Non-motor Symptoms In Parkinson's Disease Research Articles

Parkinson’s disease. Focus on early stages

The review presents current data on the peculiarities of the neurodegenerative process in the early stages of Parkinson’s disease (PD) and considers the hypothesis of the presence of body-first and brain-first subtypes of the disease onset. The earliest manifestations of the disease include symptoms such as parasomnia, constipation, hyposmia, anxiety-depressive disorder, daytime sleepiness, color perception changes, cognitive dysfunction, and mild motor manifestations. The diagnosis of PD can be made when characteristic motor manifestations occur: hypokinesia, rest tremor, muscle rigidity. Substantia nigra ultrasound, magnetic resonance imaging in SWI mode, and functional neuroimaging methods are used as confirmatory methods. The approach to the treatment of early stages of PD is age dependent. Patients over 70 years of age are recommended to start therapy with levodopa; younger patients – with dopamine receptor agonists (ADR), amantadines, MAO-B inhibitors. The mechanisms of ADR action, the possibility of their influence on the motor and non-motor symptoms of PD are analyzed. A special place is given to piribedil, which, due to the dual mechanism of action, has a positive effect on cognitive functions, depression, apathy, as well as a minimal effect on daytime sleepiness.

Moxibustion treatment for Parkinson’s disease: study protocol for a randomized controlled trial

BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism.MethodsThis is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson’s Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD.DiscussionIn conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD.Trial registrationClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.

DPP-4 inhibitors and type 2 diabetes mellitus in Parkinson's disease: a mutual relationship.

Parkinson's disease (PD) usually occurs due to the degeneration of dopaminergic neurons in the substantia nigra (SN). Management of PD is restricted to symptomatic improvement. Consequently, a novel treatment for managing motor and non-motor symptoms in PD is necessary. Abundant findings support the protection of dipeptidyl peptidase 4 (DPP-4) inhibitors in PD. Consequently, this study aims to reveal the mechanism of DPP-4 inhibitors in managing PD. DPP-4 inhibitors are oral anti-diabetic agents approved for managing type 2 diabetes mellitus (T2DM). T2DM is linked with an increased chance of the occurrence of PD. Extended usage of DPP-4 inhibitors in T2DM patients may attenuate the development of PD by inhibiting inflammatory and apoptotic pathways. Thus, DPP-4 inhibitors like sitagliptin could be a promising treatment against PD neuropathology via anti-inflammatory, antioxidant, and anti-apoptotic impacts. DPP-4 inhibitors, by increasing endogenous GLP-1, can also reduce memory impairment in PD. In conclusion, the direct effects of DPP-4 inhibitors or indirect effects through increasing circulating GLP-1 levels could be an effective therapeutic strategy in treating PD patients through modulation of neuroinflammation, oxidative stress, mitochondrial dysfunction, and neurogenesis.

Substantia Nigra Echogenicity Signal Correlated with Clinical Features in Patients with Parkinson's Disease in Xinjiang.

Transcranial sonography (TCS) is a noninvasive test that can reveal structural changes in the substantia nigra (SN) in Parkinson's disease (PD). The purpose of this study was to investigate the relationship between SN signatures and clinical features in PD patients in a multiethnic region of China. A total of 147 patients with PD were included in the study, and all of whom had underwent a TCS examination. Clinical information was collected from PD patients, and motor and nonmotor symptoms were assessed using assessment scales. There were differences in the substantia nigra hyperechogenicity (SNH) area between age of onset, visual hallucinations (VH), and UPDRS3.0 II scores (P < 0.05), patients with late onset PD had a greater SNH area than early onset (0.326 ± 0.352 vs. 0.171 ± 0.194), and PD patients presenting with VH had a greater SNH area than those without hallucinations (0.508 ± 0.670 vs. 0.278 ± 0.659), and further multifactorial analysis showed that a high SNH area was an independent risk factor for development of VH. The area under the ROC curve for predicting VH from the SNH area in PD patients was 0.609 (95% CI: 0.444-0.774). There was a positive correlation between the SNH area and UPDRS3.0-II scores, but further multifactorial analysis showed that SNH was not an independent predictor of the UPDRS3.0-II score. A high SNH area is an independent risk factor for development of VH, there is a positive correlation between the SNH area and UPDRS3.0 II score, and TCS has guiding significance in predicting clinical VH symptoms and activities of daily living in PD patients.

