The Parkinson pandemic continues to spread. Almost 12 million individuals now have the disease, nearly double the estimate from just six years ago. Its human-made nature is also increasingly clear as more studies tie env...The Parkinson pandemic continues to spread. Almost 12 million individuals now have the disease, nearly double the estimate from just six years ago. Its human-made nature is also increasingly clear as more studies tie environmental toxicants to the disease. Chief among these are certain pesticides, the dry-cleaning chemicals trichloroethylene and perchloroethylene, and air pollution. An etiological role for these toxicants-inhaled or ingested-is also consistent with the emerging brain- and body-first models of Parkinson's disease.To address the pandemic will require a "PLAN" that (1) Prevents the disease; (2) Learns why it starts; (3) Amplifies the voices of persons with the disease and their caregivers; and (4) Navigates the frontier of new treatments. Reducing or eliminating toxicants will help slow its rise. Learning why the disease begins will require investigating exposures, interactions of the environment with genes, and modifiers. Amplifying the voices of those affected can raise awareness, improve care, and change the disease's course. Vastly expanding the scale and scope of research funding will accelerate efforts to prevent the disease and find more effective therapies. If successfully implemented, such a plan will translate to bold " goals by 2035. The goals include a rise in the global incidence of Parkinson's, a increase in research funding and in the proportion devoted toward prevention, and of individuals having access to levodopa and receiving appropriate care. The results will lay the foundation for even greater ambitions, including the fall of Parkinson's disease.
BackgroundThe rest-activity rhythm (RAR) captures the distribution of rest and activity periods between and within days. Disturbed RAR has been observed in Parkinson's disease (PD), but the contribution of motor and non-...BackgroundThe rest-activity rhythm (RAR) captures the distribution of rest and activity periods between and within days. Disturbed RAR has been observed in Parkinson's disease (PD), but the contribution of motor and non-motor symptoms to RAR disturbances remains unclear.ObjectiveTo evaluate the extent to which motor and non-motor symptoms account for variations in RAR between people with PD (PwPD).Methods464 PwPD and 105 age-matched controls of the ProPark cohort underwent assessment of motor, psychiatric, sleep, and autonomic function. Participants wore a wrist motion sensor for one week to measure RAR, i.e., relative amplitude, interdaily stability, and intradaily variability. Associations between RAR, and demographic and clinical variables were examined using backward stepwise regression models.ResultsPwPD had lower relative amplitude (p < 0.001), lower interdaily stability (p < 0.001), and higher intradaily variability (p < 0.001), than healthy controls. Motor impairment (β=-0.262, 95% CI = [-0.487,-0.125], R²=6.8%) and the presence of orthostatic hypotension (OH) (β=-0.142, 95% CI = [-0.276,-0.026], R²=1.9%) were associated with lower relative amplitude. Motor impairment (β=0.129, 95% CI = [0.005,0.238], R²=2.5%), the presence of OH (β=0.182, 95% CI = [0.079,0.307], R²=3.6%), and higher age (β=0.158, 95% CI = [0.039,0.277], R²=4.0%) were associated with higher intradaily variability, while female gender (β=-0.196, 95% CI = [-0.318,-0.088], R²=4.7%) was associated with lower intradaily variability. Female gender was linked to higher interdaily stability (β=0.205, 95% CI = [0.071,0.321], R²=4.2%).ConclusionsMore severe motor impairment and having OH are associated with RAR disturbances in PwPD. Future studies are needed to evaluate whether optimizing treatment of motor impairment and OH, both symptomatic and asymptomatic, can improve RAR and increase mobility for PwPD.
