The vast majority of people with a thrashing form of sleep disorder that disproportionately affects military veterans are known to develop Parkinson's disease. But does one definitively lead to the other? And, if so, is it possible to reduce the risk?
A research team including Oregon Health & Science University was awarded $4 million over four years to find out.
Researchers at OHSU, the VA Portland Health Care System, the University of Washington and the VA Puget Sound Health Care System received a $4 million award last fall from the U.S. Department of Defense. Recruitment is now getting underway.
"On average, individuals with this sleep disorder and no other symptoms of parkinsonism are considered very early in their disease progression," said Jonathan Elliott, Ph.D., the principal investigator and an assistant professor of neurology in the OHSU School of Medicine. "Early treatment will have a greater likelihood of success."
Understanding the glymphatic system
Researchers believe answers lay in the glymphatic system, a brain-wide network of pathways that clears proteins and metabolic waste. It's especially active during deep sleep.
"Ultimately, we're looking for a way to enhance the function of the glymphatic system during sleep," said Miranda Lim, M.D., Ph.D., a sleep neurologist at OHSU and Portland VA's VISN20 Northwest Mental Illness Research, Education and Clinical Center and Parkinson's Disease Research, Education and Clinical Center. "The first step is to better understand the glymphatic system itself."
To do that, researchers will recruit three groups of people willing to undergo magnetic resonance imaging, or MRI: people affected by Parkinson's, people with the related sleep disorder, and a control group of healthy volunteers.
Parkinson's is a neurodegenerative disease that affects about 1.5 million people in the United States with symptoms that include tremor, muscle stiffness, slow movement and problems with coordination and balance.
Researchers will aim to discern the relationship between Parkinson's and REM sleep behavior disorder, or RBD. REM is short for rapid eye movement, a period of deep sleep when muscles are effectively paralyzed. In cases of RBD, muscle paralysis is impaired to the point that sufferers act out dreams in sleep, sometimes causing injuries to themselves or their partners.
It's believed to be a rare condition.
However, an earlier OHSU study involving hundreds of U.S. veterans found that proportion rose to 9% of veterans in the study and swelled to 21% among those with post-traumatic stress disorder. Worse, researchers say a staggering 96% of people with RBD go on to develop Parkinson's or conditions closely related to Parkinson's — although for some people it may take decades.
The new research initiative has three distinct projects:
- The first, led by Elliott, will use MRI to examine glymphatic function in people with RBD and later-stage Parkinson's compared with the healthy control group.
- The second, led by Lim, will examine mice treated with prazosin, a blood pressure drug sometimes used to treat post-traumatic stress disorder-associated nightmares, to see whether it improves symptoms of RBD and reduces the aggregation of a type of protein called alpha-synuclein, which is known to clump in the brain of Parkinson's patients in clusters known as Lewy bodies.
- The third will be led by Jeffrey Iliff, Ph.D., a neuroscientist at the University of Washington and the VA Puget Sound also in the VISN20 Northwest MIRECC. It will examine donated postmortem human brain tissue to closely examine glymphatic function and Parkinson's-related pathology.
"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."
The importance of sound sleep
Researchers hope to be able to measure glymphatic function, especially in people who suffer from poor sleep or RBD. Over the long term, their work could lead to the development of new medications, devices or lifestyle changes that maintain or improve function of the glymphatic system.
"We don't have a clinical biomarker yet," Lim said. "But it may be possible to use MRIs to get a snapshot of glymphatic function."
Although the initiative will enhance basic scientific understanding about the glymphatic system, researchers already know from previous research in mice over the past decade that it appears to function optimally during deep sleep. Sleep should be treated on par with diet and exercise as an essential pillar of good health, Lim said.
"It's more attainable, sustainable and rewarding than you might think," she said, "in contrast to finding a magic bullet or drug that is supposed to cure everything that ails us."
This research is supported by the U.S. Department of Defense, Parkinson's Research Program, award numbers HT9425-24-1-0774, HT9425-24-1-0775, and HT9425-24-1-0776.
All research involving animals at VA Portland must be reviewed and approved by the facility's Institutional Animal Care and Use Committee (IACUC) and Research & Development Committee. The IACUC's priority is to ensure the health and safety of research animals. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals.
