Association of body mass index with rapid eye movement sleep behavior disorder in Parkinson's disease.

Background: The association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson's disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients. Methods: In this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson's Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models. Results: We identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results. Conclusion: The current study found a significant dose-response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.

Autonomic function and motor subtypes in Parkinson's disease: a multicentre cross-sectional study.

Autonomic symptoms (AS) are critical in Parkinson's disease (PD). We aimed to determine the relative significance of clinical factors allowing predictions about incidence of AS, and examine AS profiles among PD patients by motor subtype and its relation to AS. The cross-sectional data of a multicentre sample, including 714 PD patients and 194 healthy controls from Parkinson's Progression Marker Initiative study and Pingchan granule study were analyzed, stratified by PD subtypes [postural instability and gait disturbances (PIGD), tremor dominant (TD), and indeterminate] and domain autonomic dysfunction. Compared with healthy controls, PD patients scored higher in the total Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction score and in several domain scores in particular, and there was a significant overlap in domain AS. Risk factors of individual domain autonomic dysfunction were heterogeneous. PIGD and indeterminate were the predominant subtypes in pupillomotor and thermoregulatory symptoms. TD and indeterminate were more likely to suffer from cardiovascular problem. The odd in sexual dysfunction was significant for PIGD. Gastrointestinal and urinary symptoms seemed not to be associated with a specific subtype. Our study demonstrated that AS were highly heterogeneous and 3 subtypes differed in autonomic performance, providing clues to understand mechanisms underlying AS in PD.

Electroacupuncture for motor dysfunction and constipation in patients with Parkinson's disease: a randomised controlled multi-centre trial.

Background: Motor disturbances and non-motor disturbances such as constipation are the main factors affecting the quality of life in patients with Parkinson's disease (PD). We investigated the efficacy and safety of electroacupuncture combined with conventional pharmacological treatment on motor dysfunction and constipation in PD. Methods: In this multi-centre randomised controlled trial, we enrolled 166 eligible participants between September 19, 2018 and September 25, 2019 in four hospitals in China. Participants were randomly assigned (1:1) to the electroacupuncture (EA) group and the waitlist control group. Each participant in both groups received the conventional pharmacological treatment, EA group received 3 sessions of electroacupuncture per week for 12 weeks. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to week 12. The secondary outcomes included the evaluation of functional disability in motor symptoms and constipation, the adherence and adverse events were also recorded. Registered with Chictr.org.cn, ChiCTR1800019517. Findings: At week 12, the change in the UPDRS score of the EA group was significantly higher than that of the control group, with a difference of -9.1 points (95% CI, -11.8 to -6.4), and this difference continued into weeks 16 and 24. From baseline to week 12, the 39-item Parkinson Disease Question (PDQ-39) decreased by 10 points (interquartile range, IQR -26.0 to 0.0) in the EA group and 2.5 points (IQR: -11.0 to 4.0) in the control group, the difference was statistically significant. The time and steps for the 20-m walk at week 12, as well as the changes from baseline in the EA group, were comparable with that in the control group. But the EA group had a greater decrease than the control group from baseline in the times for 20-m walks at weeks 16 and 24. From week 4 to week 24, the median values of spontaneous bowel movements (SBMs) per week in the EA group were higher than that in the control group, the differences were all statistically significant. The incidence of EA-related adverse events during treatment was low, and they are mild and transient. Interpretation: The findings of our study suggested that compared with conventional pharmacological treatment, conventional pharmacological treatment combined with electroacupuncture significantly enhances motor function and increased bowel movements in patients with PD, electroacupuncture is a safe and effective treatment for PD. Funding: Shanghai "Science and Technology Innovation Action Plan" Clinical Medicine Field Project (18401970700), Shanghai Special Project on Aging and Women's and Children's Health Research (020YJZX0134), Shanghai Clinical Research Centre for Acupuncture and Moxibustion (20MC1920500).

