Why are conditions such as chronic stress, depression, cardiovascular disease, fragmented sleep, and aging all associated with a higher risk of dementia? In a new review piece in Science , University of Rochester Medicine neuroscientist Maiken Nedergaard, MD, DMSc , proposes that many of these seemingly different conditions may converge on the same biological problem: disruption of a sleep-dependent brain rhythm that helps clear waste from the brain.
The article presents a new way of thinking about sleep, not simply as a period of rest, but as a highly organized biological state that coordinates brain chemistry, blood vessel movement, and cerebrospinal fluid flow to support the brain's nightly cleaning process. The piece also points to a potential biomarker, heart rate variability, which can already be tracked with consumer wearables, as a simple, noninvasive way to assess sleep-related brain health and identify people at increased risk for cognitive decline.
"Sleep is not a quiet or inactive state," Nedergaard said. "During sleep, the brain shifts into a coordinated rhythm that appears to support one of its most important housekeeping functions."
Nedergaard's lab at URochester Medicine helped transform neuroscience research in 2012 with the discovery of the glymphatic system , a brain-wide network that circulates cerebrospinal fluid through tissue surrounding blood vessels to help remove metabolic waste. The system is 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.
A synchronized sleep rhythm
The article focuses on neuromodulators—brain chemicals such as norepinephrine, serotonin, dopamine, and acetylcholine that regulate mood, attention, learning, and behavior during wakefulness.
These systems behave differently during non-REM sleep, becoming synchronized into slow, repeating oscillations that occur roughly every minute. These rhythms are linked to changes in brain activity, heart rate, breathing, blood vessel movement, and cerebrospinal fluid flow.
"For decades, we thought about sleep primarily in terms of memory and restoration," Nedergaard said. "What is emerging now is the idea that sleep is also a highly organized fluid-transport state that helps maintain brain health."
Sleep and the brain's cleaning system
These synchronized oscillations help power the glymphatic system by driving slow rhythmic changes in blood vessel size known as vasomotion. Those vascular movements, which are independent of the heart's pumping action, help push cerebrospinal fluid through the brain and remove waste products, including amyloid-beta and tau proteins associated with Alzheimer's disease and other dementias.
Nedergaard argues that when these rhythms are disrupted by aging, stress, psychiatric illness, cardiovascular disease, poor sleep, or certain medications, the brain becomes less efficient at clearing toxic proteins.
"Many disorders that increase dementia risk also disrupt the brain's sleep rhythms," Nedergaard said. "Our work suggests these may not be separate phenomena. They may be connected through the brain's ability to clear waste during sleep."
A potential new biomarker
The article also highlights heart rate variability, subtle changes in the timing between heartbeats, as a possible biomarker of sleep-related brain health. Researchers found that heart rate fluctuations during sleep appear closely tied to the same neuromodulator rhythms occurring in the brain.
Nedergaard believes this could eventually provide a noninvasive way to monitor the health of the brain's nighttime clearance system and potentially identify people at increased risk for cognitive decline before symptoms appear.
