BackgroundParkinson's disease (PD) is an α-synucleinopathy, and pathological α-synuclein (α-Syn) is detectable in peripheral tissues and fluids. However, the diagnostic utility of tear fluid as a minimally invasive source for α-Syn seed detection remains unclear. We aimed to detect α-Syn seeds in tear fluid and evaluate the clinical characteristics of α-Syn-positive patients.MethodsTear fluid was collected bilaterally using Schirmer strips. The α-Syn seeding amplification assay (αSynSAA) was performed using the real-time quaking-induced conversion (RT-QuIC) protocol. We analyzed 55 patients with PD and 40 control participants.ResultsThe αSynSAA revealed α- synuclein seeding activity in tear fluid, showing 52.7% sensitivity and 100% specificity. αSyn SAA-positive patients had higher Movement Disorder Society-Unified Parkinsons Disease Rating Scale part III scores than αSyn SAA-negative patients. α-Syn seeding activity was detected in tear fluid from some patients with PD but not in disease controls.ConclusionThis study demonstrates the feasibility of αSynSAA analysis in tear fluid, highlighting its potential as a novel substrate for biomarker development. Further studies in related synucleinopathies and in early or prodromal PD are needed to validate these findings and assess the diagnostic performance of this tear-based assay.
BackgroundParkinson's disease (PD) patients may harbor coexisting Alzheimer's disease (AD) pathology that accelerates cognitive and motor decline. Defining biomarker-defined AD in PD is important for prognosis, patient counseling, and trial stratification.ObjectiveTo determine the prevalence of AD biomarker positivity in α-synuclein seed amplification assay (αSyn-SAA) positive PD and assess its impact on cognitive and motor progression.MethodsWe analyzed data from the Parkinson's Progression Markers Initiative, a multinational prospective cohort of de novo PD patients. Baseline CSF biomarkers included αSyn-SAA, amyloid-β1-42 (Aβ1-42), and phosphorylated tau181 (p-tau181). AD biomarker positivity was defined by a low Aβ1-42/high p-tau181 profile using the CSF Aβ1-42/p-tau181 ratio (<39.2). αSyn-SAA-positive PD participants with and without AD biomarker positivity were compared. Outcomes included cognition, Montreal Cognitive Assessment (MoCA), neuropsychological testing, and MDS-UPDRS motor scores over follow-up.ResultsAmong 449 αSyn-SAA-positive PD patients, 42 (9.3%) met AD biomarker criteria (PD-AD). Baseline cognition and motor scores did not differ between PD-AD and PD without AD biomarkers (PD-nonAD). Over time, PD-AD patients showed greater cognitive decline, with lower MoCA scores and higher MCI prevalence at 5 years. At 8 years, PD-AD patients also demonstrated worse motor outcomes. MoCA <24 predicted AD biomarker positivity (PPV 15%; OR 6.1). APOE ε4 status was not associated with cognition.ConclusionsBiomarker-defined AD identifies a distinct PD subgroup with accelerated cognitive and motor decline, independent of APOE ε4. A ratio-based CSF Aβ1-42/p-tau181 framework offers a practical approach to detect AD copathology in PD and refine prognostic stratification.
BackgroundThe remarkable advances achieved in Parkinson's disease (PD) research across clinical science, genetics, molecular and cellular mechanisms, disease modeling, pathophysiology, biomarkers, and therapeutics reflect not only scientific innovation but also the evolution of collaborative research. The field has transitioned from single-investigator observations and isolated institutional efforts to regional networks and global consortia that now drive many of the most important PD discoveries.ObjectiveTo review the evolution of collaborative research approaches in PD, examine barriers and challenges to global research synergy, and discuss potential solutions to promote equitable and impactful international collaboration.State of the Art and Future DirectionsKey challenges to global PD research include funding inequities, regulatory and data-sharing complexities, difficulties in standardization and generalizability, language barriers, limited interdisciplinary communication, unequal resource allocation, insufficient training opportunities, regional mistrust, and the need to address diverse cultural contexts. Successful international initiatives have demonstrated the value of shared databases, harmonized protocols, cross-border funding mechanisms, and synergistic multidisciplinary, multicultural, and multinational partnerships. Future efforts should be grounded in trust, transparency, ethical reciprocity, equitable governance, and meaningful stakeholder engagement, while prioritizing capacity building, workforce development, and sustainable training opportunities.ConclusionsAccelerating progress in PD research requires collaborative frameworks that integrate diverse populations, disciplines, institutions, and regions. Strengthening research infrastructure, community engagement, culturally grounded education, participant-centered research practices, and scientific leadership, particularly in low- and middle-income countries, will be essential to ensure that all populations can contribute to and benefit from scientific advances, fostering a more equitable and effective global PD research ecosystem.
