byJustin Jackson, Phys.org

Credit: Unsplash/CC0 Public Domain

Three research hospitals in the Republic of Korea are reporting that restless leg syndrome was associated with an increased risk of Parkinson's disease, with 1.6% of patients with restless leg syndrome developing Parkinson's disease vs. 1.0% in matched controls and a shorter average time to diagnosis at a 15-year horizon.

Restless leg syndrome causes unpleasant sensations in the lower limbs, with symptoms worsening during rest and eased by movement. While pathophysiology remains unclear,clinical careoften usesdopamineagonists as first-line therapy.

Dopamine is a neurotransmitter that plays a crucial role in movement control. Dopamine agonists mimic the effects of dopamine by activatingdopamine receptors.

Parkinson's disease patients experience reduced dopamine and use dopamine agonists as the primary treatment to help improve movement control. Previous studies have examined links between the two disorders and questioned whetherrestless leg syndromecould be triggered by the same dopaminergic mechanisms.

In the study, "Risk of Parkinson Disease Among Patients With Restless Leg Syndrome,"publishedinJAMA Network Open, researchers conducted aretrospective cohort studyto assess whether restless leg syndrome is a risk factor for Parkinson's disease and whether the dopamine pathway is meaningfully associated with both conditions.

Data came from the Korean National Health Insurance Service Sample Cohort spanning 2002 to 2019, a deidentified database representing a 2% stratified random sample of the Korean population. Final analytic groups comprised 9,919 patients with restless leg syndrome and 9,919 matched controls. Mean age at enrollment measured about 50 years in both groups, with 62.8% women.

Dopamine agonist exposure was defined as receipt of pramipexole or ropinirole during two or more distinct clinical visits, forming a dopamine treated subgroup, with remaining patients classified as dopamine nontreated.

Overall incidence of Parkinson's disease reached 1.6% in the restless leg syndrome cohort, 60% higher than the 1.0% in matched controls. Subgroup analysis showed that those taking a dopamine agonist had only 0.5% Parkinson's incidence compared to 2.1% in the nontreated group.

Authors conclude that restless leg syndrome may be associated with an increased risk of developing Parkinson's disease. Patients with restless leg syndrome who were not treated with dopamine agonists tended to have an elevated risk of Parkinson's and a slightly shorter time to diagnosis.

The study does not imply that early use of dopamine agonists prevents or delays Parkinson's disease, as the design was not powered to determine this, but it could hint at a delay in diagnostic symptoms or a potential neuroprotective effect that could be the subject of future research.

Findings suggest a connection between the two conditions that may involve mechanisms beyond the dopaminergic pathway. Clarifying this association and the role of the dopamine pathway may improve understanding of the pathophysiology of both diseases.

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More information: Myeonghwan Bang et al, Risk of Parkinson Disease Among Patients With Restless Leg Syndrome, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2025.35759 Mark S. Baron, Uncertain Risk of Parkinson Disease Among People With Restless Leg Syndrome, JAMA Network Open (2025). DOI: 10.1001/jamanetworkopen.2025.35766 Journal information: JAMA Network Open