背景:快速眼动(REM)睡眠行为障碍(RBD)可在帕金森病(PD)期间出现运动症状之前或之后出现。尚不清楚RBD发作时间相对于运动症状不同的PD是否表明神经变性的时空序列不同。本研究旨在探讨RBD发病时间不同的PD关键相关脑区的疾病进展顺序。
方法:我们招募了157个PD,16隔离RBD(iRBD),和78个健康对照。PD患者被确定为(1)PD伴RBD先于运动症状(PD-preRBD,n=50),(2)PD伴RBD运动症状后方(PD-postRBD,n=31),(3)不带RBD的PD(PD-非RBD,n=75)。大脑关键区域的体积,包括T1加权成像中的基底神经节和边缘结构,提取神经黑色素敏感磁共振成像中蓝斑(LC)和黑质(SN)的对比噪声比。为了模拟横断面数据的疾病进展顺序,我们引入了基于事件的模型来估计每个组的区域参与的最大似然序列.然后,统计参数,巴塔查里亚系数(BC),用于评估序列的相似性。
结果:该模型预测,在所有PD亚组中,SN在疾病进展的最大似然序列中占据最高似然,虽然LC在iRBD中被专门定位为SN,PD的前驱期。随后在PD-preRBD和PD-postRBD中观察到LC的早期参与。相比之下,在PD-nonRBD中证实了海马旁回的萎缩,但早期相对完整的LC。然后,相似性比较显示PD-后RBD组和PD-前RBD组的BC较高(BC=0.76),但PD-后RBD组和PD-非RBD组的BC较低(BC=0.41).iRBD对PD-preRBD(BC=0.66)和PD-postRBD(BC=0.63)的BC较高,但对PD-nonRBD的BC较低(BC=0.48)。
结论:PD-pre和PD-post之间的神经变性的时空序列相似,但与PD-nonRBD不同。RBD的存在可能是区分PD退化模式的重要因素,但RBD发病的时机目前已被证明不是。
Rapid eye movement (REM) sleep behavior disorder (RBD) could develop preceding or come after motor symptoms during Parkinson\'s disease (PD). It remains unknown that whether PD with different timing of RBD onset relative to motor symptoms suggests different spatiotemporal sequence of neurodegeneration. This study aimed to explore the sequence of disease progression in crucially involved brain regions in PD with different timing of RBD onset.
We recruited 157 PD, 16 isolated RBD (iRBD), and 78 healthy controls. PD patients were identified as (1) PD with RBD preceding motor symptoms (PD-preRBD, n = 50), (2) PD with RBD posterior to motor symptoms (PD-postRBD, n = 31), (3) PD without RBD (PD-nonRBD, n = 75). The volumes of crucial brain regions, including the basal ganglia and limbic structures in T1-weighted imaging, and the contrast-noise-ratios of locus coeruleus (LC) and substantia nigra (SN) in
neuromelanin-sensitive magnetic resonance imaging, were extracted. To simulate the sequence of disease progression for cross-sectional data, an event-based model was introduced to estimate the maximum likelihood sequence of regions\' involvement for each group. Then, a statistical parameter, the Bhattacharya coefficient (BC), was used to evaluate the similarity of the sequence.
The model predicted that SN occupied the highest likelihood in the maximum likelihood sequence of disease progression in the all PD subgroups, while LC was specifically positioned earlier to SN in iRBD, a prodromal phase of PD. Subsequent early involvement of LC was observed in the both PD-preRBD and PD-postRBD. In contrast, atrophy in the para-hippocampal gyrus but relatively intact LC in the early stage was demonstrated in PD-nonRBD. Then, the similarity comparisons indicated higher BC between PD-postRBD and PD-preRBD (BC = 0.76) but lower BC between PD-postRBD and PD-nonRBD group (BC = 0.41). iRBD had higher BC against PD-preRBD (BC = 0.66) and PD-postRBD (BC = 0.63) but lower BC against PD- nonRBD (BC = 0.48).
The spatiotemporal sequence of neurodegeneration between PD-pre and PD-post were similar but distinct from PD-nonRBD. The presence of RBD may be the essential factor for differentiating the degeneration patterns of PD, but the timing of RBD onset has currently proved to be not.