Maiken Nedergaard stood at the threshold of a question that haunts millions: Why does sleep matter so much to our brains? The University of Rochester Medicine neuroscientist has spent years mapping the brain's nighttime cleanup crew—and now she's proposing a bold connection that could reshape how we think about dementia risk.
In a new review published in Science, Nedergaard argues that conditions as seemingly unrelated as chronic stress, depression, cardiovascular disease, and fragmented sleep may all share a common biological culprit: disruption of the synchronized rhythms that power the brain's nightly waste-clearance system. It's a finding that transforms our understanding of sleep from a passive state of rest into a highly organized biological operation, one where brain chemistry, blood vessels, and cerebrospinal fluid move in precise coordination to keep us cognitively sharp.
The story begins with Nedergaard's lab-changing discovery in 2012: the glymphatic system, a brain-wide network that flushes metabolic waste through tissue surrounding blood vessels. Since then, this system has become central to understanding Alzheimer's disease, Parkinson's disease, stroke, and traumatic brain injury. What's remarkable is that the glymphatic system is especially active during sleep—suggesting that our nighttime rest is far more purposeful than previously understood.
During non-REM sleep, brain chemicals called neuromodulators—norepinephrine, serotonin, dopamine, and acetylcholine—shift from their waking roles regulating mood and attention into something more synchronized. They begin oscillating in slow, repeating patterns occurring roughly every minute. These brain rhythms coordinate with changes in heart rate, breathing, blood vessel movement, and cerebrospinal fluid flow. The result is a coordinated fluid-transport state that pushes cerebrospinal fluid through the brain and flushes out toxic proteins, including amyloid-beta and tau, which accumulate in Alzheimer's disease.
Here's where the framework becomes powerful: When these rhythms are disrupted—by aging, stress, psychiatric illness, cardiovascular disease, poor sleep quality, or certain medications—the brain becomes less efficient at clearing waste. Nedergaard's hypothesis suggests that many disorders increasing dementia risk may not be separate phenomena at all, but rather different doors into the same problem: the breakdown of the brain's nighttime housekeeping.
The review also points to a simple, concrete way forward: heart rate variability, the subtle fluctuations in timing between heartbeats. Researchers found that these variations during sleep track closely with the same neuromodulator rhythms occurring in the brain. Since consumer wearables already monitor heart rate variability, this could become a noninvasive biomarker—a way to assess brain health and identify people at risk for cognitive decline before symptoms appear.
"Sleep is not a quiet or inactive state," Nedergaard said in reflecting on the research. "During sleep, the brain shifts into a coordinated rhythm that appears to support one of its most important housekeeping functions." The implication is profound: protecting sleep quality may be as fundamental to brain health as we long suspected, but now we're beginning to understand why at the biological level. For millions concerned about dementia risk, this convergence of evidence offers something unexpected—a window into prevention rooted in nightly restoration.