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However, several questions remain unanswered, pertaining to the associations with PD of environmental factors that are still in use today; the added risks of co-exposure to multiple environmental factors and gene\u2013environment interactions. Additional questions remain on the relevant time window, duration, and level of environmental exposures in relation to PD risk. Furthermore, it is unclear whether these exposures are associated with clinical progression of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PD-PEST (Parkinson\u2019s Disease\u2013Preventing Emergence of Symptoms by environmental Toxicants) is a nationwide hospital-based case\u2013control study conducted in the Netherlands. The study population consists of 1500 persons with a recent PD diagnosis and 3000 age- and sex-matched controls. Participants will be recruited from four regions across the Netherlands to ensure a representative geographical distribution in terms of urbanisation, industry, and agricultural activity. Cases must have a PD diagnosis, established by a neurologist in the Netherlands according to standard diagnostic criteria. Controls are outpatients with a different neurological condition that is unlikely to be associated with the environmental factors of interest or the risk of PD. We will collect detailed information on historical and current environmental exposures at an individual level. This includes occupational and residential histories (via questionnaires and nationwide registries) and measurements (blood, saliva, faeces, hair, and via silicone wristbands). Based on these multimodal data, we will estimate participants\u2019 individual lifetime exposure to environmental factors. Then, we will examine the associations between these exposures and the risk of PD. In addition, we will assess longitudinal associations between exposures and clinical progression of individuals with PD over 36 months. Analyses will be adjusted for possible confounders and multiple hypothesis testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The PD-PEST study aims to overcome the limitations of previous studies by examining a large, representative study population, incorporating detailed information on clinical PD diagnosis, conducting extensive assessments of historical and current environmental risk factors and collecting detailed information on possible confounders. The results are expected to enhance our understanding of the role of environmental factors in the aetiology of PD and inform preventive strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The Medical Ethical Committee Oost-Nederland approved this study (NL86526.091.24). Informed consent will be obtained from each participant prior to participation in any of the study procedures. Findings of this study will be disseminated through publications, conferences, stakeholder briefings, and tailored communication materials for participants and the wider Parkinson community.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>Open Science Framework, January 2025 (osf.io\/4q9vs).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-120886","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:54:28Z","timestamp":1782914068000},"page":"e120886","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Parkinson-PEST: protocol for a case\u2013control study on environmental risk factors and Parkinson\u2019s disease"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8275-9613","authenticated-orcid":false,"given":"Jolien S","family":"Bogers","sequence":"first","affiliation":[{"name":"Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands"},{"name":"Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirwan K L","family":"Darweesh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastiaan R","family":"Bloem","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar H","family":"Hepp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thies","family":"van Asseldonk","sequence":"additional","affiliation":[{"name":"Department of Neurology, Elisabeth-TweeSteden Ziekenhuis, Tilburg, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teus","family":"van Laar","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel C H","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Peters","sequence":"additional","affiliation":[{"name":"Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"2026070106252210000_16.7.e120886.1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(24)00038-3"},{"key":"2026070106252210000_16.7.e120886.2","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2024-080952","article-title":"Projections for prevalence of Parkinson\u2019s disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021","volume":"388","author":"Su","year":"2025","journal-title":"BMJ"},{"key":"2026070106252210000_16.7.e120886.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01419-8"},{"key":"2026070106252210000_16.7.e120886.4","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(16)30230-7"},{"key":"2026070106252210000_16.7.e120886.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.12.008"},{"key":"2026070106252210000_16.7.e120886.6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae188"},{"key":"2026070106252210000_16.7.e120886.7","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae142"},{"key":"2026070106252210000_16.7.e120886.8","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa167"},{"key":"2026070106252210000_16.7.e120886.9","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.3233\/JPD-230250","article-title":"The Etiology of Parkinson\u2019s Disease: New Perspectives from Gene-Environment Interactions","volume":"13","author":"Bogers","year":"2023","journal-title":"J Parkinsons Dis"},{"key":"2026070106252210000_16.7.e120886.10","doi-asserted-by":"crossref","unstructured":"Goldman SM , Musgrove RE , Jewell SA , et al . 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