Wei-ye Xie’s research while affiliated with Pacific Center for Neurological Disease and other places

Objective Levodopa‐induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients. Methods We enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non‐DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six‐channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group. Results Compared with the non‐DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole‐night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5–2 Hz, 0.5–4 Hz, and 2–4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low‐frequency (0.5–2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors. Conclusion PD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low‐frequency (0.5–2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD.

Background Sleep is critical in health problems including Parkinson’s disease (PD). This study examined the association between sleep characteristics and the likelihood of prodromal PD. Methods At baseline examination of the Heart and Brain Investigation in Taicang (HABIT) study, potential PD biomarkers were obtained for 8777 participants aged over 50 years, and the probability of prodromal PD was assessed based on the Chinese expert consensus and Movement Disorder Society (MDS) criteria. General and component sleep characteristics were evaluated by the Pittsburgh Sleep Quality Index (PSQI). Median regression was applied to examine the association between sleep and the probability of prodromal PD, adjusting for age, sex, education level, physical activity, obesity, fast plasma glucose, lipids, and hypertension. Results Based on China criteria, a higher level of PSQI score was significantly associated with a higher probability of prodromal PD (β = 0.02, 95% CI: 0.01–0.03) and a higher risk of having an increased probability of prodromal PD (OR = 1.04, 95% CI: 1.02–1.05). Compared to participants with good quality sleep, those with poor quality sleep had a 0.07% increased probability of prodromal PD (95% CI: 0.01–0.13) and a 19% increased risk of having a high prodromal PD probability (95% CI: 1.04–1.20). Similar associations between sleep quality and the probability of prodromal PD were also observed using the MDS criteria. Subjective sleep quality, sleep latency, habitual sleep efficiency, daytime dysfunction, and use of sleep medications were also associated with the probability of prodromal PD. Conclusion Poor sleep quality was associated with a high probability of prodromal PD. Sleep may be helpful for understanding and intervention of prodromal PD.

Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene ( GBA ) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA -AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine. In this review, we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies, focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration. These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.

Objective To determine whether the onset of rapid eye movement (REM) sleep behavior disorder (RBD) is associated with changes in brainstem neuronal pathway dysfunction as reflected by vestibular-evoked myogenic potentials (VEMPs) and to evaluate associations between VEMPs and REM sleep without atonia (RSWA) in patients with early-stage Parkinson’s disease (PD) and isolated RBD (iRBD). Methods Eighty-two early-stage PD patients, 40 iRBD patients, and 41 healthy control individuals underwent one-night video-polysomnography (vPSG) and VEMPs examination. We compared cervical (cVEMP), ocular (oVEMP), and masseter (mVEMP) VEMP parameters among PD with RBD (PD+RBD), PD without RBD (PD-RBD), iRBD, and control groups and analyzed correlations between VEMPs and RSWA in PD and iRBD groups. Results The PD+RBD group showed delays in bilateral cVEMP (Lp13, Ln23, Rn23: all p<0.05) and oVEMP (Ln10, Rn10, Rp15: all p<0.05) peak latencies compared with the PD-RBD group. Total cVEMP scores were higher in the PD+RBD group than in the iRBD group (p=0.033). In PD patients, phasic RSWA was correlated with total cVEMP scores (p=0.003), and tonic RSWA was correlated with left oVEMP scores (p=0.013). Conclusions Brainstem neurophysiology as evidenced by altered VEMPs in patients with PD and iRBD could reflect disease evolvement. Moreover, VEMPs alterations may vary depending on the presence of RBD in PD patients. The associations between altered RSWA and VEMP parameters highlight the meaningfulness of detecting brainstem dysfunction in early-stage PD.