Prevalence of Parkinson's disease among adults aged 45 years and older in China: a cross-sectional study based on the China health and retirement longitudinal study.

BACKGROUND: In recent decades, China has experienced a rapid increase in the number of elderly individuals and life expectancy, as well as industrialization, which is associated with an increased prevalence of Parkinson's disease (PD). However, inconsistent results have recently been reported. Therefore, this study aimed to investigate the prevalence and distribution characteristics of PD among individuals aged 45 years and older. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we attempted to estimate the prevalence of PD and its distribution characteristics among 19,034 individuals aged 45 years and older residing in 446 communities/villages within 27 provinces/autonomous regions/municipalities in mainland China. Cases were established based on a doctor's previous diagnosis. Crude and age-adjusted prevalence rates were calculated and stratified by age, sex, area of residence, education level, marital status, and geographic region. Logistic regression models were used to identify risk factors associated with PD. RESULTS: We identified 178 patients with PD among 19,034 residents aged 45 years and older. The crude prevalence was 0.94%, and the age-adjusted prevalence was 0.82% for individuals aged 45 years and older. The prevalence of PD increased with age (P < 0.001). No significant differences were found in terms of sex, area of residence, or education level. Stratified by geographic region, the prevalence of PD was greater in North and Northwest China and lower in southern China (p < 0.001). Multiple regression analyses showed that age was a significant risk factor for PD. CONCLUSION: The prevalence of PD increased with age in the Chinese population.

Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease.

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity. Spearman correlation analysis was employed to investigate the relationship between AutD severity and PD symptoms. Additionally, we performed multiple linear regression model analysis to determine whether associations between SCOPA-AUT scores and clinical assessments remained significant after adjusting for Hoehn and Yahr stage, sex, and age. PD patients in the AutD-M group exhibited significantly more severe NMS and motor symptoms compared to those in the AutD-S group. In correlation analysis, SCOPA-AUT scores showed significant correlations with multiple clinical symptoms, such as most of the NMS, 10-MWT and CPET parameters. Furthermore, regression analysis also revealed that more pronounced fatigue, anxiety, depressive symptoms, worse walking speed and impaired exercise capacity were associated with higher SCOPA-AUT scores. The presence of AutD is correlated with emotional disturbances, decreased exercise endurance, and impaired gait function in patients with PD. Early management of AutD may prove beneficial in alleviating some NMS and motor symptoms in PD.

The Efficacy of Wearable Cueing Devices on Gait and Motor Function in Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the efficacy of wearable cueing devices for improving gait and motor function of patients with Parkinson disease (PWP). DATA SOURCES: PubMed, Embase, and Cochrane CENTRAL databases were searched for papers published in English, from inception to October 23, 2022. STUDY SELECTION: Randomized controlled trials focusing on the effects of wearable cueing devices on gait and motor function in PWP were included. DATA EXTRACTION: Two reviewers independently selected articles and extracted the data. The Cochrane Bias Risk Assessment Tool was used to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of evidence. DATA SYNTHESIS: Seven randomized controlled trials with 167 PWP were included in the meta-analysis. Significant effect of wearable cueing devices on walking speed (mean difference [MD]=0.07 m/s, 95% confidence interval [CI]: [0.05, 0.09], P<.00001) was detected; however, after sensitivity analysis, no significant overall effect on walking speed was noted (MD=0.04 m/s, 95% CI: [-0.03, 0.12], P=.25). No significant improvements were found in stride length (MD=0.06 m, 95% CI: [0.00, 0.13], P=.05), the Unified Parkinson's Disease Rating Scale-III score (MD=-0.61, 95% CI: [-4.10, 2.88], P=.73), Freezing of Gait Questionnaire score (MD=-0.83, 95% CI: [-2.98, 1.33], P=.45), or double support time (MD=-0.91, 95% CI: [-3.09, 1.26], P=.41). Evidence was evaluated as low quality. CONCLUSIONS: Wearable cueing devices may result in an immediate improvement on walking speed; however, there is no evidence that their use results in a significant improvement in other gait or motor functions.

