Cui Can, Sun Jiangwei, Pawitan Yudi, Piehl Fredrik, Chen Honglei, Ingre Caroline, Wirdefeldt Karin, Evans Marie, Andersson John, Carrero Juan-Jesus, Fang Fang
Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Brain Commun. 2020 Sep 18;2(2):fcaa152. doi: 10.1093/braincomms/fcaa152. eCollection 2020.
Serum creatinine and C-reactive protein have been proposed as potential biomarkers for neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease. However, longitudinal studies investigating temporal patterns of these biomarkers, including the phase before diagnosis, are rare. We performed a case-control study including all newly diagnosed patients with amyotrophic lateral sclerosis ( = 525), multiple sclerosis ( = 1815) or Parkinson's disease ( = 3797) during 2006-2013 in Stockholm, Sweden, who participated in the Stockholm CREAtinine Measurements (SCREAM) project. For each case, we randomly selected up to five controls from SCREAM that were individually matched to the case by age, sex and county of residence ( = 2625 for amyotrophic lateral sclerosis, = 9063 for multiple sclerosis and 18 960 for Parkinson's disease). We collected for both the cases and the controls testing results of serum creatinine and C-reactive protein performed by healthcare providers in Stockholm during the study period. Median levels of creatinine and C-reactive protein were visualized using locally weighted smoothing curves among cases and controls. A linear mixed model was also applied to explore temporal changes within an individual. Compared to controls, patients with amyotrophic lateral sclerosis had lower levels of creatinine from 2 years before diagnosis onwards. In contrast, patients with amyotrophic lateral sclerosis had lower levels of C-reactive protein before diagnosis but higher levels after diagnosis, compared to controls. Focusing the 2 years before to 2 years after diagnosis, patients with amyotrophic lateral sclerosis displayed statistically significantly decreasing level of creatinine from 1 year before diagnosis until 2 years after diagnosis, whereas increasing level of C-reactive protein from diagnosis until 2 years after diagnosis. There were no similar patterns noted among patients with multiple sclerosis or Parkinson's disease, or the controls of the three patient groups. Patients with amyotrophic lateral sclerosis display distinct temporal patterns of creatinine and C-reactive protein before and after diagnosis, compared to amyotrophic lateral sclerosis-free controls or patients with multiple sclerosis and Parkinson's disease.
血清肌酐和C反应蛋白已被提议作为神经退行性疾病的潜在生物标志物，包括肌萎缩侧索硬化症、多发性硬化症和帕金森病。然而，研究这些生物标志物时间模式（包括诊断前阶段）的纵向研究很少。我们进行了一项病例对照研究，纳入了2006年至2013年期间在瑞典斯德哥尔摩参与斯德哥尔摩肌酐测量（SCREAM）项目的所有新诊断的肌萎缩侧索硬化症患者（n = 525）、多发性硬化症患者（n = 1815）或帕金森病患者（n = 3797）。对于每个病例，我们从SCREAM中随机选择多达五个对照，这些对照按年龄、性别和居住县与病例进行个体匹配（肌萎缩侧索硬化症为n = 2625，多发性硬化症为n = 9063，帕金森病为18960）。我们收集了研究期间斯德哥尔摩医疗服务提供者对病例和对照进行的血清肌酐和C反应蛋白检测结果。使用局部加权平滑曲线可视化病例和对照中肌酐和C反应蛋白的中位数水平。还应用线性混合模型来探索个体内部的时间变化。与对照相比，肌萎缩侧索硬化症患者从诊断前2年起肌酐水平较低。相比之下，与对照相比，肌萎缩侧索硬化症患者在诊断前C反应蛋白水平较低，但在诊断后较高。聚焦于诊断前2年至诊断后2年，肌萎缩侧索硬化症患者从诊断前1年到诊断后2年肌酐水平呈统计学显著下降，而从诊断到诊断后2年C反应蛋白水平呈上升趋势。在多发性硬化症或帕金森病患者或这三组患者的对照中未观察到类似模式。与无肌萎缩侧索硬化症的对照或多发性硬化症和帕金森病患者相比，肌萎缩侧索硬化症患者在诊断前后显示出肌酐和C反应蛋白的明显时间模式。
