BACKGROUND Non-motor symptoms (NMS) are common in Parkinson's disease (PD), but their relationships to nigrostriatal degeneration remain largely unexplored. METHODS We evaluated 18 NMS scores covering 5 major domains in relation to concurrent and future dopamine transporter (DAT) imaging in 344 PD patients from the Parkinson's Progression and Markers Initiative (PPMI). We standardized NMS assessments into z-scores for side-by-side comparisons. Patients underwent sequential DaTSCAN imaging at enrollment and at months 12, 24, and 48. Specific binding ratios (SBR) were calculated using the occipital lobe reference region. We evaluated the association of striatal DAT binding at the four time points with each baseline NMS using mixed-effects regression models. RESULTS Multiple baseline NMS were significantly associated with DAT binding at baseline and at follow-up scans. REM sleep behavior disorder (RBD) symptoms showed the strongest association - mean striatal SBR declined with increasing RBD symptom z-score (average of time-point-specific slopes per unit change in z-score: βAVG = -0.083, SE = 0.017; p < 0.0001). In addition, striatal DAT binding was linearly associated with increasing baseline z-scores: positively for the memory (βAVG=0.055, SE = 0.022; p = 0.01) and visuospatial (βAVG=0.044, SE = 0.020; p = 0.03) cognitive domains, and negatively for total anxiety (βAVG= -0.059, SE = 0.018; p = 0.001). Striatal DAT binding showed curvilinear associations with odor identification, verbal discrimination recognition, and autonomic dysfunction z-scores (p = 0.001, p = 0.0009, and p = 0.0002, respectively). Other NMS were not associated with DAT binding. CONCLUSIONS Multiple NMS, RBD symptoms in particular, are associated with nigrostriatal dopaminergic changes in early PD.

中文翻译：

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帕金森病早期的非运动症状和纹状体多巴胺转运蛋白结合。

背景非运动症状（NMS）在帕金森氏病（PD）中很常见，但与黑质纹状体变性的关系在很大程度上尚待探索。方法我们评估了帕金森病进展和标记行动（PPMI）的344名PD患者中与并发和未来多巴胺转运蛋白（DAT）成像相关的18个NMS评分，涉及5个主要领域。我们将NMS评估标准化为z得分，以进行并排比较。患者在入组时以及在第12、24和48个月接受连续的DaTSCAN成像。使用枕叶参考区域计算特异性结合率（SBR）。我们使用混合效应回归模型评估了四个时间点的纹状体DAT结合与每个基线NMS的关联。结果在基线和随访扫描中，多个基线NMS与DAT结合显着相关。REM睡眠行为障碍（RBD）症状表现出最强的关联-平均纹状体SBR随RBD症状z得分的增加而下降（z得分每单位变化的时间点特定斜率的平均值：βAVG= -0.083，SE = 0.017； p <0.0001）。此外，纹状体DAT结合与基线z分数增加呈线性相关：对记忆（βAVG= 0.055，SE = 0.022; p = 0.01）和视觉空间（βAVG= 0.044，SE = 0.020; p = 0.03）认知域呈正相关，总焦虑程度则为负（βAVG= -0.059，SE = 0.018； p = 0.001）。纹状体DAT的结合表现出与气味识别，言语辨别识别和植物神经功能障碍Z评分的曲线关联（p = 0.001，p = 0.0009和p = 0.0002，分别）。其他NMS与DAT绑定无关。结论多种NMS，特别是RBD症状，与早期PD的黑质纹状体多巴胺能改变有关。