Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease. Immunologic diseases, anti-inflammatory drugs, and Parkinson disease: a case-control study. Use of non-steroidal anti-inflammatory drugs and risk of Parkinson's disease: nested case-control study. Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. Non-steroidal anti-inflammatory drug use and the risk of Parkinson disease: a retrospective cohort study. Use of ibuprofen and risk of Parkinson disease. Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease. Nonsteroidal anti-inflammatory drugs and risk of Parkinson's disease. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. NSAID use and the risk of Parkinson's disease. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease.
Animal and epidemiologic studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of Parkinson disease (PD). The authors studied 1,258 PD cases and 6,638 controls from the General Practice Research Database. The odds ratios (95% CI) for ever vs never use were 0.93 (0.80 to 1.08) for nonaspirin NSAIDs, 1.29 (1.05 to 1.58) for aspirin, and 1.16 (1.00 to 1.35) for acetaminophen. Nonaspirin NSAID use was associated with a higher risk in women and a lower risk in men. The authors studied the association of markers of inflammation with the later development of Parkinson disease (PD) using a case-control design (196 cases and 196 matched controls). The frequency of diseases of immediate-type hypersensitivity was significantly higher in cases than controls. In addition, cases used anti-inflammatory agents less frequently than controls (nonsignificant trend). The results may support the hypothesis that there is an inflammatory component in the pathogenesis of PD. To evaluate the relation between Parkinson's disease and prior use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large cohort of men.
                Case-control analysis nested in the Physicians' Health Study.
                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.
                United States.
                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.
                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.
                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. Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti-inflammatory drug (NSAID) use have been reported individually, but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case-control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smoking, coffee, and NSAID consumption. Odds ratios were calculated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two-way and three-way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations. With respect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR = 0.13, 95% CI = 0.06-0.29). Whether this finding reflects true biologic protection needs to be investigated.
                2007 Movement Disorder Society Using the British Columbia Linked Health Databases, we explored the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of developing Parkinson's disease (PD). We followed a cohort of older adults in the Province of British Columbia from 1997 to 2003. A time-dependent Cox model was used to estimate adjusted rate ratios for users and non-users of NSAIDs. The results of our study did not show a protective effect of NSAIDs for PD (rate ratio 0.84, 95% CI 0.81-1.09). 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.
                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.
                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.
                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. To assess associations between Parkinson disease (PD) and putatively protective factors-smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen).
                Family-based case-control study.
                Academic medical center clinic.
                A total of 356 case subjects and 317 family controls who self-reported environmental exposures.
                Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti-inflammatory drugs, and non-aspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex.
                Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (P<.05) and trends in odds ratios (P<.005). Increasing intensity of coffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD.
                Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD. Inflammation and oxidative stress have been implicated as pathogenic mechanisms in Parkinson's disease (PD). Evidence from in vitro and animal studies suggests a possible protective role of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin. We investigated the risk of PD associated with use of aspirin and nonaspirin NSAIDs in a population-based case-control study among enrollees of Group Health Cooperative, a health maintenance organization in the Seattle area. Subjects included 206 cases between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 randomly selected controls frequency-matched by age, sex, duration of enrollment, and clinic. We obtained information on participants' age, smoking, and medical history from interview. Exposure to NSAIDs was ascertained from an automated pharmacy database. Medications filled within 5 years of the interview were excluded. After adjusting for age, sex, smoking, duration of enrollment, and clinic, the risk of PD among individuals who received nonaspirin NSAIDs between 1977 and 1992 was 0.90 (95% CI: 0.59-1.35) and 1.67 (95% CI: 0.60-4.60) between 1993 and 2002. Use of ibuprofen was not associated with PD (OR: 0.89; 95% CI: 0.60-1.32). The risk of PD associated with aspirin or aspirin-containing medications was 0.74 (95% CI: 0.49-1.12). We observed no trend in risk according to number of fills for these drugs. Our results provide only limited support for the hypothesis that use of aspirin may reduce the risk of this disease, and no indication of protection from other NSAIDs.
                (c) 2006 Movement Disorder Society. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce dopaminergic neuron degeneration in animal models of Parkinson disease (PD). However, no epidemiological data have been available on NSAID use and the risk of PD.
                To investigate prospectively whether the use of nonaspirin NSAIDs or aspirin is associated with decreased PD risk.
                Prospective cohorts of 44 057 men and 98 845 women free of PD, stroke, or cancer (Health Professionals Follow-up Study, 1986-2000, and Nurses' Health Study, 1980-1998). Main Outcome Measure Newly diagnosed PD.
