Restless legs syndrome (RLS) — recurrent discomfort and the urge to move the legs at rest — may be associated with an increased frequency of constipation and rapid eye movement sleep behavior disorder (RBD), two premotor symptoms of Parkinson’s disease, a study suggests.
The study, “The association between restless legs syndrome and premotor symptoms of Parkinson’s disease,” was published in the Journal of the Neurological Sciences.
RLS is more common in Parkinson’s patients than the general population. Studies have shown contradictory results, with some reporting that, similar to Parkinson’s, dopamine-mediated cell communication is impaired in people with RLS, while other researchers have found no hallmark Parkinson’s alterations in RLS patients.
To address this discrepancy, Harvard Medical School researchers conducted an analysis to identify associations between RLS symptom questionnaire responses and the development of well-known prodromal (early) Parkinson’s symptoms, including constipation; possible RBD, characterized by abnormal movements and dream-enacting behaviors during sleep; and hyposmia, or the reduced ability to smell.
This approach allowed scientists to analyze whether previous conflicting results could be due to the fact that RLS occurs during early neurodegeneration before Parkinson’s diagnosis.
Eligible participants were identified from a group of 51,529 men in health professions, ages 40-75, who took part in the prospective Health Professional Follow-up Study (NCT00005182) beginning in 1986. Questionnaires were sent biannually asking about lifestyles and medical histories. Researchers included individuals who had answered questions on RLS in both 2002 and 2008 and who had not been diagnosed with Parkinson’s disease for a total of 16,636 men.
RLS was diagnosed according to the International RLS Study Group criteria, which defines RLS as unpleasant leg sensations with motor restlessness and an urge to move the legs at rest, which worsened in the evening/night and occurred more than five times per month.
Constipation and possible RBD were determined in the 2012 questionnaire. Constipation was defined as a bowel movement every other day or less and/or laxative use at least twice weekly. Participants were considered to have possible RBD when they had been told by their sleep partners that they acted out their dreams while sleeping at least three times in the past. Hyposmia — determined in 2014 — was assessed with the 12-item Brief Smell Identification Test in 5,249 men with constipation or possible RBD and in age-matched controls.
Results revealed that the prevalence of RLS was 4.1% in 2002 (673 men) and 5% in 2008 (833). While only 232 men, with a mean age of 66.91 years, had RLS in both 2002 and 2008, 601 participants (3.8%), with a mean age of 66.38 years, became RLS-positive in 2008.
Race, body mass index, smoking history, physical activity, and alcohol, caffeine and lactose intake did not vary across the groups.
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Having RLS in 2002 and/or 2008 was associated with a higher risk of constipation in 2012, compared with controls. Only individuals who had RLS in both 2002 and 2008 (continuous) showed higher odds of having possible RBD alone, and both constipation and possible RBD in 2012, “indicating a potential association between continuous/recurrent RLS and [Parkinson’s],” according to the researchers.
They cautioned that constipation is a relatively non-specific Parkinson’s symptom and may not indicate a direct link between RLS and Parkinson’s.
No differences were found between olfactory scores of men with or without RLS. However, the team noted that olfactory scores were only available from a subset of participants. Additionally, the timing of the smell sense analysis may also have influenced this result, since a loss of sense of smell has been reported as a relatively late symptom in the early stages of Parkinson’s compared with RBD and constipation, they said.
“We assessed the association between RLS and [Parkinson’s] prodromal signs, but not between RLS and [Parkinson’s] incidence. However, our focus was on identifying whether RLS is an early indicator of the underlying common disease process in [Parkinson’s],” the authors wrote.
The authors believe that the current study alone is not sufficient to draw a definite conclusion for RLS as a long-term Parkinson’s risk; however, the “magnitudes of the associations between RLS and constipation, and RLS and pRBD were moderate but consistent with the interpretation that RLS is a risk factor for [Parkinson’s],” the authors wrote.
The findings warrant future studies for RLS and Parkinson’s incidence in the long-term, they said.
Among the study’s limitations, the authors mentioned that the link between Parkinson’s and RLS may differ by gender, since women, although they have a reduced risk for Parkinson’s, are more susceptible to RLS.
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