Pesticides and lifestyle factors are associated with disease severity of Parkinson's disease: a longitudinal study

ObjectiveTo longitudinally analyze the impact of the environment and lifestyle on PD motor sign severity in LRRK2 p. Gly2019Ser-related PD (LRRK2-PD) and idiopathic PD (iPD). BackgroundThere is increasing evidence that the environment impacts disease severity. Recent studies have shown that pesticide exposure is associated with a faster disease progression. However, the relationship between smoking, caffeine, and disease severity has not yet been investigated longitudinally. MethodsIn this longitudinal study, we included patients with iPD from the PPMI Online (N=2815) and Fox Insight (N=2319) cohorts, as well as patients with LRRK2-PD (N=81) from Fox Insight. Motor signs were assessed with the MDS-UPDRS Part II, and patients were assessed multiple times, followed up to 35 months or 60 months in the PPMI Online or Fox Insight cohort, respectively. The motor sign severity over time was analyzed by applying a linear mixed effects model. The outcome was the cumulative score of the MDS-UPDRS Part II questionnaire. Subsequently, we investigated the association between environmental exposure, lifestyle factors and motor signs. Pesticide exposure in a work setting, smoking, coffee, black tea, green tea, and caffeinated soda consumption were assessed using the validated PD-RFQ-U questionnaires. The mixed effects model included the environmental and lifestyle factors as binary (yes/no) variables. ResultsWhen comparing LRRK2-related PD and iPD, motor signs were less severe in patients with LRRK2-PD compared to iPD ({beta}=-0.23, p=0.005). In LRRK2-PD, black tea consumption was associated with less severe motor signs ({beta}=-0.51, p=0.028). In patients with iPD, we observed that pesticide exposure was associated with more severe motor signs over time in PPMI-Online ({beta}=0.23, p=3.56x10-9). Smoking was associated with a higher motor signs score in PPMI-Online ({beta}=0.13, p=0.001). Lastly, caffeinated soda was associated with more severe motor signs in patients with iPD from PPMI-Online ({beta}=0.15, p=3.84x10-8) and Fox Insight ({beta}=0.09, p=0.031). ConclusionsOur results provide further evidence of the importance of environment and lifestyle in PD, even after the disease onset. We suggest that pesticide exposure and lifestyle factors may affect disease severity in patients with LRRK2-PD and iPD; still, further validation is necessary.