Non-motor Symptoms In Parkinson's Disease Research Articles

Pathological pallidal beta activity in Parkinson’s disease is sustained during sleep and associated with sleep disturbance

Parkinson’s disease (PD) is associated with excessive beta activity in the basal ganglia. Brain sensing implants aim to leverage this biomarker for demand-dependent adaptive stimulation. Sleep disturbance is among the most common non-motor symptoms in PD, but its relationship with beta activity is unknown. To investigate the clinical potential of beta activity as a biomarker for sleep quality in PD, we recorded pallidal local field potentials during polysomnography in PD patients off dopaminergic medication and compared the results to dystonia patients. PD patients exhibited sustained and elevated beta activity across wakefulness, rapid eye movement (REM), and non-REM sleep, which was correlated with sleep disturbance. Simulation of adaptive stimulation revealed that sleep-related beta activity changes remain unaccounted for by current algorithms, with potential negative outcomes in sleep quality and overall quality of life for patients.

Comparative safety of antimuscarinics versus mirabegron for overactive bladder in Parkinson disease

BackgroundOveractive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD. ObjectivesTo assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD. MethodsWe employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods. ResultsWe identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12–1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04–1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses. ConclusionsAmong persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.

Rehabilitation for non-motor symptoms for patients with Parkinson's disease from an α-synuclein perspective: a narrative review.

Parkinson's disease (PD) is a common neurodegenerative disorder affecting aged population around the world. PD is characterized by neuronal Lewy bodies present in the substantia nigra of the midbrain and the loss of dopaminergic neurons with various motor and non-motor symptoms associated with the disease. The protein α-synuclein has been extensively studied for its contribution to PD pathology, as α-synuclein aggregates form the major component of Lewy bodies, a hallmark of PD. In this narrative review, the authors first focus on a brief explanation of α-synuclein aggregation and circumstances under which aggregation can occur, then present a hypothesis for PD pathogenesis in the peripheral nervous system (PNS) and how PD can spread to the central nervous system from the PNS via the transport of α-synuclein aggregates. This article presents arguments both for and against this hypothesis. It also presents various non-pharmacological rehabilitation approaches and management techniques for both motor and non-motor symptoms of PD and the related pathology. This review seeks to examine a possible hypothesis of PD pathogenesis and points to a new research direction focus on rehabilitation therapy for patients with PD. As various non-motor symptoms of PD appear to occur earlier than motor symptoms, more focus on the treatment of non-motor symptoms as well as a better understanding of the biochemical mechanisms behind those non-motor symptoms may lead to better long-term outcomes for patients with PD.

Neurological Insights into Sleep Disorders in Parkinson's Disease.

Parkinson's disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition and physical functioning. Sleep deprivation negatively impacts human physical, mental, and behavioral functions. Sleep disturbances include problems falling asleep, disturbances occurring during sleep, abnormal movements during sleep, insufficient sleep, and excessive sleep. The most recognizable and known sleep disorders, such as rapid-eye-movement behavior disorder (RBD), insomnia, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), sleep-related breathing disorders (SRBDs), and circadian-rhythm-related sleep-wake disorders (CRSWDs), have been associated with PD. RBD and associated emotional disorders are common non-motor symptoms of PD. In individuals, sleep disorders and cognitive impairment are important prognostic factors for predicting progressing neurodegeneration and developing dementia conditions in PD. Studies have focused on RBD and its associated neurological changes and functional deficits in PD patients. Other risks, such as cognitive decline, anxiety, and depression, are related to RBD. Sleep-disorder diagnosis is challenging, especially in identifying the essential factors that disturb the sleep-wake cycle and the co-existence of other concomitant sleep issues, motor symptoms, and breathing disorders. Focusing on sleep patterns and their disturbances, including genetic and other neurochemical changes, helps us to better understand the central causes of sleep alterations and cognitive functions in PD patients. Relations between α-synuclein aggregation in the brain and gender differences in sleep disorders have been reported. The existing correlation between sleep disorders and levels of α-synuclein in the cerebrospinal fluid indicates the risk of progression of synucleinopathies. Multidirectional approaches are required to correlate sleep disorders and neuropsychiatric symptoms and diagnose sensitive biomarkers for neurodegeneration. The evaluation of sleep pattern disturbances and cognitive impairment may aid in the development of novel and effective treatments for PD.

