Sleep Medication Reduces Levels of Alzheimer’s Proteins

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Sleep Medication Reduces Levels of Alzheimer’s Proteins

A small, 2-night sleep study has shown that people who took a sleeping pill before bed experienced a reduction in the levels of key Alzheimer’s proteins.

The study, published in Annals of Neurology, which involved suvorexant, hints at 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.

“This is a small, proof-of-concept study,” said Bredan Lucey, MD, Sleep Medicine Center at Washington University School of Medicine in St. Louis, St. Louis, Missouri. “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. 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.”

The researchers recruited 38 participants aged 45 to 65 years with no cognitive impairments to undergo a 2-night sleep study. The participants were given suvorexant 10 mg (n = 13), 20 mg (n = 12), or a placebo (n = 13) at 9 PM. Researchers withdrew a small amount of cerebrospinal fluid via spinal tap every 2 hours for 36 hours, starting 1 hour before the sleeping aid or placebo was administered, to measure how amyloid and tau levels changed over the next day and a half.

Amyloid levels were reduced 10% to 20% in the cerebrospinal fluid of people who had received the high dose of suvorexant compared with people who had received placebo, and the levels of hyperphosphorylated tau dropped 10% to 15% compared with placebo. There was not a significant difference between the people who received low-dose suvorexant and those who received the placebo.

By 24 hours after the first dose, hyperphosphorylated tau levels in the high-dose group had increased, while amyloid levels remained low compared with the placebo group. A second dose of suvorexant, administered on the second night, 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,” said Dr. Lucey. “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.”

The researchers said that studies are 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,” said Dr. Lucey. “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.

Reference: https://onlinelibrary.wiley.com/doi/10.1002/ana.26641

SOURCE: Washington University School of Medicine