Hyperglycemia affects axial signs in patients with Parkinson's disease through mechanisms of insulin resistance or non-insulin resistance.

OBJECTIVE: To investigate the influence of hyperglycemia on motor symptoms, especially axial signs, and potential mechanisms related to insulin resistance (IR) in patients with Parkinson's disease (PWP). METHODS: According to glycated hemoglobin (HbA1c) level, PWP were divided into the low-HbA1c and the high-HbA1c groups. Demographic information, glucose metabolism-related variables, Hoehn-Yahr stage, and motor function were compared between the two groups. Correlations between levels of HbA1c and the homeostatic model assessment (HOMA)-IR and motor function in PWP were further analyzed. RESULTS: HbA1c level was significantly and positively correlated with the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score, axial signs subscore, the Timed Get Up and Go test time, the center of pressure displacement of standing with eyes open and closed, and significantly and negatively correlated with the 10-m walk test comfortable gait speed. HOMA-IR level was significantly and negatively correlated with 10-m walk test comfortable gait speed, but not with others. CONCLUSIONS: PWP with high HbA1c showed worse axial symptoms, including dysfunction of automatic walking, dynamic balance, and postural control than those with low HbA1c. In PWP, the effects of hyperglycemia on automatic walking speed may be associated with the IR-related mechanisms, and the effects on dynamic balance and postural control may be related to mechanisms other than IR.

Intermittent theta-burst stimulation combined with physical therapy as an optimal rehabilitation in Parkinson's disease: study protocol for a randomised, double-blind, controlled trial.

BACKGROUND: First-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson's disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson's disease. METHODS: This randomised, double-blind clinical trial will enrol 50 Parkinson's disease patients aged 45-70 years with Hoehn and Yahr scale scores of 1-3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson's Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate. DISCUSSION: The aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson's disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson's disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson's disease. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022.

Longitudinal cognitive changes in patients with early Parkinson's disease and neuropsychiatric symptoms.

AIMS: In this study, we aimed to investigate the effect of neuropsychiatric symptoms (NPS) on the rate of cognitive decline for both global cognition and specific cognitive domains in a cohort of patients from the Parkinson's Progression Markers Initiative (PPMI). METHOD: Prospectively longitudinal data were obtained from the PPMI cohort. NPS, including depression, anxiety, apathy, psychosis, impulse control disorders (ICDs), and cognition ability, were evaluated by a series of questionnaires. Linear mixed-effects models were used to investigate the relationship between NPS and the rate of cognitive decline. Generalized estimating equations (GEEs) were used to investigate the relationship between NPS and the occurrence of mild cognitive impairment (MCI). RESULTS: In total, 423 patients with Parkinson's disease (PD) were recruited at baseline and 395, 378, 366, 346, and 315 participants were followed up at 1, 2, 3, 4, and 5 years, respectively. Depression, anxiety, apathy, and psychosis were associated with global cognitive decline. Except for those with ICDs, patients with psychosis, depression, anxiety, and apathy were more likely to meet the criteria for MCI. Patients with depression and anxiety showed a progressive decline in four major cognitive domains. Apathy and ICDs were separately associated with a progressive decline in processing speed-attention and memory, respectively. CONCLUSIONS: Neuropsychiatric symptoms, including psychosis, depression, anxiety, and apathy, could be used to predict future cognitive decline in patients with PD.

Circular RNAs in Parkinson's Disease: Reliable Biological Markers and Targets for Rehabilitation.

