What: Researcher at Washington University School of Medicine in St. Louis will discuss the study which involved a sleeping aid known as suvorexant that is already approved by the Food and Drug Administration (FDA) for insomnia, hints at the potential of sleep medications to slow or stop the progression of Alzheimer’s disease.

When: April 21st, 2PM EST

Where: Live Events Zoom Room (link will be given once you register)

Who: Dr. Brendan P. Lucey, MD -Associate Professor of Neurology, Section Head, Sleep Medicine

Researcher's info:

Brendan Lucey is associate professor of neurology and Sleep Medicine Section head. Born and raised in Burlington, Vermont, he received his undergraduate degree at the University of Vermont and his medical degree from the Johns Hopkins University School of Medicine. Following medical school, Lucey completed his neurology residency at Washington University and a clinical neurophysiology fellowship at Brigham and Women’s Hospital. From 2008-2012, Lucey was on active duty in the U.S. Air Force and then joined the Department of Neurology at Washington University.

Lucey’s current research interests are in sleep, aging and Alzheimer’s disease. His lab focuses on studying the potential of sleep interventions to prevent or delay the onset of Alzheimer’s disease. Using lumbar catheters, he investigates how sleep affects different markers of Alzheimer’s disease changes in the brain such as amyloid-beta and tau. Lucey is also interested in whether or not sleep changes may be non-invasive markers for Alzheimer’s disease progression.



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Thom: Welcome to today's newswise live event. We have with us today Dr. Brendan Lucey, MD from Washington University in St. Louis. He is Associate Professor of Neurology and section head of Sleep Medicine.

There was a recent study just off embargo that examined patients taking sleep meds and testing for the presence of key Alzheimer's proteins. So I want to ask Dr. Lucey, the lead author, your study builds on previous research in mice to demonstrate for the first time that there's a similar response in humans. So can you describe the participants in this trial and the results that were observed?

Dr. Brendan Lucey: Yeah, thank you, Tom. The participants in this trial were aged 45 to 65 years old. They didn't have any evidence of problems with their memory or thinking, we did measure their quality of their sleep using an activity monitor that's worn on the wrist. And they had evidence that their efficiency of how much they slept at night was lower. And then they were randomized to receive either placebo, or one of two doses of a drug called suvorexant 10 or 20 milligrams. And those are both FDA approved doses to treat insomnia. And our goal is to see how this drug affected the levels of amyloid beta and tau and phosphorylated tau in the fluid that's around the brain. And these proteins, amyloid and tau and phosphorylated tau, are markers for Alzheimer's disease pathology that are used to identify individuals who may have changes in the brain consistent with Alzheimer's disease, and our targets for potential interventions, we wanted to see if this drug lowered the amounts of amyloid beta, which has been shown in mice a similar type of drug has been shown to lower amyloid beta in mice. And then to extend that into looking at the tau protein as well.

Thom: We have a question from Alicia Medscape. Given that these dual orexin receptor antagonists are controlled substances, would the authors envision a time when they'd be recommended for daily use? Can you talk about the safety and efficacy and their status as controlled substance?

Dr. Brendan Lucey: Well, I think that what's exciting about this study and these results is that suvorexant is approved by the FDA for treatment of insomnia. And it's been on the market since 2015. And so it has a lot of safety data already available. The FDA also has an additional indication for suvorexant to treat insomnia in individuals with mild to moderate Alzheimer's disease. So although it's a controlled substance, in contrast to some other drugs that have been investigated as potential ad modifying drugs and interventions, you know, the safety profile is already well known. I'm thinking specifically of base inhibitors whose trials were shut down a few years ago due to adverse events.

Thom: Another question from Alicia Medscape. This being a small proof of concept study, what are your plans for larger trials? And are they already underway? And when might you expect to have further results?

