Summary: A wearable device developed by Applied Cognition enables real-time monitoring of the brain’s glymphatic system during sleep, revealing that waste clearance activity occurs not only during deep sleep but also in REM and wake transitions—contradicting prior assumptions based on rodent studies.
Key Takeaways:
- A wearable device allows real-time monitoring of the brain’s glymphatic system during natural sleep, without the need for MRI.
- Contrary to earlier rodent-based research, glymphatic activity in humans continues across deep sleep, REM sleep, and the waking transition—not just during slow-wave sleep.
- Clearance of brain waste appears to accelerate the longer a person sleeps and gradually slows upon waking, rather than operating in an on/off fashion.
- The device could help identify patients with glymphatic dysfunction who may benefit from targeted treatments.
- Applied Cognition, the developer of the device, reports early success in identifying a drug candidate that improves glymphatic clearance.
A new device that monitors the waste-removal system of the brain may help to prevent Alzheimer’s and other neurological diseases, according to a study published in Nature Biomedical Engineering.
In the study, participants were asleep when they wore the device: a head cap embedded with electrodes that measures shifts in fluid within brain tissue, the neural activity from sleep to wakefulness, and changes in the brain’s blood vessels.
By measuring these three features, the researchers found they could monitor the brain’s glymphatic system, which acts as a waste-removal and nutrient-delivery system.
Researchers tracked the flow of glymphatic fluid in individuals at different levels of sleep through a single night. Previously, these processes could only be monitored at university research centers by using MRI, an approach that is too slow to track minute changes in individuals’ sleep stages.
“We have assumed that this system operated in a sort of ‘on-off’ manner: ‘on’ during sleep — particularly during slow-wave sleep—and ‘off’ during waking,” says Jeffrey Iliff, coauthor of the study and a professor in psychiatry and neurology at the University of Washington School of Medicine, in a release.
These assumptions, Iliff adds, were based on rodent studies he and others conducted over the last decade. When the research involved human participants, however, the investigators were surprised at the findings.
They found that the glymphatic system was active in both deep and REM sleep, as well as when the person was waking up. Rather than turning on and off, switch-like, this clearance function appeared to accelerate the longer a person slept, and then slow down gradually as they woke, Iliff says.
“It lets us monitor how this system is related to sleep and how it’s affected by sleep disruption in humans—something that is critical if we are trying to understand the role that this biology plays in clinical psychiatric and neurological conditions,” Iliff says.
These findings are important because the glymphatic system plays a vital role in clearing brain proteins whose abnormal accumulation is linked to disorders such as Alzheimer’s and Parkinson’s disease, he says.
“This is a critical step in the development of therapeutics targeting glymphatic function,” Iliff says. “And if you can develop therapeutics that improve glymphatic function, you might be able to treat or prevent conditions like Alzheimer’s disease.”
The wearable device, developed by California-based Applied Cognition, could have several potential uses, Iliff suggests. It could help scientists define whether glymphatic dysfunction contributes to the development conditions such as Alzheimer’s, traumatic brain injury, and migraine headaches. It could inform the development of new therapeutics to improve glymphatic function. And it could be used to identify patients at risk for these conditions, who might benefit most from these new therapeutics.
This study was conducted with participants at the University of Washington Medical Center – Montlake and the University of Florida between October 2022 and June 2023. In all, 35 participants participated in the benchmarking study in Florida, and an additional 14 in a replication study in Seattle. Participants ranged between 56 and 66 years old.
Swati Rane Levendovszky, PhD, an MRI physicist and former director of UW Medicine’s Diagnostic Imaging Sciences Center, also worked on the project. She now works at the University of Kansas Medical Center.
“This work is pivotal in defining the role glymphatic dysfunction plays in Alzheimer’s and discovering therapies to rescue it,” says Paul Dagum, MD, PhD, CEO of Applied Cognition, in a release. “Our platform has already identified a promising drug candidate that improves glymphatic clearance in early clinical trials.”
Iliff’s lab studies the glymphatic system and its role in neurodegenerative conditions such as Alzheimer’s and traumatic brain injury.
This study was funded by Applied Cognition, where Iliff served as chair of the company’s scientific advisory board and received compensation in that role.
