Alzheimer’s, a neurological disorder, gradually deteriorates memory and cognitive abilities, ultimately rendering individuals unable to perform even the most basic tasks.

Typically, the symptoms of Alzheimer’s emerge in later life, affecting a significant proportion of the population aged 65 and above in the United States, with estimates suggesting a figure of over 6 million affected individuals.

This condition is the most prevalent form of dementia among older adults, and it is currently ranked as the seventh leading cause of death in the United States.

Given its complexity, it is unlikely that any single drug or intervention will be effective in treating all individuals with Alzheimer’s.

However, several possible treatment interventions are being developed and tested in ongoing clinical trials by researchers.

A new study published by researchers at Washington University School of Medicine offers encouraging results that suvorexant, an FDA-approved sleeping aid, may help reduce the harmful effects of Alzheimer’s disease by decreasing levels of amyloid and tau proteins in the brain.

While the findings are promising, further research is needed to determine whether sleep medications can prevent or delay the onset of Alzheimer’s disease.

Sleep disturbances are often a precursor to Alzheimer’s disease, with many patients experiencing difficulty falling and staying asleep years before cognitive symptoms emerge. The disease disrupts sleep patterns, and this disruption, in turn, accelerates the harmful changes in the brain associated with Alzheimer’s.

The Washington University School of Medicine in St. Louis has identified a potential method for breaking this cycle. A small, two-night study showed that the levels of key Alzheimer’s proteins dropped in people who took a sleeping pill before bed. This is a good sign, since higher levels of these proteins are linked to getting sicker. The study used a sleep aid called suvorexant, which is already approved by the Food and Drug Administration (FDA) for treating insomnia. It suggests that sleep medications might be able to slow or stop the progression of Alzheimer’s disease, but a lot more research is needed to confirm that this is possible.

The research was published today in Annals of Neurology.

“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,” points out senior author Brendan Lucey. “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.”

Suvorexant is a member of the group of drugs used to treat insomnia known as dual orexin receptor antagonists. A naturally occurring biomolecule called orexin encourages alertness. When orexin is suppressed, individuals nod off. The FDA has authorized three orexin inhibitors, and more are on the way.

Amyloid beta protein plaques begin to accumulate in the brain and signal the onset of Alzheimer’s disease. A second brain protein, tau, starts to create harmful tangles in the brain after years of amyloid buildup. By the time tau tangles may be seen, Alzheimer’s patients begin to show cognitive symptoms like memory loss.

Lucey and colleagues were the first to find that people who don’t get enough sleep have more amyloid and tau in their brains. Mouse experiments using orexin inhibitors have shown promise, but it is still unclear if getting enough sleep has the opposite effect—a decrease in amyloid and tau levels, and a stop or reverse in the progression of Alzheimer’s disease.

To begin evaluating how orexin inhibitors affect individuals, the team recruited 38 healthy volunteers between the ages of 45 and 65 to take part in a two-night sleep research. At nine o’clock at night, the participants were given either a lower dosage of suvorexant (10 mg) (13 individuals), a larger dose (20 mg) of suvorexant (12 participants), or a placebo (13 participants), before going to bed at a clinical research facility at Washington University. Researchers took a small amount of cerebrospinal fluid from the spinal tap every two hours for 36 hours, starting an hour before the sleeping aid or placebo was given, to see how the levels of amyloid and tau changed over the next day and a half.

As compared to those who got a placebo, the levels of an important type of tau called hyperphosphorylated tau and amyloid in the cerebrospinal fluid of those who received the high dosage of suvorexant both decreased by 10% to 20% and 10% to 15%, respectively. There is a statistically significant gap between the two groups. Low-dose suvorexant was no more effective than a placebo group, and there was no difference between the two.

By 24 hours after the first dose, the high-dose group’s levels of hyperphosphorylated tau had gone up, while the placebo group’s levels of amyloid stayed low. When the high-dose group got a second dose of suvorexant the next night, the levels of both proteins went down again.

“If we can lower amyloid every day, we think the accumulation of amyloid plaques in the brain will decrease over time,” Lucey adds. “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.”

It should be noted, however, that the study is preliminary in nature. Dr. Brendan Lucey, the lead researcher on the project, has plans to expand his investigations to include individuals at higher risk for dementia, with a focus on assessing the longer-term effects of orexin inhibitors.

Dr. Randall J. Lucey emphasized the need for future studies to extend over several months, with a focus on measuring the impact of drugs on amyloid and tau over time. The author further explained that the upcoming research will include an older cohort of participants who may still be cognitively healthy but have already developed amyloid plaques in their brains. The previous study only involved healthy middle-aged individuals, and the outcomes may not be the same for an older population.

“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 adds. “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.”

Source: 10.1002/ana.26641

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