Dr. Brendan Lucey: Let's think that's an excellent question. I mean, this is a very small trial looking at changes over hours. But an important proof of concept, as the questioner said, and we do have funding for additional trials that are getting underway now, where we'll be answering a couple of important questions. One, do we see similar changes in these biomarkers or these proteins, when these drugs are given for months? That's one question that we have. So giving longer periods of time, we're going to be testing some different doses of this class of medication to see, you know, if we give 10 milligrams of one drug do we see a much greater effect at a higher dose. And we're also looking at individuals who are cognitively unimpaired. They don't have any problems with memory and thinking, but they do have biomarker evidence of amyloid pathology. So these participants, these participants in our study, were biomarker negative. We didn't screen for them actually to get into the trial, but we did have their amyloid beta and tau phosphorylated tau protein means at the end, and we know that they don't have evidence of amyloid deposition based on those markers. But we actually want to recruit people who do. And to see if we see we see similar changes, which would suggest potential larger studies could then be done as a secondary prevention for Alzheimer's disease.

Thom: Question from Lynn at Belvoir media. Do the researchers have a theory about the mechanism for the effect of this dual orexin receptor and antagonist?

Dr. Brendan Lucey: Yeah, I mean, the our hypothesized effect was that we would be affecting sleep. And I think that that is definitely I believe that is a mechanism that plays a role. The this drug suvorexant is a dual orexin receptor antagonist. So it blocks the effect of orexin at its receptor. Orexin is weight promoting and so by blocking that you induce sleep. But orexin has a number of other roles. There's a role in metabolism, energy management, the reward system, and others that conceivably could be affecting these biomarkers as well. And so I think that those mechanisms really need to be explored to better understand what this drug is doing. A big hole in the literature is that there have not been trials of different sleep drugs that have different mechanisms head to head. So in the same trial under the same conditions, looking at drug A and drug B, that are hitting different systems in the brain. They may be affecting sleep as the outcome, but they are different neurotransmitter systems. And are you seeing similar effects? Are they different? And I think that those sorts of studies really need to be done to address that question. We also did monitor sleep during the two days that the participants were in our research unit. And just in looking at measures like total sleep time and their sleep efficiency and time in different sleep stages. There were no significant differences statistically between the groups, which I think suggests that while sleep probably played a role, there may be some other mechanisms that we need to explore. That could be important targets for future interventions.

Thom: If anybody in the audience has questions, please chat them. And I can ask them on your behalf. Or if you're interested, we can enable your audio and let you ask them yourself. Doctor, how early should people start thinking about their risk for Alzheimer's and potentially taking preventive measures?

Dr. Brendan Lucey: I think that from a prevention point of view as early as problems can certain problems can be identified that we know affect Alzheimer's disease risk and also sort of good general health should be intervened on, such as high blood pressure and sleep problems like obstructive sleep apnea. A lot of this the studies for interventions over you know, decades are, are obviously very challenging, if not impossible to get funded. But there is data showing that, you know, for instance, with sleep disturbances, very early sleep disturbances, say in midlife and your 40s have been associated with increased risk of, of having cognitive impairment or dementia as much as 25 years later. And so if you have insomnia or obstructive sleep apnea, getting that treated, you know, as early as it gets identified, has the potential to really change your risk profile and going forward.

Thom: And tell us more about the potential for those entire class of drugs for further study in relation to these effects.

Dr. Brendan Lucey: As I mentioned, the suvorexant was approved to treat insomnia in 2015. And so has a lot of safety data already available. But in the meantime, additional medications in this class have been approved. So these are dual the RX and receptor antagonists and there's now three that have been approved. And I think even within this class, there's the potential to look at different drugs like you know, maybe suvorexant isn't the best drug for potential intervention and Alzheimer's disease and maybe it's one of these other compounds. But like suvorexant, they've also been approved for treatment of insomnia, which you know, from a safety profile going forward, is very, very encouraging for future studies that these will be safe and well tolerated.

Thom: Will you be following up the participants in this study for future longitudinal results?