BackgroundAsymmetry symptoms are well recognized in Parkinson's disease (PD). However, whether handgrip strength (HGS) asymmetry can prospectively predict incident PD remains unknown.ObjectivesTo prospectively examine the association between HGS asymmetry and subsequent risk of incident PD.MethodsIncluded were 497,100 participants without PD at baseline from the UK Biobank. HGS asymmetry index was calculated by dividing the absolute inter-hand difference in HGS by the average HGS of the two hands. The primary outcome was incident PD identified through hospital admissions, death registries, and self-reported data. As secondary outcome, prodromal PD was defined as the presence of ≥3 out of 8 prodromal PD features assessed through self-reported data, hospital admission records and primary care data. The associations were evaluated using Cox regression models. Several lag analyses were conducted to examine how many years in advance could HGS asymmetry predict incident PD.ResultsDuring a median follow-up of over 13 years, 2868 participants developed PD. HGS asymmetry (highest vs. lowest quartile) was associated with higher risk of developing PD (HR = 1.23; 95% CI: 1.10, 1.37) (P-trend < 0.001). Lag analysis suggested that HGS asymmetry could even predict incident PD in 8 years. Significant association between HGS asymmetry and prodromal PD risk was also observed. The significant associations between HGS asymmetry and PD risk persisted when further excluding those with low HGS or prodromal PD.ConclusionsHigher HGS asymmetry was associated with a higher risk of incident PD, suggesting the potential of HGS asymmetry as an early indicator for PD.
BackgroundRehabilitation plays a crucial role in maintaining function and independence in neurodegenerative disorders. However, evidence on its effectiveness in atypical parkinsonian syndromes including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB) remains fragmented.ObjectiveThis scoping review aimed to comprehensively map the literature on rehabilitation interventions for PSP, MSA, CBS, and DLB, summarize intervention types and outcomes, and identify research gaps.MethodsFollowing PRISMA-ScR guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Library from inception to May 2025. Eligible studies included peer-reviewed English-language reports on non-invasive rehabilitation such as physical, occupational, and speech therapy. Two independent reviewers screened titles, abstracts, and full texts, with disagreements resolved by consensus or a third reviewer.ResultsSixty studies met inclusion criteria: PSP (n = 32), MSA (n = 20), CBS (n = 5), and DLB (n = 6). Across disorders, rehabilitation was consistently safe and feasible. Gait and balance training, voice and swallowing therapy, and multimodal programs demonstrated short-term benefits in mobility, speech, and quality of life (Class III-IV based on American Academy of Neurology classification).ConclusionsWhile rehabilitation may offer functional benefits across atypical parkinsonian syndromes, high-quality evidence remains limited. This analysis highlights significant gaps in care and underscores the need for early, multidisciplinary, and disease-specific interventions to support mobility and safety. Standardized outcome measures and long-term trials are essential to establish sustained efficacy.
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder shaped by interactions between genetic susceptibility, environmental exposures, and broader ecological change. Although pesticides, industrial solvents, heavy metals, and air pollutants have long been implicated as potentially modifiable PD risk factors, climate change is now reshaping and amplifying these hazards through rising temperatures, worsening air quality, increased pesticide demand, extreme weather events, and wildfire-related particulate matter.This narrative review moves beyond a conventional exposure-based summary by integrating environmental toxicology, climate science, epidemiology, and mechanistic neuroscience to reframe PD risk within the context of planetary health. We summarize evidence linking major environmental hazards to PD pathogenesis, emphasizing convergent mechanisms such as oxidative stress, mitochondrial dysfunction, impaired proteostasis, neuroinflammation, blood-brain barrier disruption, and α-synuclein aggregation. We further discuss how climate-related changes may intensify these pathways and disproportionately affect vulnerable populations, including agricultural workers, older adults, socioeconomically disadvantaged communities, and individuals living in rapidly industrializing or climate-sensitive regions. Importantly, we highlight clinical and public health implications by proposing that structured environmental and occupational exposure assessment should be incorporated into PD risk evaluation, early recognition, preventive counseling, and research design. We also discuss exposure reduction, workplace protection, environmental monitoring, and regulatory policy as prevention-oriented strategies. By positioning environmental hazards and climate change as interconnected, underrecognized, and potentially modifiable contributors to PD, this review provides a framework for clinicians, researchers, and policymakers seeking to reduce the future global burden of neurodegenerative disease.
