International Movement Research Articles

Multidisciplinary Complex Treatment of Parkinson's disease : Cornerstone of an individualized treatment

The inpatient Parkinson's disease multimodal complex treatment (PD-MCT) was applied more than 15,000 times in 2022, in Germany. This number is increasing as is Parkinson's disease (PD), which affects more than 400,000 people in Germany and leads to 100,000 disability-adjusted life years. In recent years, several observational studies have been conducted on the effectiveness of this kind of multidisciplinary care. To summarize and discuss the evidence on the nature, benefits and potential of PD-MCT. Anarrative review of selected empirical findings was carried out. The PD-MCT frequently lasts for 2-3 weeks and aims to maintain the quality of life of people with PD. Disease symptoms and activities of daily living are jointly improved by pharmacological strategies and activating therapies (physiotherapy, occupational therapy, speech and language therapy, physical training, art therapy). The PD-MCT is auseful measure to avoid or mitigate crisis situations in the course of the disease. A total of eight observational studies (n = 1246) have shown good effectiveness with a total mean improvement of the International Parkinson and Movement Disorder Society unified Parkinson's disease rating scaleIII (MDS-UPDRSIII) by 7.8points. The transfer of effects into everyday life through intensive and specialized community-based care must be ensured in order to achieve sustained effects on the quality of life. Ideally, this transfer can be supported by integrated PD networks and digital technologies in the future. There is potential for development in the standardization, patient selection and quality assurance of PD-MCT as well as in the embedding in care structures such as PD networks. Open research questions include aprecise definition of the target group and higher quality evidence of short-term and long-term effectiveness.

9-8-8: Suicide Crisis Helpline - Implementing a Pan-Canadian Program to Prevent Suicide.

The 9-8-8: Suicide Crisis Helpline was launched in Canada in November 2023, aligned with an international movement to ensure access to crisis supports as part of a public health approach to suicide prevention. We describe the planning and implementation of 9-8-8 in Canada using the RE-AIM framework, considering the Reach, Effectiveness, Adoption, Implementation and Maintenance of 9-8-8 within the first six months of service (Glasgow et al. 2019). There is evidence of reach and adoption of 9-8-8 across Canada, and we discuss evidence-based strategies to evaluate and enhance effectiveness, implementation and maintenance. We also consider the importance of evaluating 9-8-8 within the larger socio-ecological and health system contexts. 9-8-8 must cultivate a learning health system approach and be part of a larger learning health system focused on reducing suicide in Canada.

Stress in Musicians with and Without Focal Dystonia Is Not Reflected in Limbic Circuit Activation.

Musicians' dystonia (MD) is a movement disorder with several established risk factors, but the exact pathophysiology remains unknown. Recent research suggests dysfunction in sensory-motor, basal ganglia, cerebellar, and limbic loops as potential causes. Adverse childhood experiences are also considered risk factors. This study aimed to investigate whether MD patients have experienced more childhood trauma, leading to increased stress reactivity and neural vulnerability to movement disorders. Using functional magnetic resonance imaging and the Montreal Imaging Stress Task, 40 MD patients were compared with 39 healthy musicians (HMs). Whole-brain analysis and regions of interest analysis were performed. Parameter estimates and subjective stress levels were compared between groups and correlated with the Childhood Trauma Questionnaire. MD patients reported significantly higher childhood trauma scores than healthy control subjects, but they did not differ in their subjective stress experiences. Stress-related activity of limbic areas was neither found in the whole sample nor between the two groups. Instead, increased activity of visual association and temporal areas was observed, but this activation did not differ between patients and HMs. However, patients showed a tendency toward reduced precuneus activity under stress. Adverse childhood experiences were negatively correlated with precuneus, thalamus, and substantia nigra activity across all participants. Overall, MD patients and HMs had similar subjective and neurological reactions to stress but differed in childhood trauma experiences and precuneus activity under stress. Further research about the functional connectivity between precuneus, cerebellum, thalamus, and basal ganglia in musicians is needed. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Team Science Approaches to Unravel Monogenic Parkinson's Disease on a Global Scale.

Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at a global scale. To identify the multi-ancestry spectrum of monogenic PD. The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's Monogenic Network took a different approach by targeting PD centers underrepresented or not yet represented in the medical literature. In this article, we describe combining both efforts in a merger project resulting in a global monogenic PD cohort with the buildup of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expressivity of monogenic PD. This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Small Particles, Big Potential: Polymeric Nanoparticles for Drug Delivery in Parkinson's Disease.

Despite the availability of a number of efficacious treatments for Parkinson's disease, their limitations and drawbacks, particularly related to low brain bioavailability and associated side effects, emphasize the need for alternative and more effective therapeutic approaches. Nanomedicine, the application of nanotechnology in medicine, has received considerable interest in recent years as a method of effectively delivering potentially therapeutic molecules to the brain. In particular, polymeric nanoparticles, constructed from biodegradable polymer, have shown great promise in enhancing therapeutic efficacy, reducing toxicity, and ensuring targeted delivery. However, their clinical translation remains a considerable challenge. This article reviews recent in vitro and in vivo studies using polymeric nanoparticles as drug and gene delivery systems for Parkinson's disease with their challenges and future directions. We are also particularly interested in the technical properties, mechanism, drugs release patterns, and delivery strategies to overcome the blood-brain barrier. © 2024 International Parkinson and Movement Disorder Society.

Cooperation, Democracy, and Coercion: On the Grounds and Scope of Freedom of Movement

Abstract It is often believed that domestic principles of justice cannot ground freedom of international movement. Some argue that since principles of justice are not global in scope, justice does not require freedom of movement at the global level. This is problematic, for it confuses the grounds with the scope of justice. Given that the scope of justice is potentially global, freedom of movement must also be global in scope. Others have argued that the grounds of freedom of movement themselves are restricted in scope. If cooperation, democracy, and coercion are what presumably ground the right to freedom of movement, to the extent that they are not global in scope, freedom of movement need not be global in scope either. In this article, I argue that even if the grounds of freedom of movement are or should not be global in scope, freedom of movement must be.

A Short Progressive Supranuclear Palsy Quality of Life Scale.

The Progressive Supranuclear Palsy quality of life scale (PSP-QoL) has been shown to be a useful tool for capturing health-related quality of life of patients in "everyday life" and in progressive supranuclear palsy (PSP) research. However, at 45 items in length, the questionnaire can take a long time, exhausting PSP patients, in particular if cognitive impaired, which can have a negative impact on the assessment. The aim of this study was to establish a condensed version of the PSP-QoL for research and routine clinical care. In this retrospective study, data originating from a German cohort of PSP patients was analyzed. Data from 245 PSP patients were included in this study. The short PSP-QoL questionnaire was created using a two-factor solution and item-total and inter-item correlations for mental and physical aspects of daily living of the PSP-QoL followed by confirmatory factor analysis. The final scale included 12 items representing mental (five items) and physical symptoms (seven items). The specified two-factor model displayed an excellent fit in the confirmatory factor analysis. The short Progressive Supranuclear Palsy Quality of Life scale (PSP-ShoQoL) correlated moderately with the PSP Rating Scale (r [243] = 0.514, P < 0.001) and Geriatric depression scale (r [231] = 0.548, P < 0.001). Sensitivity to change confirmed a significant decrease in QoL after 12 months. In this study, we created a 12-item PSP-ShoQoL designed to "facilitate" daily clinical work that correlated strongly with the PSP-QoL and was sensitive to change. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sensitivity of Advanced Magnetic Resonance Imaging to Progression over Six Months in Early Spinocerebellar Ataxia.

