🎙What is Keeping a Billion People up at Night Ep 215

Ever wondered what truly happens when you sleep and why sometimes it feels so elusive? Join us for an eye-opening conversation with Dr. Michael Koren and Dr. Mitchell Rothstein, a board-certified sleep medicine specialist, as we shed light on the mysteries of sleep and sleep disorders. Discover the root causes of common sleep issues like sleep apnea, narcolepsy, and restless leg syndrome, and understand why insufficient sleep tops the list of daytime sleepiness culprits. Dr. Rothstein dives into narcolepsy’s genetic underpinnings and highlights how essential sleep is not only for survival but also for maintaining health and boosting economic productivity. Chronic sleep deprivation's severe consequences, like weakened immune responses and reduced job performance, underscore the urgency of prioritizing good sleep.

Curious about the connection between your dreams and your emotions? We explore the fascinating relationship between REM sleep and mood disorders, and learn how early antidepressants that reduced dreaming sleep showed promise in treating depression. Dr. Rothstein explains the critical role of the amygdala in managing emotions during dreaming sleep and demystifies atonia—the temporary paralysis that keeps us from acting out our dreams. We also tackle the eerie phenomenon of sleep paralysis and how circadian rhythms influence our REM sleep patterns. Take away insights into how our genetic makeup shapes our daily routines, whether you’re an early bird or a night owl.

The discussion then shifts to sleep apnea, a disorder with profound health implications. Dr. Rothstein breaks down the stages of sleep and how disruptions can wreak havoc on your life. From the dangers of drowsy driving to the cardiovascular strain caused by repeated choking events during sleep, we cover it all. Learn about the latest treatments, from CPAP machines to innovative solutions like the INSPIRE hypoglossal nerve stimulator. Explore the potential of weight-loss medications currently under clinical trials to alleviate sleep apnea symptoms. Tune in for a comprehensive guide to understanding and tackling sleep disorders, and take the first step towards better sleep and a healthier life.

Talking Topics:

• Sleep and Sleep Disorders Overview
• Dreaming Sleep, Sleep Disorders, and Paralysis
• Sleep Apnea and Its Risks
• Impact of Sleep Apnea on Health
• Advancements in Sleep Apnea Treatment

Recording Date: June 21, 2024 from WJCT Studios.

If you are interested in viewing the presentation slides, click here.

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Music: Storyblocks - Corporate Inspired

Thank you for listening!

Chapters

• 0:00 Sleep and Sleep Disorders Overview
• 9:35 Dreaming Sleep, Sleep Disorders, and Paralysis
• 19:23 Sleep Apnea and Its Risks
• 28:48 Impact of Sleep Apnea on Health
• 38:26 Advancements in Sleep Apnea Treatment

Transcript

Narrator: 0:00

Welcome to the MedEvidence podcast. This episode is a rebroadcast from a live

Narrator: 0:05

MedEvidence presentation.

Dr. Michael Koren: 0:06

Hello everybody. I'm the bot that's filling in for Dr. Michael Koren, nice, to meet you.

Dr. Mitchell Rothstein: 0:12

And I'm Mitchell Rothstein. I'm the phase one medical director, so we're going to talk a little bit about sleep and sleep disorders, which is one of my favorite topics.

Dr. Michael Koren: 0:20

Yeah, this is exciting for me. Obviously, I was joking about being a bot.

Dr. Michael Koren: 0:23

I was just playing off of Sharon's initial comments that we won't be replaced by AI. Thank God for that so any event. Here we are. We're talking about sleep. This is an amazing audience. I'm really quite impressed. Thank you for coming.

Dr. Michael Koren: 0:38

It's really a standing room only audience. You would think for a sleep talk it would be a lying room only audience, but here we have quite a few people that are really interested in the subject, and I am too, so hopefully we'll have a great opportunity to talk about things and you can teach me a lot more about healthy sleep and healthy life. And Dr. Rothstein is board certified in sleep medicine, a pulmonary and critical care physician who's been in town for a number of years, and also a fabulous clinical investigator at Jacksonville Center for Clinical Research. So, without further ado, we like to say here that there's no such thing as a free lunch, that everybody's got to work for their lunch, and so the way you guys work for your lunch is by you ask you answer the audience questions that we pose to you. So let's start with an audience question.

Dr. Michael Koren: 1:26

So what is the common causes of sleepiness, the most common cause of sleepiness? And again we make it a little bit easier by giving you multiple choice. So number one, is it sleep apnea, the most common cause of sleepiness? Is it two, narcolepsy? Is it three, insufficient sleep. Is it four, restless leg syndrome. Or is it five, nagging spouses? Okay, so who thinks it's number one, sleep apnea, all right. Who says number two, narcolepsy? Ah, that's a question for Dr. Rothstein in a second, who says number three, insufficient sleep? Oh, look at that Very smart audience. Who says restless leg syndrome D? Who says nagging spouses? Okay, keep your hands down If your spouse is here. So what is narcolepsy first?