Traditional Chinese medicine Pingchan granule for motor symptoms and functions in Parkinson's disease: A multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Pingchan granule (PCG) is a traditional Chinese medicine for Parkinson's disease (PD). HYPOTHESIS/PURPOSE: This was the first study aiming to evaluate the efficacy and safety of PCG for motor symptoms, gait impairments and quality of life in PD. STUDY DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants were included and followed for 9 months, randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcome was the severity of motor symptoms assessed by Movement Disorder Society Unified Parkinson's Rating Scale III (MDS-UPDRS-III) motor score. Secondary outcomes included timed up and go test (TUG), functional gait assessment (FGA), freezing of gait (FOG), and quality of life assessed by Parkinson's disease questionnaire (PDQ-39). Assessments were done at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-INR-1,701,194. RESULTS: Generalized estimating equation analyses revealed that PCG group had significantly better improvement in MDS-UPDRS-III motor score than placebo group, as well as its domain scores of axial symptoms, bradykinesia, rigidity, and tremor. Improvements of TUG time, FGA, FOG questionnaire (FOGQ), and PDQ39 scores were also observed. CONCLUSION: PCG had a long-lasting efficacy for motor symptoms and function in PD with good tolerance, supporting that PCG might be a viable alternative in the management of PD.

The Importance of Early Identification for Parkinson's Disease Patients with Postural Instability and Gait Disturbance.

Background: More and more evidence-based medicine has proved that Parkinson's disease (PD) patients of tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtype express great individual differences and heterogeneity. Early identification of different subtypes may be an important way to delay disease progression and improve patients' prognosis. Objective: The study aimed to compare the spectrum of motor symptoms (MS) and nonmotor symptoms (NMS) between TD and PIGD dominant in the early and middle stages of PD, and determine predictive factors that are associated with different motor subtypes. Methods: 292 PD patients in this study were divided into TD-PD and PIGD-PD, and the clinical characteristics between different motor subtypes were compared based on scales related to sleep, mood, and autonomic function. Univariate and multivariate ordered logistic regression analyses were used to analyze the independent influencing factors of disease severity between different motor subtypes. Through the establishment of binary logistic regression model, the potential independent risk factors for distinguishing TD-PD and PIGD-PD were studied. Results: Compared with TD subtype, patients with PIGD subtype have longer course of disease, higher disease severity, and higher daily dosage of levodopa. The severity of nontremor motor symptoms in PIGD-PD is greater than that of TD subtype. Only PIGD score was independently associated with disease severity for the two motor subtypes. Meanwhile, high scores (LED, total UPDRS, PIGD score, gastrointestinal, thermoregulatory, RBDSQ) and low tremor scores were the potential independent risk factors for distinguishing PIGD-PD from TD-PD. Conclusion: Specific nonmotor symptoms (RBD, gastrointestinal function and thermoregulation function) were associated with the PIGD subtype. Prompt detection and early treatment of NMSs related to the PIGD subtype based on the treatment of motor symptoms may improve patient outcomes.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Zishen pingchan granules combined with pramipexole in the improvement of depressive symptoms in Parkinson's disease: a prospective, multicenter, randomized, double-blind, controlled clinical study.

BACKGROUND AND OBJECTIVE: Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson's disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). METHODS: A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. RESULTS: After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (- 1.43 scores [- 2.50, - 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (- 3.56 scores [- 5.77, - 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. CONCLUSION: ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432.

