Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort.

BACKGROUND AND OBJECTIVES: Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD. METHODS: Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk. RESULTS: In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results. DISCUSSION: This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

Efficacy of acupuncture (Jin's three-needle) on motor symptoms and anxiety in patients with Parkinson's disease: protocol for a multicentre, randomised, assessor-blinded clinical trial.

INTRODUCTION: Parkinson's disease (PD) has a significant impact on a substantial number of individuals in China. Notably, 31% of patients with PD also grapple with the additional burden of anxiety. This dual challenge of managing both PD and anxiety underscores the complexity of the condition and the diverse range of symptoms patients may experience. Considering the circumstances, the cost and potential drawbacks associated with traditional antiparkinsonian drugs become increasingly relevant. Acupuncture emerges as a significant non-pharmacological adjunct therapy. Offering a potentially safer and more cost-effective option, acupuncture addresses the pressing need for holistic and complementary treatments that may alleviate both the motor symptoms of PD and the accompanying anxiety. METHODS AND ANALYSIS: This is a multicentre, randomised controlled and assessor-blind trial. A total of 210 eligible patients with PD will be randomly assigned (1:1) to Jin's three-needle (JTN) acupuncture group or waitlist (WL) group. Patients in the JTN group will receive acupuncture therapy three times per week for 4 weeks. Patients in the WL group will maintain their original dosage of antiparkinsonian drugs and receive acupuncture therapy after the observation period. The primary outcome measure will be the Unified Parkinson's Disease Rating Scale score. The secondary outcome measures will be the scores of the Hoehn-Yahr Rating Scale, Unified Dyskinesia Rating Scale, Non-Motor Symptoms Scale, 39-item Parkinson's Disease Questionnaire, Parkinson Anxiety Scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Zarit burden interview and the level of cortisol and adrenocorticotropic hormone. The evaluation will be executed at baseline, the end of the treatment and a follow-up period. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (K[2023]014). All patients have to provide written, informed consent. The study will be disseminated through presentations in peer-reviewed international journals and at national and international conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry; ChiCTR2300074675.

A general clinical overview of the non-motor symptoms in Parkinson's disease: Neuropsychiatric symptoms.

The heterogeneity of non-motor features observed in people with Parkinson's disease (PD) is often dominated by one or more symptoms belonging to the neuropsychiatric spectrum, such as cognitive impairment, psychosis, depression, anxiety, and apathy. Due to their high prevalence in people with PD (PwP) and their occurrence in every stage of the disease, from the prodromal to the advanced stage, it is not surprising that PD can be conceptualised as a complex neuropsychiatric disorder. Despite progress in understanding the pathophysiological mechanisms underlying the neuropsychiatric signs and symptoms in PD, and better identification and diagnosis of these symptoms, effective treatments are still a major unmet need. The impact of these symptoms on the quality of life of PwP and caregivers, as well as their contribution to the overall non-motor symptom burden can be greater than that of motor symptoms and require a personalised, holistic approach. In this chapter, we provide a general clinical overview of the major neuropsychiatric symptoms of PD.

Traditional Medicine Classification Based on the Nature and Location of Disease in Parkinson's Disease: A Clustering Study Using Pattern Identification Disassemble Presented in Clinical Studies.

Objectives: The purpose of this study was to investigate a traditional medicine (TM) classification based on the nature and location of disease for pattern identification (PI) in Parkinson's disease (PD). This study also aimed to present evidence regarding the pathogenesis of PD and provide a basis for establishment of individualized treatment strategies with TM. Methods: An electronic search was conducted in three core databases, three Korean databases, and four Chinese databases. A hierarchical clustering analysis was conducted based on the nature and location of the disease for PD, and the analysis findings were compared with PI in the existing literature. Results: A total of 79 different types of PI were confirmed in 189 PD cases. Cluster analysis using the nature and location of disease disassembled from PI identified 7 groups: group 1 (wind, blood stasis) comprised 15 studies; group 2 (fire-heat, phlegm-retained fluid) comprised 7 studies; group 3 (liver, Qi stagnation) comprised 5 studies; group 4 (kidney, Yang deficiency) comprised 10 studies; group 5 (liver-kidney, Yin deficiency) comprised 93 studies; group 6 (Qi deficiency, blood deficiency) comprised 18 studies; and group 7 (meridian and collateral) comprised 9 studies. Conclusions: The findings provide evidence for the pathogenesis of PD and have the potential to translate into more specific TM patterns for PD. The authors hope that their study results will be used as a foundation for development of traditional medical diagnostic methods and treatments tailored to PD.

