A review in Science proposes that many conditions linked to a higher risk of dementia share a common biological pathway: disruption of a sleep-dependent brain rhythm responsible for clearing waste.
Background on the Glymphatic System
Nedergaard’s laboratory discovered the glymphatic system in 2012. This is a brain-wide network that circulates cerebrospinal fluid to remove metabolic waste, a process that primarily occurs during sleep.
Proposed Mechanism
The review focuses on neuromodulators—including norepinephrine, serotonin, dopamine, and acetylcholine. During non-REM sleep, these synchronize into slow oscillations occurring approximately once per minute.
These oscillations drive vasomotion, defined as rhythmic changes in blood vessel size. This action is proposed to help propel cerebrospinal fluid through the brain, clearing waste products such as amyloid-beta and tau proteins.
Nedergaard argues that disruption of these rhythms can reduce the brain's efficiency in clearing these toxic proteins. Conditions cited in the review as potentially contributing to this disruption include:
- Aging
- Chronic stress
- Depression
- Cardiovascular disease
- Fragmented sleep
- Certain medications
Potential Biomarker
The review article identifies heart rate variability during sleep as a possible noninvasive biomarker for assessing sleep-related brain health. This is because heart rate variability is reported to correlate with the neuromodulator rhythms that drive the glymphatic system. The article suggests this could be used to identify individuals at risk for cognitive decline before symptoms appear.