Longitudinal decline in DAT binding in Parkinson's disease: connections with sleep disturbances

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). 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. 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