Potentially inappropriate medications among older patients with Parkinson's disease: a cross-sectional analysis of a national health insurance database in China.

BACKGROUND: With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson's disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China. METHODS: We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients' characteristics were estimated using multivariate logistic regression. RESULTS: A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65-74] vs. 59.5% [75-84; OR, 1.22; 95% CI, 1.14-1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38-1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72-0.82). CONCLUSIONS: Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population.

A Paradigm Shift in the Management of Patients with Parkinson's Disease.

BACKGROUND: Technological evolution leads to the constant enhancement of monitoring systems and recording symptoms of diverse disorders. SUMMARY: For Parkinson's disease, wearable devices empowered with machine learning analysis are the main modules for objective measurements. Software and hardware improvements have led to the development of reliable systems that can detect symptoms accurately and be implicated in the follow-up and treatment decisions. KEY MESSAGES: Among many different devices developed so far, the most promising ones are those that can record symptoms from all extremities and the trunk, in the home environment during the activities of daily living, assess gait impairment accurately, and be suitable for a long-term follow-up of the patients. Such wearable systems pave the way for a paradigm shift in the management of patients with Parkinson's disease.

Enhanced suppression of otoacoustic emissions by contralateral stimulation in Parkinson's disease.

Dopamine depletion affects several aspects of hearing function. Previous work [Wu, Yi, Manca, Javaid, Lauer, and Glowatzki, eLife 9, e52419 (2020)] demonstrated the role of dopamine in reducing the firing rates of inner ear cells, which is thought to decrease synaptic excitotoxicity. Thus, a lack of dopamine could indirectly increase acoustic stimulation of medial olivocochlear efferents. To investigate that, here we studied contralateral suppression of distortion product otoacoustic emissions in a population of Parkinsonian patients, compared to an age-matched control group, both audiometrically tested. To rule out activation of the acoustic reflex, middle ear impedance was monitored during testing. The results show significantly stronger contralateral suppression in the patient group.

Role of Nutraceuticals and Physical Activity in Parkinson's Disease Risk and Lifestyle Management.

BACKGROUND: Parkinson's disease is a complicated, gradually progressive neurological illness characterized by locomotor and non-motor symptomatology that impedes daily activities. Despite significant advances in symptomatic therapies with various extents of negative effects, there are currently no disease-modifying medicinal alternatives. Symptoms worsen, creating an additional strain that reduces living quality and creates the perception that prescription drugs are no longer productive. OBJECTIVE: Adopting healthy lifestyle habits can help patients feel more empowered, promote wellness, relieve symptoms, and potentially slow neurodegeneration. Nutrition, intellectual stimulation, physical exercise, and stress reduction are all examples of lifestyle habits that improve cognitive health and life satisfaction. We discuss how changes in lifestyle, nutrition, yoga, exercise, and acupuncture can help with managing the disease's symptoms. METHODS: We searched Google Scholar for various research papers and review articles from publishers, such as Bentham Science, Elsevier, Taylor and Francis, Springer Nature, and others for gathering the data for the study. RESULTS: Pesticide exposure, environmental hazards, dietary choices, stress, and anxiety all have an indirect or immediate influence on the commencement of Parkinson's disease. Naturopathic remedies, such as nutraceuticals, yoga, exercise, and acupuncture, have been shown to help with Parkinson's disease management. CONCLUSION: Various preclinical and clinical studies have shown that the various factors mentioned are beneficial in the management of the disease, but more research is needed to validate the extent to which such factors are beneficial.

Treatment of Parkinson disease by acupuncture combined with medicine based on syndrome differentiation from the perspective of modern medicine: A review.

As a multifactorial degenerative disease, Parkinson disease (PD) causes tremor, gait rigidity, and hypokinesia, which interfere with normal life. Because the disease is usually discovered in the late stage of complete degeneration of neurons, it can greatly delay treatment and even eventually lead to death. Therefore, the diagnosis of this disease is very challenging, and it is gratifying that substantial progress has been made in the development of optical coherence tomography (OCT) as a diagnostic biomarker for this disease, and genetic and imaging tests have become part of routine protocols in clinical practice. In the cognition of traditional Chinese medicine (TCM), this disease belongs to deficiency in origin and excess in superficiality, which is always caused by deficiency of liver and kidney, deficiency of qi and blood, and is closely related to wind, fire, phlegm and blood stasis. A large number of studies have shown that TCM can effectively treat motor and non-motor symptoms of PD, combat oxidative stress and reduce inflammatory response, and improve the quality of life of patients. Based on the pathophysiological mechanism of PD, this paper discusses the treatment of PD by TCM acupuncture combined with medicine based on syndrome differentiation.

