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Occupational Pesticide Exposure and Regional Brain Volume Differences in UK BioBank

Johnson, S.; Loughnan, R.; Boyle, M. E. T.; Ahern, J.; Kehl, A.

2025-12-29 epidemiology
10.64898/2025.12.22.25342092
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BackgroundParkinsons Disease (PD) is a progressive neurodegenerative disorder influenced by both genetic and environmental factors. Prolonged exposure to pesticides has been proposed as an environmental risk factor, yet its relationship with structural brain differences in human adults remains unexplored. ObjectiveTo investigate the association between occupational pesticide exposure and volumetric differences in specific brain regions, and to evaluate the relationship between pesticide exposure and PD diagnosis using data from UK BioBank. MethodsStructural MRI (T1-weighted scans) were used to extract regional brain volumes. The study population contained 21,049 UK BioBank participants, of which 912 participants indicated they had occupational pesticide exposure. General linear models were utilized to assess the association between pesticide exposure and regional brain volume differences, adjusting for participant demographics, socioeconomic status, study site where imaging was conducted, and genetic principal components as covariates. A Cox proportional hazards model was utilized to assess the association between pesticide exposure and PD diagnosis (ICD-10 code G20). ResultsSignificant negative associations were observed between occupational pesticide exposure and volumes of total gray matter, cortex, thalamus, ventral diencephalon, cerebellum cortex, cerebellum white matter, and brainstem. Significant positive associations were observed between occupational pesticide exposure and white matter hyperintensities and inferior lateral ventricle volumes. No significant hemispheric lateralization was observed, and adjusting for fluid intelligence scores did not significantly change model estimate values, demonstrating brain volumetric and pesticide associations were not confounded by differences in fluid intelligence. A trending, non-significant association between pesticide exposure and PD diagnosis was observed (Odds Ratio (95% CI) 1.36 (0.98 to 1.90) p=<0.12). ConclusionOccupational pesticide exposure is associated with structural reductions in volume within several brain regions, and increases in white matter hyperintensities and ventricular volume, supporting a possible neurodegenerative effect. This is the first large scale study to link adult pesticide exposure to region-specific brain volume differences utilizing non-invasive structural neuroimaging. These findings highlight a putative link between pesticide exposure and gross neuroanatomical changes in adulthood which may impact overall brain health.

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