Why are chronic stress, depression, cardiovascular disease, fragmented sleep, and aging all linked to a greater risk of dementia? In a new review article published in the journal Science, neuroscientist Maiken Nedergaard proposes that these seemingly different conditions may share a common biological pathway: disruption of a sleep-dependent brain rhythm that helps remove waste from the brain. Her work suggests that sleep is far more than a passive resting state. Instead, it is a highly organized biological process that coordinates brain chemistry, blood vessel activity, and cerebrospinal fluid flow to support the brain’s nightly cleaning system.
Nedergaard’s research builds on her laboratory’s groundbreaking discovery in 2012 of the glymphatic system, a brain-wide network that circulates cerebrospinal fluid through tissue surrounding blood vessels to remove metabolic waste. The system becomes especially active during sleep and has since become central to research into Alzheimer’s disease, Parkinson’s disease, stroke, traumatic brain injury, and other neurological disorders. Scientists now believe this cleaning system plays an essential role in maintaining long-term brain health by clearing away potentially harmful proteins and other waste products that accumulate during waking hours.
The review focuses on neuromodulators, brain chemicals such as norepinephrine, serotonin, dopamine, and acetylcholine that regulate mood, attention, learning, and behaviour while people are awake. During non-REM sleep, however, these chemicals shift into synchronized, slow oscillations that repeat roughly once every minute. These rhythms are closely linked to changes in brain activity, breathing, heart rate, blood vessel movement, and the flow of cerebrospinal fluid. According to Nedergaard, this coordinated state appears to create ideal conditions for the brain’s waste-clearance system to function efficiently.
These synchronized sleep rhythms help power the glymphatic system through slow, rhythmic changes in blood vessel size known as vasomotion. Unlike the heart’s pumping action, these vascular movements gently push cerebrospinal fluid through brain tissue, helping clear waste products such as amyloid-beta and tau proteins, both strongly associated with Alzheimer’s disease and other dementias. Nedergaard argues that when these rhythms are disrupted by aging, chronic stress, psychiatric illness, cardiovascular disease, poor sleep, or certain medications, the brain becomes less efficient at removing toxic proteins that may contribute to cognitive decline over time.
The article also introduces the possibility of a new biomarker for brain health: heart rate variability, which measures subtle changes in the timing between heartbeats. Researchers found that fluctuations in heart rate during sleep appear to mirror the same neuromodulator rhythms occurring in the brain. Because heart rate variability can already be monitored using consumer wearable devices, Nedergaard believes it could eventually provide a simple, noninvasive method for assessing the health of the brain’s nighttime clearance system and identifying people at elevated risk for dementia before symptoms develop.
The findings present a new way of understanding the relationship between sleep and brain health. Rather than viewing sleep solely as a period for rest, memory consolidation, or restoration, the research suggests that sleep may function as a carefully orchestrated maintenance state essential for clearing waste and preserving cognitive function. If confirmed by future studies, this work could open new opportunities for early detection, prevention, and treatment strategies aimed at protecting the brain’s natural cleaning system and reducing the risk of dementia.
More information: Maiken Nedergaard et al, The oscillatory biology of sleep: Linkage to dementia, Science. DOI: 10.1126/science.aeg2276
Journal information: Science Provided by University of Rochester Medical Center
