- Various medications are prescribed to help slow the progression of Alzheimer’s disease symptoms.
- A new small sleep study has indicated that an insomnia drug may positively influence two brain proteins linked to Alzheimer’s.
- The relationship between sleep and Alzheimer’s is complicated, and more research is required.
- Alzheimer’s patients should not use sleeping pills to treat their symptoms and speak to their doctor about any concerns.
About 6.7 million Americans live with Alzheimer’s disease, the most common form of dementia
There’s currently no cure for Alzheimer’s — instead, treatments are used to help slow disease progression. The medications most commonly used target nerve cells and chemicals in the brain.
However, new research published in Annals of Neurology has discovered that an everyday drug may influence levels of tau and amyloid — proteins in the brain linked to Alzheimer’s.
The small study showed that those who took suvorexant (Belsomra) , a sleeping pill, experienced reduced levels of these proteins.
What the study involved
The research came about as a result of a previous study, which found that a medication which blocks orexin, the brain’s ‘awake’ chemical, also impacted the critical Alzheimer’s proteins tau and amyloid.
“Work previously done in mice showed that a dual orexin receptor antagonist (almorexant in that instance) decreased both soluble amyloid-beta levels and amyloid pathology,” explained Dr. Brendan Lucey, associate professor of neurology and sleep medicine section head at Washington University School of Medicine, and first author of the study.
Lucey told Healthline they wanted to explore the effect of this medication type on Alzheimer’s proteins in humans. Instead of almorexant, they used suvorexant — another dual orexin receptor antagonist.
This sleep study lasted two nights and involved 38 individuals aged between 45 and 65, none of whom had any signs of cognitive impairment.
They were divided into three groups: the first took a placebo pill, the second took a 10mg dose of suvorexant, and the third a 20mg dose of suvorexant.
Each took a pill at 9pm, then went to sleep. Using a spinal tap procedure, the researchers took cerebrospinal fluid samples every two hours over a 36-hour period – starting one hour before the pills were given. The samples were then analyzed to see how levels of tau and amyloid changed.
People who took higher doses of a sleeping pills had fewer proteins linked to Alzheimer’s
The participants who took a higher dose or the 20mg dose of suvorexant experienced two statistically significant differences compared to people who took a placebo.
Comparatively people who took a lower dose or a 10mg dose of suvorexant showed no significant differences compared to those in the placebo group.
After 5 hours, those who took a 20 mg dose had dropped their levels of amyloid between 10-20%, while their of an important form of tau protein called hyperphosphorylated tau levels decreased by 10-15%.
After 24 hours, while the 20mg participants’ levels of amyloid remained lower, their tau levels had increased. However, after another 20mg dose the second night, both levels of the proteins dropped again.
“I was surprised by how long into the day amyloid-beta and phosphorylated tau 181 (pT181) remained lower,” stated Lucey.
Another finding he was surprised by was that some forms of tau didn’t seem to be affected by suvorexant at all. Why might this have been the case?
“This is potentially important but difficult to know at this stage,” he said. “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 continued: “Our data does not allow for us to specify why we observed the p-tau differences, but I do think the differences could be important. More research is needed!”
Not yet a way to treat Alzheimer’s disease
While this study further builds on the potential effects of suvorexant on Alzheimer’s proteins, the researchers were keen to stress that this does not mean the drug is a viable ‘treatment’ or ‘preventative’ for dementia.
“This study does not support using suvorexant and dual orexin receptor antagonists to prevent or delay Alzheimer’s disease,” asserted Lucey.
Instead, what the study does is “support or justify additional studies giving the drug for longer periods and to test that it prevents/delays Alzheimer’s disease symptoms.”
Dr. Bruce Albala, Professor (Adj) Neurology at the University of California Irvine School of Medicine, added that suvorexant is not without potential side effects — especially at higher 20mg doses.
“These include (but are not limited to) depressant effects and daytime impairment with impaired alertness and motor coordination,” he told Healthline. “Such side effects will not be good for people already experiencing cognitive impairment or dementia due to Alzheimer’s disease.”
