$4M US DOD grant to study sleep disturbances and Parkinson’s
Researchers to focus on underlying factors adding to higher disease risk
The U.S. Department of Defense has granted $4 million in funding to support an investigation by U.S. researchers into the underlying factors contributing to the increased risk of Parkinson’s disease in people who experience sleep disturbances and post-traumatic stress disorder, known as PTSD.
The focus for the researchers is the glymphatic system, a specialized network of vessels responsible for clearing waste products and toxic substances — including misfolded proteins associated with Parkinson’s disease — from the brain and spinal cord.
The funding, spanning four years, was awarded to researchers from institutions in the Pacific Northwest, including the U.S. Department of Veterans Affairs’ VA Portland Health Care System and the VA Puget Sound Health Care System. Scientists from the Oregon Health & Science University (OHSU) and the University of Washington also are part of the research team.
Sleep disturbances and sleep disorders have long been linked to Parkinson’s. But according to a university news story from the OHSU School of Medicine, “the vast majority of people with a thrashing form of sleep disorder that disproportionately affects military veterans are known to develop [the] disease.”
Sleep disturbances often seen long before Parkinson’s motor symptoms
Given the associations between sleep disturbances and Parkinson’s, the researchers will be investigating the workings of the glymphatic system, which appears to be more active during sleep. A sleep disorder called rapid eye movement sleep behavior disorder, or RBD, can precede Parkinson’s by years — sometimes long before the appearance of the motor symptoms that are the disease’s hallmark.
“On average, individuals with this sleep disorder and no other symptoms of parkinsonism are considered very early in their disease progression,” said Jonathan Elliott, PhD, an assistant professor of neurology in the OHSU School of Medicine. “Early treatment will have a greater likelihood of success.”
To better understand how the glymphatic system works in Parkinson’s, the researchers will recruit three groups of people willing to undergo magnetic resonance imaging, or MRI. The groups are delineated as Parkinson’s patients, people with RBD, and a control group of healthy volunteers.
According to Miranda Lim, MD, PhD, a sleep neurologist at OHSU, “the first step is to better understand the glymphatic system itself.” Better understanding that system could potentially lead to new treatment strategies.
“Ultimately, we’re looking for a way to enhance the function of the glymphatic system during sleep,” said Lim, who also serves as a sleep neurologist for the Portland VA’s VISN20 Northwest Mental Illness Research, Education and Clinical Center and Parkinson’s Disease Research, Education and Clinical Center.
US Department of Defense grant will fund 3 projects
Vivid dreams typically happen during rapid eye movement (REM) sleep, when the body’s muscles are temporarily paralyzed to prevent individuals from acting out their dreams. However, in RBD, this temporary paralysis doesn’t occur. As a result, individuals may unknowingly talk, move, or act out their dreams, potentially leading to self-injury or harm to a partner.
While RBD is relatively rare, possibly affecting 1% of the general U.S. population, earlier research at OHSU found that it’s more frequent among military veterans, affecting 9%. It’s even common among those with PTSD — affecting 21%, per OHSU — which develops from experiencing a traumatic event. According to the release, as many as 96% of those with RBD go on to develop Parkinson’s or a related disorder such as parkinsonism, which starts with tremor, stiffness, slowed movements, and problems with balance typical of Parkinson’s.
This is a unique collaboration. … By involving the full spectrum of research — from people, to an animal model, to postmortem tissue from human brains — we think this project will answer some fundamental questions about how … dysfunction [in the body’s brain-clearing system] may contribute to disorders like Parkinson’s disease … something we know relatively little about now.
The grant from the U.S. Department of Defense, awarded late last year, will fund three projects. The first, led by Elliott, will use MRI scans to study how the glymphatic system differs between people with RBD or advanced Parkinson’s and healthy volunteers. This could reveal differences in how the brain clears toxic substances linked to the disease.
The second project, led by Lim, will test prazosin, a blood pressure-lowering medication sometimes used for PTSD-related nightmares. The team will assess its ability to ease symptoms of RBD and prevent the clumping of misfolded alpha-synuclein proteins in the brains of mice. These clumps, called Lewy bodies, are a hallmark of Parkinson’s.
A team led by Jeffrey Iliff, PhD, a neuroscientist at the University of Washington and VA Puget Sound, will look closely into postmortem human brain tissue to better understand how the glymphatic system works and what causes Parkinson’s to develop and progress over time.
“This is a unique collaboration,” Iliff said. “By involving the full spectrum of research — from people, to an animal model, to postmortem tissue from human brains — we think this project will answer some fundamental questions about how glymphatic dysfunction may contribute to disorders like Parkinson’s disease and Lewy body dementia, something we know relatively little about now.”
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