Disrupted Sleep Rhythms May Link Many Disorders to Dementia

Why do conditions as varied as chronic stress, depression, cardiovascular disease, fragmented sleep, and aging all carry a higher risk of dementia? In a new review in Science, University of Rochester Medicine neuroscientist Maiken Nedergaard suggests these seemingly different conditions may share a common biological thread: disruption of a sleep-dependent brain rhythm that helps clear waste from the brain.

The article reframes sleep not as a simple 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. It also points to heart rate variability—already trackable through consumer wearables—as a noninvasive way to gauge sleep-related brain health and flag people at higher risk of 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."

In 2012, Nedergaard's lab at URochester Medicine helped reshape neuroscience research with the discovery of the glymphatic system, a brain-wide network that circulates cerebrospinal fluid through tissue surrounding blood vessels to flush out metabolic waste. The system is especially active during sleep and has become a central feature of research into Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury, and other neurological disorders.

The new review focuses on neuromodulators—brain chemicals such as norepinephrine, serotonin, dopamine, and acetylcholine that regulate mood, attention, learning, and behavior. During non-REM sleep, these systems shift into slow, synchronized oscillations occurring roughly once a minute. The rhythms align with 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."

The oscillations help power the glymphatic system by driving slow rhythmic changes in blood vessel diameter—a process known as vasomotion—that push cerebrospinal fluid through the brain and remove waste, including the amyloid-beta and tau proteins linked to Alzheimer's and other dementias. When aging, stress, psychiatric illness, cardiovascular disease, poor sleep, or certain medications interrupt these rhythms, Nedergaard argues, 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."