CREB5 hypermethylation involved in the ganglioside GM1 therapy of Parkinson's disease.

The treatment with monosialotetrahexosylganglioside (GM1) improves the symptoms of Parkinson's disease (PD). The alteration of DNA methylation in the blood was examined to investigate epigenetic modification by GM1 treatment. After a 28-day continuous intravenous infusion of GM1 (100mg), the motor and non-motor symptoms were evaluated by UPDRS III, Mini-mental state examination (MMSE) scores, FS-14, SCOPA-AUT, and PDQ-8. Moreover, blood samples were collected and PBMC was isolated. Genome-wide DNA methylation was performed by an 850K BeadChip. RNA levels and apoptosis were examined by RT-PCR and flow cytometry in rotenone-based cell models. The CREB5 plasmid was transfected by electroporation into SH-SY5Y cells. We also identified 235 methylation variable positions achieving genome-wide significance in 717558 differentially methylated positions (DMPs) (P = 0.0003) in comparison of pre-treatment with post-treatment measurements (statistical analysis paired-samples t-test). By searching the Gene Expression Omnibus (GEO) dataset and GWAS, 23 methylation variable positions were screened. Moreover, there are 7 hypomethylated methylation variable positions correlated with the scores of motor symptoms (UPDRS III scale). According to KEGG pathways enrichment analysis, the methylated genes CACNA1B (hypomethylated), CREB5 (hypermethylated), GNB4 (hypomethylated), and PPP2R5A (hypomethylated) were enriched in the dopaminergic synapse pathway. Pretreated with GM1 (80 μM) for 1 h, cell apoptosis and impaired neurite outgrowth were inhibited in rotenone-induced PD cell models. The RNA expression of CREB5 was increased in rotenone-treated SH-SY5Y cells. GM1 treatment decreased rotenone-induced CREB5 gene expression. The enhancement of CREB5 gene expression suppressed the protective role of GM1 in rotenone-induced cell apoptosis. The application of GM1 improves the motor and non-motor symptoms of PD associated with the decreased CREB5 expression and the hypermethylation of CREB5. https://www.chictr.org.cn/showproj.html?proj=120582t, identifier ChiCTR2100042537.

Efficacy and safety of a combination of emotional freedom technique with acupuncture versus acupuncture alone to treat psychiatric symptoms in Parkinson's disease: A protocol for a randomized, assessor-blind, parallel-group clinical trial.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases in world. As some psychiatric symptoms degrade the quality of life of patients with PD, a novel alternative non-pharmacological treatment is required. Acupuncture appears to be an effective and safe treatment for PD. The emotional freedom technique (EFT) is a type of psychological therapy that alleviates psychiatric symptoms by stimulating acupoints. In this study, we will compare the efficacy and safety of a combination of the EFT and acupuncture and acupuncture alone. This study is a randomized, assessor-blind, parallel-group clinical trial. Eighty participants will be equally divided into experimental and control groups. Each participant will receive a total of 24 interventions over 12 weeks. The experimental group will receive EFT combined with acupuncture and the control group will receive acupuncture alone. The primary outcome is the change in the Beck Depression Inventory score from baseline to 12 weeks, and the secondary outcomes include change in the following variables: Beck Depression Inventory, Parkinson's disease sleep scale, State-Trait Anxiety Inventory, the Korean version of the Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight questionnaire scale, and unified Parkinson's disease rating scale III and exercises. Acupuncture is a safe and effective treatment for motor and nonmotor symptoms in PD, and EFT appears to be safe and effective for a variety of psychiatric symptoms. In this study, we will investigate the potential of EFT combined with acupuncture to improve psychiatric symptoms in PD.

Orexin pathway in Parkinson's disease: a review.

