Turcano, Pierpaolo

Importance The role of air pollution in risk and progression of Parkinson disease (PD) is unclear. Objective To assess whether air pollution is associated with increased risk of PD and clinical characteristics of PD. Design, Setting, and Participants This population-based case-control study included patients with PD and matched controls from the Rochester Epidemiology Project from 1998 to 2015. Data were analyzed from January to June 2024. Exposures Mean annual exposure to particulate matter with a diameter of 2.5 µm or less (PM 2.5 ) from 1998 to 2015 and mean annual exposure to nitrogen dioxide (NO 2 ) from 2000 to 2014. Main Outcomes and Measures Outcomes of interest were PD risk, all-cause mortality, presence of tremor-predominant vs akinetic rigid PD, and development of dyskinesia. Models were adjusted for age, sex, race and ethnicity, year of index, and urban vs rural residence. Results A total of 346 patients with PD (median [IQR] age 72 [65-80] years; 216 [62.4%] male) were identified and matched on age and sex with 4813 controls (median [IQR] age, 72 [65-79] years, 2946 [61.2%] male). Greater PM 2.5 exposure was associated with increased PD risk, and this risk was greatest after restricting to populations within metropolitan cores (odds ratio [OR], 1.23; 95% CI, 1.11-1.35) for the top quintile of PM 2.5 exposure compared with the bottom quintile. Greater NO 2 exposure was also associated with increased PD risk when comparing the top quintile with the bottom quintile (OR, 1.13; 95% CI, 1.07-1.19). Air pollution was associated with a 36% increased risk of akinetic rigid presentation (OR per each 1-μg/m 3 increase in PM 2.5 , 1.36; 95% CI, 1.02-1.80). In analyses among patients with PD only, higher PM 2.5 exposure was associated with greater risk for developing dyskinesia (HR per 1-μg/m 3 increase in PM 2.5 , 1.42; 95% CI, 1.17-1.73), as was increased NO 2 exposure (HR per 1 μg/m 3 increase in NO 2 , 1.13; 95% CI, 1.06-1.19). There was no association between PM 2.5 and all-cause mortality among patients with PD. Conclusions and Relevance In this case-control study of air pollution and PD, higher levels of PM 2.5 and NO 2 exposure were associated with increased risk of PD; also, higher levels of PM 2.5 exposure were associated with increased risk of developing akinetic rigid PD and dyskinesia compared with patients with PD exposed to lower levels. These findings suggest that reducing air pollution may reduce risk of PD, modify the PD phenotype, and reduce risk of dyskinesia.

ObjectiveTo explore the clinical progression of the brain‐/body‐first categories within Lewy body disease (LBD): Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD dementia.MethodsWe used of the Rochester Epidemiology Project to establish a population‐based cohort of clinically diagnosed LBD. We used two definitions for differentiating between brain‐ and body‐first LBD: a previously hypothesized body‐first presentation in patients with rapid eye movement sleep behavior onset before motor symptoms onset; and an expanded definition of body‐first LBD when a patient had at least 2 premotor symptoms between constipation, erectile dysfunction, rapid eye movement sleep behavior, anosmia, or neurogenic bladder.ResultsBrain‐first patients were more likely to be diagnosed with PD (RR = 1.43, p = 0.003), whereas body‐first patients were more likely to be diagnosed with DLB (RR = 3.15, p < 0.001). Under the expanded definition, there was no difference in LBD diagnosis between brain‐first and body‐first patients (PD: RR = 1.03, p = 0.10; DLB: RR = 0.88, p = 0.58) There were no patterns between brain‐ or body‐first presentation, PD dementia under either definition (original: p = 0.09, expanded: p = 0.97), and no significant difference in motor symptoms between brain‐first and body‐first.InterpretationOur findings do not support the dichotomous classification of body‐first and brain‐first LBD with the currently proposed definition. Biological exposures resulting in PD and DLB are unlikely to converge on a binary classification of top‐down or bottom‐up synuclein pathology. ANN NEUROL 2024;96:551–559