Symptoms In Parkinson's Disease Patients Research Articles

Nonmotor Manifestations of Idiopathic Parkinson's Disease and Its Correlation with the Severity and Duration of the Disease: A Cross-sectional Study.

Parkinson's disease (PD) is a neurodegenerative disorder that is common in individuals over the age of 50 years, affecting about 1% of the population. Nonmotor symptoms (NMS) are a common occurrence in PD, but they are often ignored by motor symptoms. Studies have shown that NMS in PD show a significant impact on quality of life. The introduction of tools like nonmotor symptoms scale (NMSS) and unified Parkinson's disease rating scale (UPDRS) that have a specific nonmotor domain will assist in defining research and therapy to enhance the early identification and management of NMS in the affected population. (1) To evaluate the prevalence of NMS in different stages of idiopathic Parkinson's disease. (2) To correlate the prevalence of NMS with the duration and severity of the disease. The study involved 80 individuals who visited the Movement Disorder Clinic at Stanley Medical College and Hospital in Chennai and were diagnosed with idiopathic Parkinson's disease, which was in agreement with the United Kingdom Parkinson's Disease (UK PD) Brain Bank criteria. Out of the 80 study participants, 63.7% (n = 51) were male and 36.3% (n = 29) were female. In our study, the mean age of patients was 63.1 ± 7.01 years. The study population was predominantly aged 50-60 years (n = 36), followed by 61-70 years (n = 30), which made up more than 80% of the population. Age group of >71 years constituted only 17.5% (n = 14). Majority of the patients, that is, 42.5% (n = 34) were in stage 3 of Hoehn and Yahr (H&Y) staging. The mean and mode of H&Y stage were 2.7 ± 0.9 and 3, respectively. The mean duration of disease was 4.7 ± 2.7 years. The mean UPDRS score was 66 ± 24.5. The mean NMSS score was 32 ± 10.18. NMSs are found to be highly prevalent among Indian patients with PD according to this study. The nonmotor symptom questionnaire aids in early detection and recognition of nonmotor symptoms in PD patients.

Serum neurotransmitter analysis of motor and non-motor symptoms in Parkinson's patients.

Clinical symptoms of Parkinson's disease (PD) are classified into motor and non-motor symptoms. Mental disorders, especially depression, are one of the major non-motor manifestations of PD. However, the underlying mechanisms remain poorly understood. In the present study, 21 neurotransmitters associated with mental disorders were measured in serum samples from patients and controls using the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. Additionally, five clinical scales-the MDS Unified Parkinson's Disease Rating Scale (UPDRS), the Non-Motor Symptoms Scale (NMSS), the Mini-Mental State Examination (MMSE), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD)-were used to evaluate the severity of both motor and non-motor symptoms in PD patients. Analysis of neurotransmitter metabolism revealed significant changes in the tryptophan (Trp) metabolic pathway in PD patients. Specifically, levels of Trp, kynurenine (KYN), kynurenic acid (KA), nicotinamide (NAM), and 5-methoxyltryptamine (MeOTA) were substantially decreased. Additionally, three other excitation/inhibiting amino acids-glutamic acid (Glu), 4-aminobutyric acid (GABA), and aspartic acid (Asp)-also declined. Moreover, neurotransmitter conversion ratios, such as KA/KYN, nicotinamide/niacin (NAM/NA), 5-hydroxytryptophan/tryptophan (5-HTP/Trp), and quinolinic acid/kynurenic acid (QA/KA), provided more dynamic insights into disrupted neurotransmitter metabolism. Correlation analyses between scale scores and neurotransmitter levels showed that concentrations of xanthurenic acid (XA) and the turnover rate of 3-hydroxykynurenine (3-HK) were negatively correlated with UPDRS scores, while 5-hydroxytryptamine (5-HT) and GABA levels were negatively correlated with non-motor symptoms in PD patients. In summary, this study elucidates, for the first time, the potential association and dynamics between altered neurotransmitter metabolism and the etiology of PD in terms of motor and non-motor functions. These findings offer novel biomarkers and therapeutic targets for the treatment of PD.