BackgroundCognitive impairment and neuropsychiatric manifestations are common disabling non-motor symptoms that can negatively impact quality of life in Parkinson's disease. This review aimed to critically appraise and synthesize evidence on the prevalence, predictors, and emerging biomarkers of cognitive impairment and neuropsychiatric manifestations among patients with Parkinson's disease in Africa.MethodsWe conducted a systematic review of studies reporting cognitive and neuropsychiatric outcomes among individuals with Parkinson's disease in African populations, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We used the Critical Appraisal Skills Program checklist to determine the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to estimate the certainty of the evidence.ResultsA total of 32 studies, including 3687 patients, were analyzed. The prevalence of cognitive impairment ranged from 21.6% to 92%. Depression was the most common neuropsychiatric symptom (up to 81.7%). Consistent predictors of cognitive impairment included older age, advanced disease, and greater motor severity. Importantly, APOE ε4 homozygosity was associated with a twofold increase in the risk of cognitive impairment, while findings on LRRK2 G2019S mutations were heterogeneous across populations. Additionally, hypocalcemia and retinal nerve fiber layer thinning were linked to worse cognitive outcomes. Functional neuroimaging studies revealed altered emotional processing, with enhanced activation of limbic and cortical networks in response to positive emotional stimuli.ConclusionsEvidence from this review suggests that cognitive impairment and neuropsychiatric manifestations are common in African PD populations and may be associated with clinical, genetic, metabolic, and neurobiological factors, although the quality of the evidence is low. Larger, community-based, and longitudinal studies are warranted.
BackgroundRecruitment and retention remain major barriers to clinical research in Parkinson's disease (PD).ObjectiveWe reviewed the literature on barriers and facilitators to PD research participation, and explored motivations, perceptions, and preferences regarding clinical research participation among "underrepresented" populations (URPs) in Asia.MethodsWe reviewed published studies examining recruitment and retention in PD research. In parallel, questionnaires were administered to patients in Malaysia and Kyrgyzstan (n = 92) to assess motivations for participation, project-related preferences, and willingness to engage in different types of research. Findings from the literature and survey, and the authors' real-world research experiences were synthesized to identify practical strategies for improving participation.ResultsKey barriers identified from the literature included limited awareness of research, logistical and financial burden, disease-related disability, mistrust, stigma, and technological challenges. Across both Asian cohorts, altruistic motivations, trust in clinicians and researchers, perceived personal and societal benefit, and appreciation of healthcare services strongly influenced willingness to participate in research. Minimizing inconvenience and avoiding invasive procedures were rated as important. Most patients were willing to participate in longitudinal studies, digital monitoring, and biosample collection involving saliva, blood, urine, and stool, whereas cerebrospinal fluid sampling and brain donation were less acceptable. Solutions include integrating research into routine care, culturally-sensitive communication, patient-friendly study designs, return of research results, active engagement of URPs, and greater patient involvement throughout the research process.ConclusionsBarriers to PD research participation are multifactorial. Patient-centred, culturally-sensitive, and trust-based approaches that reduce burden while enhancing inclusivity and communication may promote more sustainable research programs.
BackgroundNeuropsychiatric symptoms such as anxiety and depression substantially impair quality of life in Parkinson's disease (PD), yet the underlying neural circuits remain poorly defined. The MitoPark (MP) mouse, a dopaminergic mitochondrial dysfunction model, recapitulates both motor and non-motor features of PD.ObjectiveTo determine whether the sustained-release GLP-1 receptor agonist PT320 (exenatide) alleviates anxiety- and depression-like behaviors in MP mice and to identify the involved neural substrates.MethodsThe temporal progression of anxiety- and depression-like behaviors was characterized in MP mice. PT320 was administered biweekly starting at either 5 weeks (early treatment) or 15 weeks (late treatment), with longitudinal evaluation until 20 weeks. Behavioral outcomes were correlated with molecular, transcriptomic, and neurochemical analyses in the nucleus accumbens (NAc), including Western blotting, bulk RNA sequencing, fast-scan cyclic voltammetry, and tyrosine hydroxylase immunostaining.ResultsEarly PT320 treatment effectively prevented the emergence of anxiety- and depression-like phenotypes in MP mice. Behavioral improvement was associated with restoration of BDNF signaling and activation of the Akt-CREB pathway in the NAc. Transcriptomic analysis revealed increased expression of Akt3, CREB, BDNF, and TrkB, along with modulation of genes related to mitochondrial homeostasis. Late PT320 treatment partially ameliorated neuropsychiatric deficits, coinciding with enhanced phasic dopamine release and recovery of tyrosine hydroxylase expression in the NAc.ConclusionsThese findings identify the NAc as a critical regulator of affective disturbances in this PD model. By restoring neurotrophic signaling and dopaminergic function, PT320 represents a promising therapeutic strategy for PD-related anxiety and depression.
