{"title":"Longitudinal decline in DAT binding in Parkinson's disease: connections with sleep disturbances.","authors":"Junli Ren, Haobo Xie, Yiyun Weng, Yaoying Ge, Ruotong Yao, Zihan Jiang, Jinxiu Zhang, Yusheng Zhu, Xiaotong Fu, Junchao Wang, Zijia Liu, Shishu Zhang, Tingxuan Zhang, Guangyong Chen, Dehao Yang","doi":"10.1186/s12916-024-03766-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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 [<sup>123</sup>I] FP-CIT SPECT.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"550"},"PeriodicalIF":7.0000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583529/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12916-024-03766-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
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 [123I] 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.
期刊介绍：
BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.
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