Influence of sleep quality, excessive daytime sleepiness, circadian features and motor subtypes on depressive symptoms in Parkinson's disease

ObjectivesThe diagnosis of Parkinson's disease (PD) is mainly based on the assessment of motor symptoms, although the influence of non-motor symptoms sometimes may be more significant on the patient's disability than the cardinal clinical signs of the disease. The predominant subtype of postural instability and gait disturbance is known to be associated with more severe non-motor symptoms of Parkinson's disease. Yet, the association between motor subtypes and specific mood symptoms remains understudied. The study aimed to analyze an association between sleep and chronotype signs, motor subtypes, with the severity of depressive symptoms in PD patients. MethodsWe have included 64 patients in the clinical study. The studied population was divided into the following groups: PIGD group – patients with PD and dominance of postural instability and gait disorders; non-PIGD group – patients with PD and dominance of tremor or intermediate motor subtype. We used the Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Munich Chronotype Questionnaire. ResultsPatients with the PIGD subtype have higher levels of depressive symptoms and excessive daytime sleepiness, poorer sleep quality, later sleep onset and mid-sleep, longer sleep latency, and sleep inertia. PIGD motor subtype (p < 0.001), poor sleep quality (p < 0.001), mid-sleep (p = 0.016), and sleep latency (p = 0.025) had a significant impact on the level of depression in univariate regression analysis. Still, only mid-sleep (p = 0.019) and poor sleep quality (p = 0.003) increased the probability of higher severity of depression in the multivariate model. ConclusionPoor sleep quality and later mid-sleep may be predictors of more severe depressive symptoms in PD.

P1 evoked by facial expression images is enhanced in Parkinson's disease patients with depressive symptoms.

Depressive symptoms are most common non-motor symptoms in Parkinson's disease (PD), which is often overlooked due to absence of rapid and objective diagnostic biomarkers. Electroencephalography (EEG)-based event-related potentials (ERPs) is commonly used to assess emotional processes. The aim of this study was to investigate changes in ERPs in PD patients exhibiting depressive symptoms and to provide a reliable biomarker for assisting in the diagnosis of PD with depressive symptoms. We conducted a case-control study involving 30 PD patients with (dPD group) or without depressive symptoms (nPD group) and 13 age matched healthy controls (HC). We recorded EEG of the patients during the emotional picture stimulation task and analyzed the difference in the early ERPs potentials (P1, N170, early posterior negativity) and their correlation with the severity of symptoms in PD patients. Our results found that P1 amplitude in the occipital region of the dPD group in response to emotional faces was significantly higher than that of nPD and HC group, and it was positively correlated with severity of depressive symptoms in PD patients. Our study shows that facial expression-induced enhancement of P1 amplitude can be utilized as a rapid and objective indicator to screen for depressive symptoms in PD.

Immediate modulatory effects of transcutaneous vagus nerve stimulation on patients with Parkinson's disease: a crossover self-controlled fMRI study.

Previous studies have evaluated the safety and efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of Parkinson's disease (PD). However, the mechanism underlying the effect of taVNS on PD remains to be elucidated. This study aimed to investigate the immediate effects of taVNS in PD patients. This crossover self-controlled study included 50 PD patients. Each patient underwent three sessions of resting-state functional magnetic resonance imaging (rs-fMRI) under three conditions: real taVNS, sham taVNS, and no taVNS intervention. We analyzed whole-brain amplitude of low-frequency fluctuations (ALFF) from preprocessed fMRI data across different intervention conditions. ALFF values in altered brain regions were correlated with clinical symptoms in PD patients. Forty-seven participants completed the study and were included in the final analysis. Real taVNS was associated with a widespread decrease in ALFF in the right hemisphere, including the superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus (voxel p < 0.001, GRF corrected). The ALFF value in the right superior parietal lobule during real taVNS was negatively correlated with the Unified Parkinson's Disease Rating Scale Part III (r = -0.417, p = 0.004, Bonferroni corrected). TaVNS could immediately modulate the functional activity of brain regions involved in superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus. These findings offer preliminary insights into the mechanism of taVNS in treating PD and bolster confidence in its long-term therapeutic potential. TaVNS appears to reduce ALFF values in specific brain regions, suggesting a potential modulation mechanism for treating PD.

Causal associations between Helicobacter Pylori infection and the risk and symptoms of Parkinson's disease: a Mendelian randomization study.

