Risk factors of levodopa-induced dyskinesia in Parkinson's disease: results from the PPMI cohort.
Risk factors of levodopa-induced dyskinesia in Parkinson's disease: results from the PPMI cohort.
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DOI：
10.1038/s41531-018-0069-x
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Parnetti L
中科院分区：
文献类型：
--
作者：
Eusebi P;Romoli M;Paoletti FP;Tambasco N;Calabresi P;Parnetti L
左旋多巴诱导的运动障碍（LID）对帕金森病（PD）患者的生活质量产生负面影响。我们在帕金森病进展标志物倡议（PPMI）中登记的一组新发PD患者中评估了LID的风险因素。这项回顾性队列研究包括入组PPMI队列的所有PD患者。主要结局是运动障碍的发生率，定义为患者首次报告MDS-EURRS第IV部分"运动障碍时间"项目中的非零分。评估了临床和人口统计学特征、多巴胺转运蛋白成像（DaTscan）模式、脑脊液（CSF）生物标志物（A β 42、总tau、磷酸化tau、总α突触核蛋白）和PD遗传风险评分对LID发生的预测价值。总体而言，分析了423例PD患者的数据。LID的累积发生率为27.4%（95%CI = 23.2 - 32.0%），平均发病时间为PD诊断后5.81年。多变量考克斯回归分析显示，几个因素预测LID的发展，包括女性性别（HR = 1.61，95%CI = 1.05 - 2.47），根据改良Schwab & England ADL量表测量，不完全功能独立（HR = 1.81，95% CI = 0.98 - 3.38），MDS-MRS第III部分评分较高（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），DaTscan尾状核不对称指数较高（HR = 1.02，95% CI = 1.00 - 1.03），多基因遗传风险评分较高（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、女性性别、运动和功能障碍的严重程度、非震颤显性临床表型、遗传风险评分、焦虑和基线DaTscan时明显的尾状核不对称模式是发生LID的独立风险因素。意大利研究人员确定了帕金森病（PD）患者左旋多巴诱导的运动障碍的七个独立风险因素。长期使用左旋多巴治疗可能会导致不受控制的不自主运动，对患者的生活质量产生不利影响。佩鲁贾大学的Lucilla Parnetti及其同事对参加帕金森病进展标志物倡议的423名患者进行了回顾性研究，以确定在诊断时预测左旋多巴诱导的运动障碍的因素。他们发现，女性患者发生运动障碍的风险更大，携带PD相关突变，在诊断时疾病严重程度更高或早期PD有神经精神症状。在PD的早期阶段考虑这些因素不仅可以改善疾病的管理，还可以设计未来的生物标志物研究和临床试验。
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. Italian researchers identify seven independent risk factors for levodopa-induced dyskinesia in Parkinson’s disease (PD) patients. Long-term treatment with levodopa can cause uncontrolled, involuntary movements which adversely affect patients’ quality of life. Lucilla Parnetti and colleagues at the University of Perugia carried out a retrospective study of 423 patients enrolled in the Parkinson’s Progression Markers Initiative to determine factors that are predictive of levodopa-induced dyskinesia at the time of diagnosis. They found that the risk of developing dyskinesia was greater in patients who were female, carried PD-associated mutations, presented higher disease severity at the time of diagnosis or neuropsychiatric symptoms in early PD. Taking these factors into consideration in the very early phase of PD could not only improve management of the disease, but also the design of future biomarker studies and clinical trials.
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影响因子：
3.3
作者：
Arabia, G;Zappia, M;Quattrone, A
通讯作者：
Quattrone, A
影响因子：
9.9
作者：
Blanchet, PJ;Fang, J;Chase, TN
通讯作者：
Chase, TN
DOI：
10.1002/mds.26374
发表时间：
2016-01
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Nalls MA;Keller MF;Hernandez DG;Chen L;Stone DJ;Singleton AB;Parkinson's Progression Marker Initiative (PPMI) investigators
通讯作者：
Parkinson's Progression Marker Initiative (PPMI) investigators
影响因子：
30.8
作者：
Nalls, Mike A.;Pankratz, Nathan;Lill, Christina M.;Do, Chuong B.;Hernandez, Dena G.;Saad, Mohamad;DeStefano, Anita L.;Kara, Eleanna;Bras, Jose;Sharma, Manu;Schulte, Claudia;Keller, Margaux F.;Arepalli, Sampath;Letson, Christopher;Edsall, Connor;Stefansson, Hreinn;Liu, Xinmin;Pliner, Hannah;Lee, Joseph H.;Cheng, Rong;Ikram, M. Arfan;Ioannidis, John P. A.;Hadjigeorgiou, Georgios M.;Bis, Joshua C.;Martinez, Maria;Perlmutter, Joel S.;Goate, Alison;Marder, Karen;Fiske, Brian;Sutherland, Margaret;Xiromerisiou, Georgia;Myers, Richard H.;Clark, Lorraine N.;Stefansson, Kari;Hardy, John A.;Heutink, Peter;Chen, Honglei;Wood, Nicholas W.;Houlden, Henry;Payami, Haydeh;Brice, Alexis;Scott, William K.;Gasser, Thomas;Bertram, Lars;Eriksson, Nicholas;Foroud, Tatiana;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.
影响因子：
14.5
作者：
Fereshtehnejad, Seyed-Mohammad;Zeighami, Yashar;Postuma, Ronald B.
通讯作者：
Postuma, Ronald B.