There's still so much we don't know about Alzheimer's disease, but the link between poor sleep and worsening disease is one that researchers are exploring with gusto.
In a recent study published earlier this year, scientists found that using sleeping pills to get some shut-eye could reduce the build-up of toxic clumps of proteins in fluid that washes the brain clean every night.
Researchers from Washington University in St. Louis found people who took suvorexant, a common treatment for insomnia, for two nights at a sleep clinic experienced a slight drop in two proteins, amyloid-beta and tau, that pile up in Alzheimer's disease.
Though only short and involving a small group of healthy adults, the study is an interesting demonstration of the link between sleep and the molecular markers of Alzheimer's disease.
Sleep disturbances can be an early warning sign of Alzheimer's disease that precedes other symptoms, such as memory loss and cognitive decline. And by the time the first symptoms develop, levels of abnormal amyloid-beta are almost peaking, forming clumps called plaques that clog up brain cells.
Researchers think promoting sleep could be one avenue to stave off Alzheimer's disease, by allowing the sleeping brain to flush itself of leftover proteins and the day's other waste products.
While sleeping pills may help in that regard, "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 research.
The study spanned just two nights and involved 38 middle-aged participants who showed no signs of cognitive impairment and had no sleep issues.
Using sleeping pills for prolonged periods is not an ideal solution for those short on sleep either, as it's quite easy to become dependent on them.
Sleeping pills may also lull people into shallower bouts of sleep rather than deep sleep phases. This could be problematic as earlier research from Lucey and colleagues found a link between less good quality, slow-wave sleep and elevated levels of tau tangles and amyloid-beta protein.
In their latest study, Lucey and colleagues 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. Past research shows that even just one night of disrupted sleep can send amyloid-beta levels rising.
A group of volunteers aged 45 to 65 years old received one of two doses of suvorexant or a placebo pill, an hour after researchers tapped their cerebrospinal fluid to collect a small sample.
The researchers continued to collect samples every two hours for 36 hours while the participants slept and during the next day and night, to measure how protein levels changed.
There were no differences in sleep between the groups, and yet amyloid-beta concentrations were reduced by between 10 and 20 percent with a dose of suvorexant usually prescribed for insomnia, compared to a placebo.
The higher dose of suvorexant also momentarily reduced levels of hyperphosphorylated tau, a modified form of the tau protein linked to the formation of tau tangles and cell death.
However, this effect was only seen with some forms of tau, and tau concentrations sprung back up 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, still hopeful that future studies in older adults testing sleeping pills for months could possibly measure a lasting effect on protein levels (whilst noting any downsides of sleeping pills).
Of course, this all rests on our understanding of what causes Alzheimer's disease.
The leading theory, that abnormal protein clumps drive Alzheimer's pathology, has come under intense scrutiny lately after decades of research aimed at lowering amyloid levels has not translated into any useful drug or therapy that actually prevents or slows the disease. This has prompted researchers to rethink how Alzheimer's disease develops.
In other words, sleeping pills may help some people get some shut-eye but using them as a preventative treatment to ward off Alzheimer's disease is still a hazy prospect that hangs on a now-shaky hypothesis of Alzheimer's pathology.
That said, there is increasing evidence linking sleep disturbances to Alzheimer's disease, a disease for which no treatments exist. Lucey says improving sleep hygiene and seeking treatment for sleep problems such as sleep apnea are both sensible approaches to improving general 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.