Alzheimer’s, there’s a sleeping pill that can reduce the proteins that cause the disease

Sleep disturbances may be among the earliest symptoms of Alzheimer’s. Many people who were later diagnosed with such a diagnosis started having trouble falling asleep and staying awake several years before the more serious cognitive problems. Alzheimer’s disease, which is the most common form of dementia (50-80% of cases), involves brain changes that can initially disturb sleep and, in a vicious circle, poor quality sleep can to accelerate further nefarious developments of the syndrome.

Now a group of researchers at the Washington University School of Medicine in St. Louis, Missouri, has identified in a study that, it must be said, is very small, a mechanism that could help to interrupt this vicious circle. The survey showed that people who took a specific sleeping pill before going to bed experienced a decline in levels of key Alzheimer’s proteins – a good sign, as higher levels of these proteins are associated with worsening of the disease. The study, which focused on a sleeping pill like the suvorexant Already approved nearly a decade ago by the US Food and Drug Administration and known commercially as Belsomra, it hints at the potential of sleeping pills to slow or halt the progression of Alzheimer’s disease, although broader investigations across all lines are obviously needed.

The study on this orexin receptor antagonist applied to Alzheimer’s has been published in Annals of Neurology. “It’s a small proof-of-concept study,” he said Brendan Luceyassociate professor of neurology and director of the Sleep Medicine Center at Washington University – it would be premature for people who are concerned about developing Alzheimer’s to interpret this as a reason to start taking suvorexant every night. We don’t know too many things: whether, for example, long-term use is effective in freezing cognitive decline, and if so, in what doses and forms. Nonetheless, explains Lucey, the results are a lot encouraging: “This drug is already available and proven safe, and we now have evidence that it affects levels of proteins that are critical to driving Alzheimer’s.”

As mentioned, suvorexant belongs to a class of insomnia drugs known as dual orexin receptor antagonists. Orexin is a natural biomolecule that stimulates wakefulness. When it’s blocked, people fall asleep. Three orexin inhibitors have already been approved by the FDA and more are in the pipeline. In turn, Alzheimer’s begins to develop when the plaques of the beta-amyloid protein begin to form in the brain. After years of amyloid buildup, a second brain protein, the tau which usually contributes to the normal functioning of the brain, begins to form toxic tangles for neurons. People with Alzheimer’s disease begin to experience cognitive symptoms such as memory loss the moment tau tangles become significant.

Poor sleep is linked to elevated levels of both beta-amyloid and tau and is therefore a risk factor. However, a hanging question remains: whether good sleep has the opposite effect – a reduction in amyloid and tau levels and halting or reversing the progress of Alzheimer’s disease. Studies in mice with orexin inhibitors appear promising in this regard. The investigations in question did however involve 38 people between 45 and 65 years without cognitive problems and for two nights. One group was given one low dose of suvorexant (10 mg), to another one elevated (20 mg) and the other a placebo and then put them to sleep in a dormitory set up in a clinical research area of ​​Washington University. The researchers took a small amount of cerebrospinal fluid by lumbar puncture every two hours for 36 hours, starting one hour before administration of the sleeping pill or placebo, to measure how levels of amyloid-beta and tau had changed over the next day and a half.

The upshot: Amyloid-beta thresholds are dropped from 10% to 20% in the cerebrospinal fluid of people who received a high dose of suvorexant compared to people who received the placebo, and levels of a key form of tau known as hyperphosphorylated tau are dropped from 10% to 15% compared to people who had received the placebo. Both differences are statistically significant. There was no significant difference between people who received a low dose of suvorexant and those who received the placebo. Within 24 hours of the first dose, levels of hyperphosphorylated tau in the high-dose group had increased again while levels of amyloid-beta protein remained low compared to the placebo group. A second dose of suvorexant, given on the second night, lowered the levels of both proteins 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,” he commented.

There is a long way to go but the premises are comforting: «Future studies will have to have people take these drugs for months and measure their effect on amyloid and tau over time – concluded Lucey – we will also study the older participants and they may still be cognitively healthy, but who already have some amyloid plaques in their brains. This study involved healthy middle-aged participants; results may be different in an older population.”

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