Up to 70 million people suffer from persistent sleep problems. A person’s risk of developing dementia and cognitive decline is increased when they don’t get enough sleep each night. Using a mouse model, a new study explains for the first time how the brain’s glymphatic system is powered by synchronized oscillations during sleep to help eliminate “waste” linked to neurodegenerative diseases. Additionally, researchers discovered that a frequently prescribed sleep aid may suppress those oscillations, interfering with the brain’s ability to eliminate waste while you sleep. It’s critical to consider every factor that could increase the risk of cognitive decline, especially in light of recent studies showing that the risk of dementia in Americans has more than doubled after the age of 55.

According to the most recent data, many adults over the age of 18 may experience persistent sleep problems like insomnia and sleep apnea, despite doctors’ recommendations that they get at least 7 hours of good sleep every night. It is estimated that 39 percent of adults over 45 in the United States alone were not getting enough sleep in 2022. According to previous research, a person’s risk of developing some illnesses, including brain-related disorders like dementia and cognitive decline, can be raised by not getting enough sleep each night. Natalie Hauglund, PhD, a postdoctoral fellow at the Universities of Copenhagen in Denmark and Oxford in the United Kingdom, told Medical News Today that sleep enables the brain to go offline, stop processing information from the outside world, and concentrate on maintenance functions like waste removal and immune surveillance. Disease development and cognitive decline are linked to sleep deprivation.

But could some sleep aids also lead to worse brain health as we age? Researching all the potential causes of cognitive decline is more crucial than ever, especially in light of a recent study in Nature Medicine that found that Americans’ risk of developing dementia after the age of 55 has more than doubled compared to previous estimates. For the first time, Hauglund is the first author of a study that uses a mouse model to describe the synchronized oscillations that occur during sleep and power the brain’s glymphatic system, which helps remove waste linked to neurodegenerative diseases. The study was published in the journal Cell. According to the survey, zolpidem, a popular prescription sleep aid sold under Ambien, may suppress these oscillations and interfere with the brain’s ability to eliminate waste while you sleep.

What powers the brain’s ‘waste-removal’ system?
For this study, scientists recorded the brain activity of mice both awake and asleep using a variety of technologies. Researchers found that the brain’s waste-removing glymphatic system is essentially powered by slow, synchronized oscillations of the neurotransmitter norepinephrine, cerebral blood, and cerebrospinal fluid (CSF) during non-REM sleep. The brain uses cerebrospinal fluid, a fluid produced inside the brain, to flush the brain tissue and wash away unwanted molecules. This makes our brain unique because it lacks lymphatic vessels, which remove waste products like dead cells and bacteria from the rest of our body, she explained.

The glymphatic system is the brain’s cleaning mechanism. Crucially, the glymphatic system only activates during non-REM sleep, which is the deepest phase of sleep. This is due to a neuromodulator called norepinephrine, which is released in slow cycles approximately every 50 seconds during non-REM sleep. Nedergaard informed us that norepinephrine causes the arteries to constrict by binding to their muscle cells. Consequently, a gradual fluctuation in the brain’s blood volume and artery diameter is caused by the slow oscillation in norepinephrine concentration. Cerebrospinal fluid is transported through the brain’s tissue and along the arteries by this dynamic change in blood volume, which functions as a pump. She explained that norepinephrine thus controls the glymphatic system by coordinating the synchronized dilatation and constriction of the blood vessels.

Sleep aids may disrupt the brain’s glymphatic system
The possibility that sleep aids could mimic the natural oscillations required for the glymphatic function was also investigated. They concentrated their investigation on zolpidem, a sedative. They found that zolpidem seemed to stop norepinephrine oscillations, which disrupted the brain’s glymphatic system’s ability to remove waste while you slept. Although our research indicates that sleep medication may not have the same positive effects as natural, restorative sleep, sleep aids may offer a shortcut to sleep, according to Hauglund. Our results highlight the importance of using sleep aids sparingly and only as a last resort. Sleep is essential because it allows the brain to complete homeostatic housekeeping functions like eliminating waste. Conversely, sleep aids hinder the brain’s ability to properly prepare for each new day by blocking the neuromodulators that control the waste removal system.

Should sleep-aid users be concerned?
As per Segal’s perspective, not being part of the recent study, the advantages derived from enhanced sleep due to the use of sleep aids like zolpidem seemingly fail to surpass any alleged negative impact this medication may have on decreasing REM sleep, consequently lowering brain neurotransmitter levels, subsequently affecting brain protein levels. The numerous ‘in turn’ assertions do not instill any worry in me that this research holds any substantial clinical relevance, he mentioned. Clinical neurologists, including myself, are not apprehensive about the possibility of zolpidem misuse leading to dementia in the elderly population struggling with insomnia.

It is difficult for clinical neurologists like me to agree that sleeping pills will cause dementia. I would tell my patients that the advantages of getting a good night’s sleep outweigh any potential risks that may arise, such as dementia or memory loss as they age. The relationship between brain health, sleep quality, and general healthPolos, who was not involved in the study, said he found the results intriguing. “There is no question that the glymphatic system can work in synchrony with different transmitters and waste products in the brain,” he said.

According to this study, changes to this delicate balance may have cellular and possibly therapeutic repercussions. Though intriguing, we must keep in mind that this is an animal study and that extrapolating results from it to humans should be done carefully, as is frequently the case. It does, however, provide physicians with a phenomenon that merits some discussion. “We definitely would like to see if studies could assess the impact of sleep aids on human glymphatic flow if more work were to be done in this area,” Polos added. Naturally, noninvasive methods and possibly some sophisticated imaging would be needed for this. Even in small quantities, such data would be useful.

He went on to say that it is impossible to overstate the connection between the brain, restful sleep, and general health. As sleep physicians, we fully support ongoing research into the relationship between the brain, sleep, and general health because the rhythmic nature of sleep and the regular cycling of sleep stages have been thoroughly studied. We have learned a lot about the effects of changes in the brain and how they affect sleep, but we still have a lot to learn.