A relatively rare sleep disorder characterized by acting out dreams during REM sleep -- often violently -- is closely linked to the movement disorder Parkinson's disease and may warn of Parkinson's decades before diagnosis.
People with REM sleep behavior disorder (RBD) do not have normal muscle paralysis during the dream phase of sleep. The loss of motor inhibition is generally accompanied by often frightening dreams, which are "acted out" with arm flailing, kicking, punching, and sometimes, screaming and shouting.
"If patients are running in their dream, they 'run' in their beds. If they are fighting with someone in their dream, their arms may flail wildly. This can be dangerous for the patient and the patient's bed partner," Marina Romero-Ramos, PhD, of Aarhus University in Denmark, told 鶹ý.
The prevalence of RBD has been estimated to be in the general population, but the sleep disorder is much more common in patients with Parkinson's disease.
In one study, 69% of patients with a diagnosis of Parkinson's , while no increased risk was seen in patients with the related movement disorders essential tremor and restless leg syndrome.
Even more significant, a large percentage of people with RBD go on to develop Parkinson's years and even decades later, said Miranda Lim, MD, PhD, of the VA Portland Health Care System in Oregon.
"It is widely believed that RBD is one of the earliest markers of Parkinson's," she told 鶹ý. "Some people convert after a few years and some convert after many decades. It's possible that everyone with RBD would develop Parkinson's if they lived long enough, but we don't yet know this."
In a multicenter study published in last spring, researchers predicted the risk of developing Parkinson's and related neurodegenerative disease in a group of 1,280 patients with idiopathic RBD (average age of 66.3; 82.5% of whom were male) treated at 24 centers.
Dementia and Parkinson's risk was estimated using the Kaplan-Meir analysis, and the researchers used the Cox proportional hazards analysis to further assess risk.
During an average follow-up of 3.6 years (range of 1-19), the overall conversion rate from RBD to documented neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12 years of follow-up.
Baseline abnormal quantitative motor testing was a risk factor for conversion (hazard ratio [HR] = 3.16), as was olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), color vision abnormality (HR = 1.69), and older age (HR = 1.54).
Patient characteristics that were not significantly predictive of conversion to Parkinson's or Parkinson's-related dementia (dementia with Lewy bodies) included sex, daytime somnolence, insomnia, restless legs syndrome, obstructive sleep apnea, urinary dysfunction, depression, and anxiety.
The study, which included the largest cohort with idiopathic RBD ever, confirmed "a high risk of phenoconversion to overt neurodegenerative disease," wrote Ronald Postuma, MD, MSc, of McGill University in Montreal, and colleagues.
Another recently published trial by Lim, et al. showed that military veterans with post-traumatic stress disorder (PTSD) had a much higher prevalence of RBD than the general public.
In all, 394 veterans (94% male, average age of 54.4±15.5), prospectively/cross-sectionally recruited from the VA Portland Health Care System, underwent overnight sleep studies from 2015 to 2017 to assess muscle activity during REM sleep.
The overall rate of RBD was 9%. The prevalence of RBD increased to 15% among study participants with PTSD, and to 21% among study subjects with both PTSD and a traumatic brain injury.
Given the strong association between RBD, Parkinson's, and other age-related neurodegenerative diseases "it remains unclear whether or not the association between RBD and traumatic brain injury/PTSD increases the risk of similar long-term neurologic sequelae," Lim and colleagues wrote in .
Lim said the study cohort will be followed in the hopes that longitudinal analysis will help answer this question.
"Of course these studies will take a long time -- probably decades," she said.
She added that patients with RBD could represent an important study group in the ongoing search for treatments that will prevent Parkinson's or dramatically slow its progression.
"The problem with current trials is that by the time people have traditional symptoms of Parkinson's, most of the dopamine neurons in the brain are already lost," she told 鶹ý. "But people with RBD may be years or even decades away from developing these symptoms."
by Romero-Ramos and colleagues suggest that the immune system may play a key role in Parkinson's disease.
When the researchers exposed blood samples from 29 Parkinson's patients and 20 control subjects to the protein alpha-synuclein, they discovered that the blood from the Parkinson's patients was worse at regulating immune markers on the cell surface. The patients' blood also secreted fewer anti-inflammatory cytokines.
"Parkinson's disease peripheral immune cells shed lower in-vitro levels of soluble CD163, which suggests a less responsive monocytic population and/or an activation status different from control cells," the team wrote.
The findings suggest that it might be possible to prevent or slow the degeneration of neurons related to Parkinson's by regulating the immune system, Romero-Ramos said.
And patients with REM sleep behavior disorder may be the perfect subjects to test the hypothesis.
"RBD is a disease where protein alpha-synuclein is aggregated, so we consider this very, very early stage Parkinson's," she told 鶹ý, adding that her research team is now studying the immune systems of patients with the sleep disorder.