alzheimer’s disease proteins reduced by sleep aid

researchers say that while the findings aren't reason enough to take sleep medication every night, they call the study data "encouraging."

by dave yasvinski

published apr 25, 2023

4 minute read

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4 minute read

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alzheimer's is another reason to get a good night's sleep

people who don't sleep well are more likely to have amyloid and tau proteins in the brain, both of which are related to alzheimer's disease. getty

a small study has revealed that people who take a sleeping pill before going to bed experience a drop in the levels of two key proteins associated with the development of alzheimer’s disease. the research, published in the journal annals of neurology, sought to explore the relationship between the progression of the disease and the inability to get a good night’s sleep through the use of a promising sleeping aid known as suvorexant.

sleep disturbances are thought to be an early sign of alzheimer’s as people who are eventually diagnosed with disease have trouble falling asleep for years before the symptoms of cognitive decline begin to emerge. this can become a vicious cycle, as the disease causes changes to the brain that make it harder to sleep and a lack of sleep accelerates these changes to the brain.

“this is a small, proof-of-concept study,” said brendan lucey, senior author of the study and an associate professor of neurology and director of washington university’s sleep medicine center. “it would be premature for people who are worried about developing alzheimer’s to interpret it as a reason to start taking suvorexant every night. we don’t yet know whether long-term use is effective in staving off cognitive decline and, if it is, at what dose and for whom.

“still, these results are very encouraging. this drug is already available and proven safe and now we have evidence that it affects the levels of proteins that are critical for driving alzheimer’s disease.”

alzheimer’s disease is the most common cause of dementia in the world, accounting for 60 to 80 per cent of all cases, according to the alzheimer’s association. more than 747,000 canadians are currently living with the disease or another form of dementia. roughly 65 per cent of people diagnosed with the disease after the age of 65 are women.

the disease develops when plaques of a protein called amyloid beta start to accumulate in the brain. after a few years, a second protein, known as tau, begins to form tangles that have a toxic effect on neurons. once these tangles become detectable, alzheimer’s patients begin to experience memory loss and other symptoms of cognitive decline.

suvorexant, the sleep aid used by researchers, belongs to a class of insomnia medications known as dual orexin receptor antagonists. orexin is a naturally produced biomolecule that helps humans stay awake; when it’s blocked, they fall asleep. three such inhibitors have already been approved by the u.s. food and drug administration, with more on the way.

lucey and his team were able to show that people who do not sleep well are more likely to have both amyloid and tau proteins in the brain. it is currently unclear if getting a good night sleep has the opposite effect and is able to reverse the process of the disease, but encouraging results have been seen in mice.

the first step for the team was to assess the effect of orexin inhibitors on humans by recruiting 38 people between the ages of 45 and 65, with no cognitive impairments for a two-night sleep study. thirteen subjects were given a low dose of suvorexant (10 mg); 12 were given a higher dose (20 mg); and the rest were given a placebo at 9 p.m. before going to sleep. the team took a small sample of cerebrospinal fluid via spinal tap from subjects every two hours for 36 hours to measure how levels of amyloid and tau changed over time.

they team found that amyloid levels dropped 10 to 20 per cent in the group who received the high dose of suvorexant compared to the placebo group. levels of a key form of tau (known as hyperphosphorylated tau) also fell by 10 to 15 per cent, compared to people who had received the placebo. both these findings are statistically significant but there was no significant difference between the groups who received a loss dose and those who received a placebo.

after 24 had passed from the first dose, hyperphosphorylated tau levels in the group who received the high dose had risen again but their amyloid levels remained low in relation to the placebo group. a second dose of the drug given on the second night of the study brought the levels of both proteins back down again.

“if we can lower amyloid every day, we think the accumulation of amyloid plaques in the brain will decrease over time,” lucey said. “and hyperphosphorylated tau is very important in the development of alzheimer’s disease, because it’s associated with forming tau tangles that kill neurons. if you can reduce tau phosphorylation, potentially there would be less tangle formation and less neuronal death.”

although the study is considered preliminary because of its small sample size, lucey has other research underway to analyze the long-term effects of orexin inhibitors in people who are at a high risk of dementia. “future studies need to have people taking these drugs for months, at least, and measuring the effect on amyloid and tau over time,” he said.

“we’re also going to be studying participants who are older and may still be cognitively healthy but who already have some amyloid plaques in their brains. this study involved healthy middle-aged participants; the results may be different in an older population. i’m hopeful that we will eventually develop drugs that take advantage of the link between sleep and alzheimer’s to prevent cognitive decline.

“we’re not quite there yet. at this point, the best advice i can give is to get a good night’s sleep if you can, and if you can’t, to see a sleep specialist and get your sleep problems treated.”

dave yasvinski is a writer with healthing.ca

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