β-Adrenoceptor Drugs and Parkinson’s Disease: A Nationwide Nested Case–Control Study

Background Potential relationships between β-adrenergic drugs and α-synuclein synthesis in Parkinson’s disease (PD) have been recently suggested. Objective This study investigated the putative association between β-adrenoceptor drug exposure and PD occurrence. Methods A nested case–control study was performed in the Echantillon Généraliste des Bénéficiaires (EGB) (a 1/97th random sample of affiliates to the French Insurance System). Incident PD patients diagnosed between 01/01/2008 and 31/12/2017 (index date) were matched 1:1 to controls by gender, birth year, and insurance scheme. Exposure to any β-agonist and to any β-antagonist was compared between cases and controls within 1–2 years before the index date, and exposure to salbutamol and to propranolol was individualized. The association between PD and β-adrenoceptor drugs was investigated through conditional logistic regression models adjusted for potential confounding factors. Because of a statistical interaction between β-agonists and diabetes, results were stratified according to the presence of diabetes. Results Among the 2225 incident PD patients identified in the EGB (mean age 75.6 ± 10.2 years, sex ratio 1.04), no significant association was found between PD and β-antagonists (adjusted odds ratio [aOR] 1.05 [95% confidence interval 0.91–1.20]), except for propranolol (aOR 2.11 [1.38–3.23]). For β-agonists, a protective association in non-diabetic patients (aOR 0.75 [0.60–0.93]) and an opposite and significant association in diabetic patients (aOR 1.61 [1.02–2.55]) were observed. Similar results were found with salbutamol. Conclusion This study did not identify an increased risk of PD occurrence after β-antagonist exposure, except for propranolol (potential protopathic bias). The discordant results observed with β-agonists in patients with or without diabetes deserve further exploration of the influence of diabetic comorbidity on PD occurrence and evolution.