Dr. Mitchell Rothstein: 2:28

for people that ask that question, so narcolepsy is a genetic condition that was discovered about 50 years ago and it involves the lack of a brain peptide that promotes wakefulness. It affects about 1 in 2,000 people and there's actually two types of narcolepsy. One is where this brain peptide is absent, and that's called narcolepsy type 1. And the other is narcolepsy type 2, where that brain polypeptide is reduced and it manifests by daytime sleepiness. That is not really improved that much during napping sleep paralysis, hypnagogic and hypnopompic hallucinations. So hypnagogic hallucination is where you have a dream just as you're kind of falling asleep, and a lot of us will have that from time to time, but this is a common occurrence. And a hypnopompic hallucination is where you have that vivid dream, kind of as you're waking up, and a lot of us will experience that from time to time too. But in narcolepsy it's a predictable recurrent event.

Dr. Michael Koren: 3:34

So the audience member is probably regretting asking the question Right, and all I can add to that really amazing discussion is that narcolepsy is not the right answer to this question and in fact it's insufficient sleep. So that is the most common cause of sleepiness, and it's kind of interesting that if you have sleepiness during the day, the first question you should ask are you sleeping enough? So let's jump right into that. So, first of all, what is sleep? Isn't that crazy when you think about it? Why do we spend a third of our lives not conscious? So once you run through that, so people can understand, what exactly are we talking about?

Dr. Mitchell Rothstein: 4:09

Yeah, when we talk about sleep, and and it's a great question because we still don't really Understand how sleep does, what it does. We know what happens if you don't get enough of it, but we know in general that sleeps a naturally occurring state characterized by unconsciousness, then reduced sensory input and complete motor inactivity for the most part, and that it's easily reversible. People can wake up from this state of unconsciousness to consciousness. It occurs in all living animals and that if you're sleep deprived for a period of time, you're not going to survive and as that time goes on, your likelihood of survival goes down further and further.

Dr. Michael Koren: 4:51

That's fascinating. I remember reading studies where, if you keep animals awake artificially, they eventually just succumb to that.

Dr. Mitchell Rothstein: 5:01

Yeah, it's a form of torture. So you know, we use sleep deprivation as a form of torture.

Dr. Michael Koren: 5:06

Interesting. So, moving on to the next slide, just give us a little bit of a foundation pun intended about sleep and the national organizations that are involved.

Dr. Mitchell Rothstein: 5:16

So, overall, we know that daytime sleepiness is a consequence of many different sleep disorders, most common being people not getting enough sleep. It occurs in about 40% of the population. 20% of the population, at any given time, have persistent sleepiness and as we age, sleepiness becomes more and more common. Chronic sleepiness leads to a number of bad health and economic outcomes. We know that it's associated with reduced immune function People are more apt to get infections, to get cancer. We know that it impairs social interaction. And we also know that the effects of sleep deprivation on any job market are negative that people take more time off from work, they don't work as efficiently and it's a drag on the economy overall.

Dr. Michael Koren: 6:02

Yeah, at our office, people that are sleeping on the job tend to not be very effective, so it's a real issue in terms of the way businesses are run. So this I found really interesting is how the amount of sleep that you get varies with age and the type of sleep you get varies with age.

Dr. Mitchell Rothstein: 6:20

Yeah, that's been a fascinating discovery. Over the last 40 years the amount of progress that's occurred in sleep medicine and the amount of understanding of how the neurophysiology of sleep works has been amazing. And one of those things has been the different types of sleep. So we divide sleep into different stages based on brainwave activity and what the muscle tone in the body is. So classically during dreaming sleep REM sleep the body is paralyzed and doesn't move, so you can't act out your dreams and the brain is very active. It's really in a kind of a waking state In the in utero period.

Dr. Mitchell Rothstein: 7:00

The amount of dreaming sleep that occurs is the majority of the sleep period that we can measure in babies in utero and then over your lifetime at birth till senescence. When you die, your amount of REM sleep goes down further and further, kind of averages out at about the age of 70. The amount of deep sleep also declines as we get older. So unfortunately, out of all the things that go on as you get older, your sleep doesn't get that much better compared to when you're in your 20s and 30s and it's also not quite as restorative as it was when you're in your 20s and 30s.

Dr. Michael Koren: 7:36

Yeah, I'd also point out on this slide that this isn't sort of even during the course of one's lifetime. It goes from zero when you're born to 20 here. So this is all developmental time, this is conception before you're born, and there's not much between 20 and death. And the reason I'm bringing that out is because the obvious implication is that there's tremendous amount of brain development that's occurring very early on in life, between zero and one year of age, and that's reflected by this pattern of REM sleep.

Dr. Mitchell Rothstein: 8:09

Yeah, and the interesting thing about REM sleep also is that you know we all think about dreaming sleep as reflective of you know. In your dreams you're going to work out something that happened during the day, some type of psychological or physical insult you had. What are babies dreaming about that are in utero? I mean, there's no real correlation. They haven't had a conscious experience that they can then work through and resolve. So there's some very interesting theories about dreaming sleep.

Dr. Michael Koren: 8:36

Interesting. Let me get to that in the question and answer session. All right, so tell us about the sleep cycle.

Dr. Mitchell Rothstein: 8:43

Sleep cycles occur in about 90-minute intervals there's some variation in the population, anywhere from about 65 to about 125 minutes and we go through stage one sleep in the very early part of the night, when you first fall asleep, and then we don't really see stage one sleep much thereafter, and then stage two and then deep sleep we used to call it stage three and four and then REM sleep and then that cycle, stage two, stage three and four, and REM repeat at these intervals between about 65 and 125 minutes during the night. Classically we'll have about four or five of them during the night and if you do that you sleep seven to eight hours. You wake up refreshed as the night goes on. There's less deep sleep, which occurs in the first half of the night, and more dreaming sleep, which occurs in the second half of the night.

