Objective: The present study aims to investigate the link between Parkinson’s disease (PD) motor subtype and PD-relevant pesticide exposures.

Background: PD is a neurodegenerative disorder that has demonstrated wide phenotypic variability, presenting with tremor-dominant, akinetic-rigid and mixed subtypes. Pesticide exposure is a known PD risk factor, but the association between specific pesticide agents and PD motor subtypes remains unexplored.

Method: PD patients were recruited as part of the Parkinson’s Environment and Gene (PEG) population-based study in Central California. We have previously linked 53 pesticides to PD in a pesticide-wide association study, which had a similar methodology to a GWAS [1]. Here, we assess exposure to these 53 pesticides and motor subtype among 826 PD patients. Estimates of ambient pesticide exposure were generated using a geographic information system (GIS) based exposure assessment tool. Motor subtypes were defined according to the ratio of each patient’s UPDRS III tremor score to his/her mean UPDRS akinetic/rigid score to make our classification most comparable to the method of Schiess et al. such that 1) a ratio ≥ 1.0 equals tremor-dominant, 2) a ratio ≤ 0.80 equals akinetic–rigid, and 3) a ratio between 0.80 and 1.0 equals mixed [3]. Subtyping was based on the participant’s UPDRS at the time of their initial study visit, which was on average 3 years from diagnosis.

Results: ​​​​​​Overall, at baseline, 203 (24.6%) patients were classified as tremor-dominant, 511 (61.8%) were akinetic–rigid, and 112 (13.6%) were mixed. Of the 53 examined pesticides, long-term exposure to 13 pesticides demonstrated a statistically significant association with the tremor-dominant subtype (p<0.05, Table 1). The pesticides most strongly associated with tremor-dominance included methidathion, copper hydroxide, glyphosate-isopropylamine salt, and prometryn. One pesticide group, mevinphos and mevinphos related pesticides, demonstrated a negative association with the tremor-dominant subtype, indicating a higher likelihood of akinetic-rigid subtype.

Conclusion: We identified several pesticide exposures which are associated with motor symptom presentation in PD. Apart from mevinphos, all pesticides were linked to a higher likelihood of the tremor-dominant subtype. This may suggest that certain environmental toxins preferentially impact neural circuits involved in tremor pathophysiology.

Pesticides Associated with TD or AR Motor Subtypes

References: 1. Paul KC, Krolewski RC, Lucumi Moreno E, Blank J, Holton KM, Ahfeldt T, Furlong M, Yu Y, Cockburn M, Thompson LK, Kreymerman A, Ricci-Blair EM, Li YJ, Patel HB, Lee RT, Bronstein J, Rubin LL, Khurana V, Ritz B. A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides. Nat Commun. 2023 May 16;14(1):2803. doi: 10.1038/s41467-023-38215-z.
2. Schiess MC, Zheng H, Soukup VM, Bonnen JG, Nauta HJ. Parkinson’s disease subtypes: clinical classification and ventricular cerebrospinal fluid analysis. Parkinsonism Relat Disord. 2000 Apr 1;6(2):69-76. doi: 10.1016/s1353-8020(99)00051-6. PMID: 10699387.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pesticide-exposure-and-parkinsons-disease-motor-subtype/