BackgroundCognitive behavioral therapy (CBT) has emerged as a promising intervention in Parkinson's disease (PD), although the available evidence remains heterogeneous in design and quality.ObjectiveThe present mixed method systematic review aims to synthesize the evidence on CBT in people with PD (PwPD) and caregivers, focusing on clinical applications and therapeutic outcomes across symptom domains.MethodsA systematic search of PubMed, Web of Science, Scopus and Cochrane databases was conducted for studies published between 1980 and 2025, following PRISMA guidelines. Eligible studies evaluated clinical applications and therapeutic outcomes of CBT-based interventions in PwPD and/or caregivers and included randomized controlled trials, observational studies, case series and single-case reports. Findings were synthesized narratively, and certainty of evidence was assessed using a simplified GRADE approach.ResultsFifty-four studies met inclusion criteria. The most robust evidence was observed for depression, with several RCTs supporting the efficacy of CBT, resulting in moderate certainty of evidence. Evidence for anxiety and sleep disorders suggests potential benefit; however, certainty was low due to heterogeneity and small sample sizes. Evidence for impulse control disorders, cognitive outcomes, motor symptoms, and caregiver -related outcomes remain limited, with low to very low certainty, Effects on motor symptoms were inconsistent and likely indirect.ConclusionsCBT represents a flexible and transdiagnostic intervention for treating non-motor symptoms in PwPD and for caregivers. While moderate-certainty evidence supports CBT use for depression, evidence for other domains remains limited. These findings should be interpreted with caution, and further large-scale, well designed RCTs are needed to strengthen the evidence base and clarify optimal therapeutic targets and delivery format.
BackgroundParkinson's disease (PD) is a multifactorial neurodegenerative disorder increasingly linked to gut microbiota alterations. However, despite advances in fecal microbiota profiling as a non-invasive approach to disease risk assessment, its clinical utility remains limited by a lack of functionally relevant microbial biomarkers.ObjectiveThis cross-sectional study aimed to identify a microbial gene marker reflecting metabolic potential associated with both the presence and severity of PD.MethodsFecal samples from patients with PD (n = 59) and healthy controls (n = 65) were analyzed by 16S rRNA sequencing to characterize taxonomic profiles. Quantitative PCR (qPCR) targeted the consensus sequence of the mucin-degrading nanA gene (nanAkk), a highly conserved within Akkermansia nan gene clusters. Differences in taxonomic composition and nanAkk abundance were examined, and correlations with clinical severity scores evaluated in the PD group.ResultsPatients with PD showed reduced abundance of short-chain fatty acid-producing taxa (Faecalibacterium, Blautia, and Anaerostipes) and increased levels of Akkermansia. Akkermansia abundance correlated positively with motor severity, including Hoehn-Yahr stage. Moreover, nanAkk levels also correlated positively with Hoehn-Yahr stage and were significantly elevated in PD patients compared with controls. Levels in the stage 4-5 group exceeded those in the stage 1-3 group (P = 0.0202), indicating a stage-related increase in mucin-degrading nanAkk abundance.ConclusionsWe have identified nanAkk as a microbial gene marker associated with both the presence and severity of PD. Our qPCR-based quantification shows potential as a non-invasive biomarker for disease stratification.
