Objective: To longitudinally analyze the impact of the environment on PD symptom severity in LRRK2 p.Gly2019Ser (LRRK2-PD) and iPD.

Background: Smoking, black tea consumption and NSAIDs intake are associated with later onset and caffeinated soda consumption with earlier onset in LRRK2-PD. There is increasing evidence that the environment impacts disease severity as well. Besides pesticides, which have recently been found to be associated with faster PD progression, the association with smoking, caffeine and NSAIDs has not yet been investigated longitudinally.

Method: We included patients with LRRK2-PD (N=153) and iPD (N=4,960) from the Fox Insight cohort. Motor signs were assessed using the MDS-UPDRS Part II, and non-motor symptoms were assessed using the “Your Non-movement Experiences” questionnaires. Patients were followed up for up to 60 months with up to seven individual assessment time points. Environmental and lifestyle data were evaluated using the validated PD-RFQ-U questionnaires. Linear mixed effect models were applied to longitudinally explore the association between environment/lifestyle and symptom severity. The outcome was the cumulative score of the sign/symptom questionnaire. The assessment time points, exposure (binary variable: yes/no), disease duration, AAO and experience of OFF episodes were used as fixed effects and the patient ID as the random effect. The analyses were exploratory and not corrected for multiple testing.

Results: In LRRK2-PD, aspirin intake (β=0.59, p=0.021) was associated with more severe motor signs, whereas no association was found with non-motor symptoms.

In iPD, we observed that pesticide exposure, caffeinated soda consumption and NSAIDs intake were associated with more severe motor signs (pesticides: β=0.12, p=0.033, caffeinated soda: β=0.09, p=0.041, ibuprofen: β=0.10, p=0.032). Furthermore, we observed that pesticide exposure, caffeinated soda consumption and NSAIDs intake were associated with more severe non-motor symptoms as well (pesticides: β=0.09, p=0.016, caffeinated soda: β=0.10, p=0.0003, smoking: β=0.06, p=0.013, ibuprofen: β=0.17, p=0.038, aspirin= β=0.09, p=0.006).

Conclusion: Our exploratory study suggests that the environment affects disease severity in patients with LRRK2-PD and iPD; still, further validation will be required.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/environmental-factors-are-associated-with-disease-severity-of-lrrk2-related-parkinsons-disease-and-idiopathic-parkinsons-disease-a-longitudinal-study/