npj Parkinson's Disease

Parkinsons disease (PD) is characterized by a long prodromal phase with a multitude of markers indicating an increased PD risk prior to clinical diagnosis based on motor symptoms. Current PD prediction models do not consider interdependencies of single predictors, lack differentiation by subtypes of prodromal PD, and may be limited and potentially biased by confounding factors, unspecific assessment methods and restricted access to comprehensive marker data of prospective cohorts. We used prosp...

Characterization of Parkinsons disease (PD) progression using real-world evidence could guide clinical trial design and identify subpopulations. Efforts to curate research populations, the increasing availability of real-world data and recent advances in natural language processing, particularly large language models, allow for a more granular comparison of populations and the methods of data collection describing these populations than previously possible. This study includes two research popu...

A definitive diagnostic test for PD remains elusive, so identification of potential biomarkers may shed light on methods for diagnosis and facilitate early intervention. Excess sebum secretion and skin pathology are recognised symptoms of early PD. It is likely these result in a unique signature of volatile organic compounds that could be used to identify early stages of disease. Numerous medical conditions produce distinctive odours, and dogs have been trained to detect many of these. A single ...

BackgroundSensitive outcome measures are critical for evaluating the efficacy of novel treatments for Parkinson disease (PD). Recently, we demonstrated that a tremor detection algorithm could reliably detect and quantify real-life PD tremor from wearable sensor data. Here, we assess the sensitivity to change of sensor-derived daily-life tremor measures over two years in an unmedicated and medicated cohort of persons with early PD. MethodsWe used two-year continuous wrist sensor data (median wea...

BackgroundThe prodromal phase of Parkinsons disease (PD), much like the disease itself, displays marked heterogeneity, with varied rates of progression and symptom severities. A detailed clinical characterization of prodromal subgroups may provide useful insights for both clinical and research settings. ObjectivesTo compare clinical assessments in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and those with isolated hyposmia. MethodsA cross-sectional study was cond...

ObjectivesIdentifying the contribution of biological sex to the heterogeneity in presentation and progression of Parkinsons disease (PD). BackgroundThe different prevalence of Parkinsons disease (PD) in men and women suggests that sex-associated mechanisms influence disease mechanisms. Investigating the contribution of sex to disease heterogeneity may uncover disease processes, and lead to new therapeutic targets. Also, understanding these differences in phenotypes will result in better patient...

BackgroundThe diagnostic precision of Parkinsonian disorders is not accurate enough. Even in expert clinics up to one in five diagnoses are incorrect. This leads to cohorts with mixed pathologies, impacting our ability to understand disease heterogeneity and posing a major challenge for clinical trials. Gold standard diagnosis is post-mortem confirmation of the underlying proteinopathy, however many clinicopathological studies focus on either a single disease or frame analyses in one temporal di...

BackgroundParkinsons disease (PD) is associated with multiple clinical manifestations including motor and non-motor symptoms, and understanding of its etiologies has been informed by a growing number of genetic mutations, and various fluid-based and brain imaging biomarkers. However, the precise mechanisms by which these phenotypic features interact remain elusive. Therefore, we aimed to generate the phenotypic association graph of multiple heterogeneous features within PD to reveal pathological...

The gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinsons disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing 10 c...

IntroductionEmerging technologies show promise for enhanced characterization of Parkinsons Disease (PD) motor manifestations. We evaluated quantitative mobility measures from a wearable device compared to the conventional motor assessment, the Movement Disorders Society-Unified PD Rating Scale part III (motor MDS-UPDRS). MethodsWe evaluated 176 subjects with PD (mean age 65, 65% male, 66% H&Y stage 2) at the time of routine clinic visits using the motor MDS-UPDRS and a structured 10-minute moto...

The aetiology of Parkinsons disease (PD) has been linked to the aggregation and spread of misfolded alpha-synuclein via the gut-brain axis. We previously reported the effects of a biological response modifier, beta-glucan, produced by the AFO-202 strain of Aureobasidium Pullulans, which improves clinical symptoms and controls gut Enterobacteriaceae associated with curli and amyloid-alpha-synuclein production. In this study, we report the effects of beta-glucan on PD. Eight patients with PD were ...

