Use of non-steroidal anti-inflammatory drugs and risk of Parkinson's disease: nested case-control study
- PMID: 21252104
- PMCID: PMC3023971
- DOI: 10.1136/bmj.d198
Use of non-steroidal anti-inflammatory drugs and risk of Parkinson's disease: nested case-control study
Abstract
Objective: To evaluate the relation between Parkinson's disease and prior use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large cohort of men.
Design: Case-control analysis nested in the Physicians' Health Study.
Participants: 22,007 male physicians aged 40-84 years without indications for or contraindications to regular NSAID use and free of Parkinson's disease at baseline. Cases and controls were matched by age alone or by age and scores for confounders (comorbidity and indicators of NSAID use). Up to five controls were matched to each of 616 cases by age and 565 cases by age and confounder scores.
Setting: United States.
Main outcome measures: Odds of having been exposed to prior non-aspirin NSAID or aspirin use by participants with Parkinson's disease and by their controls in each case-control set.
Results: Participants who had ever used non-aspirin NSAIDs had an increased risk of Parkinson's disease (odds ratio 1.28 (95% CI 1.05 to 1.56) in the age matched group but not in the group also matched on confounder scores (odds ratio 1.17 (0.94 to 1.46)). There was an increased risk of Parkinson's disease in men who had 1-2 years of regular non-aspirin NSAID use (odds ratio 1.35 (1.07 to 1.70)), a finding that remained significant after matching for confounder scores as well (odds ratio 1.35 (1.05 to 1.75)). In contrast, the significant association of use of non-aspirin NSAIDs for ≥ 5 years (odds ratio 1.48 (1.05 to 2.09)) in the age matched group was entirely attenuated in the group also matched on confounder scores (1.03 (0.70 to 1.53)). There was also a suggestion that men who regularly used aspirin had an increased risk of Parkinson's disease. Positive associations between non-aspirin NSAID or aspirin and risk of Parkinson's disease tended to disappear when analyses were limited to drug use ≥ 5 years before the disease diagnosis.
Conclusions: This case-control study did not find evidence that NSAID use reduces Parkinson's disease risk. The positive associations observed between NSAID use and Parkinson's disease might have been due to confounding by indication as the use was clustered in the few years before disease diagnosis.
Conflict of interest statement
Competing interests: All authors have completed the Unified Competing Interest form at
We report a full disclosure for the past five years for each of the authors. JAD has a research grant from the Parkinson’s Disease Foundation, the Hartford Foundation, Harvard Medical School, and a Career Development Award from the Veteran’s Administration. LL has nothing to disclose. GL has received research funding from the Amyotrophic Lateral Sclerosis Association, Italian Ministry of Health, the Apulia Region, and special funding from the Italian Ministry of Universities and has received honorariums from Pfizer, Novartis, Glaxo, and Lilly Pharmaceutical for speaking engagements. JMG has received investigator initiated research funding and support as principal investigator from National Institutes of Health, BASF, DSM Pharmaceuticals, Wyeth Pharmaceuticals, McNeil Consumer Products, and Pliva; received honoraria from Bayer and Pfizer for speaking engagements; and is a consultant for Bayer, McNeil Consumer Products, Wyeth Pharmaceuticals, Merck, Nutraquest, and GlaxoSmithKline. TK has received investigator initiated research funding from the French National Research Agency, the US National Institutes of Health, Merck, the Migraine Research Foundation, and the Parkinson’s Research Foundation; is a consultant to i3 Drug Safety and World Health Information Science Consultants, LLC; and has received honoraria from the American Academy of Neurology, Genzyme, Merck, and Pfizer for educational lectures.
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References
-
- Hunot S, Hirsch EC. Neuroinflammatory processes in Parkinson’s disease. Ann Neurol 2003;53(suppl 3):S49-60. - PubMed
-
- McGeer PL, Schwab C, Parent A, Doudet D. Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann Neurol 2003;54:599-604. - PubMed
-
- Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm Suppl 2000;(60):277-90. - PubMed
-
- Aubin N, Curet O, Deffois A, Carter C. Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. J Neurochem 1998;71:1635-42. - PubMed
-
- Mohanakumar KP, Muralikrishnan D, Thomas B. Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. Brain Res 2000;864:281-90. - PubMed
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