How and why could a sleep drug designed for insomnia fight Alzheimer's disease?
This would be one less thing to lie awake at night worrying about: In a small study, researchers found that an FDA-approved insomnia drug called suvorexant could help clear the brain of Alzheimer’s biomarkers. How and why could this be the case — what do sleep drugs and insomnia have to do with Alzheimer’s disease and dementia risk?
Despite decades of research, scientists don’t know that much about why humans sleep. But here’s one important reason: Sleep helps the brain dispose of waste — like beta-amyloid and tau — which are implicated in Alzheimer’s disease. Understanding this foundational relationship between sleep and the brain is the first clue as to why researchers are seeing such interesting results in testing sleep drugs as potential Alzheimer’s treatments.
How much sleep do you need for brain health?
Studies show that losing sleep could also cause proteins in the brain more likely to malfunction, potentially increasing the levels of these problematic plaques and even leading to Alzheimer’s. That’s why there’s so much discussion around whether or not you’re getting enough sleep to keep your brain in good shape.
So, does the act of sleeping, itself, really help the brain to wash away waste? Does it actively help proteins behave how they’re supposed to? Or is there something else about sleep that has such a protective effect on cognitive health? One way to answer this question, researchers thought, could be to look at drugs that treat sleep disorders.
Recently, a small study of 38 people conducted at the Washington University’s Sleep Medicine Center tested whether an insomnia drug called suvorexant (brand name Belsomra) helped clear Alzheimer’s proteins. What they found was that the drug actually appeared to reduce the levels of Alzheimer’s key protein biomarkers in the cerebrospinal fluid — the same outcome that new FDA-approved Alzheimer’s treatments Lequembi and Aduhelm are designed to have.
“I’m very excited about these results because they suggest that suvorexant and potentially drugs in the class could be used to prevent or delay the onset of Alzheimer’s disease,” Brendan Lucey, senior author and associate professor of neurology, told Being Patient. “These drugs are already FDA approved and are safe and effective for sleep, suggesting that we could move quickly into larger phase three clinical trials.”
The researchers recruited cognitively healthy individuals between the ages of 45 to 65. The individuals were randomly assigned to one of three groups, receiving placebo, 10 mg of suvorexant, or 20 mg of suvorexant. The levels of beta-amyloid and tau were monitored every two hours for 36 hours by sampling cerebrospinal fluid via a catheter.
The high dose of the drug lowered the levels of two Alzheimer’s biomarkers — hyperphosphorylated tau and beta-amyloid — by 10 to 20 percent. The sleep drug did not change the quality or length of sleep. That means the results can’t be attributed to participants sleeping longer or better. There may be something that the drug does that directly affects plaque clearance.
Can sleep drugs fight Alzheimer’s?
The study’s results are preliminary, and from a very small group. It’s far too early to say whether sleep drugs like Belsomra could prevent Alzheimer’s dementia in the long-term.
Previous research also points to a complicating factor: These drugs may work differently in men than in women.
An observational study found that men who took sleep drugs were four times more likely to develop the condition. For women, taking these drugs was associated with a 30 percent reduction in Alzheimer’s risk.
Of course, this observational gender study isn’t definitive either. It looked only at cognitively unimpaired individuals over one and a half days.
To make matters more perplexing, researchers are still split over whether beta-amyloid even causes Alzheimer’s to begin with — and what its role is. In other words, it isn’t known at this point how much of a difference reducing the levels of these biomarkers would make when it comes to stopping Alzheimer’s progression in the brain.
Another thing that will eventually need to be tested is safety: what the long-term side effects of these drugs might be for people at risk of developing Alzheimer’s.
What’s next for sleep drugs?
The relationship between sleep, sleep drugs, and dementia is admittedly complicated. Other sleep drugs are also appealing targets to study as well.
Dr. Roger Wong, an assistant professor at SUNY Upstate Medical University, recently published a study probing the relationship between insomnia, sleep drugs, and dementia risk over the course of 10 years. “There’s pretty clear evidence about benzodiazepines that are linked with increased dementia risk,” he said in a recent Being Patient LiveTalk. “A big issue with these studies is that older adults are not just taking one medication.” In his study, insomnia drugs did not increase the risk of dementia once adjusting for other health conditions, such as diabetes or hypertension. Interestingly, people who had trouble falling asleep after waking up, were 40 percent less likely to develop dementia in the study.
In contrast Lucey’s study is set to look for a direct relationship between Alzheimer’s biomarkers and sleep drugs. The research team says the stage is set for clinical trials in people with mild cognitive impairment and Alzheimer’s. “My lab is conducting larger studies in individuals with amyloid deposition in the brain and testing what is the effect on AD biomarkers for amyloid-beta, tau, p-tau, and others,” Lucey said.
The other intriguing finding from the study is that the sleep drugs changed the levels of key Alzheimer’s biomarkers without affecting other aspects of sleep. If the insomnia drugs aren’t working by improving sleep, there might be another mechanism at play. All of this will hopefully be revealed as the research carries on.
