A new review now argues that sleep is not just a time for the brain and body to rest and recover, but that during sleep the brain’s housekeeping services kick into action to clear waste products that, over time, can lead to cognitive decline and dementia.
In a review published in Science, neuroscientist Maiken Nedergaard, MD, DMSc, from the University of Rochester Medical Center, NY, suggests that, sleep-related mechanisms play a complex role in the maintenance of brain health.
Steven Allder, MD, consultant neurologist at Re:Cognition Health, not involved in the review, told Medical News Today that:
“What makes this review compelling is the link between sleep and this clearance process. During deep, slow-wave sleep, glymphatic activity increases significantly, allowing more efficient removal of waste. This provides a biological mechanism that helps explain why chronic sleep disruption is associated with increased risk of cognitive decline and dementia. It is important to emphasize that this is not a simple cause-and-effect relationship, but rather a key pathway in a broader network of brain health factors, including vascular function, inflammation and aging.”
During the daytime, neuromodulators such as norepinephrine, acetylcholine, serotonin, and dopamine work independently to support behavior and cognition.
However, during sleep, they act in a coordinated rhythm to support glymphatic clearance of metabolic waste.
Nedergaard told MNT that:
“There is now converging evidence from multiple lines of research suggesting that impaired glymphatic clearance during sleep plays a central role in the pathogenesis of neurodegenerative diseases. Emerging evidence further indicates that these slow brain-body rhythms are major drivers of glymphatic clearance. Together, these observations suggest that understanding how sleep rhythms regulate brain clearance may be fundamentally important for understanding aging and dementia.”
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Studies have shown that during non-REM sleep — the phases described by fitness/sleep trackers as core and deep sleep — neuromodulators are synchronised and their oscillations correspond to microarousals.
These short bursts of EEG activity that do not wake the person happen approximately every 50 seconds during non-REM sleep and last from a few hundred milliseconds to a several seconds.
The neuromodulators drive the glymphatic system by making tiny blood vessels contract and expand, moving cerebrospinal fluid (CSF) that clears away neurotoxic proteins, such as beta-amyloid and tau, which are closely associated with development of Alzheimer’s disease.
If sleep is disturbed, the rhythms are interrupted, which leads to less effective clearance of waste products, so may increase risk of cognitive decline and dementia.
“The relationship between sleep and dementia risk is increasingly understood as bidirectional and system-wide, with the glymphatic system at the centre of this model,” Allder told us.
“On one hand, impaired sleep, particularly reduced slow-wave sleep, can limit glymphatic clearance of neurotoxic waste such as amyloid-beta and tau, allowing accumulation over time. This may contribute to neuroinflammation, synaptic dysfunction and neurodegeneration,” he explained.
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“On the other hand,” he added, “early neurodegenerative changes can themselves disrupt sleep architecture, meaning sleep disturbance may also be one of the earliest clinical markers of disease. This creates a feedback loop where impaired sleep and impaired clearance reinforce each other.”
In her review, Nedergaard highlighted that heart-rate variability be a biomarker of sleep-related brain health. These subtle changes in timing between heartbeats during sleep appear to be closely tied to the neuromodulator rhythms occurring in the brain.
“Heart-rate variability appears to be regulated by the same slow physiological rhythms that coordinate glymphatic clearance during sleep. We therefore speculate that high heart-rate variability during sleep may reflect effective glymphatic function and restorative sleep,” she told MNT.
“If heart-rate variability is validated experimentally and proves to be a reliable biomarker of glymphatic clearance, it could become a simple and inexpensive tool for identifying individuals at increased risk of dementia and for monitoring treatment responses in clinical trials targeting sleep and brain clearance mechanisms,” she advised.
Allder agreed that using heart-rate variability as a biomarker was “an interesting and potentially very practical idea.”
“Heart rate variability and nocturnal cardiovascular rhythms are already recognised indicators of autonomic nervous system activity, which is closely linked to sleep architecture and deep sleep quality,” he told us.
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“Because glymphatic activity is strongly coupled with slow-wave sleep, it is biologically plausible that cardiovascular patterns during sleep could indirectly reflect how effectively this clearance system is functioning,” he noted.
“However,” he cautioned, “this remains an indirect proxy. Heart rate fluctuations are influenced by many confounders, including stress, medication, fitness level and underlying cardiovascular disease. While this could eventually contribute to a non-invasive screening tool, it would need to be validated alongside more direct imaging or biomarker-based measures of glymphatic activity before being used clinically to identify dementia risk.”
To improve the brain rhythms during sleep, and therefore help ensure that brain clearance is as efficient as possible, Nedergaard advised that people follow the advice for maintaining healthy sleep overall.
“Regular sleep schedules, sufficient sleep duration, physical activity, minimizing stress, and avoiding stimulants or bright light exposure late in the evening,“ she recommended.
“Improving sleep quality is likely beneficial because glymphatic clearance is most active during deep sleep,” said the scientist.