Increasing evidence suggests an association between Helicobacter pylori (HP) infection and Parkinson's disease (PD) and its clinical manifestations, but the causal relationship remain largely unknown. To investigate the causal relationship between HP infection and PD risk, PD symptoms, and secondary parkinsonism, we conducted two-sample Mendelian randomization (MR). We obtained summary data from genome-wide association studies for seven different antibodies specific to HP proteins and five PD-related phenotypes. The inverse-variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods were used to assess the causal relationships. Sensitivity analyses were performed to examine the stability of the MR results and reverse MR analysis was conducted to evaluate the presence of reverse causality. Genetically predicted HP antibodies were not causally associated with an increased risk of PD. However, HP cytotoxin-associated gene-A (CagA) and outer membrane protein (OMP) antibody level were causally associated with PD motor subtype (tremor to postural instability/gait difficulty score ratio; β = -0.16 and 0.46, P = 0.002 and 0.048, respectively). HP vacuolating cytotoxin-A (VacA) antibody level was causally associated with an increased risk of PD dementia [odds ratio (OR) = 1.93, P = 0.040]. Additionally, HP OMP antibody level was identified as a risk factor for drug-induced secondary parkinsonism (OR = 2.08, P = 0.033). These results were stable, showed no evidence of heterogeneity or directional pleiotropy, and no evidence of a reverse causal relationship. Our findings indicate that HP infection does not increase the risk of PD, but contributes to PD motor and cognitive symptoms. Different types of HP antibodies affect different symptoms of PD. Eradication of HP infection may help modulate and improve symptoms in PD patients.

Efficacy of hyperbaric oxygen therapy as an adjunct therapy in the treatment of sleep disorders among patients with Parkinson's disease: a meta-analysis.

To systematically evaluate the efficacy of hyperbaric oxygen therapy (HBOT) as an adjunct therapy for treating sleep disorders in patients with Parkinson's disease (PD). We conducted comprehensive searches in eight databases from inception through September 2023, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang Database. The objective was to identify randomized controlled trials (RCTs) evaluating HBOT's effectiveness in alleviating sleep disorder symptoms in PD patients as an adjunct therapy. Literature screening and data extraction were independently executed by the authors. Meta-analyses were performed using Review Manager 5.3 software, and publication bias and sensitivity analyses were assessed using Stata 17.0 software. Seven RCTs involving 461 participants were included. The findings revealed that the addition of HBOT significantly enhanced sleep efficiency (MD = 15.26, 95% CI [10.89, 19.63], p < 0.00001), increased time in bed (MD = 69.65, 95% CI [43.01, 96.30], p < 0.00001), total sleep time (MD = 75.87, 95% CI [25.42, 126.31], p = 0.003), slow-wave sleep (SWS) time (MD = 6.14, 95% CI [3.95, 8.34], p < 0.00001), and rapid eye movement sleep (REM) time (MD = 4.07, 95% CI [2.05, 6.08], p < 0.0001), and reduced awakening frequency (MD = -11.55, 95% CI [-15.42, -7.68], p < 0.00001) and sleep latency (MD = -6.60, 95% CI [-9.43, -3.89], p < 0.00001). Additionally, significant improvements were observed in the Pittsburgh Sleep Quality Index (PSQI) (MD = -2.52, 95% CI [-2.85, -2.18], p < 0.00001), Epworth Sleepiness Scale (ESS) (MD = -2.90, 95% CI [-3.34, -2.47], p < 0.00001), Unified Parkinson's Disease Rating Scale Part III (UPDRS III) (MD = -1.32, 95% CI [-2.16, -0.47], p = 0.002), and Hoehn and Yahr grading (H-Y grading) (MD = -0.15, 95% CI [-0.28, -0.01], p = 0.03). The current meta-analysis supports the efficacy of HBOT as an adjunct therapy in managing sleep disorders in PD patients. It is recommended for PD patients experiencing sleep disturbances.Systematic review registration:https://www.crd.york.ac.uk/, identifier: CRD42023462201.

Motor improvement in Parkinson's disease patients receiving caffeine adjuvants: A double-blind randomized controlled trial in Indonesia.

