Deep sleep allows the brain to wash away waste and toxic proteins more efficiently, according to a new mouse study published in the journal Science Advances. The new findings shed light on previous evidence linking Alzheimer’s disease with aging and sleep deprivation.
“Sleep is critical to the function of the brain’s waste removal system and this study shows that the deeper the sleep, the better,” said Maiken Nedergaard, MD, DMSc, co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study.
“These findings also add to the increasingly clear evidence that quality of sleep or sleep deprivation can predict the onset of Alzheimer’s and dementia.”
The study suggests that the slow and steady brain and cardiopulmonary activity linked to deep non-REM sleep are optimal for the function of the glymphatic system, the brain’s waste removal system. The findings may also explain why some forms of anesthesia can result in cognitive dysfunction in older adults.
The previously unstudied glymphatic system was first described by Nedergaard and her colleagues in 2012. Prior to this, scientists did not fully understand how the brain, which maintains its own closed ecosystem, removed waste. The team discovered a system of plumbing which piggybacks on blood vessels and pumps cerebral spinal fluid (CSF) through brain tissue to wash away waste. Another study revealed that this system primarily works while we are sleeping.
Since toxic proteins such as beta amyloid and tau are linked to Alzheimer’s disease, researchers have wondered if the dysfunction of the glymphatic system due to disrupted sleep could be a driver of the disease. This lines up with clinical observations suggesting that poor sleep is linked to Alzheimer’s risk.
In the new study, researchers conducted experiments with mice that were anesthetized with six different anesthetic regimens. While the rodents were under anesthesia, the team tracked brain electrical activity, cardiovascular activity, and the cleansing flow of CSF through the brain.
The researchers discovered that a combination of the drugs ketamine and xylazine (K/X) most closely mimicked the slow and steady electrical activity in the brain and slow heart rate associated with deep non-REM sleep. In addition, the electrical activity in the brains of mice given K/X appeared to be optimal for function of the glymphatic system.
“The synchronized waves of neural activity during deep slow-wave sleep, specifically firing patterns that move from the front of the brain to the back, coincide with what we know about the flow of CSF in the glymphatic system,” said Lauren Hablitz, PhD, a postdoctoral associate in Nedergaard’s lab and first author of the study.
Specifically, it appears that the chemicals involved in neuron firing drive a process which helps pull the fluid through brain tissue, said Hablitz.
The study reinforces the link between sleep, aging, and Alzheimer’s disease and also demonstrates that the glymphatic system can be manipulated by enhancing sleep, a finding that may point to potential clinical approaches, such as sleep therapy or other methods to boost the quality of sleep, for at-risk populations.
The study also sheds light on the cognitive problems that older patients often experience after surgery. “Cognitive impairment after anesthesia and surgery is a major problem,” said Tuomas Lilius, MD, PhD, with the Center for Translational Neuromedicine at the University of Copenhagen in Denmark and co-author of the study. “A significant percentage of elderly patients that undergo surgery experience a postoperative period of delirium or have a new or worsened cognitive impairment at discharge.”
This study suggests certain classes of drugs that could be used to avoid this issue, since mice in the study that were exposed to anesthetics that did not induce slow brain activity saw reduced glymphatic activity.