Sleeping Pills May Lower Alzheimer's Proteins During Sleep, Study Finds

Much remains unknown about Alzheimer's disease, yet scientists are keenly investigating the association between poor sleep and a worsening of the condition.

Research indicates that this relationship might be used to advantage, including by people who struggle to get enough sleep.

A study released in 2023 reported that sleeping pills used to obtain some rest may lessen the accumulation of harmful protein clumps in the fluid that cleanses the brain each night.

Participants who used suvorexant, a widely used insomnia treatment, for two nights in a sleep clinic showed a modest reduction in amyloid-beta and tau. Both proteins build up in Alzheimer's disease.

It is important to note that the trial was brief and included only a small number of healthy adults.

Nevertheless, the work by Washington University in St. Louis provides an intriguing illustration of the connection between sleep and the molecular markers of Alzheimer's disease.

Watch the video below for an overview of the findings:

Sleep, Alzheimer's disease and protein build-up

Sleep problems may be an early indicator of Alzheimer's disease, appearing before symptoms such as memory loss and cognitive decline.

When those first symptoms emerge, abnormal amyloid-beta levels are already close to their peak. The protein forms clumps known as plaques, which obstruct brain cells.

Scientists believe that encouraging sleep could offer one way to delay Alzheimer's disease, as the sleeping brain can clear away residual proteins alongside other waste products from the day.

Although sleeping pills might assist with this process, "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 neurologist Brendan Lucey, of Washington University's Sleep Medicine Center, who led the study.

Using sleeping pills over long periods is also far from an ideal answer for people lacking sleep, because dependence on them can develop quite easily.

In addition, sleeping pills can leave people in lighter periods of sleep rather than deep sleep stages. That may be an issue because earlier work by Lucey and colleagues linked poorer-quality slow-wave sleep with higher levels of tau tangles and amyloid-beta protein.

What the suvorexant trial found

The 2023 research involved 38 middle-aged participants over only two nights. None showed signs of cognitive impairment or had sleep difficulties.

Lucey and his colleagues set out to establish whether improving sleep with sleeping pills could reduce tau and amyloid-beta levels in the cerebrospinal fluid surrounding the brain and spinal cord. Previous studies have shown that a single night of interrupted sleep can increase amyloid-beta levels.

Volunteers aged 45 to 65 years were given either one of two suvorexant doses or a placebo pill. This was done an hour after researchers collected a small cerebrospinal fluid sample through a spinal tap.

Samples continued to be taken every two hours for 36 hours, while participants slept and through the following day and night, allowing the team to track changes in protein levels.

Sleep did not differ between the groups. Even so, amyloid-beta concentrations fell by between 10 and 20 percent among those given a suvorexant dose normally prescribed for insomnia, compared with placebo.

The larger suvorexant dose also temporarily lowered hyperphosphorylated tau, an altered version of the tau protein associated with tau tangle formation and cell death.

That result appeared only for certain forms of tau, however, and tau concentrations rose again within 24 hours of taking the sleeping pill.

"If you can reduce tau phosphorylation, potentially there would be less tangle formation and less neuronal death," said Lucey, who remains hopeful that future research involving older adults taking sleeping pills for months might identify a lasting effect on protein levels, whilst also recording any disadvantages of sleeping pills.

Why sleeping pills are not yet an Alzheimer's prevention treatment

Naturally, all of this depends on what is understood about the causes of Alzheimer's disease.

The dominant hypothesis is that abnormal protein clumps drive Alzheimer's pathology. However, it has faced intense scrutiny recently, after decades of efforts to lower amyloid levels failed to produce a useful drug or therapy that genuinely prevents or slows the disease. As a result, researchers are reconsidering how Alzheimer's disease develops.

Put another way, sleeping pills may help certain people get some sleep, but their use as a preventative treatment against Alzheimer's disease remains uncertain. It relies on a now-unsteady hypothesis of Alzheimer's pathology.

Even so, growing evidence connects sleep disturbances with Alzheimer's disease, for which no treatments exist. Lucey says that improving sleep hygiene and obtaining treatment for sleep conditions such as sleep apnoea are both sensible ways to support overall brain health at any age.

"I'm hopeful that we will eventually develop drugs that take advantage of the link between sleep and Alzheimer's to prevent cognitive decline," said Lucey. But he admitted, "We're not quite there yet."

The study was published in Annals of Neurology.

An earlier version of this article was published in April 2023.