Men with a high plasma urate concentration have a decreased risk of developing Parkinson’s disease, independent of potential risk factors such as age, smoking, and caffeine intake, according to research published online ahead of print January 13 in Neurology. Plasma urate concentration appears to have no association with risk of Parkinson’s disease among women, however. For men, urate could protect against Parkinson’s disease risk or slow the progression of preclinical Parkinson’s disease, according to the authors.
“Our findings, together with previous observations that urate can be elevated by administration of its precursor inosine, which is generally safe and tolerable, in early Parkinson’s disease, provide strong evidence supporting the design of a randomized trial of urate elevation in patients with early Parkinson’s disease or pre-Parkinson syndrome,” said Xiang Gao, MD, PhD, Director of the Nutritional Epidemiology Laboratory at Pennsylvania State University in University Park.
Dr. Gao and colleagues examined blood samples for more than 90,000 men and women who participated in the Health Professionals Follow-up Study, the Nurses’ Health Study, or the Cancer Prevention Study II Nutrition. The researchers confirmed cases of Parkinson’s disease based on a detailed questionnaire that the treating neurologist or internists completed, or through a movement disorder specialist’s review of medical records. Only patients with definite or probable Parkinson’s disease were included in the analysis. Between one and six controls were selected randomly for each case. The investigators used questionnaires to collect data on potential confounders, including age, smoking status, height, weight, chronic diseases, and consumption of caffeinated coffee and alcohol.
Dr. Gao’s group identified 388 new incident cases of Parkinson’s disease since blood collection and matched them with 1,267 controls. Higher baseline urate concentrations were associated with lower risk of Parkinson’s disease in men, but not in women. The multivariate-adjusted risk ratios of Parkinson’s disease, comparing the highest and lowest quartiles of urate, were 0.63 in men and 1.04 in women. Adjusting the data for cardiovascular factors, including history of cardiovascular disease and diabetes, did not affect the results.
The researchers pooled the results of their study with those of three previous investigations that included 325 patients with Parkinson’s disease. The pooled risk ratios comparing the highest and lowest categories of urate were 0.63 in men and 0.89 in women.
Animal and human studies suggest that urate is a neuroprotective agent, noted the authors. Their own previous research indicates that urate may slow disease progression during the preclinical stage of Parkinson’s disease.
The strengths of the current study include its prospective design, large sample size, and availability of information on covariates that may confound the potential association between serum urate and Parkinson’s disease risk, according to the authors. The study was based on a single measure of plasma urate, however, and did not account for within-person variability in urate levels. In addition, the results may be difficult to generalize because the majority of participants were Caucasian and had high educational attainment and socioeconomic status.
—Erik Greb