- Restless leg syndrome is a sleep and movement disorder that impacts many people in the United States alone.
- A recent population-based cohort study in the Republic of Korea found that having restless leg syndrome is associated with a higher likelihood of developing Parkinson’s disease.
- The results also found that participants with restless leg syndrome who received dopamine agonists tended to have a lower risk for Parkinson’s disease.
A study recently published in
When considering treatment of restless leg syndrome with dopamine agonists, researchers found that this subgroup had a lower incidence rate of Parkinson’s disease and a longer time before experiencing a Parkinson’s disease diagnosis.
For the study, researchers selected participants from a database called the Korean National Health Insurance Service Sample Cohort. They had access to deidentified records of demographic information and health care use.
From this group of over 1 million people, researchers selected 9,919 individuals who had restless leg syndrome based on a specific code for restless leg syndrome.
They specifically included individuals who had at least two instances of documented outpatient diagnoses of restless leg syndrome. They then matched this group with a control group that did not have restless leg syndrome. About 63% of each group were women.
Researchers defined Parkinson’s disease based on two codes and compared the incidence of Parkinson’s disease in the two groups.
They also wanted to explore how pathways related to dopamine played into the outcomes. For this reason, they took into account participants with restless leg syndrome who received dopamine agonist treatment and those who did not.
Dopamine agonists are a common treatment for restless leg syndrome, and the authors note that Parkinson’s disease is also treated with dopaminergic agents.
Researchers assumed that participants who were treated with dopamine agonists had primary restless leg syndrome, while those who did not receive this treatment were assumed to have secondary restless leg syndrome, where symptoms are more likely to be relieved with treatment of underlying problems.
In terms of covariates, researchers considered components like having a history of sleep disorders. The group with restless leg syndrome had a higher prevalence of sleeping disorders.
The group with restless leg syndrome had a higher incidence of Parkinson’s disease, and over a 15-year timeframe, was more likely to receive Parkinson’s disease diagnoses sooner. Overall, researchers found that having restless leg syndrome was linked to a higher chance of someone developing Parkinson’s disease.
When researchers considered treatment with dopamine agonists, about 3,000 participants received dopamine agonist treatment, while the rest of the participants with restless leg syndrome did not receive treatment.
The group that received treatment with dopamine agonists had a lower cumulative incidence rate of Parkinson’s disease and a longer time until diagnosis compared to the control group. In contrast, the cumulative incidence of Parkinson’s disease among the non-treatment group was higher than that of the control group, and the time until diagnosis was shorter.
This research does have noted limitations. First, it only focused on Korean individuals, limiting generalizability. Second, underdiagnosis, overdiagnosis, and misdiagnosis of both Parkinson’s disease and restless leg syndrome are possible.
Thirdly, this study cannot determine causal relationships, and more research in this area will likely be necessary to identify possible causal relationships between Parkinson’s disease and restless leg syndrome.
In terms of time before diagnosis in the 15-year timeframe, there was less than a year difference between all of the groups.
There are also limits to the researchers’ groups of restless leg syndrome participants. The authors note discontinuation of dopamine agonists in the non-dopamine agonist group could account for the higher incidence of Parkinson’s disease in this group.
It is also possible that this group further contained individuals who had conditions besides primary restless leg syndrome.
Researchers made the assumption that the dopamine agonist group was made up of primary cases of restless leg syndrome and the non-dopamine agonist group was made up of cases of secondary restless leg syndrome. However, it is possible that this was not the case, and that some people discontinued dopamine agonist treatment.
The authors further acknowledge that the research cannot confirm “shared dopaminergic pathway dysfunction between [restless leg syndrome] and [Parkinson’s disease].”
Finally, researchers in this study regarded restless leg syndrome not to be “a prodromal manifestation of” Parkinson’s disease and thus considered the use of dopamine agonists to be a way to treat symptoms rather than protective measure.
They admit that if they had regarded restless leg syndrome as an early beginning to Parkinson’s disease, that “DAs [dopaminergic agents] might have been considered to exert a neuroprotective effect in preventing progression to PD [Parkinson’s disease].”
Guy Roleau, OC, OQ, MD, PhD, Chair of the Department of Neurology and Neurosurgery at McGill University in Canada, who was not involved in this research, noted several limitations of the research to Medical News Today.
“There is no known shared genetic risk between [Parkinson’s disease] and [restless leg syndrome], and Mendelian randomisation studies also show no link between the two diseases, suggesting no causative link between the two diseases,“ Roleau told us.
“This is a retrospective study using diagnostic codes, so there are many potential sources for errors. The most obvious is that people with REM Behaviour Disorder (RBD) [which can affect people with Parkinson’s disease] can easily be misdiagnosed with [restless leg syndrome]. We know that most patients with RBD go on to develop [Parkinson’s disease]. So this could lead, at least in part, to the association they see. Also, the different finding for [restless leg syndrome] treated and not treated with dopamine agonist is troubling. I suspect that if they put all the [restless leg syndrome] together, their finding may not be significant.”
While more research is required on this topic, the results suggest that restless leg syndrome could be a risk factor for Parkinson’s disease. Identifying restless leg syndrome may help identify individuals most at risk for Parkinson’s disease.
Future research can explore the neuroprotective effects of dopamine agonists and how restless leg syndrome and Parkinson’s disease truly relate to one another.
More research into how dopamine relates to everything may be useful as well. The authors suggest that because the group that did not receive treatment with dopamine agonists tended to have a greater risk for Parkinson’s disease, “the association between [restless leg syndrome] and [Parkinson’s] might not be due to the dopaminergic pathway.”
Alex Dimitriu, MD, double board-certified in Psychiatry and Sleep Medicine and founder of Menlo Park Psychiatry & Sleep Medicine, likewise not involved in the study, told us:
“I am not sure I agree with the authors that dopamine may not be the single agent responsible for the [restless leg syndrome]- Parkinson’s relationship. In my professional work, I have seen dopamine-related conditions go hand in hand with others. Specifically, people who have akathisia (restlessness) with dopamine blocking meds, also tend to have [restless leg syndrome]. And patients with [restless leg syndrome] are more likely to develop tremor and akathisia (all symptoms of lower dopamine).”