Parkinson's disease (PD) is a progressive neurodegenerative disease (NDD) caused by dopaminergic neuron degeneration in the substantia nigra (SN). Orexin is a neuropeptide that plays a role in the pathogenesis of PD. Orexin has neuroprotective properties in dopaminergic neurons. In PD neuropathology, there is also degeneration of orexinergic neurons in the hypothalamus, in addition to dopaminergic neurons. However, the loss of orexinergic neurons in PD began after the degeneration of dopaminergic neurons. Reduced activity of orexinergic neurons has been linked to developing and progressing motor and non-motor symptoms in PD. In addition, the dysregulation of the orexin pathway is linked to the development of sleep disorders. The hypothalamic orexin pathway regulates various aspects of PD neuropathology at the cellular, subcellular, and molecular levels. Finally, non-motor symptoms, particularly insomnia and disturbed sleep, promote neuroinflammation and the accumulation of neurotoxic proteins as a result of defects in autophagy, endoplasmic reticulum (ER) stress, and the glymphatic system. As a result, this review aimed to highlight the potential role of orexin in PD neuropathology.

Differences in the gut microbiome across typical ageing and in Parkinson's disease

The microbiota-gut-brain axis' role in Parkinson's disease (PD) pathophysiology, and how this differs from typical ageing, is poorly understood. Presently, gut-bacterial diversity, taxonomic abundance and metabolic bacterial pathways were compared across healthy young (n = 22, 18–35 years), healthy older (n = 33, 50–80 years), and PD groups (n = 18, 50–80 years) using shotgun sequencing and compositional data analysis. Associations between the gut-microbiome and PD symptoms, and between lifestyle factors (fibre intake, physical activity, and sleep) and the gut-microbiome were conducted. Alpha-diversity did not differ between PD participants and older adults, whilst beta-diversity differed between these groups. Lower abundance of Butyricimonas synergistica, a butyrate-producer, was associated with worse PD non-motor symptoms in the PD group. Regarding typical ageing, Bifidobacterium bifidum, was greater in the younger compared to older group, with no difference between the older and PD group. Abundance of metabolic pathways related to butyrate production did not differ among the groups, while other metabolic pathways differed among the three groups. Sleep efficiency was positively associated with Roseburia inulinivorans in the older group. These results highlight the relevance of gut-microbiota to PD and that reduced butyrate-production may be involved with PD pathophysiology. Future studies should account for lifestyle factors when investigating gut-microbiomes across ageing and in PD.This article is part of the Special Issue on “Microbiome & the Brain: Mechanisms & Maladies”.

Speech Based Parkinson\'s Disease Detection Using Machine Learning

Abstract: The diagnosis of Parkinson's disease (PD) is often made after careful observation and evaluation of clinical indicators, such as the description of various motor symptoms. Traditional methods of diagnosis, on the other hand, may be prone to error since they depend on the subjective judgment of motions that might be difficult for human eyes to categorise. However, nonmotor symptoms of PD in its early stages may be minor and might be due to a wide variety of diseases. Thus, it is difficult to make an early diagnosis of PD since these symptoms are often disregarded. These challenges have prompted the use of machine learning approaches for the categorization of PD and healthy controls or patients with comparable clinical presentations as a means of improving diagnostic and evaluation processes for PD (e.g., movement disorders or other Parkinson an syndromes). PD has been diagnosed using a wide variety of data types and machine learning techniques; the goal of this article is to present a synopsis of these approaches. In this study, we investigate PD recognition from a spoken language using CNN, ANN, and XGB. The CNN was fed stacked 2D input maps consisting of spectrograms and other short-term characteristics. The effectiveness of PD detection was analyzed by breaking down a voice recording into its component parts and comparing the results to those obtained by fusing all of the segments at the decision level.

Serum zinc deficiency could be associated with dementia conversion in Parkinson's disease.

Association between heavy metals and Parkinson's disease (PD) is well noted, but studies regarding heavy metal levels and non-motor symptoms of PD, such as PD's dementia (PD-D), are lacking. In this retrospective cohort study, we compared five serum heavy metal levels (Zn, Cu, Pb, Hg, and Mn) of newly diagnosed PD patients (n = 124). Among 124 patients, 40 patients were later converted to Parkinson's disease dementia (PD-D), and 84 patients remained without dementia during the follow-up time. We collected clinical parameters of PD and conducted correlation analysis with heavy metal levels. PD-D conversion time was defined as the initiation time of cholinesterase inhibitors. Cox proportional hazard models were used to identify factors associated with dementia conversion in PD subjects. Zn deficiency was significant in the PD-D group than in the PD without dementia group (87.53 ± 13.20 vs. 74.91 ± 14.43, p < 0.01). Lower serum Zn level was significantly correlated with K-MMSE and LEDD at 3 months (r = -0.28, p < 0.01; r = 0.38, p < 0.01). Zn deficiency also contributed to a shorter time to dementia conversion (HR 0.953, 95% CI 0.919 to 0.988, p < 0.01). This clinical study suggests that a low serum Zn level can be a risk factor for developing PD-D and could be used as a biological marker for PD-D conversion.

