Restless Legs Syndrome Linked to Higher Parkinson’s Risk in JAMA Study

A new study published in the Journal of American Medical Association showed that individuals with restless legs syndrome (RLS) had a higher likelihood of developing Parkinson’s disease. However, dopamine agonist treatment appeared to reduce this risk, and diagnostic complexities may have influenced the study’s interpretation.

Understanding the pathophysiology of RLS and PD may be enhanced by elucidating this relationship and the function of the dopaminergic system. Thus, this study was set to determine whether RLS is a risk factor for PD and whether there is a substantial relationship between RLS and PD and the dopamine pathway.

Data from the Korean National Health Insurance Service Sample Cohort, which ran from 2002 to 2019, were utilized in this retrospective cohort analysis. Analysis of the data was done from September 2024 to March 2025. Using classifications from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, patients with PD and RLS were compared to those without RLS.

The patients with RLS who received dopamine agonist (DA) at two or more separate clinical visits were operationally classified as the DA-treated group for the secondary analysis, whereas those who did not fit this description were categorized as the DA-nontreated group. The exposure requirements were RLS diagnosis and DA therapy.

There were 9919 RLS patients and 9919 matched controls in all. The control and the RLS group had mean (SD) ages of 50.1 (16.3) and 50.3 (16.0) years at enrollment, respectively. In the RLS group, the incidence of PD was 1.6% (158 of 9919), while in the control group, it was 1.0% (99 of 9919).

RMST to PD diagnosis was 14.93 years in the control group and 14.88 years in the RLS group at the predetermined time horizon of 15 years (τ = 15), resulting in a difference of −0.05 years (95% CI, –0.07 to –0.03 years). The DA-nontreated RLS group (n = 6842) had a higher incidence rate (143 of 6842 [2.1%]) and a considerably shorter RMST to PD diagnosis (difference, –0.09 years [95% CI, –0.12 to –0.06 years]) than the control group.

The DA-treated RLS group (n = 3077) had a reduced incidence rate (15 of 3077 [0.5%]) and a considerably longer RMST to PD diagnosis (difference, 0.03 years [95% CI, 0.01-0.06 years]). Overall, a higher chance of getting Parkinson's disease was linked to RLS. These results imply that mechanisms other than the dopaminergic pathway may be involved in the pathophysiological relationship between RLS and PD.

Source:

Bang, M., Park, D., Kim, J. H., & Kim, H. S. (2025). Risk of Parkinson disease among patients with restless leg syndrome. JAMA Network Open, 8(10), e2535759. https://doi.org/10.1001/jamanetworkopen.2025.35759