The association between brominated flame retardants exposure with Parkinson's disease in US adults: a cross-sectional study of the National Health and Nutrition Examination Survey 2009-2016

Abstract

Background: Increasing evidence suggests that environmental factors play a crucial role in the pathogenesis of Parkinson's disease (PD). Humans are simultaneously exposed to multiple brominated flame retardants (BFRs) in the environment. However, the relationship between BFRs and PD remains unclear. This study was designed to investigate the overall association between BFRs and PD in a nationally representative US population and to further identify significant chemicals.

Methods: This study used data from 7,161 NHANES participants from 2009 through 2016. The serum BFRs registry included PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-153, PBDE-154, PBDE-183, PBDE-209, and PBB-153. A survey-weighted generalized logistic regression model with restricted cubic splines (RCS) was used to evaluate the association between single BFRs exposure and periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of mixed frankincense powder with periodontitis and to identify significant chemicals. Sensitivity analysis was performed to evaluate the robustness of the results.

Results: Among the 7,161 participants, 65 had PD. PD patients were older (mean age 57.79 vs. 46.57 years) and had a higher proportion of females (70.86%) compared to non-PD participants. Serum levels of PBB-153 were significantly higher in those with PD. Logistic regression analyses revealed a non-linear, inverted U-shaped relationship between serum PBB-153 and PD risk. The risk of PD increased with higher PBB-153 levels up to the 3rd quartile (Q3), beyond which the risk declined (Q3 vs. Q1: OR = 4.98, 95% CI = 1.79-13.86; Q4 vs. Q1: OR = 3.23, 95% CI = 1.03-10.08). PBB-153 (43.40%), PBDE-153 (24.75%), and PBDE-85 (19.51%) contributed most to the weighted quantile sum index associated with PD risk. Bayesian kernel machine regression confirmed the inverted U-shaped dose-response pattern for PBB-153 and the overall BFR mixture. Restricted cubic spline analyses corroborated the non-linear relationship between PBB-153 and PD, which was more pronounced among women and those aged 37-58 years. Sensitivity analyses substantiated these findings.

Conclusion: This nationally representative cross-sectional study revealed a novel non-linear, inverted U-shaped relationship between serum levels of the brominated flame retardant PBB-153 and Parkinson's disease risk in U.S. adults. The risk increased with higher PBB-153 exposure up to a point, beyond which it declined. This complex dose-response pattern highlights the importance of considering potential hormetic mechanisms and effect modifiers when evaluating environmental exposures and neurodegenerative diseases. Further research is warranted to elucidate the underlying biological pathways and inform risk mitigation strategies.

Keywords: BKMR analysis; Parkinson’s disease; The National Health and Nutrition Examination Survey; brominated flame retardants; cross-sectional study.

Figure 1

Flow chart of the study.

Figure 2

Weighted values of brominated flame retardants for PD in WQS models. (A) Bar Chart Representation of Top Compounds, (B) Box Plot of Weight Distribution Across Compounds. Models were adjusted for gender, age, race, education, PIR, marital status, BMI, MET, drinking alcohol status, smoking status and CCI.

Figure 3

Associations of the serum brominated flame retardants (BFRs) content with PD risk estimated by Bayesian Kernel Machine Regression (BKMR). (A) Exposure-response functions for each BFRs with PD. (B) Combined effects of serum brominated flame retardants on PD risk. This plot showed the estimated difference in PD risk and 95% confidence interval when all BFRs concentrations were held at particular percentiles compared to their medians. Models were adjusted for gender, age, race, education, PIR, marital status, BMI, MET, drinking alcohol status, smoking status, and CCI.

Figure 4

Relationship between brominated flame retardants and PD during 2009–2016. (A) Entirety; (B) By gender; (C) By age. Adjusted for age, sex, race, education, marital status, income, BMI, smoking, alcohol consumption, and CCI. The shaded area represents the 95% confidence interval.

Figure 5

Sensitivity analysis—relationship between brominated flame retardants and PD during 2009–2016. (A) Entirety; (B) By gender. Adjusted for age, sex, race, education, marital status, income, BMI, smoking, alcohol consumption, and CCI. The shaded area represents the 95% confidence interval.