Neuroprotective effects of osmotin in Parkinson’s disease-associated pathology via the AdipoR1/MAPK/AMPK/mTOR signaling pathways

BackgroundParkinson’s disease (PD) is the second most frequent age-related neurodegenerative disorder and is characterized by the loss of dopaminergic neurons. Both environmental and genetic aspects are involved in the pathogenesis of PD. Osmotin is a structural and functional homolog of adiponectin, which regulates the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK) via adiponectin receptor 1 (AdipoR1), thus attenuating PD-associated pathology. Therefore, the current study investigated the neuroprotective effects of osmotin using in vitro and in vivo models of PD.MethodsThe study used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced and neuron-specific enolase promoter human alpha-synuclein (NSE-hαSyn) transgenic mouse models and 1-methyl-4-phenylpyridinium (MPP+)- or alpha-synuclein A53T-treated cell models. MPTP was injected at a dose of 30 mg/kg/day for five days, and osmotin was injected twice a week at a dose of 15 mg/kg for five weeks. We performed behavioral tests and analyzed the biochemical and molecular changes in the substantia nigra pars compacta (SNpc) and the striatum.ResultsBased on our study, osmotin mitigated MPTP- and α-synuclein-induced motor dysfunction by upregulating the nuclear receptor-related 1 protein (Nurr1) transcription factor and its downstream markers tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2). From a pathological perspective, osmotin ameliorated neuronal cell death and neuroinflammation by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, osmotin alleviated the accumulation of α-synuclein by promoting the AMPK/mammalian target of rapamycin (mTOR) autophagy signaling pathway. Finally, in nonmotor symptoms of PD, such as cognitive deficits, osmotin restored synaptic deficits, thereby improving cognitive impairment in MPTP- and α-synuclein-induced mice.ConclusionsTherefore, our findings indicated that osmotin significantly rescued MPTP/α-synuclein-mediated PD neuropathology. Altogether, these results suggest that osmotin has potential neuroprotective effects in PD neuropathology and may provide opportunities to develop novel therapeutic interventions for the treatment of PD.

Enhancing Quality of Life in Parkinson’s Disease: A Systematic Review of Occupational Therapy Interventions on Balance and Reaction Time

Background: Parkinson's disease (PD) is a common neurodegenerative disorder affecting the elderly population and can lead to impaired balance, reaction time, and overall quality of life (QoL). Occupational therapy interventions have shown promise in managing the motor and non-motor symptoms of PD. This systematic review aims to evaluate the effectiveness of occupational therapy intervention on balance and reaction time to enhance the quality of life in patients with Parkinson's disease.
 Methods: A comprehensive search was conducted on various electronic databases, including PubMed, Google Scholar, and ResearchGate. Studies published between 2010 and 2022 were included in the review. Inclusion criteria were set for age, clinical diagnosis of Parkinson's disease, MoCA score, and cooperation for participation. Studies that did not meet the inclusion criteria or reported other interventions were excluded. Data from selected studies were analyzed for relevance, appropriateness, clarity, and methodology.
 Results: Out of the initial 250 potentially relevant articles, 200 were identified as duplicates and removed. Another 25 studies did not meet the inclusion criteria, and 15 studies did not provide sufficient information on the interventions. Eventually, 10 studies were included in this systematic review. All the studies were qualitative in nature and were published between 2010 and 2023.
 Conclusion: Occupational therapy interventions have shown promising results in enhancing balance, reaction time, and quality of life in patients with Parkinson's disease. The review emphasizes the importance of goal-oriented occupational therapy programs to improve the overall well-being of patients with PD. Further research in this area is warranted to strengthen the evidence and guide clinical practice for better management of Parkinson's disease.

Clinical and Non-Clinical Cardiovascular Disease Associated Pathologies in Parkinson's Disease.