Spirituality in Parkinson's Disease within a Sample from the USA.

Spirituality and religious beliefs are important for coping with medical conditions. The dopaminergic system is involved in reward behavior, and its dysfunction in Parkinson Disease (PD) raises questions about religiosity and spirituality in people with PD. This study examines the association between levels of spirituality and religiosity and the severity of PD motor and non-motor symptoms. The secondary aim investigates the perceived impact of PD diagnosis on spirituality and religiosity. This was a cross-sectional analysis of demographic, physical, mental, and spirituality and religiosity status in patients with PD recruited for the Health Outcomes Measurement (HOME) Study at the University of Maryland Parkinson Disease and Movement Disorders Center, Baltimore, USA. Spirituality and religiosity were assessed using the Spiritual Well-being Scale, and the World Health Organization Quality of Life Spiritual Religious and Personal Belief field-test instrument. The sample size was 85 PD patients. The mean age (standard deviation) was 65.5 (9.4) years and 67.1% were male. Higher levels of spirituality and religiosity were associated with younger age, sex (female), less education, religious affiliation (Christian), and mental health status. After adjusting for age, education, gender, race, marital status, religion, physical health, mental health, and comorbidity, only anxiety was associated with all of the spirituality/religiosity assessments. The majority of patients reported no change in their religious or spiritual beliefs following diagnosis. Greater spirituality and religiosity were associated with less anxiety. Also, younger women with PD showed higher levels of spirituality and religiosity. Longitudinal studies on more diverse populations are needed.

Pilot Tailored Lighting Intervention on Sleep Disturbances in Parkinson disease (P7-11.014)

<h3>Objective:</h3> To assess the effects of a short-term tailored lighting intervention therapy (TLI) on sleep disturbances in Parkinson disease (PD). <h3>Background:</h3> Sleep disturbances are a common non-motor symptom in PD, adversely affecting quality of life, mood and cognition. They suggest underlying disruptions in circadian rhythm. Based on our preliminary studies showing the positive impacts of TLI on sleep, mood and behavior in Alzheimer’s disease, we hypothesize that TLI can improve objective sleep measures in PD. <h3>Design/Methods:</h3> Baseline sleep quality and rest activity were measured with 1-week wrist actigraphy. Light exposure level was measured with a daysimeter. TLI was delivered over a 4-week period, administered for 2 hours every morning via table/floor lamps installed in the home or lighting glasses. Post-intervention actigraph and daysimeter data were collected during the last week of the 4-week intervention. Pre- and post-intervention measures were compared using paired t-tests. <h3>Results:</h3> In 20 participants (65% women, mean age 73.8 years [SD 8.6], disease duration 9.4 years [7.4]), average time of falling asleep was 19 minutes earlier (p=0.18) with TLI. Sleep time (excluding nocturnal wake after sleep onset) increased significantly by 20 minutes (p=0.049) from 381.11 to 401.36 minutes. Overall sleep duration also increased by 29 minutes but this did not reach significance (p=0.078). Sleep efficiency in this PD cohort was 85% both pre- and post-intervention. <h3>Conclusions:</h3> This pilot study demonstrates the feasibility of conducting an at home, short-term tailored lighting intervention therapy for participants with PD. In this small group, several sleep measures were improved, despite starting with an overall baseline of good sleep efficiency. Additional analyses are underway to determine effects of TLI on subjective sleep quality, daytime sleepiness, depression, anxiety and fatigue. Follow up studies in a larger cohort are warranted to assess for effects of TLI in participants with poor baseline sleep, as well as longer intervention durations. <b>Disclosure:</b> Dr. Yoo has received research support from Edmond J Safra Foundation. Roberto Ortega has nothing to disclose. The institution of Ms. Raymond has received research support from NIH. Ms. Gerber has nothing to disclose. Ms. Markgraf has nothing to disclose. Ms. Liang has nothing to disclose. Ms. Zians has nothing to disclose. Dr. Wise has nothing to disclose. Ms. Rawal has nothing to disclose. Ms. Plitnick has nothing to disclose. Ms. Brons has nothing to disclose. The institution of Dr. Bressman has received research support from Michael J Fox Foundation . The institution of Dr. Bressman has received research support from NIH . The institution of Dr. Figueiro has received research support from NIH. The institution of Dr. Figueiro has received research support from EU. The institution of Dr. Figueiro has received research support from McClung Foundation. The institution of Dr. Saunders-Pullman has received research support from NIH, Bigglesworth Family Foundation, Empire Clinical Research Investigatory Program.