Parkinson's disease (PD) manifests as a movement and brain function disorder characterized by symptoms such as resting tremors, rigidity, bradykinesia, and postural instability, leading to disability among patients. The use of psychostimulants such as caffeine has been associated with the improvement of motor symptoms in PD patients; however, studies regarding the effect of caffeine adjuvant therapy on motor function among PD patients in the Indonesian population are lacking. The aim of this study was to evaluate motor improvement as measured by the change in scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) among PD patients receiving caffeine adjuvant. A double-blind randomized controlled trial (RCT) was conducted among PD patients at Dr. Soetomo General Academic Hospital and Universitas Airlangga Hospital, Surabaya, Indonesia, from April to August 2023. A total of 27 patients were enrolled and randomly assigned to an intervention (receiving caffeine adjuvant, n=15) and control group (receiving placebo, n=12). Motor improvement was measured using the UPDRS III score prior to intervention and three weeks after. The Chi-squared test was used to analyze the difference in UPDRS III scores between the two groups. Motor improvement, as demonstrated by a reduction in the UPDRS III score, was observed in patients receiving caffeine adjuvant compared to those receiving placebo (80.0% vs 16.7%; p=0.004). Regarding the safety profile, only four out of 15 (26.6%) patients treated with caffeine reported minor adverse events. These conditions improved over time during the intervention. None of the 12 patients in the placebo reported adverse events. This study provides valuable insights into the initial dosage of caffeine that improves motor function in PD patients with minimum adverse effects.

Targeting protein-protein interactions for therapeutic intervention in Parkinson's disease to delay progression.

Background: Parkinson's disease (PD) is a neurodegenerative condition with few treatments to slow or stop development. Protein-protein interactions (PPIs) are intriguing therapeutic targets. This research examined the safety and effectiveness of a new Parkinson's disease medication targeting PPIs. Methods: After enrollment, 60 individuals were randomly assigned to the treatment and control groups. MDS-UPDRS Part III score change from baseline to week 12 was the main outcome measure. Secondary outcome measures were the Hoehn and Yahr scale, NMSS, and Montreal Cognitive Assessment. Study-wide adverse events were tracked. Results: Compared to the control group, the treatment group exhibited a substantial improvement in MDS-UPDRS Part III score (p &lt; 0.001). Additionally, the therapy group showed substantial improvements in Hoehn and Yahr stage, NMSS score, and MoCA score compared to the control group (p &lt; 0.001). No significant adverse effects were documented with the experimental medication. Conclusion: This research suggests that targeting PPIs may treat Parkinson's disease. No harmful side effects were detected with the experimental medication, which improved motor and non-motor symptoms in PD patients. These results require more study to determine the long-term safety and effectiveness of targeting PPIs in Parkinson's disease.

Gray matter volume alterations in de novo Parkinson's disease: A mediational role in the interplay between sleep quality and anxiety.

Parkinson's disease (PD) is increasingly recognized for its non-motor symptoms, among which emotional disturbances and sleep disorders frequently co-occur. The commonality of neuroanatomical underpinnings for these symptoms is not fully understood. This study is intended to investigate the differences in gray matter volume (GMV) between PD patients with anxiety (A-PD) and those without anxiety (NA-PD). Additionally, it seeks to uncover the interplay between GMV variations and the manifestations of anxiety and sleep quality. A total of 37 A-PD patients, 43 NA-PD patients, and 36 healthy controls (HCs) were recruited, all of whom underwent voxel-based morphometry (VBM) analysis. Group differences in GMV were assessed using analysis of covariance (ANCOVA). Partial correlation between GMV, anxiety symptom, and sleep quality were analyzed. Mediation analysis explored the mediating role of the volume of GMV-distinct brain regions on the relationship between sleep quality and anxiety within the PD patient cohort. A-PD patients showed significantly lower GMV in the fusiform gyrus (FG) and right inferior temporal gyrus (ITG) compared to HCs and NA-PD patients. GMV in these regions correlated negatively with Hamilton Anxiety Rating Scale (HAMA) scores (right ITG: r = -0.690, p < 0.001; left FG: r = -0.509, p < 0.001; right FG: r = -0.576, p < 0.001) and positively with sleep quality in PD patients (right ITG: r = 0.592, p < 0.001; left FG: r = 0.356, p = 0.001; right FG: r = 0.470, p < 0.001). Mediation analysis revealed that GMV in the FG and right ITG mediated the relationship between sleep quality and anxiety symptoms, with substantial effect sizes accounted for by the right ITG (25.74%) and FG (left: 11.90%, right: 15.59%). This study has shed further light on the relationship between sleep disturbances and anxiety symptoms in PD patients. Given the pivotal roles of the FG and the ITG in facial recognition and the recognition of emotion-related facial expressions, our findings indicate that compromised sleep quality, under the pathological conditions of PD, may exacerbate the reduction in GMV within these regions, impairing the recognition of emotional facial expressions and thereby intensifying anxiety symptoms.

