Pathological involvement of the noradrenergic locus coeruleus occurs early in Parkinson’s disease, and widespread noradrenaline reductions are found at post-mortem. Rapid eye movement sleep behaviour disorder (RBD) accompanies Parkinson’s disease and its presence predicts an unfavourable disease course with a higher propensity to cognitive impairment and orthostatic hypotension. MRI can detect neuromelanin in the locus coeruleus while ¹¹C-MeNER PET is a marker of noradrenaline transporter availability. Here, we use both imaging modalities to study the association of RBD, cognition and autonomic dysfunction in Parkinson’s disease with loss of noradrenergic function. Thirty non-demented Parkinson’s disease patients [16 patients with RBD and 14 without RBD, comparable across age (66.6 ± 6.7 years), sex (22 males), and disease stage (Hoehn and Yahr, 2.3 ± 0.5)], had imaging of the locus coeruleus with neuromelanin sensitive MRI and brain noradrenaline transporter availability with ¹¹C-MeNER PET. RBD was confirmed with polysomnography; cognitive function was assessed with a neuropsychological test battery, and blood pressure changes on tilting were documented; results were compared to 12 matched control subjects. We found that Parkinson’s disease patients with RBD showed decreased locus coeruleus neuromelanin signal on MRI (P < 0.001) and widespread reduced binding of ¹¹C-MeNER (P < 0.001), which correlated with amount of REM sleep without atonia. Parkinson’s disease with RBD was also associated with a higher incidence of cognitive impairment, slowed EEG activity, and orthostatic hypotension. Reduced ¹¹C-MeNER binding correlated with EEG slowing, cognitive performance, and orthostatic hypotension. In conclusion, reduced noradrenergic function in Parkinson’s disease was linked to the presence of RBD and associated with cognitive deterioration and orthostatic hypotension. Noradrenergic impairment may contribute to the high prevalence of these non-motor symptoms in Parkinson’s disease, and may be of relevance when treating these conditions in Parkinson’s disease.

中文翻译：

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帕金森氏病中去甲肾上腺素能系统的评估：¹¹ C-MeNER PET和神经黑色素MRI研究

去甲肾上腺素能蓝斑病的病理学侵袭发生在帕金森氏病的早期，并且在死后发现广泛的去甲肾上腺素减少。快速眼动睡眠行为障碍（RBD）伴有帕金森氏病，并且它的存在预示着不利的病程，对认知障碍和体位性低血压的倾向更高。MRI可以检测到蓝斑中的神经黑色素，而¹¹C-MeNER PET是去甲肾上腺素转运蛋白可用性的标志。在这里，我们使用两种成像方式来研究帕​​金森氏病中RBD，认知和自主神经功能障碍与去甲肾上腺素功能丧失之间的关系。30例非痴呆性帕金森病患者[16例RBD患者和14例无RBD患者，年龄（66.6±6.7岁），性别（22例男性）和疾病分期（Hoehn和Yahr，2.3±0.5）可比，其影像学表现为使用黑色素敏感的MRI和脑中去甲肾上腺素转运蛋白可检测¹¹位顽固性青光眼C-Mener PET。多导睡眠图检查证实RBD。用神经心理学测试电池评估认知功能，并记录倾斜时血压的变化；将结果与12名匹配的对照受试者进行比较。我们发现，患有RBD的帕金森氏病患者在MRI上显示出蓝斑脑神经黑色素信号降低（P < 0.001），并且¹¹ C-MeNER的结合广泛降低（P < 0.001），这与无心律失常的REM睡眠量有关。伴有RBD的帕金森氏病还与认知障碍，脑电图活动减慢和体位性低血压的发生率更高有关。减少¹¹C-MeNER结合与脑电图减慢，认知表现和体位性低血压相关。总之，帕金森氏病中去甲肾上腺素功能降低与RBD的存在有关，并且与认知能力下降和体位性低血压有关。去甲肾上腺素能障碍可导致帕金森氏病中这些非运动性症状的高发，并且在治疗帕金森氏病中时也可能具有相关性。