Traditional Chinese medicine syndrome differentiation and treatment by stages of Parkinson's disease: study protocol for a multicentre, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease common in aged populations. Classified by Hoehn & Yahr stages, patients are often divided into mild/early stage, moderate/middle stage, and advanced/late stage. With disease progression, PD shows high heterogeneity in each stage. Based on traditional Chinese medicine (TCM) syndrome differentiation theory and our previous works, we found that during the early stage, the main syndrome is Yin deficiency of the liver and kidney; during the moderate stage, the main syndromes are phlegm heat and wind stirring and blood stasis and wind stirring; and during the late stage, the dominant syndromes are deficiency of Yin and Yang and deficiency of Qi and blood. Hence, we proposed a new model of TCM treatment by the stage of PD. Based on Shudi Pingchan formula, an experimental formula of our team, we developed Ziyin Pingchan formula, Jiedu Pingchan formula, and Fuzheng Pingchan formula to treat each stage. This study is designed to evaluate the therapeutic effect of treating Parkinson's disease by stages using traditional Chinese medicine and to provide an evidence base for forming a standardized scheme of diagnosis and treatment. METHODS: This study is designed as a multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients will be stratified into 3 subgroups according to Hoehn & Yahr stage; 172, 168, and 72 participants will be required to be in the mild PD, moderate PD, and advanced PD subgroups, respectively, and will be randomized into the treatment or control group at a 1:1 ratio. The mild PD subgroup will receive a 48-week intervention, and the other 2 groups will receive a 24-week intervention. All groups will have a follow-up visit 12 weeks after starting the intervention. The intervention group will receive the Ziyin Pingchan formula, Jiedu Pingchan formula, or Fuzheng Pingchan formula, and the control group will receive the corresponding placebo. The primary outcomes will be the first addition of levodopa for the mild PD subgroup, the duration of the "OFF" period for the moderate PD subgroup, and the Parkinson's Disease Questionnaire (PDQ-39) for the advanced PD subgroup. The secondary outcomes will also be verified by subgroups, including the Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale-2 (PDSS-2), scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), and the nonmotor symptom scale (NMSS). EXPECTED OUTCOMES: To our knowledge, this is the first trial to combine TCM syndrome differentiation with PD clinical stages and put it into clinical practice. The results of this trial will provide clinical evidence for the therapeutic effect of TCM formulas on PD patients of all stages and help build a new TCM treatment by stage model of PD. TRIAL REGISTRATION: This trial is registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ). REGISTRATION NUMBER: ChiCTR2200056373, Date: 2022-02-04, version 1.

Pingchan Granule for Motor Symptoms and Non-Motor Symptoms of Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Pingchan granule (PCG) is a traditional Chinese medicine for treating Parkinson's disease (PD). Objective: This study aimed at evaluating the efficacy and safety of PCG for motor and non-motor symptoms of PD. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants with mild-to-moderate PD were included and followed for 36 weeks (24 week treatment, 12-week follow-up after intervention), randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcomes included the severity of motor symptoms assessed by the Unified Parkinson's disease Rating Scale (UPDRS) part 3 (UPDRS-III) score and the rate of disease progression assessed by the total UPDRS score. Secondary outcomes included non-motor symptoms assessed using the Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Parkinson's disease Sleep Scale (PDSS), 24-item Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), UPDRS part 2 (UPDRS-II), and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores. Assessments were done at baseline (T0), 12 weeks (T1), 24 weeks (T2), and 36 weeks (T3). Results: Generalized estimating equation analyses revealed that the PCG group had significantly better improvement in UPDRS-III score at T1, T2, and T3 [time-by-group interaction, T1: ß, -0.92 (95% CI, -1.59--0.25; p = 0.01); T2: ß, -2.08 (95% CI, -2.90--1.27; p < 0.001); T3: ß, -4.54 (95% CI, -5.37--3.71; p < 0.001))]. The PCG group showed a greater decrease (rate of disease change) in the total UPDRS score between T0 and T2 [-2.23 (95% CI, -2.72--1.73; p < 0.001) points per week vs. -0.21 (95% CI, -0.80-0.39; p = 0.50) points per week in the placebo group, p < 0.001]. Ameliorations of SCOPA-AUT, PDSS, HAM-D, HAM-A, UPDRS-II, and PDQ-39 scores were also observed. Conclusion: PCG had a long-lasting and extensive symptomatic efficacy for both motor and non-motor symptoms of PD with good tolerance. Trial registration: Chinese Clinical Trial Register, ChiCTR-INR-17011949.

