Objective: To explore the clinical features and correlates of excessive daytime sleepiness (EDS) in a Chinese population of Parkinson's disease (PD) patients. Methods: Patients with clinically established or clinically probable PD were recruited. Clinical and demographic data were collected, and participants were evaluated using standardized assessment protocols. Patients were divided into PD with EDS and PD without EDS groups based on the Epworth sleepiness scale (ESS) scores, with a cutoff score of 10. Clinical manifestations were compared between patients with and without EDS, and correlates of EDS were also studied. In addition, the relationship between EDS and poor nighttime sleep quality was analyzed. Results: A total of 1,221 PD patients were recruited in our study. The mean ESS (min, max) score was 7.6 ± 6.1 (0, 24), and 34.1% of the patients had ESS scores ≥10. No difference was seen in lifestyle (except for alcohol consumption), environmental factors, BMI, levodopa equivalent dose (LED), initial presentation of motor symptoms, motor subtype, and wearing off between patients with and without EDS. The PD with EDS group had a higher proportion of male patients and a higher average patient age. Moreover, the PD with EDS group showed older age at PD onset, lower educational level, and longer disease duration. Patients with EDS had higher scores on the Hoehn-Yahr scale and the Unified Parkinson's Disease Rating Scale (UPDRS) parts I, II, and III score, more severe non-motor symptoms, and poorer quality of sleep and life. Logistic regression analyses demonstrated that EDS was associated with male sex, age, cognitive impairment, PD-related sleep problems, rapid eye movement sleep behavior disorder (RBD), and worse quality of life (QoL). Conclusion: EDS is a general clinical manifestation in PD, and there were significant differences in clinical features between patients with and without EDS. Moreover, our study proved that many factors were associated with EDS, including male sex, age, cognitive impairment, PD-related sleep problems, RBD, and worse QoL. Understanding the clinical characteristics of EDS in PD patients may help identify EDS early, improve QoL, and reduce the occurrence of accidents.
Autonomic dysfunction (AutD) is one of the non-motor symptoms (NMSs) in Parkinson’s disease (PD). To investigate the prevalence and clinical features of AutD in Chinese patients with PD, a large multicenter cohort of 2,556 individuals with PD were consecutively involved in the Parkinson’s Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 1, 2017, and December 31, 2019. The assessment of AutD was performed using the Scale for Outcomes in Parkinson’s Disease for Autonomic Symptoms (SCOPA-AUT). The evaluation of motor symptoms and other NMSs were performed using well-established scales recommended by the Movement Disorder Society. We found that out of 2,556 patients with PD, 2,333 patients with PD (91.28%) had AutD. Compared with the group of patients with PD without AutD, the group of patients with PD with AutD had older age, older age of onset, longer disease duration, more severe motor symptoms, motor complications, and more frequent NMSs. As for partial correlation analysis, the total SCOPA-AUT score was significantly and positively associated with motor severity scales [Unified Parkinson’s Disease Rating Scale (UPDRS) total score] and some of the NMSs [Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBD), Epworth Sleepiness Scale, Hamilton Depression Scale], Fatigue Severity Scale, and Parkinson’s disease questionnaire. PD Sleep Scale was significantly and negatively correlated with AutD. With logistic regression analysis for potentially related factors, age, UPDRS total score, RBD, hyposmia, depression, and fatigue may be associated with PD with AutD. In conclusion, our multicenter cohort study reported the high prevalence of AutD in Chinese PD and revealed the associated factors of PD with AutD.
Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson’s disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (Pcombined = 1.47 × 10−9) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P < 5 × 10−8) for PD in Chinese population. Moreover, of the reported genome-wide significant risk variants found mostly in European ancestry populations, the correlation coefficient (rb) of effect size accounting for sampling errors was 0.91 between datasets and 63.6% attained P < 0.05 in Chinese population. Accordingly, we estimated a heritability of 0.14–0.18 for PD, and a moderate genetic correlation between European ancestry and Chinese populations (rg = 0.47, se = 0.21). Polygenic risk score (PRS) analysis revealed that individuals with PRS values in the highest quartile had a 3.9-fold higher risk of developing PD than the lowest quartile. In conclusion, the present GWAS identified PD-associated variants in Chinese population, as well as genetic factors shared among distant populations. Our findings shed light on the genetic homogeneity and heterogeneity of PD in different ethnic groups and suggested WGS might continue to improve our understanding of the genetic architecture of PD.