Dr. Michael Koren: 9:35

Interesting and a lot of people like to talk about different elements of dreaming. Is there a scientific correlation, like one thing is, when we're younger we say do you dream in color or black and white, or what does that all mean? Is that connected to any diseases or illnesses?

Dr. Mitchell Rothstein: 9:51

Well, it's very interesting that when dreaming sleep was first discovered about 50 years ago and we started to correlate sleep and mood disorders, there was a very strong movement in the field, especially after the first antidepressants came out, which were all affected dreaming sleep significantly by reducing it. That dreaming sleep led to depression Because these antidepressants all got rid of dreaming sleep during the night and then people felt better. So we knew that dreaming sleep wasn't really critical for survival or that significant in reducing sleepiness, but we still didn't kind of know what it means. More recently, really in about the last six months, there's been some papers published that show a certain part of the brain called the amygdala, which is where all your kind of emotions are centered. So when you get angry about something, that part of your brain fires off. During dreaming sleep the amygdala is very, very active. So it probably has something to do with moderating our moods and our kind of perspectives on things in general.

Dr. Michael Koren: 11:00

Interesting. All right, so getting back to the audience questions. Atonia is a temporary paralysis of nearly all muscles except those that control breathing, pulse, eye movements and a small inner ear muscle. When does it occur? During sleep?

Dr. Michael Koren: 11:20

Okay, oh my goodness, I heard an answer this audience is obviously the Mensa audience. Yeah, and they're not sleepy.

Dr. Michael Koren: 11:29

Okay, is it number one? Rapid eye movement sleep. Is it two? Deep sleep. Is it three? Bad dream sleep. Is it four? All the above? Or is it five? Make them believe you're asleep so you can hear what your kids are saying. Sleep. So who says one, okay, who says two? Who says three, okay, who says four? And who says five? Well, the answer is one, all right. So we've got some really smart people in the audience.

Dr. Mitchell Rothstein: 12:06

Yeah, and REM sleep is kind of defined by a couple of different criterion In terms of dream enactment and what you're dreaming about, and you can all think about this with your own dreams. Number one is the dreams are always active. You never dream that you're sleeping on the hammock, you know, having a nice tea, reading a book. You're always going somewhere, doing something. You don't know quite what it is, but there's always motion involved. And the number two aspect of dreams is they don't really make any sense. You know, when you think about it, what you're doing. You're kind of, as you're doing it, you're looking back at your own dream, kind of trying to figure out what's going on even while you're dreaming. So we know that dreaming sleep has motion and they're for the most part, nonsensical. They don't make any sense at all when you're in your dream.

Dr. Mitchell Rothstein: 13:01

Part of what's important in dreaming sleep is that if you're running down the street in your dream, you don't want to be running down the street in real life. And during dreaming sleep the brainwave activity mimics wakefulness. It's called a low-voltage mixed frequency pattern. So, people, when we look at their brain patterns, if you don't have any other clues, you can't really distinguish somebody's wakefulness pattern, from their dreaming pattern. So to keep us from acting out our dreams, our body actively is paralyzed, and that includes all the muscles except the breathing muscles, your eye muscles, rapid eye movement, so you can see what you're dreaming about.

Dr. Mitchell Rothstein: 13:37

And then there's a small muscle in your inner ear. So, quote you can hear what you're dreaming about. And then there's a small muscle in your inner ear. So quote you can hear what you're dreaming about, but otherwise you're paralyzed. For your own protection, and just one quick thing there are conditions where people have dreaming sleep without atonia and, as you can imagine, that is a very dangerous condition because the environment of your dream isn't the environment of where you're sleeping. So people run into walls, they are involved in violent physical activities and if they have bed partners, they're often in peril during those kind of conditions.

Dr. Michael Koren: 14:10

Fascinating. Yeah, I think all of us have had the experience where somebody wakes you up and you can't quite move right away. You become awake but your body doesn't move right away, and I guess that's the atonia.

Dr. Mitchell Rothstein: 14:22

Yeah, sleep paralysis and sleep paralysis, the atonia of dreaming sleep, can also happen in different stages of sleep and as people fall asleep and you've all probably had that especially during naps. So if you're excessively sleepy and you take a nap out of your normal sleep circadian rhythm, that sleep paralysis can occur. And they used to call it, especially in the south, the witches ride, because you were there, you were frozen, you were trying to move but you couldn't move and it's frightening for people

Dr. Michael Koren: 14:56

That suggested at that time that you go into REM sleep faster during afternoon naps than at night. Is that still believed to be the case?

Dr. Mitchell Rothstein: 15:04

Not really so. What we've learned from a physiologic standpoint is that REM sleep, except in cases where there's severe sleep deprivation is a circadian process, meaning that there's a certain time of the night when you have dreaming sleep, and for average people that don't have other sleep disorders, napping is not associated with REM sleep. Rem sleep occurs only during the night. If you're having dreams every time you take a nap, that's something you should see a physician about, because that's not normal.

Dr. Michael Koren: 15:37

Yeah, and this concept of circadian rhythms is really important in health and it's something that virtually all animal cells experience.

