Use of ibuprofen and risk of Parkinson disease

Abstract

Background: Neuroinflammation may contribute to the pathogenesis of Parkinson disease (PD). Use of nonsteroidal anti-inflammatory drugs (NSAID) in general, and possibly ibuprofen in particular, has been shown to be related to lower PD risk in previous epidemiologic studies.

Methods: We prospectively examined whether use of ibuprofen or other NSAIDs is associated with lower PD risk among 136,197 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) free of PD at baseline (1998 for NHS and 2000 for HPFS). NSAIDs use was assessed via questionnaire. Results were combined in a meta-analysis with those of published prospective investigations.

Results: We identified 291 incident PD cases during 6 years of follow-up. Users of ibuprofen had a significantly lower PD risk than nonusers (relative risk [RR], adjusted for age, smoking, caffeine, and other covariates = 0.62; 95% confidence interval [CI] 0.42-0.93; p = 0.02). There was a dose-response relationship between tablets of ibuprofen taken per week and PD risk (p trend = 0.01). In contrast, PD risk was not significantly related to use of aspirin (RR = 0.99; 95% CI 0.78-1.26), other NSAIDs (RR = 1.26; 95% CI 0.86-1.84), or acetaminophen (RR = 0.86; 95% CI 0.62-1.18). Similar results were obtained in the meta-analyses: the pooled RR was 0.73 (95% CI 0.63-0.85; p < 0.0001) for ibuprofen use, whereas use of other types of analgesics was not associated with lower PD risk.

Conclusions: The association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD.

Figure 1. Combined relative risks (RRs) of Parkinson disease according to use of each type of nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen

Adjustment for age (in months), smoking status (never smoker, past smoker, current smoker with 1–14 cigarettes/day, or current smoker with ≥15 cigarettes/day), body mass index (<23, 23–24.9, 25–26.9, 27–29.9, or ≥30 kg/m²), and intake of caffeine (quintiles), lactose (quintiles), and alcohol (none, 1–4.9, 5–9.9, 10–14.9, or ≥15 g/day for women; none, 1–9.9, 10–19.9, 20–29.9, or ≥30 g/day for men). Cox proportional hazard models were used to calculate RR. Case number: 28 for ibuprofen users and 263 for nonusers; 143 for aspirin users and 148 for nonusers; 32 for other NSAIDs users and 259 for nonusers; and 38 for acetaminophen users and 243 for nonusers.

Figure 2. Pooled relative risks (RRs) of Parkinson disease (PD) according to each type of nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen in the meta-analysis

(A) Ibuprofen; (B) aspirin; (C) other NSAIDs; and (D) acetaminophen. Rectangles indicate RRs from individual studies; error bars indicate 95% confidence intervals (CIs); unshaded diamond indicates the pooled RR from the random-effects model and 95% CI. Pooled RR: ibuprofen, 0.73 (95% CI 0.63–0.85; p < 0.0001); aspirin, 1.12 (95% CI 1.01–1.23, p = 0.03); other NSAIDs, 1.00 (95% CI 0.86–1.16; p = 1.0); acetaminophen, 1.06 (95% CI 0.94–1.19; p = 0.37). *In the General Practice Research Database (GPRD) study, RR for other NSAIDs was calculated by pooling the RR estimates for the different types of other NSAIDs (i.e., diclofenac, naproxen, and others), weighted by inverse of the variance within the study. CPS = Cancer Prevention Study; GHC = Group Health Cooperative; HPFS = Health Professionals Follow-up Study; NHS = Nurses' Health Study; REP = Rochester Epidemiology Project.