One of the presumed side effects of neurodegenerative disease has long been excessive drowsiness—but scientists have always believed it to be the result of brain maladies, not the cause.
But a comprehensive new review published in Science claims otherwise. It points out a possible link between the disruption of circadian rhythms and cognitive decline later in life. Previous studies have found that about 80 percent of people with rapid eye movement sleep behavior disorder (RBD) go on to develop Parkinson’s disease, multiple system atrophy, or dementia with Lewy bodies. In addition, sleep problems generally begin occurring much earlier than symptoms of neurodegenerative disease express themselves.
The strongest case for a link between sleep disruption and neurodegenerative disease comes from Alzheimer’s research. Scientists have discovered that levels of amyloid beta, the peptide that forms plaques in Alzheimer’s, are higher during waking hours. They also found that sleep deprivation increases plaque formation. A vicious cycle ensues: Brain deterioration exacerbates sleep troubles, and sleep troubles exacerbate further neurodegeneration. Other studies have revealed that proteins known asalpha-synuclein aggregates (associated with Parkinson’s disease) tend to congregate in the regions that regulate rapid eye movement sleep.
However, these studies don’t specifically analyze circadian rhythms (as opposed to sleep cycles—similar, yet different concepts) with respect to brain disease. In 2013, Erik Musiek and David Holtzman of Washington University School of Medicine in Saint Louis (who also wrote the review that was published in Science last month) deleted a key circadian clock gene, BMAL1, in mice brains.
Here’s Simon Makin, reporting for Scientific American:
The mice gradually developed signs of pathology, including loss of synapses (the connection points among neurons), free radical damage and signs of inflammation. “The mouse gets a kind of neuroinflammatory syndrome that’s pretty striking,” Musiek says. “Circadian clock genes clearly play some important role in maintaining the brain.”
The team also saw reduced activity of genes that defend against free radicals, suggesting lack of this protection was a major cause of damage, according to the study, which was published in 2013. Processes like free radical damage, inflammation and others have all been implicated in neurodegeneration. They can also influence, and be influenced by, the circadian clock, providing potential paths by which circadian disturbances and neurodegeneration could affect each other. “Sorting out the mechanisms of this is probably the most important next step in this field,” Holtzman says.
Other next steps, Makin reports, will include determining how large a role circadian factors play in neurodegeneration, and what drugs can be manufactured to target a person’s circadian clock.