In clinical practice, the underlying pathogenesis of Parkinson's disease (PD) remains unknown. Circular RNAs (circRNAs) have good biological properties and can be used as biological marker. Rehabilitation as a third treatment alongside drug and surgery has been shown to be clinically effective, but biomarkers of rehabilitation efficiency at genetic level is still lacking. In this study, we identified differentially expressed circRNAs in peripheral blood exosomes between PD patients and health controls (HCs) and determined whether these circRNAs changed after rehabilitation, to explore the competing RNA networks and epigenetic mechanisms affected. We found that there were 558 upregulated and 609 downregulated circRNAs in PD patients compared to HCs, 3398 upregulated and 479 downregulated circRNAs in PD patients after rehabilitation compared to them before rehabilitation, along with 3721 upregulated and 635 downregulated circRNAs in PD patients after rehabilitation compared to HCs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially expressed circRNAs may affect the stability of the cellular actin backbone and synaptic structure by influencing the aggregation of α-synuclein (a-syn). We selected two circRNAs overexpressed in PD patients for validation (hsa_circ_0001535 and hsa_circ_0000437); the results revealed that their expression levels were all reduced to varying degrees (p < 0.05) after rehabilitation. After network analysis, we believe that hsa_circ_0001535 may be related to the aggregation of a-syn, while hsa_circ_0000437 may act on hsa-let-7b-5p or hsa-let-7c-5p through sponge effect to cause inflammatory response. Our findings suggest that rehabilitation can mitigate the pathological process of PD by epigenetic means.

Association Between Mitochondrial Function and Rehabilitation of Parkinson's Disease: Revealed by Exosomal mRNA and lncRNA Expression Profiles.

Rehabilitation has been proposed as a valid measure complementary to the management of Parkinson's disease (PD). However, the mechanism underlying is not clear yet. The differential expressions of exosomal messenger RNA (mRNA) and long noncoding RNAs (lncRNAs) may play a critical role in PD progression and rehabilitation. To compare the differential expressions of exosomal mRNAs and lncRNAs, patients with PD (PWPs, Hoehn and Yahr stages 1.5-2.5, n = 6) and age- and sex-matched healthy controls (HCs, n = 6) were included in this study. All PWPs received a 2-week rehabilitation treatment in the hospital, which seemingly led to improvement in both the motor and non-motor functions. A set of differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) extracted from exosomes in blood samples via next-generation sequencing (NGS) was screened out. Compared to HCs, 2,337 vs. 701 mRNAs and 1,278 vs. 445 lncRNAs were significantly upregulated and significantly downregulated, respectively, in pre-rehabilitation (pre-rehab) PWPs; 2,490 vs. 629 mRNAs and 1,561 vs. 370 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehabilitation (post-rehab) PWPs. Compared to pre-rehab PWPs, 606 vs. 1,056 mRNAs and 593 vs. 1,136 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehab PWPs. Overall, 14 differentially expressed mRNAs (DEmRNAs) and 73 differentially expressed lncRNAs (DElncRNAs) were expressed in the blood exosomes of HCs, pre- and post-rehab PWPs, simultaneously. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 243 significantly co-expressed lncRNA-mRNA pairs. One DEmRNA of interest (ENSG00000099795, NDUFB7) and three corresponding DElncRNAs (ENST00000564683, ENST00000570408, and ENST00000628340) were positively related. Quantitative real-time polymerase chain reaction (qRT-PCR) validated that the expression levels of NDUFB7 mRNA and the 3 DElncRNAs increased significantly in pre-rehab PWPs, but decreased significantly in post-rehab PWPs compared to HCs. NDUFB7 mRNA is a marker related to mitochondrial respiration. It is reasonably believed that mitochondrial function is associated with PD rehabilitation, and the mitochondrial pathway may involve in the pathogenesis of PD.

Quality of life predicts rehabilitation prognosis in Parkinson's disease patients: Factors influence rehabilitation prognosis: Factors influence rehabilitation prognosis.

