Organophosphate pesticides and PON1 L55M in Parkinson's disease progression

- Residential proximity to agricultural organophosphate application is associated with faster cognitive and motor symptom decline among Parkinson's disease (PD) patients.
- PON1 L55M, which influences organophosphate metabolism, may modify the influence of organophosphates on cognitive decline among PD patients (p for interaction = 0.036).
- The PON1 55MM genotype, which decreases PON1 activity, is associated with faster PD motor symptom progression and depressive symptoms after Parkinson's diagnosis.

BackgroundParkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression.ObjectiveTo investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD.MethodsWe followed a longitudinal cohort of 246 incident PD patients on average over 5 years (7.5 years after diagnosis), repeatedly measuring symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures were generated with a geographic information system (GIS) based exposure assessment tool. We employed repeated-measures regression to assess associations between OP exposure and/or PON1 L55M genotype and progression.ResultsHigh OP exposures were associated with faster progression of motor (UPDRS β = 0.24, 95% CI = − 0.01, 0.49) and cognitive scores (MMSE β = − 0.06, 95% CI = − 0.11, − 0.01). PON1 55MM was associated with faster progression of motor (UPDRS β = 0.28, 95% CI = 0.08, 0.48) and depressive symptoms (GDS β = 0.07; 95% CI = 0.01, 0.13). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (β = − 1.26, 95% CI = − 2.43, − 0.09).ConclusionOur study provides preliminary support for the involvement of OP pesticides and PON1 in PD-related motor, cognitive, or depressive symptom progression. Future studies are needed to replicate findings and examine whether elderly populations generally are similarly impacted by pesticides or PON1 55M genotypes.