BackgroundFatigue in Parkinson's disease (PD) is a common, debilitating symptom often overlooked in research and clinical practice. Effective interventions are needed to mitigate its impact on people with PD.ObjectiveThi...BackgroundFatigue in Parkinson's disease (PD) is a common, debilitating symptom often overlooked in research and clinical practice. Effective interventions are needed to mitigate its impact on people with PD.ObjectiveThis pilot study evaluated the feasibility of the individual videoconference version of the program for people with PD and explored its preliminary effectiveness versus usual care to inform the design of a definitive trial. Here we report on the second objective.MethodsA two-arm, assessor-masked, randomized controlled pilot study recruited participants with PD who experience severe fatigue, have English proficiency, and internet access. Outcome measures included occupational performance, satisfaction with performance, occupational balance, fatigue impact, quality of life, and sleep. Mixed repeated-measures ANOVA and non-parametric tests were used for analysis.ResultsMixed-design ANOVA (N = 25) showed an exploratory trend toward significant for the Time × Group interaction effect differences in satisfaction with performance between groups over time ( = 0.09). Paired t-tests within the intervention group indicated significant improvement in satisfaction with performance ( 0.04). The effect size for this outcome was moderate. Small to moderate effect sizes were observed for occupational balance, occupational performance, and subscales of the Multidimensional Fatigue Inventory. Other measures showed negligible effects.ConclusionsThe results provide preliminary evidence of the program's benefits for people with PD. Larger, more rigorous studies are needed to confirm its effectiveness. Despite the small sample size and challenges posed by COVID-19, this study offers valuable insights into recruitment strategies and effect sizes to inform future trial designs.
BackgroundLevodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is linked to exaggerated gamma oscillations. Buspirone, a 5-HT1A receptor agonist, is a potent medication for psychiatric conditions, predominantly...BackgroundLevodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is linked to exaggerated gamma oscillations. Buspirone, a 5-HT1A receptor agonist, is a potent medication for psychiatric conditions, predominantly prescribed for anxiety treatment.ObjectiveThis study aims to investigate whether buspirone alleviates dyskinesia in LID rat and its effects on pathological oscillatory activity and cortico-striatal functional connectivity.MethodsWe collected motor behavior and electrophysiological data of cortico-striatal from Sham rats, unilateral 6-hydroxydopamine (6-OHDA)-lesioned PD model rats, and rats with LID. We further examined the behavioral and electrophysiological changes in LID rats following buspirone intervention.ResultsPD rats showed increased beta activity and aperiodic components at 10-50 Hz, while LID rats exhibited excessive gamma oscillations and aperiodic activity at 50-150 Hz. Additionally, gamma-band functional connectivity within the cortico-striatal circuit was significantly enhanced during on-state dyskinesia, when rats exhibited abnormal involuntary movements. Administration of buspirone effectively reduced dyskinesia severity, suppressed gamma activity, decreased aperiodic components (50-150 Hz), and disrupted gamma-band functional connectivity without compromising the antiparkinsonian effects of levodopa.ConclusionsExcessive gamma oscillations represent a key electrophysiological marker of dyskinesia. Altered gamma-band connectivity within the cortico-striatal network may contribute to its pathophysiology. Buspirone appears to be a promising candidate for the treatment of LID, potentially offering a novel therapeutic strategy.
BackgroundPeople with Parkinson's disease (PwPD) have unhealthier movement behaviours (less moderate-to-vigorous physical activity (MVPA) and more sedentary behaviour (SB)), than healthy older adults. Associations across...BackgroundPeople with Parkinson's disease (PwPD) have unhealthier movement behaviours (less moderate-to-vigorous physical activity (MVPA) and more sedentary behaviour (SB)), than healthy older adults. Associations across movement patterns and non-motor characteristics are poorly understood.ObjectivesTo investigate associations between relative time spent in MVPA, light-intensity physical activities (LIPA) and SB, and non-motor characteristics among PwPD, and to investigate theoretical changes in non-motor characteristics when time in different movement behaviours is reallocated.MethodsBaseline data from 119 participants in the STEPS randomised controlled trial was used. Movement behaviours were measured by ActiGraph GT3X accelerometers. Compositional data analysis assessed relative time in MVPA, LIPA and SB. Linear regression assessed associations between MVPA, LIPA and SB and self-reported anxiety and depression (HADS), executive function (TMT IV), self-efficacy for exercise (S-ESES) and activities-specific balance confidence (ABC). Isotemporal substitution modelling investigated theoretical changes in outcomes when time in MVPA, LIPA and SB were reallocated.ResultsBetter executive function was associated with more relative time in MVPA and less in LIPA. Higher exercise-self-efficacy was associated with more relative time in MVPA and less in SB. Better balance confidence related to more relative time in MVPA. Reallocating time showed that losing 20 min MVPA had a worse theoretical impact for these outcomes than the benefit of gaining 20 min.ConclusionsThe observed relationships between MVPA and executive function, balance confidence, and exercise-self-efficacy suggests particular importance of maintaining MVPA in PwPD. These findings can be utilized clinically by communicating the importance of maintaining time in MVPA among PwPD.