Despite considerable breakthroughs in Parkinson's disease (PD) research, understanding of non-motor symptoms (NMS) in PD remains limited. The lack of basic level models that can properly recapitulate PD NMS either in vivo or in vitro complicates matters. Even so, recent research advances have identified cardiovascular NMS as being underestimated in PD. Considering that a cardiovascular phenotype reflects sympathetic autonomic dysregulation, cardiovascular symptoms of PD can play a pivotal role in understanding the pathogenesis of PD. In this study, we have reviewed clinical and non-clinical published papers with four key parameters: cardiovascular disease risks, electrocardiograms (ECG), neurocardiac lesions in PD, and fundamental electrophysiological studies that can be linked to the heart. We have highlighted the points and limitations that the reviewed articles have in common. ECG and pathological reports suggested that PD patients may undergo alterations in neurocardiac regulation. The pathological evidence also suggested that the hearts of PD patients were involved in alpha-synucleinopathy. Finally, there is to date little research available that addresses the electrophysiology of in vitro Parkinson's disease models. For future reference, research that can integrate cardiac electrophysiology and pathological alterations is required.

Time perception reflects individual differences in motor and non-motor symptoms of Parkinson's disease

Decreasing dopaminergic function is at the core of Parkinson's disease (PD) motor symptoms and changes in dopaminergic action are associated with many comorbid non-motor symptoms in PD. Notably, dopaminergic signaling in the striatum has been shown to play a critical role in the perception of time. We hypothesize that patients with PD perceive time differently and in accordance with their specific comorbid non-motor symptoms and clinical state. This means that individual differences in clinical symptoms may be reflected in individual differences in timing behavior. To test this hypothesis, we recruited patients with PD and compared individual differences in patients' clinical state with their ability to judge intervals of time ranging from 500 ms to 1100 ms while on and off their prescribed dopaminergic medications. We show that medication state (on vs. off medications) did not affect timing behavior, but individual differences in timing behavior are able to predict individual differences in comorbid non-motor symptoms, duration of PD diagnosis, and prescribed dopaminergic medications. We show that comorbid impulse control disorder is associated with temporal overestimation; depression is associated with decreased temporal accuracy; and increased PD duration and prescribed levodopa monotherapy are associated with reduced temporal precision and accuracy. Observed differences in time perception are consistent with hypothesized dopaminergic mechanisms thought to underlie the respective motor and non-motor symptoms in PD. In future work, time perception tasks may augment clinical diagnosis strategies, or help disentangle the neural and cognitive mechanisms underlying PD motor and non-motor symptom etiology.

A Safe and Feasible Online Dance Intervention for Older Adults With and Without Parkinson's Disease.

Introduction: Dancing is one way of maintaining an active lifestyle, and online dance interventions in group settings can be a solution when in-person classes are impossible. This study investigated the feasibility and potential clinical effects of an online dance program for older adults with and without Parkinson disease (PD). Methods: Participants attended 2 weekly dance classes in the same videoconference room for 2 months. The dance activities were mainly performed while seated (around 75%). Researchers monitored feasibility (ie, adherence, attendance, and technological barriers) and safety. Pre- and post-intervention assessments investigated self-perceptions, effects on emotional domains, quality of life, activity-specific balance confidence, lower-limb functional mobility, and PD non-motor symptoms. Individuals also reported their self-perceptions regarding technology usability, enjoyment, and social interaction. Results: Most of the participants with PD (n = 12) had moderate PD (Hoehn & Yahr score) and presented a greater risk of falls when compared to participants without PD (n = 14). Overall, we found a high rate of adherence (100%), attendance (87.5%-91.7%), and safety (100%) for both groups. No falls or near-falls occurred during the sessions. Only the PD group ameliorated emotional domains (anxiety and depression) and improved lower-limb functional mobility. All participants reported feeling safe and perceived benefits, although over a third of older adults with PD reported moderate difficulties in using technology and in socializing with the group. Conclusion: This online dance protocol is feasible, safe, and a potential strategy to improve clinical parameters in older adults and people with moderate PD.

Traditional Chinese Medicine for non-motor symptoms in Parkinson disease: A systematic review and meta-analysis of RCTs.

