Common Sleeping Pill Could Slow or Stop Alzheimer’s Disease

Summary: Suvorexant, a dual orexin receptor antagonist commonly prescribed to help treat insomnia reduced levels of the Alzheimer’s-associated amyloid beta protein in the brain. The findings hint that the sleep medication could slow or stop Alzheimer’s disease, but researchers say more research is needed to confirm the viability of the approach.

Source: WUSTL

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 April 20 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.

Alzheimer’s disease begins when plaques of the protein amyloid beta start building up in the brain. After years of amyloid accumulation, a second brain protein, tau, begins to form tangles that are toxic to neurons. People with Alzheimer’s disease start experiencing cognitive symptoms such as memory loss around the time tau tangles become detectable.

Lucey and colleagues were among the first to show in people that poor sleep is linked to higher levels of both amyloid and tau in the brain. The question remains as to whether good sleep has the opposite effect — a reduction in amyloid and tau levels, and a halt in or reversal of the progress of Alzheimer’s disease — but mouse studies with orexin inhibitors have been promising.

As a first step to assess the effect of orexin inhibitors on people, Lucey and colleagues recruited 38 participants ages 45 to 65 and with no cognitive impairments to undergo a two-night sleep study. The participants were given a lower dose (10 mg) of suvorexant (13 people), a higher dose (20 mg) of suvorexant (12 people) or a placebo (13 people) at 9 p.m. and then went to sleep in a clinical research unit at Washington University.

Researchers withdrew a small amount of cerebrospinal fluid via spinal tap every two hours for 36 hours, starting one hour before the sleeping aid or placebo was administered, 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 people who had received placebo, and the levels of a key form of tau known as hyperphosphorylated tau dropped 10% to 15%, compared to people who had received placebo. Both differences are statistically significant. There was not a significant difference between the people who received a low dose of suvorexant and those who received the placebo.

By 24 hours after the first dose, hyperphosphorylated tau levels in the high-dose group had risen, while amyloid levels remained low compared to the placebo group. A second dose of suvorexant, administered on the second night, sent the levels of both proteins down again for people 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.

This shows the outline of a head
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. Image is in the public domain

“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 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.

“I’m hopeful that we will eventually develop drugs that take advantage of the link between sleep and Alzheimer’s to prevent cognitive decline,” he continued. “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.”

About this Alzheimer’s disease and neuropharmacology research news

Author: Judy Martin Finch
Source: WUSTL
Contact: Judy Martin Finch – WUSTL
Image: The image is in the public domain

Original Research: Closed access.
Suvorexant acutely decreases tau phosphorylation and Aβ in the human CNS” by Brendan Lucey et al. Annals of Neurology


Suvorexant acutely decreases tau phosphorylation and Aβ in the human CNS


In Alzheimer’s disease, hyperphosphorylated tau is associated with formation of insoluble paired helical filaments that aggregate as neurofibrillary tau tangles and are associated with neuronal loss and cognitive symptoms. Dual orexin receptor antagonists decrease soluble amyloid-β levels and amyloid plaques in mouse models overexpressing amyloid-β, but have not been reported to affect tau phosphorylation. In this randomized controlled trial, we tested the acute effect of suvorexant, a dual orexin receptor antagonist, on amyloid-β, tau, and phospho-tau.


Thirty-eight cognitively unimpaired participants aged 45 to 65 years were randomized to placebo (N = 13), suvorexant 10 mg (N = 13), and suvorexant 20 mg (N = 12). Six milliliters of cerebrospinal fluid were collected via an indwelling lumbar catheter every 2 hours for 36 hours starting at 20:00. Participants received placebo or suvorexant at 21:00. All samples were processed and measured for multiple forms of amyloid-β, tau, and phospho-tau via immunoprecipitation and liquid chromatography-mass spectrometry.


The ratio of phosphorylated-tau-threonine-181 to unphosphorylated-tau-threonine-181, a measure of phosphorylation at this tau phosphosite, decreased ~10% to 15% in participants treated with suvorexant 20 mg compared to placebo. However, phosphorylation at tau-serine-202 and tau-threonine-217 were not decreased by suvorexant. Suvorexant decreased amyloid-β ~10% to 20% compared to placebo starting 5 hours after drug administration.


In this study, suvorexant acutely decreased tau phosphorylation and amyloid-β concentrations in the central nervous system. Suvorexant is approved by the US Food and Drug Administration to treatment insomnia and may have potential as a repurposed drug for the prevention of Alzheimer’s disease, however, future studies with chronic treatment are needed. ANN NEUROL 2023

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  1. Trial Participant information request. My husband was diagnosed with Left and Right Temporal lobe degeneration – Primary Progressive Aphasia – a year ago. Neurological Testing also shows global cognitive decline. He often wakes up several times during the night, between sleep cycles. It would be helpful to see if Survoextant improves mild to moderate cognitive impairment as he is much better on days following a good night’s sleep with few or no wakeful events.

  2. This is very interesting – seems a parallel path is linked to my research. Chronic intermittent hypoxia/HIF cascade is secondary to an impaired upper airway. This in turn is far more prevalent in people who have a ‘congenitally’ small naso-maxilla. I say ‘congenitally’ but in reality, it’s an epigenetic effect of foetal exposure to tobacco-alcohol-sugar at the time of neuralation which expels what appears to be immature cranial Neural Crest Cells. Thus the nasomaxilla is in rare cases devoid of bones but frequently smaller. Given the Macey small study in 2018 where 150 5-10-year-olds were screened for ‘non-neuro issues) had MRIs and PSG it was the 10% of the cohort that snored who showed regional cortical thinning. Brit Med Jnl echoed this in a decade of MRIs of 20-year-olds showing an increase in white matter and I assume, therefore, a decrease in gray matter.
    The generation of a smaller upper airway coupled with retrusion of the mandible ensures both high volumes of afferent nociception into the trigeminal system – Ascending Reticular Activation system and Nuc of the Solitary tract – a process that elevates cortisol. Nitrous Oxide also parallels buy it influence on the immune system.
    In short your study makes more sense than most to date. Prof Ruth Iztak (UK) has attributed the neuronal downgrade to Herpes virus since the 1990s… maybe wrong stimulant- but right process. THe key is first central cortical inflammation that weakens BBB? Then the neuronal changes are set in place – the last step I suspect it the Tau issue and you have made what seems like a pretty bid step.
    David Zimmerman Auckland

  3. Sounds promising. My wife is at mid stage 4. Perhaps she could get into a trial using Suvorexant. Thank you

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