Finally, the ongoing use of some sleep-aiding drugs can affect our “sleep architecture,” said Dr. Arman Fesharaki-Zadeh, a behavioral neurologist and neuropsychiatrist at Yale New Haven Hospital and Yale Medicine.
This includes disruption to all-important REM sleep, he shared with Healthline — and not getting enough of this sleep type has been linked to increased dementia risk.
The link between Alzheimer’s and sleep
The association between sleep and Alzheimer’s is complicated, and scientists continue to explore how the two influence each other.
“There is a close relationship between sleep and cognitive performance,” said Dr. Alex Dimitriu, double board-certified in psychiatry and sleep medicine and founder of Menlo Park Psychiatry & Sleep Medicine.
For instance, he told Healthline, “sleep deficit is associated with increased risks of cognitive decline, as well as more immediate next-day decline in cognitive ability.”
But the relationship isn’t one-sided, noted Albala. “It has long been known 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.”
Regarding brain proteins specifically, “sleep-wake activity affects the clearance of amyloid-β and tau via the recently discovered glymphatic system,” explained Fesharaki-Zadeh.
“[This system] 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,” he said.
Ultimately, noted Fesharaki-Zadeh, “more comprehensive double-blind controlled studies involving a larger number of participants are necessary to draw firmer conclusions on the effect of sleep regimen and the risk of developing Alzheimer’s disease.”
How suvorexant might impact amyloid and tau proteins
Suvorexant is a sleeping aid, and it “has been shown to both improve the amount of REM sleep and sleep continuity,” Dimitriu said. “[This] would result in longer sleep times and possibly more REM sleep, both of which could contribute to the removal of built-up toxins.”
Said toxins might include proteins such as tau and amyloid.
Dr. Michael Brodeur, 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.”
He added, “it wasn’t just the effects on sleep that caused some of these changes [to proteins] — at least from what we’re able to tell from this experiment.”
Albala concurred that the association likely extends beyond suvorexant’s influence on sleep alone.
“The present paper … strongly suggests that the lower amyloid and phosphorylated tau ratios measured in the collected CSF at the high dose of 20mg of suvorexant was the result of the drug itself, and not the result of a change in sleep among the participants who received that dose.”
Lucey stated that determining the exact influence of suvorexant remains unclear and “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.”
What is suvorexant?
Suvorexant is an FDA-approved drug prescribed to treat insomnia in adults. “It helps with both falling asleep and staying asleep,” stated Dr. Jennifer Bourgeois, Pharm.D. at SingleCare.
“It typically increases onset of sleep by about 10 minutes and prolongs sleep for about 30 minutes,” added Brodeur.
So how does it work?
“Suvorexant is a highly selective orexin receptor antagonist, meaning it suppresses the effects of the hormone in keeping us awake,” Bourgeois said. “By blocking this system, suvorexant is able to suppress wakefulness.”
Although suvorexant is not currently approved to treat or slow Alzheimer’s symptoms, it is approved to aid the sleep of patients with dementia.
However, stated Brodeur, “with any sleep medication, particularly for someone with cognitive impairment, we need to be very cautious. At this point, we should not be making changes about how we’re managing patients and recommending this [drug].”
Medications for Alzheimer’s
Patients with Alzheimer’s disease — or who are worried about developing the condition — should not be using suvorexant to treat or manage their symptoms.
However, there are other prescription medications designed and approved to treat dementia. Brodeur revealed they fall into two groups:
- Cholinesterase inhibitors (including drugs such as donepezil)
- NMDA inhibitors (including drugs such as memantine),
In addition, Brodeur added, “there are some newer agents available, medications like Aduhelm, which affect beta-amyloid.”
However, he said, they “are just coming out of clinical studies, and there’s not widespread use of those yet.”
If you’re concerned about Alzheimer’s disease symptoms, speak to your primary care physician.
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