Parkinson disease (PD) is the second most common neurodegenerative disease, which has impacts on the patient's quality of life due to non-motor symptoms such as sleep disorders, anxiety, and depression. Traditional Chinese medicine (TCM) has gained increasing attention in the diagnosis and treatment of PD with the concept of "overall concepts and dialectical treatment." Therefore, exploring the characteristics of TCM in the treatment of PD can improve the level of diagnosis and treatment of PD. A comprehensive literature search was conducted using the following electronic databases: PubMed, Web of Science, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure. The inclusion criteria were randomized controlled trials (RCTs) that compared TCM intervention with conventional treatments or placebo for non-motor symptoms in PD. The quality of the included RCTs was assessed using the Cochrane risk of bias tool. A total of 9 RCTs involving 1714 participants with PD were included in this systematic review and meta-analysis. The meta-analysis showed that TCM was effective in improving non-motor symptoms, including depression (Hamilton depression rating scale [HAMD], weighted mean difference [WMD] = 4.24, 95% CI = 2.84-5.65, P < .0001), anxiety (HAMA, WMD = 4.03, 95% CI = 2.64-5.41, P < .0001), autonomic dysfunction (Scales for Outcomes in Parkinson's disease-Autonomic, WMD = 4.57, 95% CI = 1.69-7.45, P = .002), non-motor symptoms (Movement Disorder Society-Unified Parkinson's Disease Rating Scale-part 1, WMD = 0.66, 95% CI = 0.20-1011, P = .004), and quality of life (PDQ-39, WMD = 6.72, 95% CI = 0.87-12.58, P < .05), compared with baseline. Zishen Pingchan granules was particularly effective for depression (HAMD, WMD = -1.94, 95% CI = -3.07 to -0.81, P < .001, compared to placebo; HAMD, WMD = 3.40, 95% CI = 0.52-6.28, P < .05, after treatment). Pingchan granules was particularly effective for quality of life after treatment (PDQ-39, WMD = 10.20, 95% CI = 1.87-18.53, P < .05). TCM is effective and safety for improvement of depression, anxiety, autonomic dysfunctions, and quality of life in PD. Zishen Pingchan granules was particularly effective for depression; and Pingchan granules was particularly effective for quality of life.

Cannabidiol and Tetrahydrocannabinol Use in Parkinson's Disease: An Observational Pilot Study.

There is a need for more research examining the use of cannabis, tetrahydrocannabinol (THC), and cannabidiol (CBD) products in people with Parkinson's disease (PD), especially given the recent increase in the use of these products. Given the recent increase in over-the-counter CBDuse as well as the prescription of medical cannabis by treating physicians, the utilization method, effects on motor and non-motor symptoms, side effects, and attitude toward cannabis use were examined in a naturalistic sample of patients with PD. A total of 15 individuals with PD, eight of whom were prescribed CBD/THC treatment and seven who were not taking any CBD/THC product, were assessed cross-sectionally. Participants completed structured neuropsychological testing, motor assessment, and questionnaires regarding mood, subjective cognition, and symptom levels. T-tests were completed for quantitative measures and descriptive data were examined and described. Due to the small sample size, Shapiro-Wilk tests for normality were utilized and Mann-Whitney U analyses were completed when appropriate. We found a wide range of prescribed products and methods as well as variability in perceived benefits and untoward effects, even in our small sample. Individuals with PD who were taking a CBD/THC product had lower global cognition scores on the Montreal Cognitive Assessment (MoCA) but no detectable differences among more specific neuropsychological measures. They also had more non-motor symptoms of PD but no differences in motor symptomlevels. Qualitatively, some participants with PD who were taking CBD/THC reported improved pain levels, sleep, and reductions in anxiety. A few negative effects were endorsed, including sleepiness, concentration difficulties, and forgetfulness. CBD/THC utilization in PD is varied. In our small sample, individuals who utilized the treatment had lower MoCA scores, more non-motor symptoms, and descriptively reported improvements in sleep, anxiety, and pain, and had side effects of sleepiness and cognitive difficulty. Future studies should focus on clinical trials with standardized CBD/THC methods of use.