Identification of ferroptosis-related gene signatures associated with multiple sclerosis using weighted gene co-expression network analysis.

Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system leading to demyelination followed by neurological symptoms. Ferroptosis is a newly discovered pathogenic hallmark important for the progression of MS. However, the gene markers of ferroptosis in MS are still uncertain. In this study, mRNA expression profiles and clinical data of MS samples were retrieved from Gene Expression Omnibus database. Weighted gene co-expression network analysis and receiver operating characteristic curve analysis were utilized to identify ferroptosis-related gene (FRG) signatures of MS. Gene set enrichment analysis and gene set variation analysis were performed to explore the biological functions of single FRG signature. HMOX1, LPCAT3 and RPL8 were firstly identified as FRG signatures of MS with the predictive capacity confirmed. Gene set enrichment analysis and gene set variation analyses revealed that metabolism-related, immune and inflammation-related, microglia-related, oxidation-related, and mitochondria-related biological functions were enriched, providing implications of the mechanisms underlying ferroptosis in MS. This study presented a systematic analysis of FRG in MS and explored the potential ferroptosis targets for new interventional strategies in MS.

Clinical efficacy and safety of removing blood stasis and removing phlegm in the treatment of epilepsy with cognitive impairment: A protocol for systematic review and meta-analysis.

BACKGROUND: Epilepsy is a chronic encephalopathy caused by abnormal discharge of neurons in the brain, resulting in brain dysfunction. Cognitive impairment is one of the most common complications of epilepsy. The current treatment of epilepsy in the control of symptoms at the same time cause a lot of side effects, especially the aggravation of cognitive impairment. Many literatures have stated that the efficacy and safety of integrated traditional Chinese and western medicine in the treatment of epilepsy with cognitive impairment is superior to that of western medicine alone. In this systematic review, we intend to evaluate the clinical efficacy and safety of removing stasis and resolving phlegm in the treatment of epilepsy with cognitive impairment. METHODS: We will search The Cochrane Library, EMbase, Pubmed, Web of Science, Chinese Journal Full-Text Database (CNKI), Wanfang Database, and VIP database. Simultaneously we will retrieval relevant meeting minutes, eligible research reference lists, symposium abstracts, and gray literatures. We will not apply any restrictions to the language and publication date. All randomized controlled trials about the efficacy and safety of removing blood stasis and phlegm in the treatment of epilepsy with cognitive impairment will be included. Two authors will independently carry out. Any objections will be worked out by a third author through consultation. We will use the Revman 5.3 and Stata 13.0 software for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. The grading of recommendations assessment, development, and evaluation standard will be used to evaluate the quality of evidence. RESULTS: This systematic review will synthesize the data from the present eligible high quality randomized controlled trials to assess whether the treatment of removing blood stasis and phlegm is effective and safety for epilepsy with cognitive impairment from various evaluation aspects including clinical efficacy of epilepsy, EEG improvement rate, MOCA score, QOLIE-31 cognitive function score, traditional Chinese medicine symptom score, incidence of adverse reactions, frequency of seizures of epilepsy, and duration of seizure of epilepsy. CONCLUSION: The systematic review will provide evidence to assess the efficacy and safety of removing blood stasis and phlegm in the treatment of patients with epilepsy with cognitive impairment. PROSPERO REGISTRATION NUMBER: CRD42021224893.

Chinese herbal medicines for mild cognitive impairment: A protocol for meta-analysis and trial sequential analysis.