BackgroundVariants in the GBA1 gene are a common genetic risk factor for Parkinson's disease (PD). While GBA1-PD is associated with more rapid motor and cognitive decline, evidence regarding impact on survival remains debatable.ObjectivesThis systematic review and meta-analysis synthesizes longitudinal evidence of GBA1 variants as a prognostic factor for all-cause mortality in PD.MethodsWe searched MEDLINE, Embase, Cochrane (CENTRAL), ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform for studies comparing mortality in GBA1-PD versus non-carriers from inception to September 2025. Risk of bias was assessed using the Quality in Prognosis Studies tool. Hazard Ratios were pooled using a random-effects meta-analysis. Subgroup analysis was stratified by variant severity.ResultsEight studies (N = 13,690) were included. The primary meta-analysis (n = 4947) revealed GBA1 variants were associated with significantly increased all-cause mortality risk versus non-carriers (HR 1.53, 95% CI 1.24-1.87; I2 = 0.7%). A subgroup analysis suggested a possible severity-dependent effect, with severe variants showing higher point estimates (HR 1.87; 95% CI 1.24-2.82) than mild variants (HR 1.38; 95% CI 1.03-1.83), although the test for subgroup differences was not statistically significant.ConclusionsGBA1 variants are a significant prognostic marker for reduced survival in PD. This risk may increase with variant severity and persist after adjustment for dementia in the studies that examined this, although the available data is limited. Limitations include heterogeneous screening methods and predominance of European ancestry in study populations. GBA1 status should be considered a significant prognostic factor for stratification in clinical trials and management.
BackgroundAnxiety and other non-motor symptoms can greatly diminish quality of life in people with Parkinson's Disease (PD). Yet, few randomized controlled trials (RCTs) have assessed accessible, non-pharmacological mental health treatments for people with PD.ObjectiveTo assess the feasibility and impact of brief, remotely-delivered meditation and breathwork on neuropsychiatric symptoms in people with PD.MethodsIn this 18-week RCT, intervention participants attended weekly webinars for six weeks, while waitlisted controls maintained their usual routine before crossing over at six weeks. Participants were assessed for weekly compliance trends (primary outcome) and changes in anxiety (primary outcome), depression, perceived stress, and other non-motor symptoms at 6-week intervals: baseline and weeks 6 (T2), 12 (T3), and 18 (T4). Weekly compliance was collected in each group for 12 weeks. Anxiety was measured using the Parkinson's Anxiety Scale.ResultsThere was a significant decrease in the primary outcome, anxiety, in the intervention group (n = 17) compared to the waitlist control (n = 21) after 6 weeks of meditation and breathwork practice (mean difference (MD)= -5.0, 95% CI [-9.5, -0.49], P = .03). Within-group analysis further confirmed a significant reduction in anxiety (MD = -4.7, 95% CI [2.10,7.33], P < .001) in the intervention group (n = 28). Thirty-one percent of participants met the compliance definition.ConclusionRemotely-delivered meditation and breathwork through the BSM program significantly reduced anxiety in individuals with PD in our study and may be a promising non-pharmacological therapy. A larger RCT with continuous wellness coaching is warranted to more rigorously assess efficacy and optimize protocols.Clinical trial registration: ClinicalTrials.gov, NCT05335850, https://clinicaltrials.gov/study/NCT05335850.
Background Sleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms. Methods Randomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n = 15) or red light placebo (n = 15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms. Results There was a significant group × time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores ( p = 0.021). Between-group analyses showed that at two weeks a trend toward significance was observed ( p = 0.065), while sleep quality significantly improved at five weeks compared to placebo ( p = 0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group ( p < 0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% ( p = 0.005). Conclusions Blue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.
Juvenile Parkinson's disease (JPD) is a rare condition characterized by the onset of parkinsonian motor symptoms before the age of 21. Sixteen patients with JPD who presented to the Mayo Clinic between 1990-2020 were included. The median age of symptoms onset was 18.5 years, and six cases had pathogenic PRKN mutations. Resting tremor was the most frequent initial symptom (81.3%), and non-motor symptoms were notably common, including mild cognitive impairment (56.3%), anxiety (62.5%), and depression (56.3%). Levodopa responsiveness was suboptimal in 9 patients and 14 exhibited motor fluctuations. JPD demonstrates distinct clinical characteristics compared with early-onset and late-onset PD.
