Plasma Urate and Risk of Parkinson's Disease

Abstract

Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson's disease. Urate, a potent antioxidant, could be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of Parkinson's disease, the authors conducted a nested case-control study among participants in the Health Professionals Follow-up Study, a cohort comprising over 18,000 men who provided blood samples in 1993-1995. Eighty-four incident cases of Parkinson's disease were diagnosed through 2000, and each was randomly matched to two controls by year of birth, race, and time of blood collection. Rate ratios of Parkinson's disease according to quartile of uricemia were estimated by use of conditional logistic regression. The mean urate concentration was 5.7 mg/dl among cases and 6.1 mg/dl among controls (p = 0.01). After adjustment for age, smoking, and caffeine, the rate ratio of Parkinson's disease for the highest quartile of uricemia compared with the lowest was 0.43 (95% confidence interval: 0.18, 1.02; p(trend) = 0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection (rate ratio = 0.17, 95% confidence interval: 0.04, 0.69; p(trend) = 0.010). These results suggest that high plasma urate concentrations may decrease the risk of Parkinson's disease, and they raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's disease.

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…This study observed no interaction between serum uric acid levels and smoking [661]. A metaanalysis of these three prospective studies yielded a RR of 0.80 (95% CI 0.71-0.90) per 1.32 mg/dl increase in serum uric acid concentration (corresponding to 1 standard deviation in the Health Professionals Follow-up Study) [661].…”

“…The inverse association was stronger in non-smokers than smokers [659].The Rotterdam study also found lower PD risk with increasing baseline serum uric acid (p for trend 0.04), but no interaction by smoking status or gender [660]. Similarly, a case-control study nested within the Health Professionals Follow-up Study of men reported an inverse association between baseline serum uric acid and PD (RR 0.43, 95% CI 0.18-1.02 for highest versus lowest quartile of serum uric acid, p for trend 0.017) [661]. The association was stronger when cases with serum uric acid measurement within 4 years prior to PD diagnosis were excluded (RR 0.17, 95% CI 0.04-0.69 for highest versus lowest quartile of serum uric acid).…”

“…A metaanalysis of these three prospective studies yielded a RR of 0.80 (95% CI 0.71-0.90) per 1.32 mg/dl increase in serum uric acid concentration (corresponding to 1 standard deviation in the Health Professionals Follow-up Study) [661]. Another prospective study based on the Atherosclerosis Risk in Communities Cohort, including men and women, and Black Americans as well as Caucasians, also reported an inverse association between baseline serum uric acid and PD (OR 0.4, 95% CI 0.2-0.8 for highest versus lowest quartile) [662].…”

Serum uric acid levels in Parkinson's disease and related disorders

“…Based on the case–control studies, subjects with increased levels of serum UA and gout were associated with a decreased risk for developing PD (Weisskopf, O'Reilly, Chen, Schwarzschild, & Ascherio, 2007), although in one study, the plasma UA levels in women were not significantly associated with the risk of PD (O'Reilly et al., 2010). Based on a prospective population study, higher levels of serum UA were also associated with a decreased risk of PD (Chen, Mosley, Alonso, & Huang, 2009; de Lau, Koudstaal, Hofman, & Breteler, 2005).…”

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

“…In longitudinal cohort studies, urate levels correlate with risk of developing PD later in life, with higher levels being associated with reduced disease risk [13][14][15][16][17]. History of gout is associated with reduced risk of developing either PD [48] or Alzheimer's disease [21].…”