BACKGROUND: Rehabilitation has been reported to improve the quality of life (QoL) of patients with Parkinson's disease (PD). Nevertheless, not all patients are satisfied with rehabilitation outcomes and could achieve a significant improvement in QoL. OBJECTIVE: To detect possible predictors of QoL improvement in patients with PD after rehabilitation. METHODS: A total of 86 PD patients were included and followed up for 3 months with a 39-item Parkinson's Disease Questionnaire summary index (PDQ-39 SI) as the primary endpoint. All patients received 2 weeks of multidisciplinary intensive rehabilitation treatment (MIRT). Changes in patients' QoL were assessed using the PDQ-39 at baseline and at the 3-month follow-up. The reliable change index (RCI) was adapted to determine the individual QoL outcome. The predictors of QoL outcome were detected using logistic regression analysis. RESULTS: After a 3-month follow-up, PDQ-39 SI decreased significantly from 22.95 ± 9.75 to 18.73 ± 10.32 (P < 0.001). Scores for QoL improved (RCI>10.9) after rehabilitation for 18.6% of the patients, and 74.4% of patients reported an unchanged QoL (-10.9≤RCI≤10.9), while 7.0% of patients reported a worsening of QoL (RCI<-10.9). Among the baseline parameters, the PDQ-39 SI was a baseline predictor for changes in QoL in the logistic regression model (OR: 1.15, CI: 1.07-1.24, P < 0.001). CONCLUSIONS: MIRT could improve QoL for some patients with PD, and PDQ-39 score at baseline is the most important predictor for QoL improvements after rehabilitation for this patients.

The quality of life in patients with Parkinson's disease: Focus on gender difference.

BACKGROUND: To improve understanding of gender differences on quality of life (QoL) in patients with Parkinson's disease (PWP) of a different race, the differences of clinical features and health-related quality of life (HRQoL) between male and female PWP were studied in a small cohort early to middle stage of Chinese PWP. METHODS: A cross-sectional study was carried out. PWP were consecutively included from April 2020 to July 2021 in Beijing Rehabilitation Hospital. HRQoL, motor symptoms, and nonmotor symptoms in each patient were evaluated. The differences of demographic, motor symptoms assessments, nonmotor symptoms assessments, and QoL between two gender groups were tested using t-test statistics, Mann-Whitney-Wilcoxon test, or χ2 depending on the data type. To eliminate the possible factors contributing to the QoL, linear regression models were constructed to sort out the effect of gender. RESULTS: One hundred and sixty-two Parkinson's disease (PD) patients were included. Demographic, clinical characteristics, and symptom scale assessments had no statistical differences except for levodopa equivalent daily dose, Hamilton Anxiety Rating Score, REM sleep behavior disorder sleep questionnaire, and Hyposmia Rating Scale score. After baseline imbalance corrections, a significantly higher score of PD Questionnaire-39 (PDQ-39) in female than in male patients(p<.05) was found. In the questionnaire, summary Index and bodily discomfort, stigma, and emotional well-being subscores were the main contribution differences. CONCLUSIONS: Gender differences are associated with the QoL in the early to middle stage PWP in China. Female patients have poorer QoL than male patients, especially bodily discomfort, stigma, and emotional well-being.

Characteristics of oscillatory pallidal neurons in patients with Parkinson's disease.

BACKGROUND: Excessive neuronal activity in the globus pallidus internus (GPi) is believed to promote parkinsonian akinesia/bradykinesia, but not tremor. Parkinsonian tremor is thought to result from dysfunction in the basal ganglia and cerebello-thalamo-cortical circuits. Whether the GPi is involved in tremorgenesis has not been fully elucidated. This study was designed to quantify the characteristics of oscillatory GPi neurons in patients with Parkinson's disease. METHODS: Nine patients undergoing surgery were studied. Microelectrode recordings in the GPi and electromyographic (EMG) activity in the limbs were recorded and the mean spontaneous firing rates (MSFRs) were calculated. Spectral analysis was used to assess neuronal oscillatory patterns. Coherence analysis was applied to explore the relationship between oscillatory neurons and EMG. RESULTS: Of 79 GPi neurons, 50.6% oscillated at the tremor frequency; 25.3% oscillated at ß frequency, and 24.1% did not oscillate. The MSFR of all neurons was 81.5 ± 7.4 spikes/s. Among neurons oscillating at tremor frequency, 40% were coherent with the tremor. In four neurons, the pattern changed from tremor frequency to ß frequency or vice versa. It appeared that the tremor began before the GPi fired bursts. CONCLUSION: Some neuronal activity in the GPi correlates with tremor and this correlation might be due to either feedback, maintenance, or initiation. Since there were examples of EMG tremor prior to GPi activity, initiation seems least likely. The data further support the prediction of the classic pathophysiology model of Parkinson's disease.