ObjectiveTo rapidly identify areas of need and improve care in people with Parkinsons disease (PwPD) affected by the COVID-19 pandemic, we deployed a survey focusing on the presentation and complications of COVID-19 infection and the effect of the COVID-19 pandemic among those not infected. MethodsIndividuals with and without PD participating in the online study Fox Insight (FI) were invited to complete an online survey between April 23-May 23, 2020. Among people reporting COVID-19 diagnosis, w...

Fecal gut microbiota changes are associated with Parkinsons disease (PD). However, disease related changes cannot readily be discerned from medication effects, as almost all participants in previous studies were using PD medication, and conclusive longitudinal data related to treatment initiation is lacking. Here, fecal gut microbiota composition was assessed in 62 de novo PD participants who were untreated at baseline and used PD medication at one-year follow-up, by means of 16S-sequencing. In ...

BackgroundHyposmia, motor impairment and probable REM-sleep behaviour disorder (RBD) are markers for Parkinsons disease (PD). Proposed PD risk prediction models have dichotomised test results and applied likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance prediction models. MethodsSmell and probable RBD data for PD patients were taken from the Tracking Parkinsons study (n=1046). For motor impairment previously published d...

Speech-related changes hold promise as biomarkers in Parkinsons disease (PD), yet evidence remains preliminary and higher-order language alterations are under-characterised. Leveraging data from 1,168 participants with PD and 541 controls within the Australian Parkinsons Genetics Study, we report population-level evidence of PD-associated linguistic and affective alterations. Participants with PD exhibited reduced fluency and expressivity, with slower rate, lower reading accuracy, reduced output...

Background and ObjectivesIsolated Rapid Eye Movement (REM) sleep behavior disorder (iRBD) is a sleep disorder associated with neurodegenerative diseases such as Parkinsons disease and dementia with Lewy bodies. Predicting which iRBD patients will phenoconvert to neurodegenerative diseases is crucial for prognosis and management. The objective of this study is to develop a machine learning model using clinical markers to predict phenoconversion in patients with RBD. MethodsAnalyzing a cohort of ...

BackgroundData-driven approaches identified Mild Motor Predominant (MMP), Intermediate (IM), and Diffuse Malignant (DM) as Parkinsons Disease (PD) subtypes with different motor and non-motor impairment at diagnosis. It remains unclear whether these subtypes remain stable over time or whether they represent distinct biological substrates. The alpha-synuclein seed amplification assay in CSF (CSF-Syn-SAA) might provide further insights. Objectiveto evaluate the association between baseline CSF-Syn...

Apathy is a prevalent non-motor symptom that significantly impacts the quality of life in Parkinsons disease (PD) patients. Although previous studies have investigated the neural correlates of apathy in PD, the longitudinal relationships between regional brain atrophy, white matter hyperintensities (WMHs), and apathy progression remain underexplored. Using longitudinal, multisite data of de novo PD patients from the Parkinsons Progression Markers Initiative (PPMI), the present study aims to inve...

BackgroundBrain structure abnormalities throughout the course of Parkinsons disease (PD) have yet to be fully elucidated. Inconsistent findings across studies may be partly due to small sample sizes and heterogeneous analysis methods. Using a multicenter approach and harmonized analysis methods, we aimed to overcome these limitations and shed light on disease stage-specific profiles of PD pathology as suggested by in vivo neuroimaging. MethodsIndividual brain MRI and clinical data from 2,367 PD...

Despite extensive research, current treatment of Parkinsons Disease (PD) remains symptomatic and disease modifying approaches are urgently required. A promising approach is to target the gut-brain-axis by modifying the intestinal microbiota and the herein produced metabolites. We decided to test this approach by modifying key metabolites of bacterial intestinal fermentation: short chain fatty acids (SCFA), known to be decreased in PD patients. A prospective, controlled pilot study was conducted...