Deep Brain Stimulation of Subthalamic Nucleus Improves Quality of Life in General and Mental Health Domains in Parkinson’s Disease to the Level of the General Population

ObjectivesParkinson’s disease (PD) leads to significant impairment in quality of life (QoL) across various domains. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is known to improve motor and nonmotor symptoms in PD. The aim was to study whether STN-DBS could improve the QoL of patients with PD to the level of the general population, and to determine factors predicting better motor outcomes. Materials and MethodsThe retrospective analysis included 43 patients who underwent either primary or revision STN-DBS. Patients filled out a general QoL questionnaire (RAND 36-item health survey) before and 12 months after surgery, and scores were compared with age- and sex-adjusted national population values. In addition, motor scores were calculated using Unified Parkinson Disease Rating Scale part 3 (UPDRS 3) with the best PD medication. Levodopa equivalent daily dose (LEDD) was also collected. Changes in the QoL were compared with operation age, disease duration, and preoperative QoL. ResultsPreoperatively, patients had significantly impaired QoL in all subsections compared with that of the general population. The mean postoperative UPDRS 3 improvement was 50.0%, and reduction in LEDD was 69.0%. Statistically significant QoL improvements were found in Physical Function, Mental Health, Social Function, Vitality, and Role Physical 12 months postoperatively compared with baseline. The mean differences compared with a healthy population were not statistically significant in General Health, Mental Health, Vitality, and Role Emotional. Furthermore, disease duration was found to be negatively correlated with improvements in UPDRS 3 score, and worse preoperative QoL positively correlated with changes in Physical Function. ConclusionsPatients experienced significant QoL improvements after STN-DBS. The General Health and Mental Health of patients were postoperatively most comparable with age- and sex-adjusted population values. Moreover, earlier stimulation predicted better motor improvements, which emphasizes the importance of earlier timing of STN-DBS surgery and minimizing loss of function at a critical disease stage.

Therapeutic education for empowerment and engagement in patients with Parkinson's disease: A non-pharmacological, interventional, multicentric, randomized controlled trial.

In 1997 the European Parkinson's Disease Associations launched the Charter for People with Parkinson's disease that stated the right of patients to be informed and trained on the disease, its course, and treatments available. To date, few data analyzed the effectiveness of education program on motor and non-motor symptoms of PD. The aim of this study was to evaluate the efficacy of an education program as it was a pharmacological treatment, thus choosing as the primary endpoint the change in daily OFF hours, the most widely used outcome in pharmaceutical clinical trials on PD patients with motor fluctuations. Secondary outcomes were change in motor and non-motor symptoms, quality of life and social functioning. The long-term efficacy of the education therapy was also evaluated by analyzing data collected at 12- and 24-weeks follow-up outpatient visits. One hundred and twenty advanced patients and their caregivers were assigned to the intervention or control group in a single-blind, multicentric, prospective, randomized study evaluating an education program structured in individual and group sessions over a 6-weeks period.At the end of study, the intervention group showed a significant reduction in daily OFF hours compared to control patients (-1.07 ± 0.78 vs. 0.09 ± 0.35, p < 0.0001) and a significant improvement was also reported in most secondary outcomes. Patients retained significant medication adherence and daily OFF hours reduction at 12- and 24-weeks follow-up. The results obtained demonstrated that education programs may translate in a notable improvement in motor fluctuations and non-motor symptoms in advanced PD patients.Clinical Trial Registration:Clinicaltrials.gov, identifier NCT04378127.

