帕金森病中多巴胺转运体结合的纵向下降：与睡眠障碍的关联。
Longitudinal decline in DAT binding in Parkinson's disease: connections with sleep disturbances.
机构信息
Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
出版信息
BMC Med. 2024 Nov 21;22(1):550. doi: 10.1186/s12916-024-03766-5.
BACKGROUND
The nigrostriatal dopamine (DA) system plays a critical role in regulating the sleep-wake state. The relationship between baseline striatal DA transporter (DAT) specific binding ratios (SBR) and rapid eye movement sleep behavior disorder (RBD) has been established. This study aimed to investigate the association between the progression of striatal DA dysfunction and sleep disturbances, including excessive daytime sleepiness (EDS) and probable RBD (pRBD), in patients with Parkinson's disease (PD).
METHODS
Data were obtained from the Parkinson's Progression Markers Initiative (PPMI). Six hundred twenty-one newly diagnosed PD patients and followed up for 4 years were included in this longitudinal study. EDS and pRBD were defined using the Epworth Sleepiness Scale (ESS) and RBD Screening Questionnaire (RBDSQ). Striatal DAT SBR was evaluated by [I] FP-CIT SPECT.
RESULTS
Using a linear mixed-effects model across all contemporaneous data points, we found a negative correlation between striatal DAT SBR and sleep disturbances (EDS/pRBD). The interaction between striatal DAT SBR and year was specific to RBDSQ score (β = - 0.102, 95% CI: - 0.187 to - 0.017, p = 0.019), with no evidence of a similar interaction for ESS score. Additionally, the association between the alpha-synuclein gene (SNCA) and sleep disturbances was mediated by the SBR (ESS score: total effect = - 2.717, p = 0.022; direct effect = - 3.222, p = 0.007; indirect effect = 0.505, p < 0.05; RBDSQ score: total effect = 1.402, p = 0.026; direct effect = 1.209, p = 0.057; indirect effect = 0.193, p < 0.05).
CONCLUSIONS
Our findings support the role of striatal DA dysfunction in sleep disturbances in early PD patients. Furthermore, we demonstrated that genetic variations in causative genes of PD contribute to the development of sleep disturbances. Striatal DAT imaging may be a useful risk indicator for sleep disturbances, providing early intervention strategies.
背景
黑质纹状体多巴胺（DA）系统在调节睡眠-觉醒状态方面起着关键作用。纹状体 DA 转运体（DAT）特异性结合率（SBR）与快速眼动睡眠行为障碍（RBD）之间的关系已经建立。本研究旨在探讨帕金森病（PD）患者纹状体 DA 功能障碍进展与睡眠障碍（包括日间过度嗜睡（EDS）和可能的 RBD（pRBD））之间的关系。
方法
数据来自帕金森病进展标志物倡议（PPMI）。本纵向研究纳入了 621 名新诊断的 PD 患者，并随访 4 年。EDS 和 pRBD 使用 Epworth 嗜睡量表（ESS）和 RBD 筛查问卷（RBDSQ）定义。纹状体 DAT SBR 通过[I] FP-CIT SPECT 进行评估。
结果
使用线性混合效应模型对所有同期数据点进行分析，我们发现纹状体 DAT SBR 与睡眠障碍（EDS/pRBD）呈负相关。纹状体 DAT SBR 与年份之间的相互作用仅与 RBDSQ 评分相关（β=-0.102，95%CI：-0.187 至-0.017，p=0.019），而与 ESS 评分无类似的相互作用。此外，α-突触核蛋白基因（SNCA）与睡眠障碍的关联受 SBR 介导（ESS 评分：总效应=-2.717，p=0.022；直接效应=-3.222，p=0.007；间接效应=0.505，p<0.05；RBDSQ 评分：总效应=1.402，p=0.026；直接效应=1.209，p=0.057；间接效应=0.193，p<0.05）。
结论
我们的研究结果支持纹状体 DA 功能障碍在早期 PD 患者睡眠障碍中的作用。此外，我们证明 PD 致病基因的遗传变异导致了睡眠障碍的发生。纹状体 DAT 成像可能是睡眠障碍的有用风险指标，为早期干预策略提供了依据。
Zotero 插件