Association of Restless Legs Syndrome with Incident Parkinson Disease.

Abstract The association between restless legs syndrome (RLS) and Parkinson's Disease (PD) has been extensively studied with inconclusive results, therefore we prospectively examined the associations of the presence of RLS with development of incident PD. From a nationally representative prospective cohort of almost 3.5 million US veterans (age: 60±14 years, 93% male, median follow-up time of 7.8 years (IQR: 6.4-8.4 years)), we created a propensity-matched cohort of 100,882 PD-free patients and examined the association between prevalent RLS and incident PD. This association was also assessed in the entire cohort. Associations were examined using Cox models. There were 68 incident PD events (0.13%, incidence rate 1.87 [1.48-2.37]/10,000 patient-years) in the RLS negative group, and 185 incident PD events (0.37%, incidence rate 4.72 [4.09-5.45]/10,000 patient-years) in the RLS positive group in the propensity-matched cohort. Prevalent RLS was associated with more than two-fold higher risk of incident PD (hazard ratio (HR): 2.57, 95% confidence interval (CI): 1.95-3.39) compared to RLS negative patients. Qualitatively similar results were found when we examined the entire 3.5-million cohort: prevalent RLS was associated with more than two-fold higher risk of incident PD (multivariable adjusted HR: 2.81, 95%CI: 2.41-3.27). RLS and PD share common risk factors. In this large cohort of US veterans, we found that prevalent RLS is associated with higher risk of incident PD during 8 years of follow-up, suggesting that RLS could be an early clinical feature of incident PD.