Neurological update: non-motor symptoms in atypical parkinsonian syndromes.

Among people with Parkinson's disease (PD), non-motor symptoms (NMS) are a well-recognised cause of significant morbidity and poor quality of life. Yet, it is only more recently that NMS have been recognised to affect the lives of patients with atypical parkinsonian syndromes in a similar fashion. The aim of this article is to highlight and compare the relative prevalence of NMS among patients with atypical parkinsonian syndromes in the published literature, which largely remain underreported and unaddressed in routine clinical practice. All NMS that are recognised to occur in PD are also found to commonly occur in atypical parkinsonian syndromes. In particular, excessive daytime sleepiness is more prevalent among atypical parkinsonian syndromes (94.3%) compared to PD (33.9%) or normal controls (10.5%) (p < 0.001). Urinary dysfunction (not limited to urinary incontinence) is not only found to occur in MSA (79.7%) and PD (79.9%), but has also been reported in nearly half of the patients with PSP (49.3%), DLB (42%) and CBD (53.8%) (p < 0.001). Apathy is significantly more common among the atypical parkinsonian syndromes [PSP (56%), MSA (48%), DLB (44%), CBD (43%)] compared to PD (35%) (p = 0.029). Early recognition and addressing of NMS among atypical parkinsonian syndromes may help improve the holistic patient care provided and may encompass a range of conservative and pharmacotherapeutic treatments to address these symptoms.

Effects of a biomechanical-based Tai Chi program on gait and posture in people with Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is associated with changes in gait and posture, which increases the rate of falls and injuries in this population. Tai Chi (TC) training enhances the movement capacity of patients with PD. However, the understanding of the effect of TC training on gait and postural stability in PD is lacking. This study aims to examine the effect of biomechanical-based TC training on dynamic postural stability and its relationship with walking performance. METHODS/DESIGN: A single-blind, randomized control trial of 40 individuals with early-stage PD was conducted (Hoehn and Yahr stages 1 to 3). Patients with PD will be randomly assigned to either the TC or control group. The TC group will participate in a biomechanical-based TC training program that is formed based on the movement analysis of TC and will be practiced thrice a week for 12 weeks. The control group will be required to engage in at least 60 min of regular physical activity (PA) on their own for three times per week for 12 weeks. The primary and secondary outcomes will be assessed at baseline and at 6 and 12 weeks after commencing the study protocol. The primary outcome measures will include dynamic postural stability indicated by the center of mass and center of pressure separation distance and clearance distance of the heel and toe measured during fixed-obstacle crossing. The secondary measures are gait speed, cadence, step length during level surface walking (simple task), and fixed-obstacle crossing (challenging task). The Unified Parkinson's Disease Rating Scale, single leg-stance test with eyes open and closed, and three cognitive scores (Stroop Test, Trail Making Test Part B, and the Wisconsin Card Sorting Test) were also employed. DISCUSSION: This protocol could lead to the development of a biomechanics TC training program for the improvement of gait and postural stability among individuals with PD. The program could enhance the understanding of the effect of TC training on gait and postural stability and could help improve or preserve the postural stability, self-confidence, and active participation in social activities of the participants, thus enhancing their overall quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04644367. Registered on 25 November 2020.

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.

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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.

Effects of intensive speech treatment on Mandarin speakers with Parkinson's Disease: A review.

BACKGROUND: Benefits of intensive speech treatment have been documented for a range of speech signs in English speakers with Parkinson's Disease (PD). However, the answer to a critical question that whether the same treatment benefits speech variables including intelligibility in Mandarin speakers is still unclear. In order to develop a targeted speech treatment for Mandarin speakers with PD, we reviewed the efficacy of intensive speech treatment to improve vocal loudness and functional communication and discuss possible explanations for efficacy on Mandarin speakers with PD. METHODS: Literatures about intensive speech treatment for Mandarin speakers with PD were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Database for Chinese Technical Periodicals (VIP) Database. Search strategy was (voice therapy OR speech therapy OR voice treatment OR speech treatment OR voice training OR speech training OR voice rehabilitation OR speech rehabilitation OR Lee Silverman voice treatment OR intensive speech treatment) and (Parkinson's disease) and (Mandarin speakers OR Chinese OR Chinese people). RESULTS: Five randomized controlled trials were selected and possible explanations for efficacy on individuals with PD are discussed. Further research directions are suggested. CONCLUSION: The existing evidence from treatment efficacy studies of intensive speech treatment provides support for improving vocal loudness, speech intelligibility, pitch and rate in Mandarin speakers with PD. Our future research will continue to work to conduct a large sample multicenter randomized controlled trial to provide high quality evidence and understand the basic mechanisms accompanying treatment-related change.