BACKGROUND: Mild cognitive impairment (MCI), as a common neurodegenerative aging disease representing an intermediate stage between normal cognitive functioning and dementia, poses an excessive burden on health care. The clinical benefit of Chinese herbal medicines (CHMs) for MCI remains inconclusive. This study is aimed at evaluating the efficacy and acceptability of CHMs through meta-analysis and trial sequential analysis (TSA). METHODS: We applied extensive strategies on preliminary literature screening to identify relevant randomized controlled trials which meticulously compare any of CHMs interventions with placebo groups as monotherapy for MCI. The primary outcome of this study is the change of global cognitive function, and the secondary outcomes include assessments of activities of daily living, mood, and adverse events. Data synthesis, risk of bias assessment, sensitivity and subgroup analyses, and TSA will be conducted with application of Review Manager, Stata, and TSA software. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument. INPLASY registration number: INPLASY202190006 (https://inplasy.com/inplasy-2021-9-0006/). RESULTS: This study will confirm the clinical efficacy and safety of CHMs when used in the treatment of patients with MCI. CONCLUSION: This study will provide reliable evidence and references for the selection of CHMs in therapy and future clinical research of MCI.

Prevalence and Clinical Features of FOG in Chinese PD Patients, a Multicenter and Cross-Sectional Clinical Study.

Objectives: Freezing of gait (FOG) is generally considered as an independent symptom of Parkinson's disease (PD) with a complex pathophysiology. There is a wide range of associated clinical features of FOG reported from different studies without consistent conclusion. Thus, a multicenter, cross-sectional study was designed to investigate the prevalence and clinical features of FOG together with its unique contribution quality of life in Chinese PD patients. Methods: Eight hundred and thirty eight PD patients were consecutively recruited into this study from 12 hospital centers in six provinces in China. Clinical information, including motor and neuropsychological features as well as pharmacological details, was collected. Results: Of 827 PD patients, 245 (29.63%) reported FOG. The prevalence of FOG was strongly correlated with modified H-Y stages and symptomatic duration (p < 0.01). 84.90% freezers experienced FOG during turning and 88.98% experienced when initiating the first step. Compared with non-freezers, freezers reported longer disease duration (7.73 ± 5.44 vs. 4.69 ± 3.94, p < 0.000), higher frequent PIGD phenotype (61.22 vs. 35.91%, p < 0.000), higher scores of UPDRS III (32.85 ± 15.47 vs. 22.38 ± 12.89, p < 0.000), HAMA (10.99 ± 7.41 vs. 7.59 ± 6.47, p < 0.000), HAMD (15.29 ± 10.29 vs. 10.58 ± 8.97, p < 0.000) and lower MMSE score (25.12 ± 5.27 vs. 26.63 ± 3.97, p < 0.000), and higher daily levodopa dosage (432.65 ± 264.31 vs. 319.19 ± 229.15, p < 0.000) with less frequent initial use of dopaminergic agonist (8.57 vs. 14.78%, p < 0.05). Using binary logistic regression, the associated factors of FOG might be non-tremor dominant onset (OR = 3.817, p < 0.000), the presence of anxiety (OR = 2.048, p < 0.000) and imbalance (OR = 4.320, p = 0.012). Freezers had poorer quality of life than non-freezers and FOG impacted PDQ-8 independently. Conclusion: Nearly one third of the PD patients experienced FOG. Its frequency increased with PD progression and FOG reduced independently the quality of life. Non-tremor dominant, disease progression, and anxiety were risk factors of FOG.