Deep brain stimulation (DBS) can improve Parkinson's disease symptoms; however, its effectiveness depends on selecting optimal settings. DBS parameter selection can be challenging, as objective metrics to guide the proce...Deep brain stimulation (DBS) can improve Parkinson's disease symptoms; however, its effectiveness depends on selecting optimal settings. DBS parameter selection can be challenging, as objective metrics to guide the process are lacking. This n-of-1 study explored using functional near-infrared spectroscopy (fNIRS) to guide DBS programming. Led by the participant, the study embedded a patient perspective at the center of the project. Multiple DBS settings were tested, and their effects on gait and cortical functional connectivity were measured. The DBS program that best supported gait had the lowest functional connectivity with the left dorsolateral prefrontal cortex as seed. This suggests fNIRS may be used to guide individual optimization of DBS treatment.
Music therapy has emerged as a promising complementary intervention for Parkinson's disease (PD). PARKinSOUND, a non-randomized clinical trial, evaluated the feasibility of a community orchestra intervention for individu...Music therapy has emerged as a promising complementary intervention for Parkinson's disease (PD). PARKinSOUND, a non-randomized clinical trial, evaluated the feasibility of a community orchestra intervention for individuals with PD (n = 22), compared to a control group (n = 21). After the intervention, the orchestra group showed a modest improvement in depressive symptoms compared to baseline (Beck Depression Inventory: -0.5, p = 0.049) and controls (-5.5, p = 0.011), while motor scores (MDS-UPDRS III) remained stable. Self-reported overall improvements (PGI-C) were also higher in the orchestra group (p = 0.003). Although placebo effects may partly explain the benefits, these findings suggest emotional benefits and perceived overall improvement, providing insights for future research.
Diagnosing α-synucleinopathies and assessing target engagement in trials is hindered by the lack of reliable biomarkers. Here, we introduce a first-in-kind quantitative, highly sensitive, and disease-specific diagnostic...Diagnosing α-synucleinopathies and assessing target engagement in trials is hindered by the lack of reliable biomarkers. Here, we introduce a first-in-kind quantitative, highly sensitive, and disease-specific diagnostic assay, named Seeding Amplification ImmunoAssay (SAIA), developed and validated to detect synucleinopathy-linked disorders. To this end, we used wide range of specimens, including 38 brain homogenates (BH) and 559 cerebrospinal fluid (CSF) samples from subjects with diverse synucleinopathy disorders, non-synucleinopathy diseases, idiopathic REM sleep behavior disorder (iRBD), and controls. SAIA generated robust results detecting disease-related α-synuclein seeds in BH samples at attogram levels, as referenced to preformed fibrils of α-synuclein. Furthermore, we conducted side-by-side comparisons between SAIA and a traditional Seeding Amplification Assay (SAA), which revealed high concordance. Further, SAIA distinguished synucleinopathies from non-synucleinopathies and controls with sensitivities and specificities ranging between 80-100% and area under the curve values exceeding 0.9. SAIA also accurately identified 24/24 (100%) iRBD cases, considered a prodromal state of PD, with 100% sensitivity and 80% specificity. Further optimization of SAIA through timepoint analyses revealed that shorter incubation times enhanced the assay's specificity for distinguishing MSA from PD highlighting the potential for improved differentiation between specific synucleinopathies. In conclusion, SAIA represents a novel, high-throughput method to screen, diagnose, and monitor synucleinopathy disorders in living subjects, offering significant improvements over existing methods through its quantitative output, shorter incubation time, and simplified workflow, features that enhance its suitability for clinical trial applications.
Physical activity (PA) remains critical in the slowing of disease progression in early Parkinson's disease (PD), although the longitudinal follow-up of such studies remain scarce. Using data from an early PD Cohort, we l...Physical activity (PA) remains critical in the slowing of disease progression in early Parkinson's disease (PD), although the longitudinal follow-up of such studies remain scarce. Using data from an early PD Cohort, we longitudinally examined the impact of unprescribed PA on symptoms of early PD, controlling for demographics and medications. Over five years, the reported PA in early PD declined significantly annually. When maintained, the overall PA had significant association with improved motor symptoms, cognition, and quality of life Higher PA maintained longitudinally is associated with a slower progression of motor and non-motor symptoms, and predict better quality of life in patients with early PD.
