，健康对照组1.97年），我们使用T1加权MRI测量了“大脑预测年龄”。我们比较了MS患者、CIS患者和健康对照者以及疾病亚型之间的脑PAD。结果MS患者的脑PAD明显高于健康对照组（平均脑PAD +10.3年; 95% CI = 8.5-12.1），而健康对照组为4.3年; 95% CI = 2.1 - 6.4; p < 0.001）。脑PAD最高的是继发性进展性MS（+13.3岁; 95% CI = 11.3-15.3）。研究入组时的脑PAD可预测残疾进展时间（风险比1.02; 95% CI = 1.01-1.03; p < 0.001）;尽管正常化的脑体积是一个更强的预测因子。更大的年化脑PAD增加与更大的年化EDSS评分相关（r = 0.26; p < 0.001）。基线时较高的脑PAD与更快的残疾进展相关，脑PAD的变化率与残疾恶化相关。潜在地，“脑年龄”可以用作早期MS的预后生物标志物，以跟踪疾病进展或对临床试验招募的患者进行分层。ANN NEUROL 2020
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