Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Department of Neurology, Myongji Hospital, 55, Hwasu-ro 14beon-gil, Deogyang-gu, Goyang-si, Gyeonggi-do 10475, South Korea.
Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
Parkinsonism Relat Disord. 2018 Aug;53:96-100. doi: 10.1016/j.parkreldis.2018.05.008. Epub 2018 May 10.
The present study aimed to investigate whether the level of presynaptic dopamine neuronal loss predicts future development of wearing-off in de novo Parkinson's disease.
This retrospective cohort study included a total of 342 non-demented patients with de novo Parkinson's disease who underwent dopamine transporter positron emission tomography scans at their initial evaluation and received dopaminergic medications for 24 months or longer. Onset of wearing-off was determined based on patients' medical records at their outpatient clinic visits every 3-6 months. Predictive power of dopamine transporter activity in striatal subregions and other clinical factors for the development of wearing-off was evaluated by Cox proportional hazard models.
During a median follow-up period of 50.2 ± 18.9 months, 69 patients (20.2%) developed wearing-off. Patients with wearing-off exhibited less dopamine transporter activity in the putamen, particularly the anterior and posterior putamens, compared to those without wearing-off. Multivariate Cox proportional hazard models revealed that dopamine transporter activities of the anterior (hazard ratio 0.556; p = 0.008) and whole putamens (hazard ratio 0.504; p = 0.025) were significant predictors of development of wearing-off. In addition, younger age at onset of Parkinson's disease, lower body weight, and a motor phenotype of postural instability/gait disturbance were also significant predictors for development of wearing-off.
The present results provide in vivo evidence to support the hypothesis that presynaptic dopamine neuronal loss, particularly in the anterior putamen, leads to development of wearing-off in Parkinson's disease.
本研究旨在探讨新诊断帕金森病患者的突触前多巴胺神经元丢失程度是否可以预测药物开期波动的发生。
本回顾性队列研究共纳入 342 例新发帕金森病且无痴呆的患者，他们在初次评估时接受了多巴胺转运体正电子发射断层扫描（PET）检查，并接受了至少 24 个月的多巴胺能药物治疗。根据患者在门诊就诊时的病历记录，每 3-6 个月随访一次，以确定药物开期波动的发生时间。采用 Cox 比例风险模型评估纹状体亚区多巴胺转运体活性和其他临床因素对药物开期波动发生的预测能力。
在中位随访期 50.2±18.9 个月期间，69 例患者（20.2%）出现药物开期波动。与无药物开期波动的患者相比，出现药物开期波动的患者纹状体的多巴胺转运体活性较低，特别是在前部和后部纹状体。多变量 Cox 比例风险模型显示，前部（危险比 0.556；p=0.008）和整个纹状体（危险比 0.504；p=0.025）的多巴胺转运体活性是药物开期波动发生的显著预测因素。此外，帕金森病发病年龄较小、体重较低以及姿势不稳/步态障碍的运动表型也是药物开期波动发生的显著预测因素。
本研究结果为突触前多巴胺神经元丢失，特别是在前部纹状体，导致帕金森病药物开期波动的假说提供了体内证据。
