The age‐standardized prevalence of Parkinson's disease (PD) has increased substantially over the years and is expected to increase further. This emphasizes the need to identify modifiable risk factors of PD, which could form a logical entry point for the prevention of PD. The World Health Organization (WHO) has recommended reducing exposure to specific environmental factors that have been reported to be associated with PD, in particular pesticides, trichloroethylene (TCE), and air pollution. In this review we critically evaluate the epidemiological and biological evidence on the associations of these factors with PD and review evidence on whether these putative associations are causal. We conclude that when considered in isolation, it is difficult to determine whether these associations are causal, in large part because of the decades‐long lag between relevant exposures and the incidence of manifest PD. However, when considered in tandem with evidence from complementary research lines (such as animal models), it is increasingly likely that these associations reflect harmful causal effects. Fundamentally, whilst we highlight some evidence gaps that require further attention, we believe the current evidence base is sufficiently strong enough to support our call for stronger policy action. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease‐modifying therapies.Objective: The aim was to evaluate a blood‐based α‐synuclein seed amplification assay (α‐syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase.Methods: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α‐syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α‐syn‐SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed.Results: All individuals with PD showed positive immunoblots and a positive α‐syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α‐syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α‐syn SAA. All healthy controls had a negative SAA.Conclusions: We here demonstrate the possibility to detect and amplify pathological α‐syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood‐based α‐syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The increasing global burden of Parkinson’s disease (PD), termed the PD pandemic, is exceeding expectations related purely to population aging and is likely driven in part by lifestyle changes and environmental factors. Pesticides are well recognized risk factors for PD, supported by both epidemiological and experimental evidence, with multiple detrimental effects beyond dopaminergic neuron damage alone. The microbiome-gut-brain axis has gained much attention in recent years and is considered to be a significant contributor and driver of PD pathogenesis. In this narrative review, we first focus on how both pesticides and the microbiome may influence PD initiation and progression independently, describing pesticide-related central and peripheral neurotoxicity and microbiome-related local and systemic effects due to dysbiosis and microbial metabolites. We then depict the bidirectional interplay between pesticides and the microbiome in the context of PD, synthesizing current knowledge about pesticide-induced dysbiosis, microbiome-mediated alterations in pesticide availability, metabolism and toxicity, and complex systemic pesticide-microbiome-host interactions related to inflammatory and metabolic pathways, insulin resistance and other mechanisms. An overview of the unknowns follows, and the role of pesticide-microbiome interactions in the proposed body-/brain-first phenotypes of PD, the complexity of environmental exposures and gene-environment interactions is discussed. The final part deals with possible further steps for translation, consisting of recommendations on future pesticide use and research as well as an outline of promising preventive/therapeutic approaches targeted on strengthening or restoring a healthy gut microbiome, closing with a summary of current gaps and future perspectives in the field.

Objective To evaluate the point of view of patients with Parkinson disease (PD) on early detection and risk disclosure in the prodromal phase of PD and to derive recommendations for an ethical framework for the recruitment of prodromal PD cohorts. Methods A standardized questionnaire to evaluate the patients9 perception on early diagnosis in PD was designed by an interdisciplinary study group. After testing in a preliminary feasibility study (n = 20), the survey was performed retrospectively with patients from our clinic. Results A total of 101 patients with PD answered the questions. The majority of patients reported that time from onset of motor symptoms to diagnosis was burdensome, including false diagnoses and many consultations of various medical specialists. However, most of the patients evaluated early risk disclosure with skepticism. Freedom of choice and the potential of changes in lifestyle were rated as important. Conclusion Although patients with PD reported the time to diagnosis retrospectively as burdensome, the majority was skeptical regarding early disclosure of risk, especially with regard to the lack of pharmacologic options. Circumstances under which early detection and disclosure would have been approved by the majority of patients were (1) advice on lifestyle changes (exercise, nutrition) as potentially disease course–modifying therapy; (2) the establishment of an early diagnosis “culture,” including early clarification of the patients9 wish to know; and (3) regular support and follow-up of individuals after risk disclosure.

Background: Skin biopsy is a potential tool for the premortem confirmation of an α‐synucleinopathy.Objective: The aim was to assess the aggregation assay real‐time quaking‐induced conversion (RT‐QuIC) of skin biopsy lysates to confirm isolated rapid eye movement sleep behavior disorder (iRBD) as an α‐synucleinopathy.Methods: Skin biopsies of patients with iRBD, Parkinson's disease (PD), and controls were analyzed using RT‐QuIC and immunohistochemical detection of phospho‐α‐synuclein.Results: α‐Synuclein aggregation was detected in 97.4% of iRBD patients (78.4% of iRBD biopsies), 87.2% of PD patients (70% of PD biopsies), and 13% of controls (7.9% of control biopsies), with a higher seeding activity in iRBD compared to PD. RT‐QuIC was more sensitive but less specific than immunohistochemistry.Conclusions: Dermal RT‐QuIC is a sensitive method to detect α‐synuclein aggregation in iRBD, and high seeding activity may indicate a strong involvement of dermal nerve fibers in these patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.