BackgroundThe diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility.ObjectiveThe study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD.MethodsA prospective, diagnostic case‐control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug‐naïve patients with PD, and 185 non‐PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification.ResultsIn the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%–96%), 95% (95% CI: 93%–97%), and 19.16 (95% CI: 13.52–27.16) and 0.10 (95% CI: 0.05–0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug‐naïve were 89% (95% CI: 75%–96%), 86% (95% CI: 81%–91%), and 6.6 (95% CI: 4.51–9.66) and 0.13 (95% CI: 0.05–0.32), respectively.ConclusionsTests using sniffer dogs may be a useful, noninvasive, fast, and cost‐effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.
Background There is a lack of large multicenter Parkinson's disease (PD) cohort studies and limited data on the natural history of PD in China. Objectives The objective of this study was to launch the Chinese Parkinson's Disease Registry (CPDR) and to report its protocol, cross‐sectional baseline data, and prospects for a comprehensive observational, longitudinal, multicenter study. Methods The CPDR recruited PD patients from 19 clinical sites across China between January 2018 and December 2020. Clinical data were collected prospectively using at least 17 core assessment scales. Patients were followed up for clinical outcomes through face‐to‐face interviews biennially. Results We launched the CPDR in China based on the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network (PD‐MDCNC). A total of 3148 PD patients were enrolled comprising 1623 men (51.6%) and 1525 women (48.4%). The proportions of early‐onset PD (EOPD, age at onset ≤50 years) and late‐onset PD (LOPD) were 897 (28.5%) and 2251 (71.5%), respectively. Stratification by age at onset showed that EOPD manifested milder motor and nonmotor phenotypes and was related to increased probability of dyskinesia. Comparison across genders suggested a slightly older average age at PD onset, milder motor symptoms, and a higher rate of developing levodopa‐induced dyskinesias in women. Conclusions The CPDR is one of the largest multicenter, observational, longitudinal, and natural history studies of PD in China. It offers an opportunity to expand the understanding of clinical features, genetic, imaging, and biological markers of PD progression. © 2022 International Parkinson and Movement Disorder Society.
Objective: To investigate the clinical features and factors associated with Parkinson's disease (PD) patients with probable rapid eye movement sleep behavior disorder (PD-pRBD). Methods: A total of 2,440 patients with clinically established or clinically probable PD were divided into two groups: PD-pRBD and PD without pRBD (PD-NRBD), according to the RBD questionnaire-Hong Kong. Data collection included demographic data, basic clinical history, and motor and non-motor symptoms. Based on the onset time of pRBD and the motor symptoms in PD, PD-pRBD patients were further divided into the pRBD prior to PD (PD-prRBD) group and the pRBD posterior to PD (PD-poRBD) group. Clinical features were compared between the PD-pRBD and PD-NRBD groups, as well as the PD-prRBD and PD-poRBD groups. The associated factors of pRBD were also explored. Results: The prevalence of pRBD was 41.4% (1,010 out of the total of 2,440) in our PD cohort. Further, compared with the PD-NRBD group, the PD-pRBD group had longer disease duration and more severe motor symptoms. Moreover, the PD-pRBD group had significantly higher levodopa equivalent daily dose and a higher ratio of dyskinesia, wearing-off, and offset of the Hoehn-Yahr stage. The scores on the non-motor symptom rating scale (NMSS), cognitive impairment, Parkinson's disease sleep scale (PDSS), excessive daytime sleepiness, constipation, hyposmia, depression, and the 39-item Parkinson's disease questionnaire also appeared worse in the PD-pRBD group. Significant differences in the educational level, disease duration, disease progression, Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, tremor, rigidity, bradykinesia, posture gait, frozen gait, levodopa equivalent daily dose, dyskinesia, wearing-off, Hoehn-Yahr stage, NMSS-6, PDSS, and communication score widely existed between the PD-prRBD and PD-poRBD groups. Late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia were all identified as the risk factors for PD-pRBD. Long et al. Study on PD With RBD Conclusions: Compared with the PD-NRBD group, the PD-pRBD group may have more severe motor symptoms, motor complications, and non-motor symptoms as well as a substandard quality of life. Further, late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia can be risk factors for RBD in PD. Differences also occurred between the PD-prRBD and PD-poRBD groups.
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