Transcutaneous auricular vagus nerve stimulation improves anxiety symptoms and cortical activity during verbal fluency task in Parkinson's disease with anxiety

ObjectiveTo investigate the effect of 20/4Hz transcutaneous auricular vagus nerve stimulation (taVNS) on anxiety symptoms in Parkinson's disease (PD) and the potential neural mechanism. MethodsIn the current randomized, double-blind, sham-controlled trial, 30 PD patients with anxiety (PD-A), 30 PD patients without anxiety (PD-nA), and 30 healthy controls (HCs) were enrolled. PD-A patients were randomly (1:1) allotted to real taVNS stimulation group (RS) or sham stimulation group (SS) to explore the efficacy of a two-week treatment of taVNS to promote anxiety recovery. Simultaneously, all participants were measured activation in the bilateral prefrontal cortex during verbal fluency task (VFT) using functional near-infrared spectroscopy. ResultsPD-A patients showed significantly decreased oxyhemoglobin in the left triangle part of the inferior frontal gyrus (IFG) during VFT, which was negatively related to the severity of anxiety symptoms. After two-week treatment of taVNS, the interaction of group and time had significant effect on HAMA scores (F = 18.476, p < 0.001, η2 = 0.398). In RS group, compared with baseline, HAMA scores decreased significantly in the post-treatment and follow-up condition (both p < 0.001). Meanwhile, in RS group, HAMA scores were lower than those in SS group in the post-treatment and follow-up condition (p = 0.006, <0.001, respectively). Furthermore, the 20/4Hz taVNS remarkably ameliorated anxiety symptoms in PD patients, directly correlated with the increased activation of the left triangle part of the IFG during VFT in RS group. ConclusionOur results depicted that taVNS could ameliorate the anxiety symptoms of PD-A patients and regulated the function of the left triangle part of the IFG.

Inhibition of calcium-stimulated adenylyl cyclase subtype 1 (AC1) for the treatment of pain and anxiety symptoms in Parkinson's disease mice model.

Pain and anxiety are two common and undertreated non-motor symptoms in Parkinson's disease (PD), which affect the life quality of PD patients, and the underlying mechanisms remain unclear. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical long-term potentiation (LTP) and injury induced synaptic potentiation in the cortical areas including anterior cingulate cortex (ACC) and insular cortex (IC). Genetic deletion of AC1 or pharmacological inhibition of AC1 improved chronic pain and anxiety in different animal models. In this study, we proved the motor deficit, pain and anxiety symptoms of PD in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model. As a lead candidate AC1 inhibitor, oral administration (1 dose and seven doses) of NB001 (20 and 40mg/kg) showed significant analgesic effect in MPTP-treated mice, and the anxiety behavior was also reduced (40mg/kg). By using genetic knockout mice, we found that AC1 knockout mice showed reduced pain and anxiety symptoms after MPTP administration, but not AC8 knockout mice. In summary, genetic deletion of AC1 or pharmacological inhibition of AC1 improved pain and anxiety symptoms in PD model mice, but didn't affect motor function. These results suggest that NB001 is a potential drug for the treatment of pain and anxiety symptoms in PD patients by inhibiting AC1 target.