Clinical trials for upcoming disease-modifying therapies of spinocerebellar ataxias (SCA), a group of rare movement disorders, lack endpoints sensitive to early disease progression, when therapeutics will be most effective. In addition, regulatory agencies emphasize the importance of biological outcomes. READISCA, a transatlantic clinical trial readiness consortium, investigated whether advanced multimodal magnetic resonance imaging (MRI) detects pathology progression over 6 months in preataxic and early ataxic carriers of SCA mutations. A total of 44 participants (10 SCA1, 25 SCA3, and 9 controls) prospectively underwent 3-T MR scanning at baseline and a median [interquartile range] follow-up of 6.2 [5.9-6.7] months; 44% of SCA participants were preataxic. Blinded analyses of annual changes in structural, diffusion MRI, MR spectroscopy, and the Scale for Assessment and Rating of Ataxia (SARA) were compared between groups using nonparametric testing. Sample sizes were estimated for 6-month interventional trials with 50% to 100% treatment effect size, leveraging existing large cohort data (186 SCA1, 272 SCA3) for the SARA estimate. Rate of change in microstructural integrity (decrease in fractional anisotropy, increase in diffusivities) in the middle cerebellar peduncle, corona radiata, and superior longitudinal fasciculus significantly differed in SCAs from controls (P < 0.005), with high effect sizes (Cohen's d = 1-2) and moderate-to-high responsiveness (|standardized response mean| = 0.6-0.9) in SCAs. SARA scores did not change, and their rate of change did not differ between groups. Diffusion MRI is sensitive to disease progression at very early-stage SCA1 and SCA3 and may provide a >5-fold reduction in sample sizes relative to SARA as endpoint for 6-month-long trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Parkinson's Disease Gene Screening in Familial Cases from Central and South America.

Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prokineticin-2 Is Highly Expressed in Colonic Mucosa of Early Parkinson's Disease Patients.

Elevated levels of prokineticin-2 (PK2), regarded as a protein involved in modulating immune/inflammatory responses, have been detected in the substantia nigra, serum, and olfactory neurons of Parkinson's disease (PD) patients. Of note, emerging evidence suggests that gut alterations, including dysbiosis and enteric inflammation, play a role in PD via the gut-brain axis. Our goal was to investigate the expression of PK2 in colonic biopsies of PD patients. Mucosal biopsies from the descending colon were obtained in 11 PD patients and five asymptomatic subjects. Biopsy samples were processed for PK2 immunofluorescence and western blot. We revealed an increased PK2 expression in colonic mucosa from PD patients in the early stages compared to controls. In addition, we found that PK2 was expressed by activated enteric glial cells and macrophages. PK2 is highly expressed within neurogenic/inflammatory cells of colonic mucosa from early PD patients, suggesting a potential role of PK2 in gut inflammation, especially in the early stages of PD. © 2024 International Parkinson and Movement Disorder Society.

Linking Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: A Randomized Trial.

Recent imaging studies identified a brain network associated with clinical improvement following deep brain stimulation (DBS) in Parkinson's disease (PD), the PD response network. This study aimed to assess the impact of neuromodulation on PD motor symptoms by targeting this network noninvasively using multifocal transcranial direct current stimulation (tDCS). In a prospective, randomized, double-blinded, crossover trial, 21 PD patients (mean age 59.7 years, mean Hoehn & Yahr [H&Y] 2.4) received multifocal tDCS targeting the a-priorinetwork. Twenty-minute sessions of tDCS and sham were administered on 2 days in randomized order. Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) scores were assessed. Before intervention, MDS-UPDRS-III scores were comparable in both conditions (stimulation days: 37.38 (standard deviation [SD] = 12.50, confidence interval [CI] = 32.04, 42.73) vs. sham days: 36.95 (SD = 13.94, CI = 30.99, 42.91), P = 0.63). Active stimulation resulted in a reduction by 3.6 points (9.7%) to 33.76 (SD = 11.19, CI = 28.98, 38.55) points, whereas no relevant change was observed after sham stimulation (36.43 [SD = 14.15, CI = 30.38, 42.48], average improvement: 0.5 [1.4%]). Repeated-measures analysis of variance (ANOVA) confirmed significance (main effect of time: F(1,20)=4.35, P < 0.05). Tukey's post hoc tests indicated MDS-UPDRS-III improvement after active stimulation (t [20] = 2.9, P = 0.03) but not after sham (t [20] = 0.42, P > 0.05). In a subset of patients that underwent DBS surgery later, their DBS response correlated with tDCS effects (R = 0.55, P(1) = 0.04). Noninvasive, multifocal tDCS targeting a DBS-derived network significantly improved PD motor symptoms. Despite a small effect size, this study provides proof of principle for the successful noninvasive neuromodulation of an invasively identified network. Future studies should investigate repeated tDCS sessions and their utility for screening before DBS surgery. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Phytosanitary Cold Treatment of the Spotted Wing Drosophila (Diptera: Drosophilidae) in Postharvest ‘Red Globe’ Grapes