Stimulation of the Tibial nerve Repetitively to Improve Incontinence in Parkinson's Electronically (STRIPE trial): a randomised control trial of tibial nerve stimulation for bladder symptoms in Parkinson's disease using a self-contained wearable device.

BACKGROUND: Bladder symptoms are common in Parkinson's disease (PD), affecting half of all individuals. These have significant impact on quality of life as well as implications for morbidity, contributing to falls and hospital admission. The treatment of bladder symptoms can be complicated by the tendency to side-effects in people with PD including cognitive impairment and gait instability with anti-muscarinics. The development of new, better treatments is therefore warranted. Tibial nerve stimulation is a form of neuromodulation demonstrated to improve overactive bladder symptoms in non-neurogenic cohorts. Previously requiring hospital attendance, we aim to explore the use of this intervention using a simple device that can be used by patients at home. METHODS: STRIPE is a phase II randomised control trial of tibial nerve stimulation delivered by the Geko™ device, a small, self-adhesive neuromuscular stimulation device currently used for thromboembolism prophylaxis post-surgery. Active tibial nerve stimulation will be compared to sham stimulation, with participants blinded to treatment allocation and undertaking outcome assessment whilst still blinded. Participants will be asked to self-administer stimulation at home twice per week, for 30 min per session, over the course of 3 months. Primary outcome measure will be the International Consultation on Incontinence Overactive Bladder Questionnaire (OAB) at week 12. Secondary outcomes will include pre- and post-intervention bladder diary (frequency, urgency episodes, nocturia), patient perception of global change, bowel function and bladder-related quality of life. Participants will be recruited from the Proactive Integrated Management and Empowerment (PRIME) cross-sectional trial in which participants have been screened for bladder symptoms and invited to take part, as well as clinician referral from around the region. DISCUSSION: This trial will involve a randomised control trial of a novel and easy to use method of delivering tibial nerve stimulation for PD in the patient's own home. This may potentially have huge benefit, avoiding the problems with side effects that can be seen with anti-muscarinics and providing a new potential modality of treatment. TRIAL REGISTRATION: ISRCTN11484954. Registered on 22 June 2021.

Use of Laughter for the Detection of Parkinson's Disease: Feasibility Study for Clinical Decision Support Systems, Based on Speech Recognition and Automatic Classification Techniques.

Parkinson's disease (PD) is an incurable neurodegenerative disorder which affects over 10 million people worldwide. Early detection and correct evaluation of the disease is critical for appropriate medication and to slow the advance of the symptoms. In this scenario, it is critical to develop clinical decision support systems contributing to an early, efficient, and reliable diagnosis of this illness. In this paper we present a feasibility study for a clinical decision support system for the diagnosis of PD based on the acoustic characteristics of laughter. Our decision support system is based on laugh analysis with speech recognition methods and automatic classification techniques. We evaluated different cepstral coefficients to identify laugh characteristics of healthy and ill subjects combined with machine learning classification models. The decision support system reached 83% accuracy rate with an AUC value of 0.86 for PD-healthy laughs classification in a database of 20,000 samples randomly generated from a pool of 120 laughs from healthy and PD subjects. Laughter could be employed for the efficient and reliable detection of PD; such a detection system can be achieved using speech recognition and automatic classification techniques; a clinical decision support system can be built using the above techniques. Significance: PD clinical decision support systems for the early detection of the disease will help to improve the efficiency of available and upcoming therapeutic treatments which, in turn, would improve life conditions of the affected people and would decrease costs and efforts in public and private healthcare systems.

Predictive risk factors of phenoconversion in idiopathic REM sleep behavior disorder: the Italian study "FARPRESTO".