Pingchan granule for depressive symptoms in parkinson's disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Depression in Parkinson's disease (dPD) is closely related to quality of life. Current studies have suggested that Pingchan Granule (PCG) might be effective for treating dPD. OBJECTIVE: This study determines the efficacy of PCG for depressive symptoms in Parkinson's disease (PD). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This was a randomized, double-blind, placebo-controlled trial, conducted in Longhua Hospital, Shanghai, China. Patients diagnosed with idiopathic PD and clinically significant depressive symptoms (defined by a 24-item Hamilton Rating Scale for Depression [HAM-D] score ≥ 8) were included in this study, randomly assigned to PCG or placebo group in a 1:1 ratio and followed for 24 weeks. MAIN OUTCOME MEASURES: The primary outcome was the change from baseline to week 24 in HAM-D score among the set of patients who completed the study following the treatment protocol (per-protocol set). Secondary outcomes included changes in scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part 2 (UPDRS-II), UPDRS part 3 (UPDRS-III), Parkinson's Disease Sleep Scale (PDSS) and Hamilton Rating Scale for Anxiety (HAM-A), between baseline and week 24. RESULTS: Eighty-six patients were enrolled, and 85 patients were included in the per-protocol set. HAM-D scores decreased by an adjusted mean of 11.77 (standard error [SE] 0.25) in the PCG group and 3.86 (SE 0.25) in the placebo group (between-group difference = 7.91, 95% confidence interval [7.22, 8.80], P < 0.001), in the multivariable linear regression. Improvements in scores on the UPDRS-II, UPDRS-III, PDSS, and HAM-A scales were also observed. CONCLUSION: Treatment with PCG was well tolerated and improved depressive symptoms and motor and other non-motor symptoms in PD. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR-INR-17011949.

Wearing-off Identification in Parkinson's Disease: The shapd-woq Study.

Objectives: To clarify the frequency of wearing-off phenomenon (WO) and the validity of the Chinese version of the 9-item wearing-off questionnaire (CWOQ-9) in WO identification in this large population. Methods: Parkinson's patients treated with antiparkinsonian medications were consecutively recruited into this observational, cross-sectional investigation. Patients completed the CWOQ-9 prior to the independent clinician assessment. Results: A total of 1,385 patients were included in the analysis. The mean age was 69.7 ± 9.5 years and the mean disease duration was 5.8 ± 4.7 years. Clinicians identified WO in 763 patients, with an overall prevalence of 55.1%. In patients within 1 year of disease duration, clinicians diagnosed WO in eight patients, with a percentage of 12.9%. With the disease progression, the WO frequency gradually increased to 76.2% in patients with 10-15 years of disease duration. Then, it slowly decreased at a longer disease duration. The occurrence of WO was closely associated with the disease duration, H&Y staging, and levodopa daily dose. CWOQ-9 identified 1,071 patients (1071/1398, 77.33%) that had WO-related symptoms. The mean CWOQ-9 score was 3.4 ± 1.6. CWOQ-9 corresponded with clinician assessments of WO in 734 of 763 cases; clinicians disagreed with the CWOQ-9 considering the presence of WO in 337 of 1,071 cases. The sensitivity and specificity of CWOQ-9 were 96.2 and 45.8%, respectively. Conclusions: WO occurred frequently at the early and middle stage of PD. CWOQ-9 was qualified as a pre-visiting screening tool for clinicians to better identify WO.

Personalized prediction of depression in patients with newly diagnosed Parkinson's disease: A prospective cohort study.

BACKGROUND: Depressive disturbances in Parkinson's disease (dPD) have been identified as the most important determinant of quality of life in patients with Parkinson's disease (PD). Prediction models to triage patients at risk of depression early in the disease course are needed for prognosis and stratification of participants in clinical trials. METHODS: One machine learning algorithm called extreme gradient boosting (XGBoost) and the logistic regression technique were applied for the prediction of clinically significant depression (defined as The 15-item Geriatric Depression Scale [GDS-15] ≥ 5) using a prospective cohort study of 312 drug-naïve patients with newly diagnosed PD during 2-year follow-up from the Parkinson's Progression Markers Initiative (PPMI) database. Established models were assessed with out-of-sample validation and the whole sample was divided into training and testing samples by the ratio of 7:3. RESULTS: Both XGBoost model and logistic regression model achieved good discrimination and calibration. 2 PD-specific factors (age at onset, duration) and 4 nonspecific factors (baseline GDS-15 score, State Trait Anxiety Inventory [STAI] score, Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire [RBDSQ] score, and history of depression) were identified as important predictors by two models. LIMITATIONS: Access to several variables was limited by database. CONCLUSIONS: In this longitudinal study, we developed promising tools to provide personalized estimates of depression in early PD and studied the relative contribution of PD-specific and nonspecific predictors, constituting a substantial addition to the current understanding of dPD.