The spotted wing drosophila, Drosophila suzukii (Matsumura), is currently distributed in the main soft-skinned fruits production areas in China and 59 other countries, presenting a significant threat to importing nations. Optimal phytosanitary treatments, including fumigation, irradiation, and cold treatment, have been developed to prevent the international movement of this invasive fly. To determine the most cold-tolerant stage and facilitate the development of the technical schedules requested by the Technical Panel on Phytosanitary Treatment (TPPT), cold treatments of D. suzukii immature stages in ‘Red Globe’ grapes were conducted. Dose–mortality data at 0 °C and 2 °C from repeated trials were subjected to analysis of covariance, linear regression, and probit analysis. Results identified 3 d old pupae as the most cold-tolerant stage, followed by 1 d old pupae, 4 d old larvae, and 6 h old eggs with similar tolerance. The 2 d old larvae were the most sensitive stage. In subsequent confirmatory tests, 3 d old pupae were subjected to cold treatment at 0 °C for 9 and 10 days, and at 2 °C for 10 and 12 days, based on the probit estimation of the probit-9 value. No adult emergence occurred in the confirmatory tests except for one deformed adult from a 2 °C 10 d treatment. Therefore, the recommended treatment schedule requires fruit temperatures below 0.00 °C (or 1.62 °C) for no less than 10 (or 12) continuous days, with treatment efficacy not less than 99.9960% (or 99.9955%) at a 95% confidence level, respectively. These schedules are intended for submission to TPPT for the development of phytosanitary treatment standards.

Epidemiology of Huntington's Disease in Latin America: A Systematic Review and Meta-Analysis.

Latin America has played a crucial role in advancing our understanding of Huntington's disease (HD). However, previous global reviews include limited data from Latin America. It is possible that English-based medical search engines may not capture all the relevant studies. We searched databases in Spanish, Portuguese, and English. The names of every country in Latin America in English-based search engines were used to ensure we found any study that had molecular ascertainment and provided general epidemiological information or subpopulation data. Additionally, we contacted experts across the region. The search strategy yielded 791 citations; 24 studies met inclusion criteria, representing 12 of 36 countries. The overall pooled prevalence was 0.64 per 100,000 (prediction interval, 0.06-7.22); for cluster regions, it was 54 per 100,000 (95% CI, 34.79-84.92); for juvenile HD, it was 8.7% (prediction interval, 5.12-14.35), and 5.9% (prediction interval, 2.72-13.42) for late-onset HD. The prevalence was higher for Mexico, Peru, and Brazil. However, there were no significant differences between Central America and the Caribbean versus South America. The prevalence of HD appears to be similar across Latin America. However, we infer that our findings are underestimates, in part because of limited research and underdiagnosis of HD because of limited access to molecular testing and the availability of neurologists and movement disorders specialists. Future research should focus on identifying pathways to improve access to molecular testing and education and understanding differences among different ancestral groups in Latin America. © 2024 International Parkinson and Movement Disorder Society.

Neuroinflammation Parallels 18F-PI-2620 Positron Emission Tomography Patterns in Primary 4-Repeat Tauopathies.

Preclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4-repeat (4R) tauopathies and its role in accelerating disease progression. We tested whether microglial activation (1) progresses in similar spatial patterns as the primary pathology tau spreads across interconnected brain regions, and (2) whether the degree of microglial activation parallels tau pathology spreading. We examined in vivo associations between tau aggregation and microglial activation in 31 patients with clinically diagnosed 4R tauopathies, using 18F-PI-2620 PET and 18F-GE180 (translocator protein [TSPO]) PET. We determined tau epicenters, defined as subcortical brain regions with highest tau PET signal, and assessed the connectivity of tau epicenters to cortical regions of interest using a 3-T resting-state functional magnetic resonance imaging template derived from age-matched healthy elderly controls. In 4R tauopathy patients, we found that higher regional tau PET covaries with elevated TSPO-PET across brain regions that are functionally connected to each other (β = 0.414, P < 0.001). Microglial activation follows similar distribution patterns as tau and distributes primarily across brain regions strongly connected to patient-specific tau epicenters (β = -0.594, P < 0.001). In these regions, microglial activation spatially parallels tau distribution detectable with 18F-PI-2620 PET. Our findings indicate that the spatial expansion of microglial activation parallels tau distribution across brain regions that are functionally connected to each other, suggesting that tau and inflammation are closely interrelated in patients with 4R tauopathies. The combination of in vivo tau and inflammatory biomarkers could therefore support the development of immunomodulatory strategies for disease-modifying treatments in these conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Skin α-Synuclein Seeding Activity in Patients with Type 1 Gaucher Disease.

