NSAID use is not associated with Parkinson's disease incidence: A Norwegian Prescription Database study.

Brage Brakedal,Ole-Bjørn Tysnes,Charalampos Tzoulis,Kristoffer Haugarvoll,Claudio Liguori

doi:10.1371/journal.pone.0256602

Brage Brakedal, Ole-Bjørn Tysnes + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0256602

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Journal: PloS one	Publication Date: Sep 7, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: University of Bergen, Haukeland University Hospital

Abstract

Whether use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of incident Parkinson's disease (PD) remains unresolved. Here, we employed the Norwegian Prescription Database to examine whether NSAID use is associated with a lower incidence of PD. We compared the incidence of PD among users of NSAIDs in a population-based retrospective study using the Norwegian Prescription Database from 2004 to 2017. In total 7580 PD patients were identified using dopaminergic therapy over time as proxy for PD diagnosis. Analyses were performed with minimum 90 and 365 defined daily dose (DDD) NSAID exposure, respectively. Time-dependent Cox regression model and a binary logistic regression analysis with a 5-year lag until PD diagnosis were performed for all NSAIDs. There was overall no decrease in incidence of PD among NSAID users compared to controls. Using a minimum of 90 or 365 DDD threshold of exposure produced similar results. Analysis of individual NSAIDs did not show difference in PD incidence compared to controls Age-specific incidence rates of PD were comparable to reported age-specific incidence rates in previous studies. Our findings provide no evidence that cumulative high exposure to NSAIDs affects the risk of developing PD.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder [1]
There was overall no decrease in incidence of PD among Nonsteroidal anti-inflammatory drugs (NSAID) users compared to controls
Analysis of individual NSAIDs did not show difference in PD incidence compared to controls Age-specific incidence rates of PD were comparable to reported age-specific incidence rates in previous studies

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder [1]. While the etiology and pathogenesis of PD remain largely unknown, several processes have been implicated in its pathophysiology, including lysosomal and mitochondrial dysfunction, as well as neuroinflammation [2, 3]. A meta-analysis published in 2010 suggested that regular and long-term non-ASA NSAIDs use could have a protective effect, but the individual studies included in the meta-analysis showed conflicting results [6]. Another meta-analysis suggested that ibuprofen may be protective whereas a recent meta-analysis did not find that NSAIDs in general reduced the risk of PD [7,8,9]. It remains unclear whether the use of non-ASA NSAID reduces the risk of PD. Because PD is treated with dopaminergic drugs that are prescribed, we use dispensed dopaminergic drugs specific to PD as a proxy for PD diagnosis [10,11,12,13,14]

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