Mild cognitive impairment and dementia are common symptoms in people with Parkinson's disease (PwPD) that impair the quality of life of those affected. However, PD-specific concepts for the prevention of cognitive declin...Mild cognitive impairment and dementia are common symptoms in people with Parkinson's disease (PwPD) that impair the quality of life of those affected. However, PD-specific concepts for the prevention of cognitive decline are rarely incorporated into routine care. Here, we provide key data on cognitive impairment in PwPD and a framework for primary, secondary, and tertiary prevention in this context. The importance of cognitive reserve as a protective buffer for cognitive decline in PwPD is highlighted. Relevant lifestyle and health-related factors, including cognitive aspects, physical and social activity, diet, hearing loss, and cardiovascular factors, are discussed. Evidence on the efficacy of possible cognition-enhancing interventions in PwPD-pharmacological, cognitive, physical, nutritional, and multidomain interventions-is summarized. On this basis, and the recommendations of the European Task Force for Brain Health Services, a proposal is developed outlining options for preventing cognitive impairment in PwPD that could be implemented in routine care, as well as further developments needed to achieve a best-case scenario. The main pillars of a strategic agenda for this purpose include: (i) regular assessment of cognitive state, overall risk, and risk factors for cognitive decline; (ii) risk communication and education concerning modifiable risk factors with standardized procedures; (iii) risk reduction with multi-domain interventions for secondary prevention; and (iv) cognitive enhancement with cognitive and physical training for tertiary prevention. As the proposal makes clear, the prevention of cognitive impairment in PwPD requires interdisciplinary collaboration organized throughout PD care networks.
J Parkinsons Dis
· 2025 Dec · PMID 41026967
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Full text
BackgroundImpaired gait initiation is a debilitating motor symptom in people with Parkinson's disease (PD). During self-paced (uncued) gait initiation, anticipatory postural adjustments (APAs) are often absent or attenua...BackgroundImpaired gait initiation is a debilitating motor symptom in people with Parkinson's disease (PD). During self-paced (uncued) gait initiation, anticipatory postural adjustments (APAs) are often absent or attenuated, and the first steps are abnormally short. External sensory cues can significantly improve APAs.ObjectiveThe effect of external cueing on lower limb muscle activation during gait initiation, compared to self-initiated steps, was examined in people with PD and healthy older adults (HOA).MethodsGround reaction forces, center of pressure excursions, and lower-limb surface electromyographic profiles (in seven bilateral muscles) were examined in 32 individuals with PD (off-medication) and 10 age-matched HOA during the APA and first step of self-paced or acoustically cued gait initiation.ResultsAnterior (tibialis anterior, vastus lateralis, rectus femoris) and gluteus medius muscles were primarily activated during the early phases of gait initiation, while later phases predominantly involved posterior (soleus, gastrocnemius, biceps femoris) and gluteus medius activations. Cueing facilitated anterior muscles and suppressed posterior muscle activity in both groups, however, activation patterns in PD were not restored to HOA levels. Instead, the PD group had lower early activity during the APA (compared to HOA) and higher late activity.ConclusionsCueing increased anterior muscle activation during gait initiation, rather than evoking a global gain across muscles and timings, demonstrating that cueing predominantly facilitates neural circuitry critical for early APA phases. People with PD showed enhanced late phase activity, probably to compensate for ineffective APAs, and thus have a stronger need to facilitate cue-evoked improvements.
Exercise is an essential part of the treatment of Parkinson's disease. However, certain symptoms can make exercise difficult. In this viewpoint, we describe an under recognized symptom called running-induced dystonia (RI...Exercise is an essential part of the treatment of Parkinson's disease. However, certain symptoms can make exercise difficult. In this viewpoint, we describe an under recognized symptom called running-induced dystonia (RID), which can prevent people with Parkinson's from exercising in their preferred way. We summarize the existing literature and use three case studies to outline potential mechanisms, aggravating and relieving factors and both pharmacological and non-pharmacological therapies to get rid of RID.