Efficacy of electroacupuncture for the treatment of constipation in Parkinson's disease: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Constipation is one of the most common non-motor symptoms in Parkinson's disease (PD). Acupuncture can have a positive on chronic functional constipation and PD, but its efficacy for the treatment of constipation in PD has not yet been confirmed by high-quality clinical trials. Therefore, this study aims to evaluate the efficacy and safety of electroacupuncture (EA) in the treatment of constipation in PD. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial. A total of 124 qualified patients with PD and constipation will be randomly divided into the intervention group (62 participants will receive 12 weeks of EA +usual care) or the waitlist control group (62 participants will receive 12 weeks of usual care). EA will be performed three times per week from weeks 1-8, two times per week during weeks 9 and 10, and once a week during weeks 11 and 12. The primary outcome is the change in mean weekly spontaneous bowel movements from baseline to weeks 8 and 9. The secondary outcomes are the changes from baseline in mean weekly bowel movements, mean weekly stool consistency, and mean weekly straining. Other secondary outcomes include the weekly doses of defecation drugs, Visual Analogue Scale for subjective improvements in stool symptoms, Unified Parkinson's Disease Rating Scale, and the time and number of steps required to walk 20 m. Outcomes will be assessed at baseline, week 4, 8, 12 (intervention period); as well as at week 16, 24 (follow-up period). ETHICS AND DISSEMINATION: Ethical approval has been obtained from four local ethics committees. The results of the study will be published in peer-reviewed journals and will be disseminated through national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900021053.

Metabolic pattern analysis of 18F-FDG PET as a marker for Parkinson's disease: a systematic review and meta-analysis.

A large number of articles have assessed the diagnostic accuracy of the metabolic pattern analysis of [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in Parkinson's disease (PD); however, different studies involved small samples with various controls and methods, leading to discrepant conclusions. This study aims to consolidate the available observational studies and provide a comprehensive evaluation of the clinical utility of 18F-FDG PET for PD. The methods included a systematic literature search and a hierarchical summary receiver operating characteristic approach. Sensitivity analyses according to different pattern analysis methods (statistical parametric mapping versus scaled subprofile modeling/principal component analysis) and control population [healthy controls (HCs) versus atypical parkinsonian disorder (APD) patients] were performed to verify the consistency of the main results. Additional analyses for multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) were conducted. Fifteen studies comprising 1446 subjects (660 PD patients, 499 APD patients, and 287 HCs) were included. The overall diagnostic accuracy of 18F-FDG in differentiating PD from APDs and HCs was quite high, with a pooled sensitivity of 0.88 [95% confidence interval (95% CI), 0.85-0.91] and a pooled specificity of 0.92 (95% CI, 0.89-0.94), with sensitivity analyses indicating statistically consistent results. Additional analyses showed an overall sensitivity and specificity of 0.87 (95% CI, 0.76-0.94) and 0.93 (95% CI, 0.89-0.96) for MSA and 0.91 (95% CI, 0.78-0.95) and 0.96 (95% CI, 0.92-0.98) for PSP. Our study suggests that the metabolic pattern analysis of 18F-FDG PET has high diagnostic accuracy in the differential diagnosis of parkinsonian disorders.

Zishenpingchan granules for the treatment of Parkinson's disease: a randomized, double-blind, placebo-controlled clinical trial.

