{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T09:43:18Z","timestamp":1776418998483,"version":"3.51.2"},"posted":{"date-parts":[[2026,3,18]]},"group-title":"Occupational and Environmental Health","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,14]]},"abstract":"<jats:sec>\n                  <jats:title>Background\/Objectives<\/jats:title>\n                  <jats:p>Occupational exposure to neurotoxicants, including pesticides and metals, has been implicated in Parkinson\u2019s disease (PD) and Parkinsonism. However, the cumulative impact of lifetime occupational exposures remains insufficiently characterized. This study evaluated whether semi-quantitative, ALOHA+ Job-Exposure Matrix (ALOHA+-JEM) \u2013 derived cumulative occupational exposures were associated with PD and Parkinsonism.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a hospital-based matched case\u2013control study in Brescia, Italy, (n = 668; 334 PD\/Parkinsonism cases and 334 matched controls), 1:1 matched on sex, age, and lifetime occupational duration. Lifetime occupational histories were coded using ISCO classification and linked to the ALOHA+-JEM to derive cumulative exposure metrics (unexposed\/low\/high) for major occupational agent families. Associations were estimated using conditional logistic regression adjusting for smoking, parental history of PD\/tremor, and SNCA rs356219 genotype. Weighted Quantile Sum (WQS) regression was applied as a secondary analysis to explore co-exposure structure and relative contributions to a composite occupational exposure burden index.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Parental history of PD or tremor (OR = 4.55, 95% CI: 2.44\u20138.48; q &lt; 0.001) and the SNCA rs356219 CC genotype (OR = 2.17, 95% CI: 1.33\u20133.52; q = 0.013) were associated with disease, consistent with established risk factors. High cumulative pesticide exposure was nominally associated with increased odds of combined PD and Parkinsonism (OR = 2.98, 95% CI: 1.23\u20137.25) and PD alone (OR = 3.56, 95% CI: 1.25\u201310.15); however, these associations did not remain statistically significant after false discovery rate correction. Other exposure families were not consistently associated with disease. In WQS analyses, the composite occupational exposure burden index showed modest positive association with combined PD and Parkinsonism (OR = 1.15, 95% CI: 1.00\u20131.30). All pesticides and metals contributed most strongly to the index, although estimates were imprecise, particularly in the subgroup analysis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ALOHA+-JEM-derived cumulative occupational exposures showed suggestive but modest associations with PD and Parkinsonism, with pesticides contributing most consistently across analyses. These findings should be interpreted cautiously given the semi-quantitative nature of exposure assessment and limited statistical significance after multiple testing correction. Overall, the results support a potential role for cumulative occupational exposures in Parkinsonian disorders, while highlighting the need for studies incorporating more resolved exposure assessment approaches.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.16.26348171","type":"posted-content","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:40:18Z","timestamp":1773873618000},"source":"Crossref","is-referenced-by-count":0,"title":["LIFETIME JEM-DERIVED OCCUPATIONAL EXPOSURE BURDEN AND ODDS OF PARKINSON\u2019S DISEASE AND PARKINSONISM IN A MATCHED CASE-CONTROL STUDY"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5606-8926","authenticated-orcid":false,"given":"Freeman","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Renzetti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, Parma 43121, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Goulett","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somaiyeh","family":"Azmoun","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishnavi","family":"Sundar","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahnoor","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Pitta","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Shoieb","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margherita","family":"Caci","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Borghesi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"Covolo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Oppini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umberto","family":"Gelatti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Padovani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-6606","authenticated-orcid":false,"given":"Andrea","family":"Pilotto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulvio","family":"Pepe","sequence":"additional","affiliation":[{"name":"Clinic of Neurology, Poliambulanza Foundation, Brescia 25124, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinella","family":"Turla","sequence":"additional","affiliation":[{"name":"Clinic of Neurology, Esine Hospital of Valcamonica, Esine 25040, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Crippa","sequence":"additional","affiliation":[{"name":"Teresa Camplani Foundation, Domus Salutis, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Boffetta","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, Bologna 40126, Italy"},{"name":"Department of Family, Population and Preventive Medicine Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Pani","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena 41121, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roel","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3584 CJ, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Kromhout","sequence":"additional","affiliation":[{"name":"Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3584 CJ, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Lambertini","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Colicino","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine and Climate Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Placidi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Lucchini","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"},{"name":"Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, sede ex-Sc. 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