Parkinson's disease (PD) is a rapidly developing neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the basal ganglia of the brain. Its prevalence is estimated to exceed 1.2 million cases...Parkinson's disease (PD) is a rapidly developing neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the basal ganglia of the brain. Its prevalence is estimated to exceed 1.2 million cases in the United States by 2030. Emerging evidence suggests that PD may originate in the gut and hence is linked to gastrointestinal (GI) dysfunctions such as inflammatory bowel disease and GI cancers. Colorectal cancer (CRC) is one of the most common cancers seen worldwide. It shares several risk factors with PD, including advancing age, male gender, genetic predispositions, and environmental exposures. Although these shared factors indicate a possible correlation, the studies evaluating this relationship have suggested inconsistent results. Some research proposes an increased risk of CRC in PD patients, potentially due to overlapping genetic and inflammatory pathways. Alternatively, others argue an inverse relationship due to opposing underlying mechanisms of neuro degeneration in PD and cellular proliferation in CRC. This narrative review explores the intricate relationship between PD and CRC and seeks to understand how neurodegenerative and malignant diseases may overlap.
BackgroundSleep disturbances are prevalent and debilitating non-motor symptoms in patients with Parkinson's disease (PD).ObjectiveThis study aimed to explore sleep architecture and the prevalence of polysomnographic (PSG...BackgroundSleep disturbances are prevalent and debilitating non-motor symptoms in patients with Parkinson's disease (PD).ObjectiveThis study aimed to explore sleep architecture and the prevalence of polysomnographic (PSG) sleep findings in PD, examining the associations between sleep parameters and other clinical characteristics.MethodsThe study included 97 PD patients (age: 67.1 ± 7.9) and 42 non-PD controls (age: 64.7 ± 9.7). Participants underwent clinical assessment and video-PSG. Sleep parameters, apnea-hypopnea index (AHI), periodic limb movements index (PLMI), and REM sleep without atonia (RSWA) were obtained. General linear models were used to explore interactions between disease duration and sleep variables in predicting PD symptoms.ResultsNearly 94% of PD patients showed at least one video-PSG-assessed sleep finding, including AHI-defined obstructive sleep apnea (OSA), periodic limb movements, and RSWA. Sleep alterations correlated with disease severity, with reduced sleep duration and efficiency, higher sleep latency, and higher AHI being associated with worse PD severity. Sleep efficiency was more strongly associated with motor symptoms and disease severity at longer disease duration, while AHI exhibited a stronger relationship with motor symptoms at shorter disease duration. Finally, PD patients showed significant alterations in sleep macrostructure compared to controls, including reduced sleep duration ( = 0.75) and efficiency ( = 1.15) and decreased percentage of stage 3 non-REM sleep ( = 0.37).ConclusionsThe study showed a high prevalence of video-PSG-defined sleep findings in PD, with interactions between disease duration, sleep efficiency, and AHI. The present results support personalized management of sleep disturbances in PD to potentially improve symptoms and reduce the burden of illness.
Mancini et al.'s framework for gait assessment in Parkinson's disease (PD) is a valuable contribution, enabling a harmonization of study protocols in this research field and, consequently, a substantial improvement of da...Mancini et al.'s framework for gait assessment in Parkinson's disease (PD) is a valuable contribution, enabling a harmonization of study protocols in this research field and, consequently, a substantial improvement of data interpretation across different cohorts. However, we believe that recommendations concerning data curation and software use should be provided in more detail. To ensure data interoperability and facilitate robust data aggregation from such protocols, appropriate and harmonized data formatting and metadata standards are necessary. We further advocate for the open sharing of gait analysis algorithms, to enhance reproducibility and foster collaborative development.
BackgroundApathy, defined as a quantitative reduction in goal-directed activity, is a non-motor manifestation that can be present in Parkinson's disease (PD). It seems to be a risk factor for conversion to dementia (PDD)...BackgroundApathy, defined as a quantitative reduction in goal-directed activity, is a non-motor manifestation that can be present in Parkinson's disease (PD). It seems to be a risk factor for conversion to dementia (PDD) in this population. Amyloid-β deposition also predicts progression to PDD.ObjectiveWe aimed to investigate whether PD patients with apathy showed higher amyloid burden than those without, as well as how these features may influence the rate of progression to dementia.MethodsWe conducted an observational cross-sectional and longitudinal study. Forty-eight PD patients were recruited, including 20 with apathy and 28 without it according to the Starkstein Apathy Scale. They underwent clinical and cognitive evaluations and [F]-Flutemetamol PET. The neuropsychological assessment was repeated after 3 years. The predictive value of apathy and amyloid burden for conversion was assessed via logistic regression. Longitudinal trajectories across neuropsychological tests were modeled with linear mixed-effects.ResultsPatients with apathy showed worse performance on several cognitive domains. Using disease duration and global cognition Z-score as covariates, amyloid burden was higher in apathetic vs. non-apathetic patients, mainly in the frontal and temporal cortices. Non-apathetic patients did not have regions with higher amyloid burden in comparison with apathetic patients. After 3 years' follow-up, the conversion rate to worse cognitive state was significantly higher in apathetic (47.4%) vs. non-apathetic (12.0%) patients (p < 0.05). Logistic regression showed that amyloid burden, but not apathy, predicted 3-year cognitive conversion (χ² = 9.95, p < 0.05).ConclusionsApathetic patients exhibit greater amyloid burden and higher cognitive deterioration over time than their non-apathetic counterparts.