                We documented 415 incident PD cases (236 men and 179 women). Participants who reported regular use of nonaspirin NSAIDs at the beginning of the study had a lower risk of PD than nonregular users during the follow-up; the pooled multivariate relative risk was 0.55 (95% confidence interval, 0.32-0.96, P =.04). Compared with nonusers, a nonsignificantly lower risk of PD was also observed among men and women who took 2 or more tablets of aspirin per day (relative risk, 0.56; 95% confidence interval, 0.26-1.21).
                These findings are consistent with the hypothesis that use of NSAIDs may delay or prevent the onset of PD. Markers of neuroinflammation, including activated microglia and increased levels of circulating proinflammatory cytokines, have been observed in the brains and CSF of patients with Parkinson disease (PD). Yet the link between anti-inflammatory agents and PD in humans remains uncertain, despite indications that neuroinflammation may contribute to cell death in the PD brain and experimental evidence of anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) exerting neuroprotective effects in animal models.
                Using a population-based approach, we studied NSAID use among 293 incident idiopathic PD cases and 286 age-, race-, and gender-matched controls from three rural California counties.
                Our data suggested a decreased risk of PD among regular (>or=2 pills/week for at least 1 month) aspirin NSAID users (OR, 0.80; 95% CI, 0.56 to 1.15). A stronger protective effect was observed for regular nonaspirin NSAID users (OR, 0.52; 95% CI, 0.35 to 0.79), particularly those who reported 2 or more years of use (OR, 0.44; 95% CI, 0.26 to 0.74). The aspirin effect estimates differed by gender, showing a protective effect only in women, especially among long term (>or=24 months) regular users (OR, 0.51; 95% CI, 0.26 to 1.02).
                Our study contributes to the growing body of literature suggesting a protective role for nonsteroidal anti-inflammatory drugs (NSAIDs) in Parkinson disease (PD). Given our results and the biologic plausibility of a neuroprotective function for NSAIDs there is a pressing need for further studies elucidating the protective role such drugs may play in PD. Several lines of evidence suggest a role of inflammatory processes in Parkinson disease, although it is still unclear whether inflammation is a cause or rather a consequence of neurodegeneration.
                In a prospective population-based cohort study among 6,512 participants aged >or=55 years, with repeated in-person examination, we evaluated the association between cumulative use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease. Complete information on filled prescriptions was available from automated pharmacy records. Data were analyzed by means of Cox proportional hazards regression analysis, adjusted for age, sex, smoking habits and coffee consumption.
                After an average 9.4 years of follow-up, 88 new cases of Parkinson disease were detected. No association was found between use of NSAIDs and the risk of Parkinson disease (adjusted hazard ratio for any NSAID use, 1.50; 95% confidence interval, 0.95-2.37).
                Our findings do not support the hypothesis that NSAIDs might decrease the risk of Parkinson disease.
                (c) 2007 S. Karger AG, Basel. Parkinson's disease (PD) is a neurodegenerative disease with limited pharmacologic therapies. Recent animal studies and one large retrospective study have found NSAIDs to be protective against the development of PD. We decided to test this hypothesis by conducting a nested case-control study using the Saskatchewan drug plan database. Entry to the cohort was defined as the first prescription of an antihypertensive agent between 1980 and 1987 and followed until 1999. Cases were defined as those having received three prescriptions for a dopamine agonist within a year. For each case, ten controls were selected matched to the case by age, calendar time and index date. Conditional logistic regression was used to estimate rate ratios adjusting for gender, previous use of arthritis medication and previous antipsychotic use. Current users of NSAIDs had a slightly higher risk of developing PD (RR=1.49 [95% CI, 1.11-2.01]). This effect was not seen with past users (RR=1.18 [95% CI, 0.89-1.59]). Based on the results of our study current users of NSAIDs may be at a slightly higher risk of developing PD. More studies are needed to confirm this finding. We investigated whether nonsteroidal antiinflammatory drug use was associated with a lower risk for Parkinson's disease (PD) in a large cohort of US men and women. PD risk was lower among ibuprofen users than nonusers. Compared with nonusers, the relative risks were 0.73 for users of fewer than 2 tablets/week, 0.72 for 2 to 6.9 tablets/week, and 0.62 for 1 or more tablets/day (p trend = 0.03). No association was found between the use of aspirin, other nonsteroidal antiinflammatory drugs, or acetaminophen and PD risk. The results suggest that ibuprofen use may delay or prevent the onset of PD.