Dr. Mitchell Rothstein: 15:48

Absolutely.

Dr. Michael Koren: 15:49

It's really fascinating is that the way we respond during the course of the day is kind of programmed in our genes.

Dr. Mitchell Rothstein: 15:55

Yeah, absolutely, and there are different types of people. So some of us are early birds and some of us are owls, and that's actually to a large part, as you can imagine, behaviorally dependent. But in sleep studies, where they isolate people in caves or in rooms where they can't tell what time of day it is or what part of the day it is, some of us are early bird programmed and some of us are owl programmed, and I venture to guess that 80% of couples here are represented two different types. So one person's always an early bird and one person is always an owl Interesting, yeah.

Dr. Michael Koren: 16:33

Huh, all right. So explain to everybody the difference between apnea and hypopnea. All right.

Dr. Mitchell Rothstein: 16:43

So finally we got to the meat of why most of you are here. So the science of sleep apnea has really developed over about 35 years. When I first went into practice, sleep medicine was just becoming a subspecialty and since sleep apnea involved breathing and I was involved in lung disease, the two kind of went hand in hand. So people that were in pulmonary subspecialties got interested in sleep apnea.

Dr. Mitchell Rothstein: 17:08

So when we look at patients' sleep during the night just in terms of their breathing, we kind of rate them in terms of whether they're making noise or not, whether their breathing is normal, and that ranges from primary snoring where the person will just snore, you know, during their sleep it doesn't interrupt their sleep. It's brutal for the bed partner but their sleep isn't particularly interrupted to people on the far end from primary snoring, to people who actually stop breathing and they're not stopping breathing and their airway is obstructed by their tongue falling back and the pharyngeal walls kind of collapsing Like if you're sucking through a straw too hard. That's what happens in the upper airway and that period of apnea where there's no airflow can last from 10 seconds to 60 seconds and can be frightening for the bed partner. Sleep apnea has always been a two-person disease, because both people wake up exhausted in the morning the person that has sleep apnea and their bed partner, because the bed partner is frightened that they're not going to breathe again.

Dr. Mitchell Rothstein: 18:12

In between that snoring and the apnea is something called hypopneas, where the person's still moving air but it's not to the same amount that occurs during normal breathing. So those two are the kind of extremes. And then in that middle, with the hypopneas, something called upper airway resistance, where we know that people that snore, they're not obstructing but their brain is kind of activated, kind of to wake them up a little bit, not to full consciousness, but just enough to wake them up to get that motor tone back in their airway. And they have tons of interruptions during the night, virtually one a minute during the night. So you can imagine if you're sleeping during the night, Mike, and every minute I lean over and give you one of those. Not enough that you wake up and go hey, cut that out, but just enough to rattle your sleep.

Dr. Michael Koren: 19:04

You're going to feel like you never went to bed. Right right Interesting. Now, one of the things that you've taught me in the past that I thought was interesting is that a certain amount of apnea is actually normal.

Dr. Mitchell Rothstein: 19:12

Right.

Dr. Michael Koren: 19:13

And so I don't want people to be scared if they see that their bed partner stops breathing for 15, 20, 30 seconds, because some of that might be normal.

Dr. Michael Koren: 19:22

So why don't you explain that?

Dr. Mitchell Rothstein: 19:23

So as we go to sleep, I always tell people that you know, sleep is a different stage than wakefulness. There's actually three stages of consciousness and unconsciousness that normal people experience during their lifetime there's wakefulness, there's non-REM sleep and there's REM sleep. And when you start mixing those things together, that's when you have sleep disorders. So the whole idea biologically for us is that we're either awake or asleep. There's no survival advantage to being like half awake and half asleep. So you either want to be awake in dreaming sleep or in non-dreaming sleep and nothing in between. While you're asleep.

Dr. Mitchell Rothstein: 20:06

Part of the sleep stage is that our body's systems change from a sympathetic, dominant, you know, awake, active kind of state to a parasympathetic, dominant, relaxed, quiet, non-responsive state. When that occurs, our brains also change in terms of their pattern During that transformation from wakefulness to sleep and muscle relaxation. In general, people can have mild obstruction of their upper airways. In all the population studies that have been done, we kind of arbitrarily drew a line and said for adults, if you're having these obstructive events and they're occurring less than five times an hour, that that will consider normal and that that's not interrupting your sleep enough to result in daytime sleepiness, and for children the number is one. So kids up to about the age of 12 are allowed to have one of these obstructive events per hour, and that's still considered normal. If they're having more than that, then they had classically identified as having sleep apnea as children as well interesting.

Dr. Michael Koren: 21:12

Okay, so I think you kind of cover this. Any other comments about the definition?

Dr. Mitchell Rothstein: 21:16

no, no other comments, except that in people that have this upper airway resistance syndrome, where they're not obviously stopping breathing, the effects on daytime functioning, daytime activity, other kind of reflections of how they're doing cognitively is as severely affected as the ones who completely stop breathing. So just because nobody stops breathing, if they're snoring heavily and that snoring is awakening their brain numerous times per hour, they're going to be just as affected as people that have complete cessation of breathing.

Dr. Michael Koren: 21:54

One other question just came to my mind. Sharon Smith, who you met when we started, supplied these adorable pictures of the puppies. And do dogs get sleep apnea? Do other animals get?

