Chronic sleep deprivation may increase the risk of Alzheimer’s

Prolonged periods of poor sleep increase levels of proteins involved in Alzheimer’s disease, research suggests, although quality, not quantity, of sleep is at the root of the issue.

While previous research has revealed that bad sleep can increase levels of these proteins, known as beta-amyloid and tau, it was unclear which aspect of shut-eye was behind the uptick.

Now researchers say that poor sleep quality, and disruption of the deep, restful sleep known as slow-wave sleep, both play a key role.

“[The study] shows specifically that slow wave sleep, or deep sleep, is important for lowering the levels of amyloid overnight,” said Yo-El Ju, a neurologist at Washington University in St Louis, Missouri, and a co-author of the research. “We think that not getting good sleep chronically over the years would increase the risk of the amyloid and tau clumping up and causing Alzheimer’s disease.”

Published in the journal, Brain, the study involved a group of healthy participants aged between 35 and 65, who each undertook two sleep experiments a month apart. In both experiments, participants were asked to complete a sleep diary at home over a period between five days and two weeks, during which they also wore sensors to track their movements during sleep.

At the end of the period, they spent a night asleep in the laboratory where they had their brain-waves tracked and, the following morning, they each had a lumbar puncture taken.

While asleep in the laboratory setting, all participants wore headphones, but while one group had no noises played to them, the other group were played a series of beeps of increasing loudness when it was detected that they had entered slow-wave sleep. “Our goal was to get them to just get out of slow-wave sleep, but not wake up,” said Ju.

The results, based on data from 17 participants, revealed that disruption of slow-wave-sleep had an impact.

Among those who showed a response to the disruption, the team found on average levels of beta amyloid were about 10% higher when the beeps were played.

“The more we were able to disrupt their slow-wave sleep, the more the amyloid increased,” added Ju. But, she noted, not all participants showed a response to the sleep disruption – a result Ju says is down to them having little slow wave sleep in the first place.

Since tau levels take longer to change than beta-amyloid, Ju says it was not surprising that the experiment did not show an impact on tau levels.

But data collected by the participants at home revealed an effect. While sleep duration or the proportion of time in bed spent asleep did not affect beta-amyloid levels, the latter was linked to increased levels of tau. “The worse your sleep quality, the more your tau increased,” said Ju.

The authors say the findings suggest that repeated disruption of slow wave sleep, or poor quality sleep, could lead to a buildup of beta-amyloid and tau, increasing the risk of plaques and tangles forming in the brain and eventually increasing the risk of Alzheimer’s disease.

“We should all be working to sleep at the better end of our abilities, because it does seem to make a difference,” said Ju. But, she added, only chronic bad sleep is cause for concern. “One bad night is not bad for you and people should not stress over it,” she said.

While the study size was small, experts say the research is an exciting step in unpicking the early stages of Alzheimer’s disease.

“It’s one of the first studies showing a biological link between sleep and generating the proteins involved in Alzheimer’s disease in humans,” said Tara Spires-Jones, interim director of the Centre for Cognitive and Neural Systems at the University of Edinburgh, who was not involved in the research. But, she noted, it was not clear whether helping people to sleep better could prevent or treat Alzheimer’s disease.

Doug Brown, director of research at Alzheimer’s Society, agreed. “While this contributes to a growing body of evidence which highlights the importance of good sleep, the study didn’t test whether people went on to develop Alzheimer’s, so we can’t yet say whether better sleep could reduce risk of the disease,” he said.

Written by Nicola Davis and first published in, ‘The Guardian’, 10 July 2017.

The original scientific research paper was published in Brain: A Journal of Neurology, May 2017.


Slow wave sleep disruption increases cerebrospinal fluid amyloid-ß levels
Yo-El S. Ju, Sharon J. Ooms, Courtney Sutphen, Shannon L. Macauley, Margaret A. Zangrilli, Gina Jerome, Anne M. Fagan, Emmanuel Mignot, John M. Zempel, Jurgen A.H.R. Claassen, David M. Holtzman

Abstract

Sleep deprivation increases amyloid-ß, suggesting that chronically disrupted sleep may promote amyloid plaques and other downstream Alzheimer’s disease pathologies including tauopathy or inflammation. To date, studies have not examined which aspect of sleep modulates amyloid-ß or other Alzheimer’s disease biomarkers. Seventeen healthy adults (age 35–65 years) without sleep disorders underwent 5–14 days of actigraphy, followed by slow wave activity disruption during polysomnogram, and cerebrospinal fluid collection the following morning for measurement of amyloid-ß, tau, total protein, YKL-40, and hypocretin. Data were compared to an identical protocol, with a sham condition during polysomnogram. Specific disruption of slow wave activity correlated with an increase in amyloid-ß40 (r = 0.610, P = 0.009). This effect was specific for slow wave activity, and not for sleep duration or efficiency. This effect was also specific to amyloid-ß, and not total protein, tau, YKL-40, or hypocretin. Additionally, worse home sleep quality, as measured by sleep efficiency by actigraphy in the six nights preceding lumbar punctures, was associated with higher tau (r = 0.543, P = 0.045). Slow wave activity disruption increases amyloid-ß levels acutely, and poorer sleep quality over several days increases tau. These effects are specific to neuronally-derived proteins, which suggests they are likely driven by changes in neuronal activity during disrupted sleep.


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You will learn about the latest Alzheimer’s research in plain English in this section of Decoding Alzheimer’s. It will usually be written by me, but from time-to-time we will have other scientists and science writers making a guest appearance.