Sleeping pill could reduce levels of Alzheimer’s proteins

Difficulty falling asleep and staying asleep can be an early sign of Alzheimer’s disease, a vicious cycle that can accelerate harmful changes to the brain.

As a way of possibly breaking this cycle, researchers at Washington University School of Medicine in St Louis conducted a two-night study on 38 participants aged 45 to 65 with no cognitive impairments.

Participants who took a sleeping pill before bed experienced a drop in the levels of key Alzheimer’s proteins — which is a positive sign, since higher levels of such proteins track with worsening disease.

The sleeping pill, known as suvorexant, which has been approved by the Food and Drug Administration (FDA), is used to aid insomnia and “hints 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,” a press release by the university said.

Suvorexant belongs to a class of insomnia medications known as dual orexin receptor antagonists.

Orexin is a natural biomolecule that promotes wakefulness and when orexin is blocked, people fall asleep.

“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,” Professor Lucey added.

In their latest study, Professor Lucey and the team wanted to see if improving sleep with the aid of sleeping pills could lower levels of tau and amyloid-beta in the cerebrospinal fluid that bathes the brain and spinal cord.

Thirteen people were given a lower dose (10 mg) of suvorexant, 12 people were given a higher dose (20 mg) of suvorexant, and 13 were given a placebo.

The participants then proceeded to sleep at 9pm in a clinical research unit at Washington University.

Scientists then withdrew a small amount of cerebrospinal fluid via spinal tap every two hours for 36 hours.

Researchers started 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.

For people who received a higher dose of suvorexant, amyloid levels dropped 10 per cent to 20 per cent and levels of a key form of tau known as hyperphosphorylated tau dropped 10 per cent to 15 per cent compared to people who had received a placebo.

This showed that there was not a significant difference between the people who received a low dose of suvorexant and those who received the placebo.

When the study hit 24 hours after the first dose, hyperphosphorylated tau levels had increased while amyloid levels remained low in the high-dose group compared to the placebo group.

Once participants were given their second dose of suvorexant, on the second night, this 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,” Professor Lucey said.

“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.”

Professor Lucey and the team have further 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.

“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,” Professor Lucey said.

“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.”

In 2020, as many as 5.8 million Americans were living with Alzheimer’s disease, according to the Centers for Disease Control and Prevention (CDC).

There is still a lot that remains undiscovered with Alzheimer’s disease and the CDC says there is likely not one single cause but rather several factors that can affect people differently.

Some of the warning signs of Alzheimer’s may be memory loss, difficulty with completing tasks, misplacing things or being unable to retrace steps and mood changes.

The study was published on 20 April in Annals of Neurology.