Dr. Michael Koren: 22:10

it Is that something you should be concerned about for your pets,

Dr. Mitchell Rothstein: 22:12

Absolutely, in fact. Bulldogs English bulldogs number one cause of death pulmonary hypertension from obstructive sleep apnea, and that has to do with upper airway anatomy.

Dr. Michael Koren: 22:22

Wow, okay, all right, two main types of sleep apnea. You kind of went into this a little bit. Any other comments? There's your bulldog there.

Dr. Mitchell Rothstein: 22:30

Yeah, and that goes for pugs too, so you can just tell by the way their face looks. They don't have that much of an airway behind that kind of flattened faces. But central sleep apnea is something we haven't talked about and central sleep apnea is another form of breathing and cessation and that's controlled not by airway obstruction but by brain function and brain dysfunction. That occurs in patients that have prolonged circulation time, also if they have problems with their acid-base balance in their bloodstream. Those are the things that drive our breathing. If those are abnormal, then those patients kind of have this. We call it chain-Stokes respirations, which you're very familiar with from heart failure and in heart failure about 50% of patients with heart failure with reduced ejection fraction have central sleep apnea.

Dr. Mitchell Rothstein: 23:19

And what that looks like is a pattern where people they have this kind of cyclic response where they hyperventilate, then they stop breathing and then they hyperventilate again, and that's associated with arousals and sleep fragmentation and can cause the same kind of daytime symptoms as obstructive sleep apnea Interesting and again referencing the picture on the screen.

Dr. Michael Koren: 23:51

Is it good to sleep with your tongue out or in, or it doesn't really matter?

Dr. Mitchell Rothstein: 23:57

Well funny there's actually an answer for this. So in patients that have obstructive sleep apnea and if they have large posterior base tongues, one of the treatments is something called a tongue retaining device. So it's a mouthpiece and it has a little suction area in it. So you stick your tongue in it and then you relax and the mouth presses against your lips and keeps your tongue from falling backwards. Now it works in the laboratory but, as you can imagine, compliance and patient satisfaction is less than successful and there's actually surgeries that are done to do tongue advancement. Where they take, you know, your frenulum is that thing that sticks down on the bottom part of your tongue to the bottom of your mouth. They can actually pull that forward surgically and that can help some patients with sleep apnea as well.

Dr. Michael Koren: 24:50

Interesting so tongue out Okay, there we go, all righty. So back to work audience. Which of the following increases the risk of developing obstructive sleep apnea? One being overweight or obese. B smoking. C drinking alcohol before bed. D all of the above or boring lectures. Actually, let's remove that last one. Just the first four. So who says A, b, c, d?

Dr. Mitchell Rothstein: 25:32

All right, look at that Is that the right answer. That's the right answer.

Dr. Michael Koren: 25:35

All right, there you go, and then there's a mass there. Do you want to comment on that?

Dr. Mitchell Rothstein: 25:41

Sure, let me talk a little bit about being overweight also. 30 years ago, our patient demographics in general and for all of us have changed quite a bit. Our country has gained weight, our BMI has gone up and you just don't gain weight in your hips and around your middle. You also gain weight in the back of your throat, so that back part of your throat becomes more and more obstructive and larger. And we know that in patients who are overweight and have sleep apnea that in general, if you lose 20% of your body weight, your sleep apnea goes away 95% of the time.

Dr. Michael Koren: 26:20

That's crazy, that's incredible.

Dr. Mitchell Rothstein: 26:21

We know that smoking does basically the same thing. Just by the irritant smoke effect on the back of your throat you get a lot of adema and swelling and that also leads to obstruction. And drinking alcohol is the same thing. In fact, one of the Frequent problems we had in the sleep lab was everybody that comes to the sleep lab drives over to the sleep lab at night. You know 8 or 9 o'clock and they get out of their car and they go to their room and they fall asleep and they don't snore and they dont have sleep apnea, but inthe office their wife's complaint was that they snored like crazy, but hey were drinking three or four beers before they went to bed. In the sleep lab they didnt do it. They didn't do it, so they didn't have that muscle relaxation, so they didn't exhibit the same behavior that they had at home. So we learned that we told our patients bring the beer, drink it to lab before you go in and get hooked up, so we can duplicate those same kind of conditions.

Dr. Michael Koren: 27:16

That's super interesting. A lot of people feel that having a glass of alcohol before they go to sleep helps them sleep Right. Is there any?

Dr. Mitchell Rothstein: 27:23

There's definitely a hypnotic effect to the use of alcohol. So alcohol is a neurodepressant, so it helps people fall asleep, but as it's metabolized and your brain starts to wake up again, people don't maintain their sleep. So often in people that are somewhat heavy drinkers, before they go to bed they'll have no trouble falling asleep, but two or three hours later, after the alcohol is metabolized, they're waking up, either from sleep apnea or just from their brain being overactive and relieved from the hypnotic effect of the alcohol.

Dr. Michael Koren: 27:56

Interesting. So let's talk about the causes and comorbidities of sleep apnea. Obviously, it touches a lot of areas of medicine.