Most patients with idiopathic REM sleep behavior disorder (iRBD) will develop an overt α-synucleinopathy over time, with a rate of phenoconversion of 73.5% after 12 years from diagnosis. Several markers of phenoconversion were identified; however, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without standardized data collection methods. The risk FActoRs PREdictive of phenoconversion in idiopathic REM sleep behavior disorder: the Italian STudy (FARPRESTO) is a multicentric longitudinal retrospective and prospective study with a cohort of incident (prospective recruitment) and prevalent (retrospective recruitment) iRBD patients, whose primary aim is to stratify the risk of phenoconversion, through the systematic collection by means of electronic case report forms of different biomarkers. Secondary aims are to (1) describe the sociodemographic and clinical characteristics of patients with iRBD; (2) collect longitudinal data about the development of α-synucleinopathies; (3) monitor the impact of iRBD on quality of life and sleep quality; (4) assess the correlation between phenoconversion, cognitive performance, and loss of normal muscle atony during REM sleep; (5) identify RBD phenotypes through evaluating clinical, biological, neurophysiological, neuropsychological, and imaging biomarkers; and (6) validate vPSG criteria for RBD diagnosis. The FARPRESTO study will collect a large and harmonized dataset, assessing the role of different biomarkers providing a unique opportunity for a holistic, multidimensional, and personalized approach to iRBD, with several possible application and impact at different levels, from basic to clinical research, and from prevention to management. The FARPRESTO has been registered at clinicaltrials.gov (NCT05262543).

Prevalence and patterns of the concurrent use of anticholinergics for the motor symptoms of Parkinson's disease and acetylcholinesterase inhibitors in Parkinson's disease patients with dementia: a cross-sectional study using Korea National Health Insurance claims data.

BACKGROUND: The concurrent use of anticholinergics and acetylcholinesterase inhibitors (ACHEIs) in Parkinson's disease (PD) patients with dementia should be avoided because the opposing pharmacological actions of both drugs reduce the treatment efficacy. We aimed to investigate the prevalence of the concurrent use of these two types of drugs in Korean patients. METHODS: In the 2017 Health Insurance Review and Assessment Service-National Aged Patient Sample data, comprising insurance claims records for a 10% random sample of patients aged ≥ 65 years in Korea, "concurrent use" was defined as the overlapping of anticholinergic and ACHEI doses for at least 2 months. RESULTS: Among 8,845 PD patients with dementia, 847 (9.58%) were co-administered anticholinergics, used to treat the motor symptoms of PD, and ACHEIs for a mean duration of 7.7 months. A total of 286 (33.77% of all co-administered) patients used both drug types concurrently all year. About 80% of concurrent users were prescribed each drug by the same prescriber, indicating that coadministration may not be due to a lack of information sharing between providers. Logistic regression analysis showed that patients mainly treated at clinics (odds ratio (OR), 1.541; 95% confidence interval (CI), 1.158-2.059), hospitals (OR, 2.135; 95% CI, 1.586-2.883), and general hospitals (OR, 1.568; 95% CI, 1.221-2.028) were more likely to be co-prescribed anticholinergics and ACHEIs than those mainly treated at tertiary-care hospitals. PD patients with dementia treated at healthcare organizations located in areas other than the capital city had an approximately 22% higher risk of concurrent use (OR: 1.227, 95% CI: 1.046-1.441). CONCLUSIONS: The concurrent use of anticholinergics for the motor symptoms of PD and ACHEIs in elderly Korean PD patients with dementia cannot be ignored, and strategies that mitigate potentially inappropriate concurrent drug use are required.

Stimulation of the tibial nerve-a randomised trial for urinary problems associated with Parkinson's-the STARTUP trial.

BACKGROUND: non-motor symptoms such as bladder dysfunction are common (80%) in people with Parkinson's increasing the risk for falls with a negative impact on health-related costs and quality of life.We undertook STARTUP to evaluate the clinical and cost-effectiveness of using an adhesive electrode to stimulate the transcutaneous tibial nerve stimulation (TTNS) to treat bladder dysfunction in people with Parkinson's disease (PD).Study design, materials and methods: STARTUP was a parallel two-arm, multi-centre, pragmatic, double-blind, randomised controlled trial. Each participant attended one clinic visit to complete consent, be randomised using a computer-generated system and to be shown how to use the device.The trial had two co-primary outcome measures: International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the International Prostate Symptom Score (IPSS). These were completed at baseline, 6 and 12 weeks. A bladder frequency chart and resource questionnaire were also completed. RESULTS: two hundred forty two participants were randomised. About 59% of participants were male, the mean age was 69 years and mean time since diagnosis was 6 years. Questionnaire return rate was between 79 and 90%.There was a statistically significantly lower score in the active group at 6 weeks in the IPSS questionnaire (mean difference (Standard deviation, SD) 12.5 (6.5) vs 10.9 (5.5), effect size -1.49, 95% CI -2.72, -0.25). There was no statistically significant change in any other outcome. CONCLUSION: TTNS was demonstrated to be safe with a high level of compliance. There was a significant change in one of the co-primary outcome measures at the end of the treatment period (i.e. 6 weeks), which could indicate a benefit. Further fully powered RCTs are required to determine effective treatments.

