Study details

For the study, researchers split 38 participants between the ages of 45 and 65 who had no signs of cognitive impairment into three groups. The first group took a placebo pill, the second group took a 10mg dose of suvorexant, and the third took a 20mg dose of the pill.

Suvorexant is a dual orexin receptor antagonist, blocking the biochemical orexin, which promotes wakefulness, in the brain.

Each group took their pill at 9pm and went to sleep. The researchers then took cerebrospinal fluid samples through a spinal tap procedure every two hours over a 36-hour period beginning one hour before the pills were given and analyzed those samples to determine how much tau and amyloid proteins had changed. 

They found that, compared to the placebo group, those who took the 10mg dose of suvorexant saw no significant differences in amyloid or tau proteins. However, those who took the 20mg dose saw their levels of amyloid proteins drop by 10% to 20% after five hours and their levels of hyperphosphorylated tau drop by 10% to 15%.

After 24 hours, the participants who took 20mg doses of suvorexant still had lower amyloid levels than the other groups, but their tau levels had risen. However, following another 20mg dose of suvorexant the following night, both protein levels dropped again.

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Brendan Lucey, an associate professor of neurology, sleep medicine section head at  Washington University School of Medicine and first author on the study, said, "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," he added. "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."

Lucey said he was surprised "by how long into the day amyloid-beta and phosphorylated tau 181 (pT181) remained lower." He was also surprised some forms of tau weren't affected by suvorexant at all. "pT181 is the most abundantly phosphorylated tau form, so we may have seen a difference because the other tau forms need longer time on drug to decrease," he said, adding that more research is needed to determine why there were differences among tau protein levels.

Lucey also cautioned that the study "does not support using suvorexant and dual orexin receptor antagonists to prevent or delay Alzheimer's disease."

Bruce Albala, an adjunct professor of neurology at the  University of California Irvine School of Medicine, noted that suvorexant does come with side effects, especially at higher doses like 20mg.

"These include (but are not limited to) depressant effects and daytime impairment with impaired alertness and motor coordination," he said. "Such side effects will not be good for people already experiencing cognitive impairment or dementia due to Alzheimer's disease."

Arman Fesharaki-Zadeh, a behavioral neurologist and neuropsychiatrist at  Yale New Haven Hospital, also noted that using sleep-aiding drugs could affect a person's "sleep architecture," including disruption to REM sleep.

The link between sleep and Alzheimer's risk

Research  has found that chronic sleep deprivation in midlife has been linked to increased risk of dementia and Alzheimer's disease, potentially because the brain gets rid of neurotoxins that affect memory during sleep.

"There is a close relationship between sleep and cognitive performance," said Alex Dimitriu, founder of  Menlo Park Psychiatry & Sleep Medicine. For example, "sleep deficit is associated with increased risks of cognitive decline, as well as more immediate next-day decline in cognitive ability," Dimitriu said.

However, Albala noted that "advancing cognitive impairment and dementia due to Alzheimer's can be disruptive to normal sleep cycles. Many advanced Alzheimer's patients have trouble sleeping through the night."

According to Fesharaki-Zadeh, "sleep-wake activity affects the clearance of amyloid-β and tau via the recently discovered glymphatic system," a system that is "responsible for clearing metabolic waste products from the brain while we sleep [and] disrupted clearance of the glymphatic network can result from poor sleep."

This could potentially be why suvorexant may impact amyloid and tau protein levels. Dimitriu noted that suvorexant "has been shown to both improve the amount of REM sleep and sleep continuity. [This] would result in longer sleep times and possibly more REM sleep, both of which could contribute to the removal of built-up toxins."

Michael Brodeur, a professor of pharmacy and geriatric pharmacotherapy at  Albany College of Pharmacy and Health Sciences, said "there's probably some kind of downstream effect that orexin is modulating. But I don't think we can say with certainty what that is yet."

Lucey noted that figuring out the exact relationship between suvorexant and amyloid and tau proteins "is likely complicated. Orexin has many effects on sleep, metabolism, and other systems that could affect amyloid and tau. Further study is needed to determine what mechanism(s) are involved." (Abramson, Washington Post, 4/24; Pattemore, Healthline, 4/24; George, MedPage Today, 4/21; Murez, HealthDay/U.S. News & World Report, 4/21)

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