Max-Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Department of Neurology, Charles University, First Faculty of Medicine, Prague, Czech Republic; Department of Radiology, Na Homolce Hospital, Prague, Czech Republic.
Neuroimage Clin. 2019;21:101636. doi: 10.1016/j.nicl.2018.101636. Epub 2018 Dec 10.
We aimed at testing the potential of biomarkers in predicting individual patient response to dopaminergic therapy for Parkinson's disease. Treatment efficacy was assessed in 30 Parkinson's disease patients as motor symptoms improvement from unmedicated to medicated state as assessed by the Unified Parkinson's Disease Rating Scale score III. Patients were stratified into weak and strong responders according to the individual treatment response. A multiple regression was implemented to test the prediction accuracy of age, disease duration and treatment dose and length. Univariate voxel-based morphometry was applied to investigate differences between the two groups on age-corrected T1-weighted magnetic resonance images. Multivariate support vector machine classification was used to predict individual treatment response based on neuroimaging data. Among clinical data, increasing age predicted a weaker treatment response. Additionally, weak responders presented greater brain atrophy in the left temporoparietal operculum. Support vector machine classification revealed that gray matter density in this brain region, including additionally the supplementary and primary motor areas and the cerebellum, was able to differentiate weak and strong responders with 74% accuracy. Remarkably, age and regional gray matter density of the left temporoparietal operculum predicted both and independently treatment response as shown in a combined regression analysis. In conclusion, both increasing age and reduced gray matter density are valid and independent predictors of dopaminergic therapy response in Parkinson's disease.
我们旨在测试生物标志物在预测帕金森病患者对多巴胺能治疗的个体反应中的潜力。通过统一帕金森病评定量表评分 III 评估未经药物治疗和药物治疗的帕金森病患者的运动症状改善情况,评估了 30 名帕金森病患者的治疗效果。根据个体治疗反应将患者分为弱反应者和强反应者。实施多元回归以测试年龄、疾病持续时间和治疗剂量和长度对预测准确性的影响。应用单变量基于体素的形态计量学在年龄校正的 T1 加权磁共振图像上比较两组之间的差异。应用多元支持向量机分类基于神经影像学数据预测个体治疗反应。在临床数据中,年龄增长预示着治疗反应较弱。此外,弱反应者的左颞顶叶脑回出现更大的脑萎缩。支持向量机分类显示,该脑区的灰质密度(包括补充运动区和初级运动区以及小脑)能够以 74%的准确率区分弱反应者和强反应者。值得注意的是,年龄和左颞顶叶脑回的区域灰质密度在联合回归分析中显示出对多巴胺能治疗反应的预测作用,并且是独立的预测因素。总之,年龄增长和灰质密度降低都是帕金森病多巴胺能治疗反应的有效且独立的预测因子。