One of the most important functions of sleep is that it provides an opportunity for the brain to do some de-cluttering.

A recent study looked at how the brain clears out cellular waste associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease during restorative sleep.

“I compare restorative sleep to a tune-up on a car. You are not changing any parts, you are just getting the whole thing to work better,” Maiken Nedergaard, lead author of the study, told TheDoctor

Over long-term use, zolpidem [Ambien] increases the risk of beta amyloid and tau accumulation.

Nedergaard and her and her colleagues at the University of Rochester and the University of Copenhagen developed a method called flow fiber photometry to better track the clearance of cellular waste from the brain by the glymphatic system. The process made it possible to record the flow of blood and cerebral spinal fluid (CSF) through the brains of mice during natural (unanesthetized) non-REM sleep, REM sleep and wakefulness.

The researchers found that the brain chemical norepinephrine controls this flow of blood and cerebral spinal fluid in the brain. Levels of norepinephrine in the brain go up and down or oscillate in rhythmic waves.

During restorative sleep, norepinephrine is released about every 50 seconds. Norepinephrine, a powerful vasoconstrictor, acts as a pump. When norepinephrine levels are high, blood vessels constrict to pump CSF into the glymphatic system of the brain to clear cellular waste.

When norepinephrine levels are low, the blood vessels relax and cerebral spinal fluid flows out of the brain, taking waste products such as the beta amyloid and tau proteins that build up in the brains of those with neurodegenerative diseases, with it.

“I compare restorative sleep to a tune-up on a car. You are not changing any parts, you are just getting the whole thing to work better.”

Waste removal from the brain is nonspecific. Nedergaard compared it to garbage removal. “You are just dumping everything into a container to get rid of it.”

The team was interested in why sleep aids such as zolpidem, sold under the brand name Ambien, have well-documented risks associated with their use. Using flow fiber photometry to see what was happening in the brains of mice given zolpidem, they found that it interfered with the oscillations of norepinephrine needed for the glymphatic system, a recently discovered waste clearance system in the brain, to function properly.

Zolidem reduced the norepinephrine oscillations in the brains of mice by 50 percent and the clearance of nerve cell waste by 30 percent. Nedergaard called this effect remarkable. Over long-term use, zolpidem increases the risk of beta amyloid and tau accumulation.

This is especially concerning in older adults or those who have started to show signs of mild cognitive impairment. Their glymphatic clearance is already reduced and sleep aids reduce it even further, Nedergaard explained, accelerating tau and beta amyloid accumulation in the brain.

“...[O]nly take zolpidem over a very limited period, such as after surgery or on a long-haul flight, if it is needed at all,” Nedergaard, co-director of the Center for Translational Neuromedicine at the University of Rochester, warns.

She hopes this study will be a wake-up call to develop new sleep aids that do not inhibit glymphatic system function.

The study is published in the journal, Cell.