Nonmotor Predictors for Levodopa Requirement in De Novo Patients With Parkinson's Disease
Nonmotor Predictors for Levodopa Requirement in De Novo Patients With Parkinson's Disease
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DOI：
10.1002/mds.26076
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发表时间：
2015-03-01
影响因子：
8.6
通讯作者：
Barone, Paolo
中科院分区：
文献类型：
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作者：
Erro, Roberto;Picillo, Marina;Barone, Paolo
帕金森病（PD）临床表型的变异性表明存在几种亚型的疾病。PD的运动异质性已得到证实，但非运动异质性尚未得到证实。目前，我们无法根据可靠的生物标志物预测PD的进展速度。我们的目的是通过尝试识别与运动进展和功能下降率相关的非运动因素来检查PD的异质性，这些因素是通过在一个原发PD患者队列中诊断后前4年内达到左旋多巴治疗需求的时间来衡量的。有泌尿系统症状的患者中位左旋多巴导入时间明显短于无症状患者（20个月对37个月; P=0.001）。考克斯回归模型显示，尿域与开始使用左旋多巴的可能性较高相关（风险比：2.1; P=0.002）。性别、年龄、基线运动功能、多巴胺激动剂和/或单胺氧化酶B抑制剂的使用以及总左旋多巴等效日剂量等混杂因素均无影响。有泌尿系统症状的患者比无症状的患者有更高的基线和随访运动和非运动障碍。我们的研究表明，存在一个亚组的患者显示泌尿系统症状沿着整体较高的运动和非运动负荷。这些患者在疾病的前4年内容易表现出快速的功能衰退。泌尿系统症状可能是严重程度的临床标志物，也可能是PD的非运动亚型。(c)2015年国际帕金森和运动障碍协会
The variability in the clinical phenotype of Parkinson's disease (PD) suggests the existence of several subtypes of the disease. Motor heterogeneity of PD is well established, but not nonmotor heterogeneity. At present, we are unable to predict the rate of progression of PD based on robust biomarkers. We aimed to examine the heterogeneity of PD by attempting to identify nonmotor factors associated with the rate of motor progression and functional decline, as measured by the time to reach the need for levodopa therapy during the first 4 years from diagnosis in a cohort of de novo PD patients. The median time to introduction of l-dopa for patients with urinary symptoms was significantly shorter than that for those without (20 vs. 37 months; P=0.001). Cox's regression models showed that the urinary domain was associated with a higher probability of starting l-dopa (hazard ratio: 2.1; P=0.002). There was no influence of such confounders as sex, age, baseline motor features, use of dopamine agonists and/or monoamine oxidase B inhibitors, and total l-dopa equivalent daily dosage. Patients with urinary symptoms had higher baseline and follow-up motor and nonmotor disturbances than those without. Our study suggests the existence of a subgroup of patients who show urinary symptoms along with an overall higher motor and nonmotor burden. Such patients are prone to manifest a rapid functional decline over the first 4 years of the disease. Urinary symptoms might be a clinical marker of severity as well as a possible nonmotor subtype of PD. (c) 2015 International Parkinson and Movement Disorder Society