Patients with type 1 Gaucher disease (GD1) have a significantly increased risk of developing Parkinson's disease (PD). The objective of this study was to evaluate skin α-synuclein (αSyn) seeding activity as a biomarker for GD1-related PD (GD1-PD). This single-center study administered motor and cognitive examinations and questionnaires of nonmotor symptoms to adult patients with GD1. Optional skin biopsy was performed for skin αSyn seed amplification assay (αSyn SAA) using real-time quaking-induced conversion assay. Forty-nine patients were enrolled, and 36 underwent skin biopsy. Two study participants had PD. Ten participants were αSyn SAA positive (27.8%), 7 (19.4%) were intermediate, and 19 (52.8%) were negative. Positive αSyn seeding activity was observed in the single GD1-PD case who consented to biopsy. αSyn SAA positivity was associated with older age (p = 0.043), although αSyn SAA positivity was more prevalent in patients with GD1 than historic controls. Longitudinal follow-up is required to determine whether skin αSyn seeding activity can be an early biomarker for GD1-PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pilot Study of Acute Behavioral Effects of Pallidal Burst Stimulation in Parkinson's Disease.

Burst-patterned pallidal deep brain stimulation (DBS) in an animal model of Parkinson's disease (PD) yields significantly prolonged therapeutic benefit compared to conventional continuous DBS, but its value in patients remains unclear. The aims were to evaluate the safety and tolerability of acute (<2 hours) burst DBS in PD patients and to evaluate preliminary clinical effectiveness relative to conventional DBS. Six PD patients were studied with DBS OFF, conventional DBS, and burst DBS. Unified Parkinson's Disease Rating Scale III (UPDRS-III) and proactive inhibition (using stop-signal task) were evaluated for each condition. Burst and conventional DBS were equally tolerated without significant adverse events. Both stimulation patterns provided equivalent significant UPDRS-III reduction and increased proactive inhibition relative to DBS OFF. This pilot study supports the safety and tolerability of burst DBS, with acute effects similar to conventional DBS. Further larger-scale studies are warranted given the potential benefits of burst DBS due to decreased total energy delivery. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Khảo sát tình hình điều trị thuốc cho người bệnh parkinson tại Bệnh viện Đại học Y dược TP. Hồ Chí Minh

Background: Parkinson's disease is one of the most common progressive neurodegenerative disorders. There's currently no cure for Parkinson's disease. Current therapies only help patients relieve the symptoms and improve their quality of life. Objectives: To determine the rate of drugs prescribed to treat Parkinson's disease motor symptoms, the rate of the types of drug combinations, and the frequency of drug-induced motor complications in Parkinson's disease patients. Methods: This cross-sectional study was conducted at the University Medical Center HCMC, Ho Chi Minh City. The patient was diagnosed with Parkinson's disease based on the criteria of the International Parkinson's Disease and Movement Disorder Society (IPMDS). Patients' demographic data, information about Parkinson's disease, and medications used to treat Parkinson's disease were collected. Rating scales include MDS-UPRRS (Movement Disorder Society-Unified Parkinson's Disease Rating Scale), and Hoehn &amp; Yahr. Results: Among 218 Parkinson's patients, 33 (15.1%) patients received levodopa monotherapy, 126 (57.8%) patients received combination therapy of levodopa and dopamine agonists, 07 (3.2%) ) patients received combination therapy of levodopa and trihexyphenidyl, 1 (0.5%) patient received combination therapy of dopamine agonist and trihexyphenidyl, and 51 (23.4%) patients received combination therapy of both levodopa, dopamine agonist and trihexyphenidyl. A total of 217 patients were prescribed levodopa at a median dose of 375 mg. The median daily levodopa equivalent dose was 500 mg. A total of 177 patients (81.2%) used the dopamine agonist (pramipexole) with a median dose of 0.75 mg. 27.9 % of patients used an anticholinergic drug (trihexyphenidyl) with a median dose of 2 mg. The proportion of Parkinson's disease patients with motor complications was 32.6%. Conclusion: Levodopa was the medication most commonly prescribed to treat motor symptoms in patients with Parkinson's disease. The combination of levodopa and dopamine agonist was most popularly used. Drug-induced motor complications were common in Parkinson’s disease.