ИСТОРИЯ ИЗУЧЕНИЯ БОЛЕЗНИ ПАРКИНСОНА

This article discusses the history of studying Parkinson’s disease (PD), one of the most common neurodegenerative diseases in the world and Russia. Many famous personalities suffer from this disease, including a Hollywood actor Michael J. Fox. However, the history of studying PD consists of several stages. The phenomenological stage is associated with the work «An Essay on Shaking Palsy» by James Parkinson, where the author described six patients. Fifty years after the essay was published, Jean Martin Charcot drew attention to patients with shaking palsy, and based on the Parkinson’s essay, put forward the theory that the main symptom of the disease is slowness. At the pathomorphological stage, the role of the loss of substantia nigra neurons in the development of PD was determined. The key work was the nigral theory of Konstantin Tretyakov. At the beginning of the 21st century, German scientists led by Heiko Braak put forward the stages of the neurodegenerative process theory, which explained the preclinical non-motor symptoms of PD, as well as a wide range of severe non-motor and axial disorders in the late stages of the disease. The neurobiological stage is associated with the establishment of the role of dopamine in the development of PD and the start of levodopa therapy. Since 1911, levodopa had been studied in the laboratory, but it was not until the 1950s that the Swedish pharmacologist Arvid Karlsson put forward the theory about the role of dopamine deficiency in the development of PD and suggested the therapeutic effect of levodopa. For his outstanding discovery, Arvid Karlsson was awarded the Nobel Prize in Physiology or Medicine in 2000. The clinical use of levodopa is associated with the names of Oleg Hornykiewicz and George Cotzias. In parallel, neurosurgical treatment of PD is being developed, deep brain stimulation and thalamotomy under the influence of focused ultrasound are being introduced. At the moment, there is a further improvement in the diagnosis of the disease, the genetics of PD is being studied, along with it, the range of treatment options is expanding.

Effect of the Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulator Dipraglurant on Motor and Non-Motor Symptoms of Parkinson's Disease.

Parkinson's disease (PD) patients suffer not only from the primary motor symptoms of the disease but also from a range of non-motor symptoms (NMS) that cause disability and low quality of life. Excessive glutamate activity in the basal ganglia resulting from degeneration of the nigrostriatal dopamine pathway has been implicated in the motor symptoms, NMS and dyskinesias in PD patients. In this study, we investigated the effects of a selective mGlu5 negative allosteric modulator (NAM), dipraglurant, in a rodent motor symptoms model of PD, but also in models of anxiety, depression and obsessive-compulsive disorder, all of which are among the most prevalent NMS symptoms. Dipraglurant is rapidly absorbed after oral administration, readily crosses the blood-brain barrier, and exhibits a high correlation between plasma concentration and efficacy in behavioral models. In vivo, dipraglurant dose-dependently reduced haloperidol-induced catalepsy, increased punished licks in the Vogel conflict-drinking model, decreased immobility time in the forced swim test, decreased the number of buried marbles in the marble-burying test, but had no effect on rotarod performance or locomotor activity. These findings suggest that dipraglurant may have benefits to address some of the highly problematic comorbid non-motor symptoms of PD, in addition to its antidyskinetic effect demonstrated in PD-LID patients.

Effect of probiotic supplementation on gastrointestinal motility, inflammation, motor, non-motor symptoms and mental health in Parkinson’s disease: a meta-analysis of randomized controlled trials

BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Gut dysbiosis is hypothesized to cause PD; therefore, whether probiotics can be used as adjuvants in the treatment of PD is being actively investigated.AimsWe performed a systematic review and meta-analysis to evaluate the effectiveness of probiotic therapy in PD patients.MethodsPUBMED/MEDLINE, EMBASE, Cochrane, Scopus, PsycINFO and Web of Science databases were searched till February 20, 2023. The meta-analysis used a random effects model and the effect size was calculated as mean difference or standardized mean difference. We assessed the quality of the evidence using the Grade of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsEleven studies involving 840 participants were included in the final analysis. This meta-analysis showed high-quality evidence of improvement in Unified PD Rating Scale Part III motor scale (standardized mean difference [95% confidence interval]) (− 0.65 [− 1.11 to − 0.19]), non-motor symptom (− 0.81 [− 1.12 to − 0.51]), and depression scale (− 0.70 [− 0.93 to -0.46]). Moderate to low quality evidence of significant improvement was observed in gastrointestinal motility (0.83 [0.45–1.10]), quality of life (− 1.02 [− 1.66 to − 0.37]), anxiety scale (− 0.72 [− 1.10 to − 0.35]), serum inflammatory markers (− 5.98 [− 9.20 to − 2.75]), and diabetes risk (− 3.46 [− 4.72 to − 2.20]). However, there were no significant improvements in Bristol Stool Scale scores, constipation, antioxidant capacity, and risk of dyslipidemia. In a subgroup analysis, probiotic capsules improved gastrointestinal motility compared to fermented milk.ConclusionProbiotic supplements may be suitable for improving the motor and non-motor symptoms of PD and reducing depression. Further research is warranted to determine the mechanism of action of probiotics and to determine the optimal treatment protocol.

