Common sleep medication may prevent brain from clearing ‘waste’

Corrie Pelc

• As many as 70 million people have consistent sleeping issues.
• Not getting enough sleep each night can raise a person’s risk for several health concerns, including cognitive decline and dementia.
• For the first time a new study describes the synchronized oscillations during sleep that power the brain’s glymphatic system to help remove ‘waste’ associated with neurodegenerative diseases, via a mouse model.
• Researchers also found that a commonly prescribed sleep aid might suppress those oscillations, disrupting the brain’s waste removal during sleep.
• Looking at all the possible factors that might contribute to potential cognitive decline risk is important, particularly as new research estimates that dementia risk the risk after the age of 55 among Americans has now more than doubled.

Although doctors recommend that adults over the age of 18 get at least 7 hours of quality sleep each night, the most recent data suggest that many may face consistent sleep issues, such as insomnia and sleep apnea.

Data from 2022 suggest that, in the United States alone, 39% of adults over the age of 45 were not getting sufficient sleep.

Past studies report that not getting enough sleep each night can increase a person’s risk for several health concerns, including brain-related conditions, such as cognitive decline and dementia.

“Sleep allows the brain to go offline, shut down processing of the external world and focus on maintenance tasks, such as immune surveillance and removal of waste,” Natalie Hauglund, PhD, a postdoctoral fellow at the Universities of Copenhagen in Denmark, and Oxford in the United Kingdom, explained to Medical News Today. “The lack of sleep is associated with cognitive impairment and disease development.”

But could some sleep aids also contribute to poorer brain health as we age? It is now more important than ever to study all the possible factors that might contribute to cognitive decline, particularly seeing that a new study published in Nature Medicine estimates that dementia risk after the age of 55 among Americans has more than doubled, compared to past figures.

Hauglund is the first author of another study, which appears in the journal Cell, and that, for the first time, describes the synchronized oscillations during sleep that power the brain’s glymphatic system to help remove “waste” associated with neurodegenerative diseases, via a mouse model.

The study also reports that the commonly prescribed sleep aid zolpidem — marketed under the name Ambien — may suppress those oscillations, disrupting the brain’s waste removal during sleep.

What powers the brain’s ‘waste-removal’ system?

For this study, researchers used various technologies to record brain activity while mice were both awake and asleep.

Scientists observed that slow synchronized oscillations of the neurotransmitter norepinephrine, along with cerebral blood and cerebrospinal fluid (CSF), combine during non-rapid eye movement (non-REM) sleep, essentially power the brain’s waste-removing glymphatic system.

“Our brain is unique in that it does not have lymphatic vessels, which removes waste products such as dead cells and bacteria from the rest of our body,” Maiken Nedergaard, MD, PhD, professor at the Universities of Rochester and Copenhagen and lead author of this study told MNT.

“Instead, the brain uses cerebrospinal fluid, a brain fluid that is produced inside the brain, to flush the brain tissue and wash away unwanted molecules,” she explained.

“Norepinephrine binds to the muscle cells of the arteries, which makes them constrict,” Nedergaard told us. “Therefore, the slow oscillation in norepinephrine concentration drives a slow fluctuation in the diameter of the arteries and in the blood volume in the brain.”

”This dynamic change in blood volume works like a pump to transport cerebrospinal fluid along the arteries towards the brain and through the brain tissue. Thus, norepinephrine coordinates the synchronized constriction and dilation of the blood vessels which drives the glymphatic system,” she detailed.

Sleep aids may disrupt brain’s glymphatic system

Researchers also examined if sleep aids might replicate the natural oscillations needed for glymphatic function. They focused their research on the sedative zolpidem.

They discovered that zolpidem appeared to halt norepinephrine oscillations, interrupting the glymphatic system’s waste removal in the brain during sleep.

“Sleep aids may provide a short-cut to sleep, but our study shows that the sleep you get with sleep medication may lack the beneficial effects of natural, restorative sleep,” Hauglund said. “Our findings underscore that sleep aids should only be used for short periods of time and as a last resort.”

Nedergaard explained that:

“Sleep is crucial as it gives the brain time to perform homeostatic housekeeping tasks such as waste removal. On the contrary, sleep aids block the neuromodulators that drive the waste removal system and prevent the brain [from] properly preparing for a new day.”