Untreated restless legs syndrome may increase risk of Parkinson’s disease

Restless legs syndrome (RLS) is a common neurological sleep disorder characterized by an uncontrollable urge to move the legs, which often worsens at night. Parkinson’s disease (PD), a progressive neurodegenerative disorder, is characterized by tremors, rigidity, and slow movements. Both conditions are associated with dysfunction in the brain’s dopaminergic system, but their causal relationship remains unclear.

A joint research team from Korea University Ansan Hospital, Pohang Stroke and Spine Hospital, and Ilsan Hospital of the National Health Insurance Service (Republic of Korea) has now clarified that untreated RLS can increase the risk of developing PD, while dopamine (DA) agonist therapy can significantly reduce that risk. The study was published online in JAMA Network Open, Volume 8, Issue 10, 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 Korea National Health Insurance Service sample cohort (2002-2019). The researchers identified 9,919 people with RLS and compared them with an equal number of matched controls without the disease.

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

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

Professor Jong Hun Kim, Department of Neurology, Korea University Ansan Hospital, Republic of Korea

To strengthen the validity of their conclusions, the team employed target test 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 of symptoms.

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

“This dual pattern underlines the importance of early recognition and treatment of restless legs syndrome,” adds Professor Kim. “Monitoring and treating RLS can not only improve sleep quality, but could also influence long-term neurological health.”