A Brief Analysis on the Modulation Effect of Ba Duan Jin on Non-Motor Symptoms of Parkinson’s Disease

Parkinson’s disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. The non-motor symptoms of PD, such as depression and anxiety, are often ignored in the face of typical motor symptoms such as tremor and bradykinesia. Non-motor symptoms in PD will not only increase the burden of patients, affect the quality of life, but also reduce the effect of PD drug treatment. A vicious circle is formed. At present, PD cannot be cured. Drugs are the first-line treatment, but long-term use in clinical practice will bring various side effects. Clinical studies have shown that Ba duan Jin as an adjuvant treatment can improve the non-motor symptoms of PD and delay the progression of PD. However, the regulatory mechanism of Ba duan jin on non-motor symptoms of PD is still unclear, which needs to be further elaborated in combination with the theory of traditional Chinese medicine.

Therapeutic Approaches to Non-Motor Symptoms of Parkinson's Disease: A Current Update on Preclinical Evidence.

Despite being classified as a movement disorder, Parkinson's disease (PD) is characterized by a wide range of non-motor symptoms that significantly affect the patients' quality of life. However, clear evidence-based therapy recommendations for non-motor symptoms of PD are uncommon. Animal models of PD have previously been shown to be useful for advancing the knowledge and treatment of motor symptoms. However, these models may provide insight into and assess therapies for non-motor symptoms in PD. This paper highlights non-motor symptoms in preclinical models of PD and the current position regarding preclinical therapeutic approaches for these non-motor symptoms. This information may be relevant for designing future preclinical investigations of therapies for nonmotor symptoms in PD.

Serum inflammatory cytokines levels and the correlation analyses in Parkinson's disease.

Objective: To investigate the serum levels of inflammatory cytokines and the correlations with Parkinson's disease (PD) clinical symptoms. Methods: Serum levels of the cytokines, including IL-6, IL-8, and TNF-α, were measured in 273 PD patients and 91 healthy controls (HCs). The clinical manifestations of PD were assessed with nine different scales to evaluate the cognitive function, non-motor symptoms, motor symptoms, and disease severity. The differences in these inflammatory indicators were examined between PD patients and HCs, and the correlations of these inflammatory indicators with clinical variables were analyzed in PD patients. Results: Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in PD patients were higher than those in HCs, but serum interleukin-8 (IL-8) level was not significantly different from that in HCs. In PD patients, serum IL-6 level was positively correlated with age of onset, the Hamilton Depression Scale (HAMD), and the Non-Motor Symptom Scale (NMSS), UPDRS part I, part II, and part III, but it was inversely correlated with the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) scores. Serum TNF-α level was positively correlated with age of onset and H&Y stage in PD patients (p = .037), but negatively correlated with FAB scores in PD patients (p = .010). However, no associations were found between all the clinical variables and the serum IL-8 level. The forward binary logistic regression model revealed that serum IL-6 level was associated with MoCA (p = .023) and UPDRS I scores (p = .023), but no associations was found with the remaining factors. The ROC curve of TNF-α for the diagnosis of PD showed the area under the curve (AUC) was .719 (p < .05, 95% CI: .655-.784), and the critical value of TNF-α was 5.380pg/ml, with a diagnostic sensitivity of 76.0% and a specificity of 59.3%. Conclusion: Our results suggest increased serum levels of IL-6 and TNF-α in PD, we further found that IL-6 level was associated with non-motor symptoms and cognitive dysfunction, and IL-6 may play a role in the pathophysiology of non-motor symptoms in PD. At the same time, we also propose that TNF-α has a good diagnostic value for PD despite its irrelevance to clinical symptoms.