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Risk factors of levodopa-induced dyskinesia in Parkinson’s disease: results from the PPMI cohort
npj Parkinson's Disease ( IF 9.304 ) Pub Date : 2018-11-16 , DOI: 10.1038/s41531-018-0069-x
Paolo Eusebi 1 , Michele Romoli 1 , Federico Paolini Paoletti 1 , Nicola Tambasco 1 , Paolo Calabresi 1, 2 , Lucilla Parnetti 1
Affiliation  

Levodopa-induced dyskinesias (LID) negatively impact on the quality of life of patients with Parkinson’s disease (PD). We assessed the risk factors for LID in a cohort of de-novo PD patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI). This retrospective cohort study included all PD patients enrolled in the PPMI cohort. Main outcome was the incidence rate of dyskinesia, defined as the first time the patient reported a non-zero score in the item “Time spent with dyskinesia” of the MDS-UPDRS part IV. Predictive value for LID development was assessed for clinical and demographical features, dopamine transporter imaging (DaTscan) pattern, cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau, phosphorylated tau, total α synuclein) and genetic risk score for PD. Overall, data from 423 PD patients were analyzed. The cumulative incidence rate of LID was 27.4% (95% CI = 23.2–32.0%), with a mean onset time of 5.81 years from PD diagnosis. Multivariate Cox regression analysis showed several factors predicting LID development, including female gender (HR = 1.61, 95% CI = 1.05–2.47), being not completely functional independent as measured by the modified Schwab & England ADL scale (HR = 1.81, 95% CI = 0.98–3.38), higher MDS-UPDRS part III score (HR = 1.03, 95% CI = 1.00–1.05), postural instability gait disturbances or intermediate phenotypes (HR = 1.95, 95% CI = 1.28–2.96), higher DaTscan caudate asymmetry index (HR = 1.02, 95% CI = 1.00–1.03), higher polygenic genetic risk score (HR = 1.39, 95% CI = 1.08–1.78), and an anxiety trait (HR = 1.02, 95% CI = 1.00–1.04). In PD patients, cumulative levodopa exposure, female gender, severity of motor and functional impairment, non-tremor dominant clinical phenotype, genetic risk score, anxiety, and marked caudate asymmetric pattern at DaTscan at baseline represent independent risk factors for developing LID.



中文翻译:

帕金森病左旋多巴引起的运动障碍的危险因素:PPMI 队列的结果

左旋多巴引起的运动障碍 (LID) 对帕金森病 (PD) 患者的生活质量产生负面影响。我们评估了参加帕金森病进展标志物计划 (PPMI) 的一组新发帕金森病患者的 LID 危险因素。这项回顾性队列研究包括 PPMI 队列中登记的所有 PD 患者。主要结果是运动障碍的发生率,定义为患者第一次在 MDS-UPDRS 第 IV 部分的“运动障碍所花费的时间”项目中报告非零分数。通过临床和人口统计特征、多巴胺转运蛋白成像 (DaTscan) 模式、脑脊液 (CSF) 生物标志物(Aβ42、总 tau、磷酸化 tau、总 α 突触核蛋白)和 PD 遗传风险评分来评估 LID 发展的预测价值。总体而言,分析了 423 名 PD 患者的数据。LID 的累积发病率为 27.4%(95% CI = 23.2–32.0%),自 PD 诊断起平均发病时间为 5.81 年。多变量 Cox 回归分析显示,预测 LID 发展的多个因素,包括女性(HR = 1.61,95% CI = 1.05–2.47),根据改良的 Schwab & England ADL 量表(HR = 1.81,95% CI = 1.05–2.47)测量,这些因素并不完全功能独立。 CI = 0.98–3.38),较高的 MDS-UPDRS 第 III 部分评分(HR = 1.03,95% CI = 1.00–1.05),姿势不稳步态障碍或中间表型(HR = 1.95,95% CI = 1.28–2.96),较高DaTscan 尾状核不对称指数(HR = 1.02,95% CI = 1.00–1.03)、较高的多基因遗传风险评分(HR = 1.39,95% CI = 1.08–1.78)和焦虑特质(HR = 1.02,95% CI = 1.00–1.04)。在 PD 患者中,累积左旋多巴暴露量、女性、运动和功能障碍的严重程度、非震颤主导的临床表型、遗传风险评分、焦虑以及基线时 DaTscan 的明显尾状核不对称模式代表了发生 LID 的独立危险因素。

更新日期:2018-11-16
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