Dr. Mitchell Rothstein: 28:06

Yeah, and sleep's been associated, and lack of sleep or bad sleep, with just about everything but the most common things. That we know for sure that sleep deprivation has effects on your mood. You know you can imagine if you were only getting three or four hours of sleep a night, you wouldn't be that happy of a person the next day. And if you don't get any relief from the sleep that you are able to get, there's kind of a hopeless cycle where you always feel bad in the morning, you nap during the day but you don't quite feel better and you just don't get any relief. So we know it's associated with depression, anxiety and other mood disorders.

Dr. Mitchell Rothstein: 28:44

We know that obesity is a risk factor for sleep apnea. And once your brain gets sleepy, your brain wants energy and the energy for your brain is glucose. So what tired brain is a hungry brain. So you get into this vicious cycle of you're not sleeping well at night, your brain's tired, you're looking for calories to help your brain feel better, and then that kind of cycle just cycles around more and more. We know that poor sleep is associated with daytime sleepiness. So the one thing that I think is still kind of under-publicized in the general community is that we know that drowsy driving is responsible for about 5,000 deaths a year, and they're driving along. When you do that, which we've all done, you nod off. That nodding off process is not really a consciously motivated, acknowledged thing. That happens when your brain falls asleep. You have this perceptual Disengagement so you don't really see what you're looking at anymore, and that can occur for about 15 to 30 seconds before your brain recognizes that you were asleep. So when you do this, what you actually did was this Wake up, wake up.

Dr. Mitchell Rothstein: 30:12

Yeah, 15 to 30 seconds before your brain says, oh, I was actually asleep, so that you can imagine it 65 miles an hour, that can be a bad thing.

Dr. Michael Koren: 30:22

Yeah, wow, scary

Dr. Mitchell Rothstein: 30:23

so heart failure.

Dr. Mitchell Rothstein: 30:24

We know that every time people obstruct, you can imagine this choking event that occurs.

Dr. Mitchell Rothstein: 30:29

So if during the night, someone was standing next to your bed and you know 15 to 20 times an hour, they leaned over and kind of choked you for about 15 or 20 seconds and then let you breathe again, that's a huge cardiovascular burden for you to handle. I mean, you're having this fight or flight activity every you know 15 to 20 to 40 times an hour. That occurs all night long. We know that leads to hypertension. We know that leads to eventually strains on your heart and can make heart failure a lot worse. And we also know that it's definitely associated with atrial fibrillation and you can probably talk about this at some length. And we know that if you're diagnosed with atrial fibrillation and you have sleep apnea and you get to go back into sinus rhythm and your sleep apnea isn't treated, there's about a 60% chance at six months that you'll be back in atrial fibrillation again, where, if it is treated, there's only about a 20% to 30% chance that you'll be back in atrial fibrillation.

Dr. Michael Koren: 31:25

Yeah, that's a great point. It's a huge problem. Atrial fibrillation for those of you that are not familiar with the term is an arrhythmia, an irregular heartbeat that starts at the top of the heart and could be very rapid and could be associated with strokes and feeling poorly. And, to your point, it's much harder to treat atrial fibrillation if somebody also has sleep apnea, and the flip side of that is, sometimes people get treated for sleep apnea and they respond to atrial fibrillation treatments that they didn't respond to previously, . So it's a really important point and that's also the truth for high blood pressure.

Dr. Mitchell Rothstein: 31:59

They're all related phenomena and glucose control with diabetes type 2. People that have untreated sleep apnea have much higher HbA1c levels that glycosylated hemoglobin, showing how good your control is of your diabetes, even if they're following their maintenance routines adequately than people who have controlled sleep apnea.

Dr. Michael Koren: 32:21

Yeah, and we do research studies for people that have high blood pressure and we get into some of the details as to what's driving the high blood pressure. So often we'll have people that have quote refractory high blood pressure, meaning they're on four or five drugs and probably the most important treatment is the treatment for sleep apnea, and once that occurs you can reduce the number of drugs you're on. So that is the research we do and if you guys are interested, let us know We'd be happy to look at you for those type of studies.

Dr. Michael Koren: 32:48

Okay, moving on Risk factors

Dr. Mitchell Rothstein: 32:51

And we've kind of gone over these a lot but anything that obstructs your upper airway outside of your chest cavity, so from the top of your clavicles up, anything that makes that airway smaller, whether it's enlarged tonsils, a posterior base tongue, whether it's nasal congestion, whatever it is is going to increase. We call it the closing pressure is going to increase. What reduces the closing pressure of how much sucking force causes your upper airway to obstruct, and that's what the problem is. So anything from here up that gets enlarged, inflamed or otherwise restricts the airway is going to lead to more sleep apnea. We know that sleep apnea increases with age. We know that men are more affected by sleep apnea. We know that sleep apnea increases with age. We know that men are more affected by sleep apnea in general than women. We know.

Dr. Michael Koren: 33:38

I thought that question was yes, no.

Dr. Mitchell Rothstein: 33:43

Well, that can be associated with how bad your sleep apnea is. Okay, I'm sorry. We know that as your weight increases, your risk for sleep apnea increases. We know that anything that causes your muscles to relax whether it's sleeping pills, alcohol or other sedatives is also going to increase your risk from sleep apnea. And again, it's based on collapsing that upper airway. We know that smoking, because it leads to edema and swelling in the upper airway, can lead to more snoring and sleep apnea.