Levodopa preparations remain the preferred drug for Parkinson's disease. However, long-term use of levodopa may lead to a series of motor complications. Previous studies have shown that the combination of levodopa and Zishenpingchan granules (consisting of Radix Rehmanniae preparata, Lycium barbarum, Herba Taxilli, Rhizoma Gastrodiae, Stiff Silkorm, Curcuma phaeocaulis, Radix Paeoniae Alba, Rhizoma Arisaematis, Scorpio and Centipede) can markedly improve dyskinesia and delay the progression of Parkinson's disease, with especially dramatic improvements of non-motor symptoms. However, the efficacy of this combination has not been confirmed by randomized controlled trials. The current study was approved by the Hospital Ethics Committee and was registered in the Chinese Clinical Trial Register (registration number: ChiCTR-INR-1701194). From December 2014 to December 2016, 128 patients (72 males and 56 females, mean age of 65.78 ± 6.34 years) with Parkinson's disease were recruited from the Department of Neurology of Longhua Hospital and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine in China. Patients were equally allocated into treatment and control groups. In addition to treatment with dopamine, patients in treatment and control groups were given Zishenpingchan granules or placebo, respectively, for 24 weeks. Therapeutic efficacy was assessed using the Unified Parkinson's Disease Rating Scale, on-off phenomenon, Hoehn-Yahr grade, Scales for Outcomes in Parkinson's disease-Autonomic, Parkinson's disease sleep scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Mini-Mental State Examination, and the Parkinson's Disease Quality of Life Questionnaire. Artificial neural networks were used to determine weights at which to scale these parameters. Our results demonstrated that Zishenpingchan granules significantly reduced the occurrence of motor complications, and were useful for mitigating dyskinesia and non-motor symptoms of Parkinson's disease. This combination of Chinese and Western medicine has the potential to reduce levodopa dosages, and no obvious side effects were found. These findings indicate that Zishenpingchan granules can mitigate symptoms of Parkinson's disease, reduce toxic side effects of dopaminergic agents, and exert synergistic and detoxifying effects.

Effect of Zishenpingchan granule prepared from Chinese medicinal substances on the c-Jun N-terminal protein kinase pathway in mice with Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

OBJECTIVE: To investigate the regulatory mechanism of the c-Jun N-terminal protein kinase (JNK) signaling pathway in substantia nigra (SN) dopaminergic neurons inflammation and apoptosis, and the neuroprotective effect of Zishenpingchan granules in mice with Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHODS: PD model mice were established by intraperitoneally injecting MPTP. Sixty mice were divided into a model group, Traditional Chinese Medicine (TCM) group and control group. The mice of the TCM group were administered Zishenpingchan granules 7 days before PD induction. Seven days after PD induction, we examined locomotor activity, and performed the rotarod test and swimming test, to evaluate limb movement function. Furthermore, we used immunohistochemistry and western blotting to examine the expression of tyrosine hydroxylase (TH), cyclooxygenase-2 (Cox-2), caspase-3 and p-JNK. The terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method was used to examine neuron apoptosis in the SN. RESULTS: Compared with the control group, the mean score of locomotor activity, rotarod test and swimming test was significantly lower in the model group (P < 0.05); the TH-positive neuron expression was significantly decreased in the SN pars compacta (SNpc); the protein expression levels of Cox-2, caspase-3 and p-JNK was obviously increased; and the number of TUNEL-positive neurons in the SN was increased (P < 0.01). Compared with the model group, the mean score of neurobehavioral tests in the TCM group was obviously higher, the loss of TH-positive neurons ignificantly decreased, the protein expression levels of Cox-2, caspase-3 and p-JNK obviously decreased, and the number of TUNEL- positive neurons in the SN clearly decreased (P < 0.01). CONCLUSION: The JNK pathway plays an important role in the regulation of inflammation and apoptosis in nigral cells in PD mice. TCM can suppress the over-activation of the JNK pathway in the SN, and alleviate the inflammatory response in nigral cells and dopaminergic neuron apoptosis in PD mice.