Association of Restless Legs Syndrome with Incident Parkinson Disease

Restless legs syndrome has been reported as a risk factor for PD... as with many of the other so called risk factors it is difficult to established whether they truly increase risk of PD or whether the association arises as a result of confounding by prevalent disease... in other words reverse causality. This means that Parkinson's disease is present, but not yet diagnosed, and restless legs syndrome is a symptom of Parkinson's. RLS gets diagnosed, followed by Parkinson's some years later... Parkinson's likely starts many years before a diagnosis is made...

Sleep. 2016 Nov 28. pii: sp-00400-16. [Epub ahead of print]
Bro D, O'Hara R, Primeau M, Hanson-Kahn A, Hallmayer J, Bernstein JA.

STUDY OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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. KEYWORDS: