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Neurology. 2019 Jul 9;93(2):e135-e142. doi: 10.1212/WNL.0000000000007694. Epub 2019 May 24.

Use of β2-adrenoreceptor agonist and antagonist drugs and risk of Parkinson disease.

Author information

1
From the Department of Psychiatry and Psychotherapy (F.H.), Ludwig-Maximilians-Universität München, Germany; Department of Neurology (F.H., G.K., G.D.), UKSH, Christian-Albrechts-University Kiel, Germany; Unit of Epidemiology, Biostatistics and Biodemography (M.W., K.C.), Danish Twin Registry (M.W., K.C.), Danish Aging Research Center (M.W., K.C.), and Department of Clinical Research (M.B.) and Clinical Pharmacology and Pharmacy (A.P.), Department of Public Health, University of Southern Denmark, Odense; Department of Neurology (G.U.H.), Hannover Medical School, Germany; Department of Neurology (G.U.H., T.W.R.), Technical University of Munich; German Center for Neurodegenerative Diseases (G.U.H., T.W.R.); Munich Cluster for Systems Neurology (G.U.H., T.W.R.), Germany; and Departments of Neurology (M.B.), Clinical Genetics (K.C.), and Clinical Biochemistry and Pharmacology (K.C.), Odense University Hospital, Denmark.
2
From the Department of Psychiatry and Psychotherapy (F.H.), Ludwig-Maximilians-Universität München, Germany; Department of Neurology (F.H., G.K., G.D.), UKSH, Christian-Albrechts-University Kiel, Germany; Unit of Epidemiology, Biostatistics and Biodemography (M.W., K.C.), Danish Twin Registry (M.W., K.C.), Danish Aging Research Center (M.W., K.C.), and Department of Clinical Research (M.B.) and Clinical Pharmacology and Pharmacy (A.P.), Department of Public Health, University of Southern Denmark, Odense; Department of Neurology (G.U.H.), Hannover Medical School, Germany; Department of Neurology (G.U.H., T.W.R.), Technical University of Munich; German Center for Neurodegenerative Diseases (G.U.H., T.W.R.); Munich Cluster for Systems Neurology (G.U.H., T.W.R.), Germany; and Departments of Neurology (M.B.), Clinical Genetics (K.C.), and Clinical Biochemistry and Pharmacology (K.C.), Odense University Hospital, Denmark. apottegaard@health.sdu.dk.

Abstract

OBJECTIVE:

To verify the previously reported association between long-term use of β2-adrenoreceptor (β2AR) agonist and antagonist with reduced and increased risk of Parkinson disease (PD), respectively.

METHODS:

We obtained odds ratios (ORs) associating time of β2AR agonist and antagonist use with PD risk in nationwide Danish health registries.

RESULTS:

We included 2,790 patients with PD and 11,160 controls. Long-term β2AR agonist use was associated with reduced PD risk (OR 0.57, 95% confidence interval [CI] 0.40-0.82) in this cohort. Unexpectedly, short-term β2AR agonist use was equally associated (OR 0.64, 95% CI 0.42-0.98). Because β2AR agonists are prescribed mostly for chronic obstructive pulmonary disease (COPD), often caused by long-term nicotine abuse, we analyzed other markers of smoking. Diagnosis of COPD (OR 0.51, 95% CI 0.37-0.69) and use of inhaled corticosteroids (OR 0.78, 95% CI 0.59-1.02) or inhaled anticholinergics (OR 0.41, 95% CI 0.25-0.67) were also inversely associated with PD. Increased PD risk was not found for all β2AR antagonists but only for propranolol and metoprolol. Associations were markedly stronger for short-term than long-term use.

CONCLUSION:

We confirmed β2AR agonist use to be associated with reduced PD risk and β2AR antagonist use with increased PD risk. However, our data indicate the association of β2AR agonists to be indirectly mediated by smoking, which is repeatedly associated with reduced risk of PD. The association of β2AR antagonists indicates reverse causation, with PD symptoms triggering their prescription rather than β2AR antagonists causing PD. Thus, current epidemiologic data do not support a causal link between β2AR agonists and antagonists and PD risk.

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