Dr. Mitchell Rothstein: 34:12

And we know genetics are also affected. If you come from a family that's genetically prone to have posterior base tongues and small posterior airways, even if your weight is excellent, you'll still be at risk for sleep apnea. We know that, for example, patients with Down syndrome have about a 35 to 40% chance of having sleep apnea. And then there are other medical conditions that can lead to this. Specifically, acromegaly has been associated with it and that's where you have, you know, increase in bony structures in your face and other parts of your body, and when it occurs in the jaw, it makes the jaw hypertrophy and the back posterior base of the tongue is also pushed backward in that condition, leading to sleep apnea as well.

Dr. Michael Koren: 34:58

Well, this picture is frightening to me. It looks like there's no room at all for the airway.

Dr. Mitchell Rothstein: 35:04

And that's the choking that occurs during sleep apnea, over and over again during the course of a night.

Dr. Michael Koren: 35:11

Okay, symptoms.

Dr. Mitchell Rothstein: 35:14

So obviously snoring is the most obvious symptom, especially for the bed partners. The consequences of sleep apnea if you're not getting a good night's sleep, you're sleepy during the day, you wake up with headaches. If it's associated with severe sleep fragmentation and also if your oxygen level is going down during the night. Dry mouth in the morning is also a sign of sleep apnea, and restlessness during the night from these repeated arousals that occur also is very, very common. We know that people that have sleep apnea do not have inhibition of urinary production during the night. That occurs in people who don't have sleep apnea. So for normal sleepers we're not getting up every two or three hours to go to the bathroom because the amount of urine we produce during the night is reduced compared to the amount that we produce during the day. So some people felt that this was just opportunistic, that you woke up and since you were awake you went to the bathroom. But we actually know now that that reduction in urine that occurs during normal sleep doesn't occur during ensleevement. It leads to irritability and frustration.

Dr. Michael Koren: 36:23

Interesting Making the diagnosis.

Dr. Mitchell Rothstein: 36:26

So the diagnosis is historical. And then there are two major types of diagnostic procedures that people undergo. One is a home sleep test and that just measures a few parameters of sleep mostly airway, heart rate, oxygen level but it doesn't include sleep staging what part of sleep you're in or on. A lot of these studies doesn't include the position. And then the other one is an attended sleep study, where you go to a sleep lab and they wire you up and you go to sleep and they measure all those things, both the stage of sleep, the position of sleep and the breathing that occurs during sleep and how it's affected.

Dr. Michael Koren: 37:06

My sense is that more studies are being done at home now than they used to be. Is that correct?

Dr. Mitchell Rothstein: 37:10

Yeah, for patients that are, you know we have risk questionnaires for sleep apnea and for people that are rated fairly high on these risk questionnaires, a home sleep test can be diagnostic in 80% of them. You miss those patients that are having that upper airways resistance syndrome and we know that's a bigger and bigger part of the population. So those patients may have to go to a sleep lab to get that diagnosis made after a home sleep test Complications. So, as you can imagine, the primary cause for death in the United States is still cardiovascular disease and we know that sleep apnea is a risk factor for cardiovascular disease. We know that we see it in type 2 diabetes disease. We know that we see it in type 2 diabetes.

Dr. Mitchell Rothstein: 37:58

About 50% of patients with type 2 diabetes have sleep disordered breathing. That includes anything from mild sleep apnea, which means it's occurring more than five but less than 15 times per hour, to severe sleep apnea over 30 times per hour. We know that patients with pulmonary hypertension will often have their pulmonary hypertension as a consequence of these repeated choking episodes that it can affect not just the blood pressure they measure on your arm but the blood pressure internally from the right side of your heart. We know that it's associated with poor memory, we know that it's associated with mood disorders and we know that the primary time for people with sleepiness during the day to be involved in a motor vehicle accident associated with sleep apnea are those periods of time.

Dr. Mitchell Rothstein: 38:44

You know where our circadian drive is adding to already this burden of this reduced sleep that they got at night and causes them to be even more sleepy during the day. So those circadian drives occur at two times during the day. They occur at 1 to 2 in the afternoon you know your nooner, your nap time and then they occur in the evening at 1 to 2 in the morning is where your peak sleepiness occurs. So we don't like to wait for the peak sleepiness to go to bed. We want to go to bed somewhere on the ascending limb of that. But we know that lack of sleep and poor sleep, even if you're getting enough sleep, if your sleep isn't good and is interrupted by sleep apnea, you're gonna be sleepy during the day interesting.

Dr. Mitchell Rothstein: 39:25

Treatment. So the primary Treatment that we've been using traditionally in sleep medicine for years is has been CPAP continuous positive airway pressure. So that's the mask with the hose to the machine. Now there's different variations of CPAP and we have not only the continuous positive airway pressure but we also have BiPAP, which has one pressure when you're breathing in and then when you start to exhale the machine regulates to a lower pressure so it's easier to exhale against. And that's been a major breakthrough in sleep medicine, because a lot of people that fail CPAP have we call it back pressure intolerance. So when they start to exhale and they're sensing that force they have trouble sleeping. So they devised a machine that acknowledges that and works with that. And then ADAPT is a machine that works primarily for people with the central type of sleep apnea. So it maintains a normal kind of regular airflow even during those periods of time when the patients have kind of stopped breathing and they're waiting for the acid level to build back up so they start breathing again. So it's avoiding those complications.

