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This condition affects more than 3 million Americans, mostly adults over age 50, who often unknowingly act out their dreams physically with vocal sounds or sudden, violent arm and leg movements during sleep, leading to significant harm to themselves or bed partners.
The new study, published in the Journal of Neuroscience, outlines a new model to better characterize how REM sleep behavior disorder develops as a result of neurodegeneration – when brain cells lose function over time – which is associated with the accumulation of tau- egg white. This model provides an early biomarker of impending brain decline, which could guide future prevention and treatment.
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The paper also shows for the first time that sleep medications known as dual orexin receptor antagonists — commonly used to treat insomnia, or difficulty falling asleep and staying asleep — can significantly reduce REM sleep behavior disorder. Current therapeutic options for this condition are mainly limited to melatonin and clonazepam, also known as Klonopin, so these findings suggest a promising new treatment with potentially fewer side effects.
“We were interested in understanding all the ways sleep quality deteriorates as neurodegeneration progresses and whether there are ways to mitigate such changes,” said corresponding author Andrew W. Varga, MD, PhD, associate professor of medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai. “We identify a new model in which REM sleep behavior disorder can arise, due to neurodegeneration associated with tau protein accumulation, and a new therapy that could minimize REM sleep behavior disorder.”
Mount Sinai researchers used a mouse model to study neurodegenerative disorders by examining the brain after abnormal deposits of tau, a protein that normally helps stabilize the internal skeleton of nerve cells in the brain. They analyzed behavioral states, including wakefulness, phases of REM (sleep with dreams), phases of non-REM (sleep without dreams), sleep duration, transitions from wakefulness to sleep, and how some factors are related to age. Nearly one-third of the older subjects exhibited dream-actualizing behaviors reminiscent of REM sleep behavior disorder, including chewing and extremity stretching.
After administering a dual orexin receptor antagonist twice over a 24-hour period to evaluate sleep in light and dark phases, the researchers noted that the medication not only reduced the time it took to fall asleep and both the quality as sleep duration increased, but also decreased levels of dream performance.
Researchers hope their findings will encourage future trials of dual orexin receptor antagonists to treat REM sleep behavior disorder in humans, as the medication is already FDA-approved and available to treat people with insomnia.
“We expected a deterioration in sleep quality with progressive neurodegeneration related to tau accumulation, but the observation of dream performance was a surprise,” said lead author Korey Kam, PhD, assistant professor of medicine (Pulmonary, Critical Care and Sleep Medicine) at Icahn Mount Sinai. “It was even more surprising and exciting to see that a dual orexin receptor antagonist could significantly minimize the dream-execution behavior.”
Reference: Korey Kam, Kenny Vetter, Rachel A. Tejiram, et al. Effect of aging and a dual orexin receptor antagonist on sleep architecture and NREM oscillations, including a REM behavior disorder phenotype in the PS19 mouse model of tauopathy. J Neurosci. 2023: JN-RM-1828-22. doi: 10.1523/JNEUROSCI.1828-22.2023
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