Organophosphate and pyrethroid pesticides are widely used, but their combined effects on brain health remain unclear. This study analyzed observational research from 2014 to 2024 on their simultaneous exposure and its association with neurobehavioral, neurodegenerative, and neurological disorders through a systematic review following PRISMA guidelines in PubMed and Web of Science. Studies assessing co-exposure with validated methods and reporting brain health outcomes were included, while reviews, animal studies, and those without simultaneous exposure data were excluded. Risk of bias in cohort studies was evaluated using ROBINS-E. Of the 34 studies included, nine were cohort studies, four with low risk of bias and four with concerns related to sample size or exposure assessment. Three linked co-exposure to attention deficits and cognitive decline in children. Evidence on neurodegenerative diseases and autism spectrum disorder was inconsistent due to conflicting results. Cross-sectional and case-control studies associated co-exposure with depression and anxiety but lacked follow-up data. Variability in exposure assessment reduced comparability. Research remains limited, indicating possible neurodevelopmental effects and the need for standardized methodologies to refine risk assessment.

The authors have declared no competing interest.

Funding for this study was provided by FONDECYT 1240899, awarded by the Agencia Nacional de Investigacion y Desarrollo (ANID) of the Chilean Government

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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The data used in the systematic review are derived from publicly available sources (PubMed and Web of Science). Supplementary datasets could be available only from the corresponding author on reasonable request (mtmunozuchile.cl)

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