Restless legs syndrome (RLS) is a common neurological sleep disorder characterized by an uncontrollable urge to move the legs, often worsening at night. Parkinson’s disease (PD), a progressive neurodegenerative disorder, is marked by tremor, rigidity, and slowed movement. Both conditions are associated with dysfunction in the brain’s dopaminergic system, but their causal relationship has remained unclear.

A joint research team from Korea University Ansan Hospital, Pohang Stroke and Spine Hospital, and National Health Insurance Service Ilsan Hospital, Republic of Korea, has now clarified that untreated RLS may increase the risk of developing PD, while dopamine-agonist (DA) therapy may significantly reduce that risk. The study was published online in Volume 8, Issue 10 of the journal JAMA Network Open on October 6, 2025.

This retrospective cohort study, led by Professor Jong Hun Kim from the Department of Neurology, Korea University Ansan Hospital, Republic of Korea, analyzed data from the Korean National Health Insurance Service Sample Cohort (2002–2019). The researchers identified 9,919 individuals with RLS and compared them with an equal number of matched controls without the condition.

Over a median follow-up of 15 years, PD developed in 1.6% of RLS patients compared with 1.0% of controls, confirming a heightened risk. When analyzed by treatment status, the results revealed a striking divergence. Patients with untreated RLS showed the highest PD incidence (2.1%) and an earlier onset whereas, DA-treated patients showed a markedly lower PD incidence (0.5%) and a delayed onset compared with controls.

“These findings indicate the existence of ‘heterogeneity within RLS’ which allows for multiple interpretations. One of the interpretations is that restless legs syndrome may serve as an early clinical marker for Parkinson’s disease, particularly among untreated individuals. Our results also indicate that DA therapy, used for symptom control, may confer protective benefits to the brain’s motor pathways,” explains Prof. Kim.

To strengthen the validity of their conclusions, the team employed target-trial emulation methods, an advanced analytical approach that reduces bias in observational research. This methodological rigor reinforces the biological plausibility of a link between RLS and PD rather than a mere overlap in symptoms.

The authors propose that beyond dopamine dysfunction, other factors—such as sleep disruption, iron deficiency, and immune or metabolic pathways—may mediate this association. The protective trend observed with DA therapy could reflect neuroprotective mechanisms or improved identification of genuine RLS cases that are distinct from early-stage PD.

“This dual pattern underscores the importance of recognizing and managing restless legs syndrome early,” adds Prof. Kim. “Monitoring and treating RLS may not only improve sleep quality but could also influence long-term neurological health.”