Dr. Brendan Lucey: We don't have any plans right now to do that. A number of participants have reached out who were in the study did you know indicate they are interested in future studies and we do plan that if they seem to be eligible based on what we know from this study, reaching out to them if they expressed interest about enrolling in some of our future studies, we are looking to move in addition to amyloid positive individuals also into older adults who are at a higher risk of Alzheimer's disease. So there are many participants in the study who wouldn't qualify for some of those studies because it was a 45 to 65 year old age range.

Thom: And looking at patients who have potential sleep disturbances at that earlier midlife age, when it's maybe decades before Alzheimer's would present, your advice to anybody with those kinds of sleep disturbance in light of this research, what would you say?

Dr. Brendan Lucey: Yeah, I get asked that question a lot. And, and I think the state of the research is such that, the recommendations are fairly general, you know, this is really a proof of concept study, and certainly does not support going out and taking suvorexant to prevent or delay Alzheimer's disease. But, you know, I think that individuals need to allow themselves enough time to sleep. Most people on average need seven, seven and a half hours of time to sleep that's not interrupted, has a good sleep environment with the lower temperature and it's dark and quiet, sleeping at night, rather than during the day. And when I tell folks is that, you know, if they're sleep is a problem, where it's, you know, impacting their, you know, certainly their daily lives, you know, because they're, they're too tired to perform at work or to do things that they want to do in their lives, that they should certainly get that checked out. If they're having insomnia and difficulty maintaining sleep at night, if they have symptoms of sleep disorders, like sleep apnea was snoring and pauses in their breathing while sleeping that they've been told about that those should be investigated. And, and treated. And I get that at this point. That's really the best advice that we can, we can give.

Thom: If there are any other questions from our audience, please do chat them to us. And we'll also make sure to share the contact information for the communicators at Washington University who can help get in touch with Dr. Lucey for any further follow up questions. Dr. Lucey, it seems to me that if someone's experiencing sleep disturbances, they already have lots of reasons to maybe get that checked out. But now this is just one more reason to say the importance of sleep can really not be overstated. Would you agree with that?

Dr. Brendan Lucey: Absolutely. I think that one of the great aspects of sleep, but also a real challenge in doing these sorts of studies is that sleep affects everything. So you know, sleep disturbances have negative effect on Heart, heart disease outcomes, pulmonary function, the endocrine system metabolism, it's more, it's probably more fruitful to find a system that doesn't, that isn't affected by sleep. And so I think it's part of good, good general health. And it's definitely one that I think that our society in general has somewhat neglected. And, and hopefully, that's beginning to change, because I think there's increasing recognition of the importance of sleep to health.

Thom: Absolutely. Well, thank you for contributing your study to that knowledge about the importance of sleep, and expanding our understanding of what can be early signs and early prevention of Alzheimer's. I think these are two really important areas that people need to be more and more aware of for their health. So thank you so much for taking the time to answer our questions. I will chat here, the contact information for Judy at Washington University so she can help any other reporters who'd like to get in touch with Dr. Lucey, for further questions, you can do that. And we'll also provide a transcript and a recording of this discussion. So any members of the media can utilize that for any articles that they're writing about this. Dr. Lucey, anything you'd like to say in conclusion before we wrap things up here about your study?

Dr. Brendan Lucey: No, I think we've covered it and I really appreciate the opportunity to present this study to everyone who's on the call.

Thom: Thank you, Dr. Lucey and we look forward to the bigger and more in depth studies on this topic as we learn more about the results here. Thank you so much and good luck with the next steps of everything.

Dr. Brendan Lucey: Thank you, appreciate it.

Thom: Thank you, everyone!

Lucey’s current research interests are in sleep, aging and Alzheimer’s disease. His lab focuses on studying the potential of sleep interventions to prevent or delay the onset of Alzheimer’s disease. Using lumbar catheters, he investigates how sleep affects different markers of Alzheimer’s disease changes in the brain such as amyloid-beta and tau. Lucey is also interested in whether or not sleep changes may be non-invasive markers for Alzheimer’s disease progression. 

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