Dr. Mitchell Rothstein: 40:34

Oral appliances you've probably all seen advertised on TV is just a mouthpiece and it moves your lower jaw forward. And when it moves your lower jaw forward it pulls your tongue away from the back of your throat. Some people only have sleep apnea when they're on their back, and in those cases we do something called positional therapy or tennis ball therapy, where you can sew a tennis ball or safety pin a tennis ball in a sock to the back of somebody's shirt to keep them off their back at night, which cures their sleep apnea. There's been surgical options too, very sophisticated upper airway surgeries like the type we started talking about. That also include getting rid of the tonsils and adenoids and then moving the tongue forward tracheostomy, since that will bypass the rest of the upper air wave, often, curiously, bapnea, but for some reason people weren't really active to want to have that form of therapy.

Dr. Mitchell Rothstein: 41:31

More recently, you've probably heard of this device called INSPIRE, this hypoglossal nerve stimulator, and that's a pacemaker that's implanted subcutaneously. The sensing end is at your diaphragm and then the other end goes up to the back of your tongue. So what that does is when you start to inhale, the device senses that it stimulates the back of your tongue and that makes your tongue protrude. So it's like you stick your tongue out every time you start to breathe, and for some patients that can be, if not curative, helpful it tends to go in terms of how good it is. As your body weight goes up, its responsiveness goes down. We know that bariatric surgery because it gets rid of that 20% of weight for patients that are markedly overweight will help sleep apnea tremendously. And currently there's been a move towards medical treatment for sleep apnea, some of them directed at weight and some of them directed at other stimulant therapy to kind of help keep that upper airway tone active during sleep so it doesn't relax and collapse.

Dr. Michael Koren: 42:37

Well, speaking of clinical trial, well, this is a quick conclusion. Sleep is an active process. Get enough sleep, everybody, and if you're sleepy, get evaluated. So I think those are important take-home lessons. But I wanted to jump to some of the clinical trial stuff that you're involved with.

Dr. Mitchell Rothstein: 42:53

So there's been a number of clinical trials going on with medications that are primarily been designed to reduce weight, and you've probably heard of all of them. When we reduce patients' weight, there is a myriad of other medical conditions that improve as well. So we know that people that lose weight their blood pressure goes down, we know that their glucose levels improve, we know that their heart failure improves and these things are all interconnected with each other. That overall stress response of carrying around a lot of weight seems to be reduced.

Dr. Mitchell Rothstein: 43:30

And we're particularly looking now at an indication for one of these medications reducing weight and its effect on sleep apnea. So we kind of know what the answer is already going to be, but we have to prove it. And to prove it, we're doing a study where patients that have a BMI a body mass index over 27, and have sleep apnea and type 2 diabetes, are given this medication for a total of 80 weeks, and the primary endpoint for this study is going to be the effect on sleep apnea. So we're not looking at all the other things as the primary endpoint, it's looking at its effect on sleep apnea, and since we've been recommending to patients that are overweight with sleep apnea for years that they lose weight. This is a study that we're very excited to be part of and we're hoping that it's going to have the conclusion that we all are anticipating that it's going to have.

Dr. Michael Koren: 44:24

Yeah, these are really nice opportunities for patients. So this study, for example, involves drugs like Ozempic and Mounjaro that are very expensive drugs. They're on the market but a lot of people can't get them because of insurance restrictions or the cost, and in this study, you'll have potential access to these drugs at no cost. In fact, you'll get a little check for keeping a diary of your sleep, and so it's a nice opportunity for people, and it's one of many studies that we're working with on diabetes issues, cardiac risk factor issues and sleep issues. So if you're interested, please let us know. We'd love to get you more information and again, there's no cost, no insurance involved, so that is your free lunch.

Dr. Michael Koren: 45:04

That's actually a time when you can get information for free and, if nothing more, I think you'll love being part of the ENCORE ENCORE is an acronym for Encouraging Community Research and Education, and that's what we're all about. So by just having email access to you, you'll get a lot of information. You'll get all these slides on the MedEvidence website and you'll get updates about what's happening here in Northeast Florida in clinical research and again, all free of charge. So I'd really highly encourage you to be part of it. We have hundreds of physicians that work with us, and it's a wonderful community and a community where we share just fabulous information and help a lot of people. So, final exam, final exam. I don't think I showed you this slide.

Dr. Mitchell Rothstein: 45:51

No, but I saw it before when I was looking through it exam. I don't think I showed you this slide?

Dr. Michael Koren: 45:56

Okay, okay, I'll be really impressed if somebody knows who this is. Anybody in the audience knows who this is. Before I give you choices, have you seen him on the streets? Okay, we'll give you some choices. Is this a candidate for obstructive sleep apnea? Is this a guy who discovered the genes regulating circadian rhythms? Is this a professor who taught Dr. Koren's college biology class? That being me? Is this a Nobel Prize winner or all the above? You guys are smart. Yep, this is actually my sophomore year biology professor at Brandeis University, who was recently awarded the Nobel Prize for discovering what we just talked about, which is that all animal cells have circadian rhythms that are driven by genes, and all the stuff they were doing is based on this incredible biological insight. So thank you, Dr. Hall. Thanks for joining the MedEvidence podcast. To learn more, head over to MedEvidence. com or subscribe to our podcast on your favorite podcast platform.