Study Suggests Neuronal Activity, Brain Waste Clearance During Sleep Correlates With Alzheimer’s Risk

Jared Kaltwasser

Patients with Alzheimer’s disease or who were at high risk for the disease had a weaker correlation between brain activity and cerebrospinal fluid flow while sleeping.

New evidence is lending credence to the idea that sleep plays an important role in the prevention of Alzheimer’s disease (AD).

The findings reported in PLOS Biology are part of a larger trend in sleep research looking for possible associations between sleep problems and a variety of neurological disorders.

At the center of the new report is the brain’s glymphatic system, which has been described as a drainage system that clears toxins out of the brain. The system mainly functions at night, suggesting that sleep is an important factor in the waste-clearing process.

As Anthony L. Komaroff, M. D., described it in a recent commentary in JAMA, the glymphatic system, mingles “fresh” cerebrospinal fluid (CSF) with waste product–rich brain interstitial fluid (ISF) rich in brain-related waste products and flushes it out of the bran and into the circulation.

In the “brain waste” are the toxic beta-amyloid and tau proteins. The cause of Alzheimer's is still elusive, but theories point to he buildup of those proteins as playing a role in the development of Alzheimer’s.

In the PLOS Biology study, corresponding author Xiao Liu, Ph.D., and colleagues from Pennsylvania State University examined global brain activity and its impact on toxin buildup. They wondered whether tracking neuronal activity would uncover connections between the levels of such activity and the risk of Alzheimer’s.

Liu and colleagues enrolled 118 subjects who were participants in the Alzheimer’s Disease Neuroimaging Initiative project. Of those, 7 had been diagnosed with Alzheimer’s, 62 with mild cognitive impairment, and 18 had been diagnosed with significant memory concerns. The study also included 31 people as healthy controls.

The study’s subjects underwent resting-state fMRI scans in order to measure global brain activity and CSF flow. The same scan was completed to years later, and investigators compared the findings to neurobiological and neuropsychological markers of Alzheimer’s, including levels of beta-amyloid.

They found that the link between global fMRI activity and CSF influx correlated with AD pathology. The strength of the connection between neuronal activity and CSF flow was stronger in healthy controls and weaker in patients with Alzheimer’s or who were at higher risk of the disease.

“The finding highlights the potential role of low-frequency (<0.1 Hz) resting-state neural and physiological dynamics in the neurodegenerative diseases, presumably due to their sleep dependent driving of cerebrospinal fluid flow to wash out brain toxins,” Liu said, in a press release.

Liu added that additional research should be directed at better understanding how global brain activity and its associated physiological modulations affect glymphatic clearance and neurodegenerative diseases more broadly.

Komaroff, who is a clinical epidemiologist not than a sleep expert, said the links between the glymphatic system, “brain waste,” sleep deprivation, and other neurological disorders could be more extensive than previously realized. He told Managed Healthcare Executive that it is clear that sleep plays an important physiological function so gaining a better understanding of it is critical.

“I think that any activity that humans are biologically forced to do, and to spend about a third of their lives doing, is very important to understand, both because it’s intrinsically interesting, and because having a better understanding of the biological reasons for sleep is likely to improve human health,” he said.