In a small study, clues that a sleeping pill could help prevent Alzheimer’s disease

By Cara Murez HealthDay Reporter

FRIDAY, April 21, 2023 (HealthDay News) — Taking a particular sleeping pill may help ward off Alzheimer’s disease, but it’s too early 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 lower levels of key Alzheimer’s proteins.

“This is a small proof-of-concept study. It would be premature for people who fear developing Alzheimer’s disease to interpret this as a reason to start taking suvorexant every night,” said the study’s lead author. Dr. Brendan Luceyassociate professor of neurology and director of the Sleep Medicine Center at the University of Washington.

“We don’t yet know if long-term use is effective in warding off cognitive decline, and if so, at what dose, and for whom,” he added in a university press release. “Nevertheless, these results are very encouraging. This drug is already available and proven to be safe, and we now have evidence that it affects protein levels that are critical to driving Alzheimer’s disease.

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

In Alzheimer’s disease, plaques of beta-amyloid protein build up in the brain. Years after amyloid begins to accumulate, another brain protein called tau begins to form tangles that are toxic to neurons.

As these tangles become detectable, people with Alzheimer’s disease begin to lose their memory.

In previous research, Lucey and her colleagues linked poor sleep to higher levels of amyloid and tau in the brain.

What they don’t know is whether good sleep would reduce these levels, and with that stop or reverse the progression of Alzheimer’s disease. Mouse studies with orexin inhibitors have been promising.

For this study, the researchers recruited 38 people aged 45 to 65 without mental disabilities.

The 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 administered at 9 p.m. The researchers took a small amount of cerebrospinal fluid from the participants via lumbar puncture every two hours for 36 hours. It started one hour before the administration of the sleeping pill or the placebo. The aim was to measure how amyloid and tau levels changed over the next day and a half.

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

These differences are considered statistically significant.

No significant difference was found between 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 fell again in the high dose group.

“If we can reduce amyloid every day, we think the buildup 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 is associated with the formation of tau tangles that kill neurons. If you could reduce tau phosphorylation, there would potentially be less tangle formation and less neuronal death.

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

“Future studies need to get people on these drugs for months, at least, and measure the effect on amyloid and tau over time,” Lucey said. “We will also study participants who are older and may still be cognitively healthy, but who already have amyloid plaques in their brains.”

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

“I hope we will eventually develop drugs that take advantage of the link between sleep and Alzheimer’s disease to prevent cognitive decline,” Lacey said. “We are not there yet. At this point, the best advice I can give you is to get a good night’s sleep if you can, and if you can’t, see a sleep specialist and get your sleep issues treated.

SOURCE: University of Washington, press release, April 19, 2023

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