Assessment of noninvasive brain stimulation interventions in Parkinson’s disease: a systematic review and network meta-analysis

A network meta-analysis of randomized controlled trials was conducted to compare and rank the effectiveness of various noninvasive brain stimulation (NIBS) for Parkinson's disease (PD). We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases from the date of database inception to April 30th, 2024. Two researchers independently screened studies of NIBS treatment in patients with PD based on inclusion and exclusion criteria. Two researchers independently performed data extraction of the included studies using an Excel spreadsheet and assessed the quality of the literature according to the Cochrane Risk of Bias Assessment Tool (RoB2). Network meta-analysis was performed in StataMP 17.0. A total of 28 studies involving 1628 PD patients were included. The results showed that HF-rTMS over the SMA (SMD = − 2.01; 95% CI [− 2.87, − 1.15]), HF-rTMS over the M1 and DLPFC (SMD = − 1.80; 95% CI [− 2.90, − 0.70]), HF-rTMS over the M1 (SMD = − 1.10; 95% CI [− 1.55, − 0.65]), a-tDCS over the DLPFC (SMD = − 1.08; 95% CI [− 1.90, − 0.27]), HF-rTMS over the M1 and PFC (SMD = − 0.92; 95% CI [− 1.71, − 0.14]), LF-rTMS over the M1 (SMD = − 0.72; 95% CI [− 1.17, − 0.28]), and HF-rTMS over the DLPFC (SMD = − 0.70; 95% CI [− 1.21, − 0.19]) were significantly improved motor function compared with sham stimulation. The SUCRA three highest ranked were HF-rTMS over the SMA (95.1%), HF-rTMS over the M1 and DLPFC (89.6%), and HF-rTMS over the M1 (73.0%). In terms of enhanced cognitive function, HF-rTMS over the DLPFC (SMD = 0.80; 95% CI [0.03,1.56]) was significantly better than sham stimulation. The SUCRA three most highly ranked were a-tDCS over the M1 (69.8%), c-tDCS over the DLPFC (66.9%), and iTBS over the DLPFC (65.3%). HF-rTMS over the M1 (SMD = − 1.43; 95% CI [− 2.26, − 0.61]) and HF-rTMS over the DLPFC (SMD = − 0.79; 95% CI [− 1.45, − 0.12)]) significantly improved depression. The SUCRA three highest ranked were HF-rTMS over the M1 (94.1%), LF-rTMS over the M1 (71.8%), and HF-rTMS over the DLPFC (69.0%). HF-rTMS over the SMA may be the best option for improving motor symptoms in PD patients. a-tDCS and HF-rTMS over the M1 may be the NIBS with the most significant effects on cognition and depression, separately.Trial registration: International Prospective Register of Systematic Review, PROSPERO (CRD42023456088)

Associations between gut microbiota characteristics and non-motor symptoms following pharmacological and surgical treatments in Parkinson's disease patients.

The gut microbiota has been implicated in Parkinson's disease (PD), with alterations observed in microbial composition and reduced microbial species richness, which may influence gastrointestinal symptoms in PD patients. It remains to be determined whether the severity of gastrointestinal symptoms correlates with microbiota variations in PD patients treated pharmacologically or with subthalamic nucleus deep brain stimulation (STN-DBS) therapy. This study aims to explore how these treatments affect gut microbiota and gastrointestinal symptoms in PD, identifying specific microbial differences associated with each treatment modality. A total of 42 individuals diagnosed with PD, along with 38 age-matched household control participants, contributed stool samples for microbiota characterization. Differences in the gut microbiota across various groups of PD patients and their households were identified through comprehensive sequencing of the 16S rRNA gene amplicon sequencing. Differences in microbial communities were observed between PD patients and controls, as well as between PD patients receiving pharmacological treatment and those with STN-DBS. Pharmacologically treated advanced PD patients have higher gastrointestinal dysfunctions. Gut microbiota profile linked to STN-DBS and reduced levodopa consumption, characterized by its anti-inflammatory properties, might play a role in diminishing gastrointestinal dysfunction relative to only pharmacological treatments. Advanced PD patients on medication exhibit more gastrointestinal issues, despite relatively stable microbial diversity, indicating a complex interaction between gut microbiota, PD progression, and treatment effects. An imbalanced gut-brain axis, particularly due to reduced butyrate production, may lead to constipation by affecting the enteric nervous system, which emphasizes the need to incorporate gut microbiome insights into treatment strategies.