Gut microbiome alterations are increasingly linked to Parkinson's disease (PD), yet regional signatures remain underexplored. We performed shotgun metagenomic sequencing of stool samples from Egyptian PD patients and hea...Gut microbiome alterations are increasingly linked to Parkinson's disease (PD), yet regional signatures remain underexplored. We performed shotgun metagenomic sequencing of stool samples from Egyptian PD patients and healthy controls. PD patients exhibited depletion of short-chain fatty acid-producing taxa, and enrichment of pathobionts. Our findings suggested a pro-inflammatory gut shift in PD and emphasized the need for geographically diverse microbiome studies. While limited in sample size (n = 7 PD patients and n = 6 controls), this pilot addressed a critical gap in African PD microbiome research.
BackgroundAtypical parkinsonian syndromes are highly prevalent in the French West Indies (FWI), making up 70% of degenerative parkinsonisms and including "Caribbean Atypical Parkinsonism". Environmental neurotoxins from...BackgroundAtypical parkinsonian syndromes are highly prevalent in the French West Indies (FWI), making up 70% of degenerative parkinsonisms and including "Caribbean Atypical Parkinsonism". Environmental neurotoxins from plants are implicated. Despite close ties, parkinsonism data for French Guiana remain limited.ObjectiveThis study aimed to compare atypical parkinsonism frequencies between French Guiana and FWI, assess clinical characteristics in French Guiana, and evaluate potential environmental toxin exposure.MethodsDegenerative parkinsonism patients were recruited from a community-based population in French Guiana and compared with a FWI cohort.ResultsAmong 372 patients (67 from French Guiana, 305 from FWI), atypical parkinsonian syndromes accounted for 41.8% in French Guiana, lower than in FWI (66.2%, p < 0.001). In French Guiana, these syndromes were more common in males (sex-ratio: 3 vs. 1.22 in FWI, p = 0.044; adjusted p-value = 0.281) and often involved cerebellar symptoms (p < 0.001). Cases not fitting classical subtypes were classified as "other atypical parkinsonian syndromes" (35.7% in French Guiana, 41.6% in FWI), with a supranuclear palsy-like phenotype often presenting with additional rapid eye movement (REM) sleep behavior disorder, hallucinations, or orthostatic hypotension. consumption was higher in FWI (93%) than in French Guiana (79.2%, p < 0.001), while alcohol use was more common in French Guiana (p = 0.005).ConclusionsAtypical parkinsonism in French Guiana resembles that in FWI but is less common, with an intermediate prevalence between Caucasian and Caribbean populations. Shared environmental factors, such as exposure, may contribute to this presentation, supporting the term "Caribbean Atypical Parkinsonism" for both regions.
Previous studies have shown differences in the microbiota of patients with Parkinson's disease (PD) compared to healthy controls (HC). To deduce a possible causality, it is highly relevant to examine changes in the prodr...Previous studies have shown differences in the microbiota of patients with Parkinson's disease (PD) compared to healthy controls (HC). To deduce a possible causality, it is highly relevant to examine changes in the prodromal phase. This study investigated the microbiome in stool samples of individuals with isolated REM sleep behavior disorder (iRBD, n = 32) compared to clinical PD (n = 23) and HC (n = 34) and showed significant changes of beta-diversity in PD and iRBD patients compared to HC ( = 0.025; = 0.003), with an increase in proinflammatory species in iRBD and PD and decrease in SCFA-producing bacteria in PD.