A long-term analysis using Korean national health data has found that individuals diagnosed with restless legs syndrome (RLS) are more likely to develop Parkinson’s disease (PD) compared to those without RLS. The study, published in JAMA Network Open, also examined how treatment choices for RLS may influence the timing and risk of developing PD.
Researchers analyzed records from the Korean National Health Insurance Service Sample Cohort, which included one million anonymized individuals between 2002 and 2019. They identified nearly 10,000 patients with RLS and matched them to an equal number of controls based on factors such as age, sex, income, region, and comorbidity scores.
The findings showed that PD developed in 1.6% of RLS patients versus 1% of controls during the study period. This corresponded to incidence rates of 10.1 per 10,000 patient-years for those with RLS and 6.3 per 10,000 patient-years for controls. The average time until a PD diagnosis was slightly shorter for RLS patients than for those without the condition.
The study further divided RLS patients into two groups: those treated with dopamine agonists (DAs), commonly used drugs such as ropinirole and pramipexole, and those who did not receive these medications. Of the DA-treated group—considered likely to have primary RLS—only fifteen went on to develop PD, resulting in an incidence rate of 1.3 per 10,000 patient-years. In contrast, among patients who did not receive DA treatment—a group considered to have secondary RLS—143 developed PD at a much higher rate of 27.3 per 10,000 patient-years.
“RLS was associated with a higher risk of PD development in this cohort,” the authors stated in their publication. “RLS patients were more likely to have a PD diagnosis earlier than controls.”
They also noted differences within subgroups: “RLS patients who were not treated with DAs had a higher PD incidence and shorter time to PD diagnosis, while those treated with DAs had lower PD incidence and longer time to PD diagnosis.”
However, the researchers cautioned against drawing direct conclusions about causality or interpreting DA use as protective against Parkinson’s: “These findings reflect associations rather than proven causal effects,” they wrote. “DA use should not be interpreted as protective without further evidence.”
The authors suggested that while their results support an association between restless legs syndrome and increased Parkinson’s risk—and highlight potential differences depending on treatment—the underlying mechanisms connecting both conditions remain unclear.
“These findings suggest that the pathophysiological links between PD and RLS may involve mechanisms beyond the dopaminergic pathway,” they concluded.