Headache and Dizziness as Prevailing Clinical Manifestations in Parkinson's Patients Following COVID-19

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has posed significant global health challenges, particularly for vulnerable populations. Objectives: This retrospective report from the Iranian Network for Research in Viral Diseases (INRVD) investigates the common clinical symptoms of COVID-19 in individuals with Parkinson's disease (PD). Research suggests neurological complications can occur during SARS-CoV-2 infection, but there are limited studies on neurological symptoms in PD patients with COVID-19. Given the probable heightened vulnerability of PD patients, evaluating clinical symptoms, especially neurological manifestations, is crucial. Methods: Data from 54 patients were collected from the INRVD from March 2020 to May 2021. Nasal, oropharyngeal, and nasopharyngeal swabs were collected from patients presenting with respiratory symptoms, following Iranian CDC guidelines. Following sample collection, RT-PCR assays were performed for COVID-19 confirmation. Statistical analysis was conducted using the Chi-square test and Fisher's exact test. Results: Among the 54 PD patients included in the study, 27 tested positive for COVID-19. Of the 54 subjects analyzed, 38.9% were female and 61.1% were male. Comparison of COVID-19 symptoms revealed a higher rate of sore throat (74%) and shortness of breath (81%) in the COVID-19 positive group as common clinical symptoms of the disease. Interestingly, higher rates of dizziness (67%) and headache (74%) were observed in PD patients with COVID-19. Conclusions: This study enhances our understanding of the diverse clinical manifestations of COVID-19 and its impact on individuals with underlying health conditions such as PD. The increased prevalence of neurological symptoms among PD patients underscores the need for further investigation to clarify whether these symptoms directly result from COVID-19 infection or if they may also be influenced by PD itself or its treatment. It is important to consider that while neurological symptoms in Parkinson's patients can be attributed to the underlying disorder or linked to medication and medical interventions, respiratory symptoms are typically associated with COVID-19.

Effects of Continuous Dopaminergic Stimulation on Parkinson's Disease Gait: A Longitudinal Prospective Study with Levodopa Intestinal Gel Infusion.

Gait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson's disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time. To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and their correlation with changes in gait parameters and FoG severity. This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores. Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 p = 0.018; T2-T0 p < 0.001). Improvement of MDS-UPDRS-IV (T0-T2, p = 0.002, T0-T1 p = 0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation. Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy.

Effectiveness and Safety of Meridian Activation Remedy System for Alleviating Motor Symptoms in Parkinson's Disease: an Observational Study.

Parkinson's disease (PD) lacks disease-modifying drugs or sustainable interventions, creating an unmet treatment need. Investigating complementary and alternative medicines aims to improve PD patients' quality of life by alleviating symptoms and delaying the course of the disease. In this single-center, prospective, observational, single-arm study, we aimed to assess the effectiveness and safety of acupuncture combined with exercise therapy and the Meridian Activation Remedy System (MARS). From March to October 2021, 13 PD patients with Hoehn and Yahr stages 1 to 3 were recruited. For 8 weeks, MARS intervention was carried out twice a week. T-statistics were used to evaluate functional near-infrared spectroscopy (fNIRS) and GAITRite outcomes. All of the remaining outcome variables were evaluated using the Wilcoxon signed-rank test. The MARS intervention significantly reduced PD patients' Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDSUPDRS) Part III score (from 20.0 ± 11.8 to 8.8 ± 5.5, p = 0.003), 10-meter walk test speed (from 9.5 ± 1.8 to 8.7 ± 1.3 seconds, p = 0.040), and timed up and go time (from 9.8 ± 1.8 to 8.9 ± 1.4 seconds, p = 0.040). Moreover, the MDS-UPDRS Part II, fNIRS hemodynamics, 360-degree turn test, fall efficacy scale, and Parkinson's Disease Questionnaire 39 scores improved but not significantly. All participants completed the 8-week intervention without any adverse reactions. An 8-week MARS intervention improved motor symptoms in PD patients. In particular, improvements in UPDRS Part III scores exhibited large clinically important differences. The findings are encouraging, and a randomized controlled trial will be conducted to determine the efficacy and cost-effectiveness of MARS intervention.

The effect of home-based exercise on motor and non-motor symptoms with Parkinson's disease patients: A systematic review and network meta-analysis.