Vagus nerve cross-sectional area decreases in Parkinson's disease

IntroductionMorphological alterations of the vagus nerve (VN) in Parkinson's disease (PD) are discussed controversially. Several studies reported no difference in VN cross-sectional area (CSA) in PD patients in nerve ultrasound, others found a reduced CSA interpreted as atrophy of the VN and involvement of the dorsal nucleus of VN. MethodsIn a prospective comparative cross-sectional study, CSA of the VN bilaterally and the right ulnar nerve, clinical PD scales, non-motor symptoms and autonomic tests were compared between 49 PD patients and 24 healthy controls. Nerve ultrasound was performed by two independent investigators, patients and controls were compared at Bonferroni corrected p < 0.025 using results of both investigators and averaged results. Blinding included CSA measurements and PD scores, but not PD diagnosis. ResultsBilateral averaged VN CSA was significantly lower in PD patients than in controls (Right VN PD mean 2.70 mm2 SD 0.69, controls 3.30 mm2 SD 0.49, p < 0.001. Left VN PD mean 2.45 mm2 SD 0.57, controls 2.77 mm2 SD 0.46, p = 0.012). No difference was found in the ulnar nerve. There was a weak negative correlation between the right VN CSA and the Unified Parkinson Disease Rating Scale (−0.08 mm2 per 10 points). The area under the receiver operating characteristic curve for the right VN was 0.78 (p < 0.001). ConclusionThe present results support the hypothesis of atrophy of the VN in PD. Reduction of VN CSA is a weak marker of disease progression. Nerve ultrasound of the VN might represent a supplementary method in diagnosis of PD.

Acupuncture Improves Sleep Disorders and Depression among Patients with Parkinson's Disease: A Meta-Analysis.

Parkinson's disease (PD) is associated with a range of non-motor symptoms that lack effective treatments. Acupuncture is a popular alternative therapy for PD patients that has been shown to improve motor symptoms. However, the efficacy of acupuncture in treating non-motor symptoms has remained controversial. The goal of our study was to systematically assess the existing evidence for acupuncture's efficacy in treating PD non-motor symptoms of sleep disorders, depression, anxiety, and fatigue. We conducted a meta-analysis of clinical trials by searching Pubmed, Embase, CINAHL, and Web of Science as electronic databases to evaluate acupuncture treatment for PD non-motor symptoms. Thirteen clinical trials met our inclusion criteria, and their methodological quality was assessed using the modified Jadad scale, indicating a moderate overall quality. Our results showed that acupuncture improved PD-related sleep disorders and depression but had no effect on anxiety and fatigue. Our meta-analysis suggests that acupuncture can be used as a complementary treatment for sleep disturbances and depression in PD patients and may exhibit a dual therapeutic effect on motor and non-motor symptoms. However, further well-designed clinical trials with larger sample sizes are needed to confirm these findings. Overall, our study highlights the potential of acupuncture as a viable complementary therapy for the treatment of PD non-motor symptoms of sleep disorders and depression, which can improve the quality of life of PD patients.

Collaborative plasma biomarkers for Parkinson's disease development and progression: a cross-sectional and longitudinal study.

Relying on a single biomarker for early diagnosis of Parkinson's Disease (PD) may not yield accurate results. We aimed to assess the combined diagnostic value of multiple biomarkers, including plasma CCL2, plasma CXCL12, and plasma neuronal exosomal α-synuclein (α-syn) for early-stage PD diagnosis and their predictive value in PD progression. This study included both cross-sectional and longitudinal designs. The CCL2, CXCL12, and neuronal exosomal α-syn levels were analyzed in 50 healthy controls (HCs) and 50 early-stage PD patients. Then, a prospective follow-up of 30 early-stage PD patients was performed. In early-stage PD, we observed a significant increase in CCL2, CXCL12, and plasma neuronal exosomal α-syn compared to HCs (P < 0.05). Utilizing a combined diagnostic approach of CCL2, CXCL12and α-syn significantly improved the area under the curve (AUC= 0.89, P < 0.001). Spearman correlation analysis revealed that CCL2 levels were correlated with PD clinical stage and autonomic symptoms (P < 0.05). CXCL12 levels were associated with non-motor symptoms (P < 0.05). Plasma neuronal exosome α-syn levels were connected to the clinical stage, motor symptoms, and non-motor symptoms in early-stage PD (P < 0.01). In the longitudinal cohort, the Cox regression analysis showed that high CCL2 levels were associated with motor progression after a mean follow-up of 24 months. Our study suggested that the combined measurement of plasma CCL2, CXCL12, and neuronal exosomal α-syn can improve early-stage PD diagnosis, and CCL2 may serve as a prognostic marker for PD progression.

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.