Levels of Alzheimer’s proteins reduced by sleeping pill

April 25, 2023

Sleep disturbances can be an early sign of Alzheimer’s disease. Many people eventually diagnosed with Alzheimer’s start experiencing difficulty falling and staying asleep years before cognitive problems such as memory loss and confusion emerge. It’s a vicious cycle: Alzheimer’s disease involves changes to the brain that disrupt sleep, and poor sleep accelerates harmful changes to the brain.

Researchers at Washington University School of Medicine in St. Louis have identified a possible way to help break that cycle. A small, two-night study has shown that people who took a sleeping pill before bed experienced a drop in the levels of key Alzheimer’s proteins — a good sign, since higher levels of such proteins tracks with worsening disease. The study, which involved a sleeping aid known as suvorexant that is already approved by the Food and Drug Administration (FDA) for insomnia, hints at the potential of sleep medications to slow or stop the progression of Alzheimer’s disease, although much more work is needed to confirm the viability of such an approach. The study is published in Annals of Neurology

“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 author Brendan Lucey, MD, 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. 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 belongs to a class of insomnia medications known as dual orexin receptor antagonists. Orexin is a natural biomolecule that promotes wakefulness. When orexin is blocked, people fall asleep. Three orexin inhibitors have been approved by the FDA, and more are in the pipeline. 

The study is preliminary, since it only looked at the effect of two doses of the drug in a small group of participants. Lucey has studies underway to assess the longer-term effects of orexin inhibitors in people 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. This study involved healthy middle-aged participants; the results may be different in an older population. 

WUSTL release