To evaluate the effects of home-based exercise in Parkinson's disease (PD) patients. A network meta-analysis of randomized controlled trials. This study systematically searched PubMed, MEDLINE, Embase, Cochrane library and Web of Science. The quality of the literature was assessed using the Cochrane Risk of Bias 2.0 criteria. The data were pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI). Thirty studies involving 2264 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD: -.28, 95% Crl [-.43; -.14]), improving quality of life (SMD = .15 [.03, .26]), walking speed (SMD = .30 [.04, .56]), balance ability (SMD = .18 [.04, .33]; p < .0001) and finger dexterity (SMD = .28 [.10, .46]). Mixed exercise (Mix) had better effects on improving motor symptoms and quality of life. In addition, the results of dose analysis showed that only mixed exercise exceeding 850 METs-min per week and more than 18 weeks can significantly alleviate the overall motor symptoms of PD patients. Home-based exercise was an effective form of therapy for alleviating motor symptoms. In addition, Mix appeared to be more suitable for PD patients engaging in home-based exercise. Existing evidence suggested that significant therapeutic effects were achieved with a Mix, with a weekly exercise volume exceeding 850 METs and a duration of more than 18 weeks. Home-based exercise had a small effect in relieving overall motor symptoms in PD patients, improving quality of life, walking speed, balance ability and finger dexterity. In terms of exercise dosage, we recommend the exercise period is no less than 18 weeks and the dose per is no less than 850 METs-min. No Patient or Public Contribution.

The role of HLA-DR on plasmacytoid dendritic cells in mediating the effects of Butyrivibrio gut microbiota on Parkinson's disease.

Parkinson's disease (PD) is viewed as a progressively deteriorating neurodegenerative disorder, the exact etiology of which remains not fully deciphered to this date. The gut microbiota could play a crucial role in PD development by modulating the human immune system. This study aims to explore the relationship between gut microbiota and PD, focusing on how immune characteristics may both directly and indirectly influence their interaction. Utilizing cumulative data from genome-wide association studies (GWAS), our research conducted a two-sample Mendelian randomization (MR) analysis to clarify the association between the gut microbiome and PD. Additionally, by employing a two-step MR approach, we assessed the impact of gut microbiota on PD development via immune characteristics and quantified HLA-DR mediation effect on plasmacytoid dendritic cells (pDCs). We discovered significant associations between PD and microbiota, comprising one class, one order, two families, and two genera. Furthermore, we explored the extent to which HLA-DR on pDCs mediates the effect of Butyrivibrio gut microbiota on PD. Our study emphasizes the complex interactions between the gut microbiota, immune characteristics, and PD. The relationships and intermediary roles identified in our research provide important insights for developing potential therapies that target the gut microbiome to alleviate symptoms in PD patients.

Assessment of Psychometric Characteristics of Parkinson's Disease Sleep Scale 2 and Analysis of a Cut-Off Score for Detecting Insomnia in Italian Patients with Parkinson's Disease: A Validation Study.

Sleep disorders are frequent non-motor symptoms affecting patients with Parkinson's disease (PD). Insomnia represents the most common sleep disorder. Parkinson's disease Sleep Scale 2 (PDSS-2) is a specific tool to investigate sleep problems in PD. The General Sleep Disturbances Scale (GSDS) was a general scale validated for the Italian population. Our goal was to assess the psychometric characteristics of PDSS-2 and the GSDS in this population, calculating a cut-off score for insomnia symptoms by using subitems of PDSS-2. Patients admitted at the PD Unit of the Hospital of Rome Tor Vergata outpatient clinic and those afferent to PD associations were asked to complete PDSS-2 and GSDS to be correlated to identify a cut-off for insomnia symptoms. Items 1,2,3,8,13 of PDSS-2 were used to detect insomnia. An ROC curve to assess a cut-off score for insomnia was determined. A cross-cultural analysis of PD population characteristics was performed. In total, 350 PD patients were recruited. Cronbach's alpha was high for the total score (0.828 for PDSS-2 and 0.832 for GSDS). A cross-cultural analysis did not show any significant p-value. The ROC curve yielded an AUC of 0.79 (CI: 0.75-0.84). The cut-off value for insomnia disorder based on items 1,2,3,8,13 of PDSS-2 was >10, demonstrating a sensitivity of 76% and a specificity of 69% in determining the presence of subjective insomnia symptoms in PD. PDSS-2 is demonstrated to be a valid, specific tool to address sleep disturbances in PD patients. A cut-off score of 10 for items 1,2,3,8,13 was identified for detecting insomnia symptoms in PD patients.