Study Objectives The diagnosis of rapid eye movement (REM) sleep behavior disorder (RBD) is of clinical interest, as there is a high rate of future conversion to Parkinson's disease and related neurodegenerative disorders. The clinical standard for diagnosis of RBD relies on human scoring of REM sleep without atonia (RSWA) via polysomnography, which is labor-intensive, costly, and unsuitable for long-term monitoring. Existing (semi-)automatic detection methods often depend on prior manual annotation of REM or suffer from low REM classification performance in this population. We here propose a fully automated system using only a single-channel chin electromyography (EMG) for both REM scoring and RSWA quantification. Methods We analyzed 485 polysomnographic recordings, including 30 recordings of subjects with RBD. Using the recently introduced factorized score-based diffusion model, we automatically scored REM epochs based on single-channel chin EMG data, and subsequently quantified RSWA using the REM atonia index from literature. Results The proposed system demonstrated strong performance in REM scoring in both subjects with and without RBD (REM sensitivity ≥0.80, specificity ≥0.97, positive predictive value ≥0.81). The REM atonia index derived from automatic scoring showed strong agreement with manually scored data, with minimal bias (≤0.03), narrow limits of agreement (≤0.13), and strong linear correlation (Peason's r ≥ 0.88). Conclusions Fully automated RSWA quantification using single-channel chin EMG is feasible and performs comparable to semi-automatic methods that rely on human sleep stage scoring based on polysomnography. This single-sensor approach can improve RBD screening accessibility, particularly in ambulatory settings, and facilitate long term monitoring of RSWA. Plain language summary title A new way to detect sleep problems linked to Parkinson’s risk using just one chin sensor
Background Burst deep brain stimulation (DBS) is a promising alternative to conventional deep brain stimulation (cDBS), incorporating paradigms such as theta burst stimulation (TBS), burst cycling (BC), and coordinated reset (CR). Findings from transcranial magnetic stimulation, spinal cord stimulation and focused ultrasound neuromodulation inspire its potential application in Parkinson's disease (PD). Objective This review evaluates the evidence on the efficacy and safety of burst DBS in PD. Methods A systematic literature search was conducted in PubMed, Embase, and Web of Science. Inclusion criteria encompassed peer-reviewed primary preclinical or clinical studies in English, reporting motor outcomes and burst stimulation parameters. Methodological quality was assessed using SYRCLE and a modified Newcastle-Ottawa Scale. Data extraction was performed systematically, and findings were synthesized narratively. Results 19 studies met inclusion criteria: nine preclinical and ten clinical studies. Eight focused on BC (three including safety), four examined TBS (two including safety), and seven addressed CR (one including safety). Burst DBS showed mostly similar acute efficacy to cDBS, with distinct post-stimulation effects. No major adverse events were reported. However, stimulation settings varied widely, with no consensus on optimal parameters. Conclusion Efficacy and safety of burst DBS appear to be comparable to cDBS, with potential benefits such as post-stimulation effects. However, the risk of bias, variability in stimulation settings, inconsistent terminology, and other methodological considerations limit the interpretation of previous research. Further randomized studies are crucial to better refine the stimulation parameters and establish standardized clinical protocols that can be used to compare burst DBS with cDBS.
BackgroundMachine learning offers new avenues for complementing traditional epidemiological approaches by analyzing routinely collected, population-based administrative health data.ObjectiveThis study aimed to identify potential exposomic predictors (hypothesis generation) for Parkinson's disease (PD) across the entire French agricultural workforce.MethodsWe applied XGBoost adapted for Cox proportional hazards modeling to assess approximately 180 exposomic factors derived from nationwide administrative health data within the TRACTOR project. Shapley Additive Explanation (SHAP) values were used to assess the importance of each predictor. To provide both model-based and statistical perspectives, SHAP analysis was complemented with classical Cox regression, allowing for transparent assessment of each predictor's contribution to the model and its statistical association with survival. Sensitivity analyses incorporating different exposure lags were conducted. The study included 424,725 farm managers (6,265 PD cases) and 544,788 farmworkers (2,848 PD cases) aged 50+, analyzed separately due to differences in available variables and coding structures.ResultsSeveral occupational factors, including duration of involvement in crop farming and viticulture, emerged as key promoting predictors, surpassing age in predictive importance. Beyond conventional predictors such as type 2 diabetes, less conventional predictors were identified, including work diversification, seasonal employment, hypercholesterolemia, epilepsy, antidepressant use, anxiolytic use, and antibiotic use.ConclusionsThese results contribute to a growing body of evidence supporting the integration of occupational health considerations into PD research and highlight the importance of exploring and identifying potential farming-related risk factors in PD development.Plain language summary titleUsing nationwide French farming data and machine learning to explore potential factors linked to Parkinson's disease. This study investigates how work-related and health-related factors may contribute to Parkinson's disease risk among farm managers and farmworkers.
