From the Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
Neurology. 2018 Sep 4;91(10):e894-e905. doi: 10.1212/WNL.0000000000006134. Epub 2018 Aug 8.
To investigate whether REM sleep behavior disorder (RBD) is associated with worse motor and cognitive decline in Parkinson disease (PD) METHODS: Four-hundred twenty-one drug-naive patients with early-stage PD and 196 controls without PD were included in this study. All participants underwent a [I]FP-CIT SPECT scan, CSF assessment, 3-tesla MRI, and thorough clinical assessments.
At cross-sectional analyses, patients with PD and probable RBD (PD-RBD) had lower CSF β-amyloid 1-42 (Aβ) levels and higher total tau to Aβ CSF ratio, higher nonmotor symptoms burden, and worse scores on neuropsychological tests of processing speed, visuospatial functioning, and delayed recognition memory compared to patients with PD without RBD. At longitudinal analyses, the presence of RBD was associated with faster motor progression (hazard ratio [HR] = 1.368, 95% confidence Interval [CI] = 1.036-1.806; = 0.027) and cognitive decline (HR = 1.794, 95% CI = 1.163-2.768; = 0.008) over 60-month follow-up. The presence of RBD was a predictor for motor progression only in patients with PD who had both low α-synuclein levels and low [I]FP-CIT uptake in the striatum (HR = 2.091, 95% CI = 1.116-3.918; = 0.021) and a predictor for cognitive decline only in patients with PD who had both low Aβ and low α-synuclein levels (HR = 2.810, 95% CI = 1.462-5.400; = 0.002). In the population of controls without PD, the presence of RBD was not associated with cognitive decline or any baseline pathologic changes.
The presence of RBD in PD is associated with faster motor progression in patients with greater synuclein and dopaminergic pathology, and with higher risk of cognitive decline in patients with greater synuclein and amyloid pathology. Our findings provide an important direction toward understanding phenotypes and their prognosis in PD.
探讨 REM 睡眠行为障碍（RBD）是否与帕金森病（PD）患者的运动和认知功能下降有关。
本研究纳入了 421 例未经药物治疗的早期 PD 患者和 196 例无 PD 的对照组。所有参与者均接受了[I]FP-CIT SPECT 扫描、CSF 评估、3 特斯拉 MRI 和全面的临床评估。
在横断面分析中，与无 RBD 的 PD 患者相比，PD-RBD 患者的 CSF β-淀粉样蛋白 1-42（Aβ）水平更低，总 tau 与 Aβ CSF 比值更高，非运动症状负担更重，以及在处理速度、视空间功能和延迟识别记忆的神经心理学测试中得分更差。在纵向分析中，RBD 的存在与更快的运动进展（风险比 [HR] = 1.368，95%置信区间 [CI] = 1.036-1.806； = 0.027）和认知下降（HR = 1.794，95%CI = 1.163-2.768； = 0.008）有关，随访 60 个月。在 PD 患者中，RBD 的存在仅在同时具有低α-突触核蛋白水平和纹状体低[I]FP-CIT 摄取的患者中是运动进展的预测因素（HR = 2.091，95%CI = 1.116-3.918； = 0.021），并且在同时具有低 Aβ 和低α-突触核蛋白水平的 PD 患者中是认知下降的预测因素（HR = 2.810，95%CI = 1.462-5.400； = 0.002）。在无 PD 的对照组人群中，RBD 的存在与认知下降或任何基线病理变化无关。
PD 中 RBD 的存在与更大的突触核蛋白和多巴胺能病理相关的更快的运动进展有关，并且与更大的突触核蛋白和淀粉样蛋白病理相关的更高的认知下降风险有关。我们的发现为理解 PD 中的表型及其预后提供了一个重要方向。
