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• Posted April 21, 2023

In Small Study, Hints That a Sleeping Pill Might Help Prevent Alzheimer's

Taking a particular sleep medication may help stave off Alzheimer's disease, but it's too soon to say for sure after a preliminary study.

Researchers at Washington University School of Medicine in St. Louis found that participants who took a sleeping pill called suvorexant before bed had a drop in levels of key Alzheimer's disease proteins.

"This is a small, proof-of-concept study. 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,"said senior study author Dr. Brendan Lucey, an associate professor of neurology and director of Washington University's Sleep Medicine Center.

"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," he added in a university news release. "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."

Suvorexant (Belsomra), a dual orexin receptor antagonist, is one of three in this class of drugs that are already approved by the U.S. Food and Drug Administration for insomnia. Orexin is a natural biomolecule that promotes wakefulness. When it is blocked, people fall asleep, according to the study.

In Alzheimer's disease, plaques of the protein amyloid beta build up in the brain. Years after amyloid begins accumulating, another brain protein called tau, starts forming tangles that are toxic to neurons.

As those tangles become detectable, people with Alzheimer's disease start experiencing memory loss.

In past research, Lucey and his colleagues have linked poor sleep to higher levels of both amyloid and tau in the brain.

What they don't know is whether good sleep would reduce those levels, and with that halt or reverse progress of Alzheimer's disease. Mouse studies with orexin inhibitors have been promising.

For this study, researchers recruited 38 people between the ages of 45 and 65 who had no mental impairments.

Researchers gave 13 of them a lower dose -- 10 milligrams (mg) -- of suvorexant. Twelve others received a 20 mg dose, while 13 participants received a placebo.

The doses were each given at 9 p.m. Researchers withdrew a small amount of cerebrospinal fluid from participants via spinal tap every two hours for 36 hours. This began an hour before the sleeping aid or placebo was administered. The purpose was to measure how amyloid and tau levels changed over the next day and a half.

Amyloid levels dropped 10% to 20% in the cerebrospinal fluid of people who had received the high dose of suvorexant compared to those who received a placebo. Levels of a key form of tau known as hyperphosphorylated tau dropped 10% to 15%, researchers found.

These differences are considered statistically significant.

No significant difference was found between the people who received a low dose of suvorexant and those who received the placebo.

Investigators administered another dose of suvorexant on the second night. Levels of both proteins again dropped in the high-dose group.

"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."

The findings were published April 20 in Annals of Neurology.

Lucey cautioned that the study is preliminary. Ongoing studies aim to assess the longer-term effects of orexin inhibitors in people who are at higher 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,"Lucey 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."

He noted that this study involved healthy middle-aged participants. Results may be different in older participants.

"I'm hopeful that we will eventually develop drugs that take advantage of the link between sleep and Alzheimer's to prevent cognitive decline,"Lacey said. "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."

More information

The U.S. Centers for Disease Control and Prevention has more on Alzheimer's disease.

SOURCE: Washington University, news release, April 19, 2023