Smartphone Voice Calls Provide Early Biomarkers of Parkinsonism in Rapid Eye Movement Sleep Behavior Disorder.

Speech dysfunction represents one of the initial motor manifestations to develop in Parkinson's disease (PD) and is measurable through smartphone. The aim was to develop a fully automated and noise-resistant smartphone-based system that can unobtrusively screen for prodromal parkinsonian speech disorder in subjects with isolated rapid eye movement sleep behavior disorder (iRBD) in a real-world scenario. This cross-sectional study assessed regular, everyday voice call data from individuals with iRBD compared to early PD patients and healthy controls via a developed smartphone application. The participants also performed an active, regular reading of a short passage on their smartphone. Smartphone data were continuously collected for up to 3 months after the standard in-person assessments at the clinic. A total of 3525 calls that led to 5990 minutes of preprocessed speech were extracted from 72 participants, comprising 21 iRBD patients, 26 PD patients, and 25 controls. With a high area under the curve of 0.85 between iRBD patients and controls, the combination of passive and active smartphone data provided a comparable or even more sensitive evaluation than laboratory examination using a high-quality microphone. The most sensitive features to induce prodromal neurodegeneration in iRBD included imprecise vowel articulation during phone calls (P = 0.03) and monopitch in reading (P = 0.05). Eighteen minutes of speech corresponding to approximately nine calls was sufficient to obtain the best sensitivity for the screening. We consider the developed tool widely applicable to deep longitudinal digital phenotyping data with future applications in neuroprotective trials, deep brain stimulation optimization, neuropsychiatry, speech therapy, population screening, and beyond. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid β (Aβ) from the brain. Higher Aβ levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

Parkinson's Disease Progression and Exposure to Contaminated Water at Camp Lejeune.

We recently reported an increased risk of Parkinson's disease (PD) in service members who resided at Marine Base Camp Lejeune, North Carolina, when water supplies were contaminated with trichloroethylene and other volatile organic compounds (VOCs). Prior studies suggest that environmental exposures may affect PD phenotype or progression, but this has not been reported for VOCs. The objective of this study was to test whether PD progression is faster in individuals exposed to VOCs in water at Camp Lejeune. A cohort of 172,128 marines residing at Camp Lejeune between 1975 and 1985 was previously assembled. We identified individuals with PD in Veterans Health Administration and Medicare databases between 2000 and 2021. Using estimates derived by the US Agency for Toxic Substances and Disease Registry, we classified individuals as exposed or unexposed to VOCs in residential water. We used Kaplan-Meier and Cox regression models to test differences between exposed and unexposed groups in the time from PD diagnosis until psychosis, fracture, fall, or death. Among 270 persons with PD, 177 (65.6%) were exposed to VOCs in residential water. Median cumulative exposure was 4970 μg/L-months, >50-fold the permissible level. Time until psychosis, fracture, and fall were all shorter in the exposed group, with adjusted hazard ratios (HRs) exceeding 2: psychosis HR, 2.19 (95% confidence interval [CI]: 0.99-4.83); fracture HR, 2.44 (95% CI: 0.91-6.55); and fall HR, 2.64 (95% CI: 0.97-7.21). A significant dose response was observed for time to fall (P trend, 0.032). No differences were observed for time until death. PD progression may be faster in persons exposed to trichloroethylene and other VOCs in water decades earlier. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.