The Sleep-Deprived Brain

Sleep is what biologists call a primary biological need, something that no animal can live without, like food and water. The average person spends 25 years, or one third of their lifespan, in this unconscious – and highly vulnerable – state; and yet, the precise function of sleep eludes us.

The past two decades has seen huge leaps in our understanding, however. We now know that sleep plays an important role in learning and memory, with the brain activity patterns associated with newly-acquired information being “replayed” during certain stages of sleep to consolidate it. [See “Decoding the Patterns in Sleep” and “The Sleeping Brain”]

It is also clear that sleep is vital for maintaining good overall brain health, and that prolonged periods of sleep deprivation can have severe consequences. Sleep disturbances are associated with neurodegenerative diseases and psychiatric disorders, so maintaining good sleep hygiene likely reduces one's risk of developing such conditions. [See “The Link Between Depression, Sleep, and Stress”]

A new study now shows that just one night of sleep deprivation results in the accumulation in the brain of a protein implicated in Alzheimer's, highlighting once again the importance of good sleep hygiene for brain health.

Waste disposal

The brain does most of its housekeeping while we sleep, and one housekeeping duty in particular – waste disposal – seems to be acutely sensitive to a lack of sleep. The brain disposes of its waste via the glymphatic system, which is thought to consist of a network of vessels that runs alongside blood vessels in the scalp and drains waste-filled cerebrospinal fluid from the organ.

Waste products cleared away by this system include insoluble clumps of misfolded proteins that are deposited in the brain; these occur as a normal part of the aging process and also in neurodegenerative diseases. Alzheimer's disease, for example, is associated with the deposition of two such proteins: amyloid-beta, which aggregates to form plaques around brain cells, and tau, which forms tangles inside them.

The finding that the glymphatic system works best while we sleep helps to explain why sleep disturbances are linked to neurodegenerative diseases: Poor sleep hygiene likely reduces the efficiency of the brain's waste disposal system, so that the insoluble protein clumps that would normally be cleared away by it remain in place. Prolonged periods of poor sleep could result in these clumps accumulating to toxic levels, and these, in turn, could worsen sleeping difficulties in a vicious cycle. [See “Cleaning the Dirty Brain?”]

We have all had late or sleepless nights, and most of us probably consider this to be completely harmless, even though we know from experience that losing sleep has dramatic effects on our mental abilities and well-being. Sleep deprivation makes us moody and irritable, and impairs brain functions such as memory and decision-making. It also negatively impacts the rest of the body – it impairs the functioning of the immune system, for example, making us more susceptible to infection.

Better brain imaging now enables researchers to examine exactly how sleep deprivation affects brain function. One study, published in 2009, showed that sleep deprivation alters functional connections between the prefrontal cortex and the brain's reward- and emotion-processing centers, impairing so-called executive functions. As a result, we become hypersensitive to rewarding stimuli, our emotional responses are heightened, and we start acting irrationally.

The latest of these studies shows that one night of sleep deprivation results in the deposition of amyloid-beta plaques in parts of the brain that are affected in Alzheimer's. Earlier research had shown that circulating amyloid-beta levels fluctuate with the sleep-wake cycle in mice, and that sleep deprivation significantly increases amyloid-beta levels in the animals' brains, but it was not clear if these findings also apply to humans.

Ehsan Shokri-Kojori of the National Institutes of Health and his colleagues may now have resolved this issue. They injected 20 healthy participants with a radioactive tracer that binds to amyloid-beta, and used positron emission tomography (PET) to see where the tracer was distributed in their brains, once after one night of rested sleep and again after one night of sleep deprivation.

In a paper published in the Proceedings of the National Academy of Sciences, they reported that total amyloid beta levels increased by approximately 5 percent after one night of sleep deprivation, in the right hippocampus and thalamus, both of which are affected early on in Alzheimer's. Furthermore, study participants with the largest increases in amyloid-beta levels also reported worse moods the following day.

“We did not determine the extent to which the elevated amyloid levels subside,” says Shokri-Kojori, “but it is likely that sleep will clear away these effects, especially when amyloid-beta is in the soluble form.”

He adds the caveat that they did not differentiate between the soluble and insoluble forms of the protein, however. “We really don't know whether these changes are lasting, but consistently higher levels of amyloid-beta would likely increase the risk of plaque formation.”

A sleep-deprived society?

Researchers and clinicians now agree that good sleep hygiene is a pillar of the neuroprotective lifestyle, and there is compelling evidence that improving sleep can have huge benefits for overall well-being. One recent study of more than 7,500 British university students showed that digital cognitive behavioral therapy for insomnia not only improved the students' sleep but also reduced the level of delusions and hallucinations they experienced.

“We can now think of sleep as a therapeutic target,” says study co-author Russell Foster, director of the Sleep and Circadian Neuroscience Institute at the University of Oxford. “By stabilizing sleep, we actually reduced the severity of their psychiatric symptoms.”

The latest findings, presented at the SLEEP 2018 conference in Baltimore in June, show that a daytime lighting intervention improves sleep and mood in Alzheimer’s patients, adding more weight to the idea of targeting sleep to treat both psychiatric and neurological conditions.

Yet many remain largely unaware of the importance of sleep. Some experts argue that we live in a sleep-deprived society, in which large sections of the population do not get enough rest or have otherwise unhealthy sleep patterns – including shift workers with irregular schedules and schoolchildren who start their day as early as 7:30 am.v “Sleep is the best cognitive enhancer we've got, but we're doing a very poor job translating this information across to the health community,” says Foster, “and it seems extraordinary to me there are no proper educational packages that teach kids about the importance of sleep.”

“We don't have longitudinal studies of kids showing poor sleep, so we need to invest in research to resolve unanswered questions. What are these kids' educational outcomes? Can their disrupted sleep be accommodated, or are they suffering long-term health consequences?

CONTENT PROVIDED BY

The Dana Foundation

The Dana Foundation is a private philanthropic organization that supports brain research through grants and educates the public about the successes and potential of brain research.