Evaluation of curcumin as add-on therapy in patients with Parkinson's disease: A pilot randomized, triple-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Preclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson's disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life. MATERIAL AND METHODS: Idiopathic PD patients aged ≥30≥ 30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n = 30, 80 mg/day) or placebo (n = 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Parkinson's Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis. RESULTS: Although the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P = 0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P = 0.25) and gastroesophageal reflux (P = 0.42). CONCLUSION: While curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients.

A holistic approach to evaluating Parkinson's disease, using the Delphi method: a linear evaluation index / Un enfoque holístico para evaluar la enfermedad de Parkinson con el método Delphi: un índice evaluativo lineal

ABSTRACT Background: Parkinson's disease (PD) is a chronic disease that presents a multitude of symptoms, with symptoms of both motor and nonmotor nature. The Delphi method is widely used to create consensuses among experts in a field of knowledge. Objective: In order to reach a consensus on the values that should be assigned to the different motor and nonmotor manifestations of Parkinson's disease, a linear evaluation index (LEI) was created. Subsequently, the metric properties of this index were studied. Methods: 120 consecutive patients with a Parkinson's diagnosis were chosen in accordance with the UKPDSBB criteria. The Delphi method was used to reach a consensus among experts regarding the values of each of the manifestations included. Subsequently, the following attributes were analyzed: quality and acceptability of the data; reliability, in terms of internal consistency, reliability index, Cronbach's alpha and standard error of measurement; and validity, in terms of convergent validity and validity for known groups. Results: Twenty-five experts participated. The importance factor did not differ between the first round and the second round (chi-square test). We analyzed the responses that assigned percentage values to the 10 dimensions of the LEI. Both in the first and in the second round, the values of the scattering coefficient Vr were always close to 0. The homogeneity index was 0.36; the corrected-item total correlation values ranged from 0.02 to 0.7; Cronbach's α was 0.69; and the SEM was 4.23 (55.1%). Conclusions: The LEI was obtained through rigorous recommended methodology. The results showed adequate metric properties.

RESUMO Antecedentes: La enfermedad de Parkinson (EP) es una enfermedad crónica que presenta una multitud de síntomas, tanto de naturaleza motora cuanto no motora. El método Delphi se utiliza ampliamente para crear un consenso entre expertos de un campo del conocimiento. Objetivos: Con el fin de llegar a un consenso sobre los valores que deben asignarse a las diferentes manifestaciones motoras y no motoras de la enfermedad de Parkinson, se creó el "Índice de Evaluación Lineal" (linear evaluation index - LEI). Posteriormente, se estudiaron las propiedades métricas de este índice. Métodos: Se eligieron 120 pacientes consecutivos con diagnóstico de Parkinson según los criterios del UKPDSBB. Se utilizó el método Delfos para llegar a un consenso entre los expertos sobre los valores de cada una de las manifestaciones incluidas. Posteriormente, se analizaron los siguientes atributos: Calidad y aceptabilidad de los datos. Fiabilidad: consistencia interna, índice de fiabilidad, alfa de Cronbach y error estándar de medida. Finalmente, Validez: validez convergente y validez para grupos conocidos. Resultados: Participaron 25 expertos, el factor de importancia entre la primera y la segunda rondas (prueba chi-cuadrado), no fue diferente. Analizamos las respuestas que asignaron valores porcentuales a las 10 dimensiones del LEI; tanto en la primera como en la segunda rondas, los valores del coeficiente de dispersión Vr siempre estuvieron cerca de 0. El índice de homogeneidad fue de 0,36; los valores corregidos de correlación ítem-total variaron de 0,02 a 0,7; alpha de Cronbach fue de 0,69. El SEM fue 4,23 (55,1%). Conclusiones: El LEI se ha obtenido siguiendo una rigurosa metodología recomendada. Los resultados han mostrado propiedades métricas adecuadas.