# A Master Class on Sleep

An episode of [Ground Truths](https://invisiblenetwork.ai/podcast/1728526108), 6 Mar 2026, 57 min.

Audio: https://api.substack.com/feed/podcast/188405660/31d038e62d878b792abb6f06ad4834d6.mp3

Yo-El Ju is the Barbara Burton and Reuben Morris Professor of Neurology at Washington University, St. Louis. She got her AB from Harvard and MD from Columbia and actively practices sleep medicine and is a prolific researcher, one of the top sleep scientists in the country. Here are some of the topics we discussed and a few related hyperlinked citations: —Importance of Deep Sleep (and her paper on what happens when deep sleep is purposely disrupted, how it is modulated, effect of alcohol —The Orexin Antagonist drugs that promote sleep (and a study that shows they can reduce p-tau217 and other neuroinflammation markers —Link of sleep regularity with less all-cause, cardiovascular, and cancer related mortality Figure 3.9 from SUPER AGERS (SRI-sleep regularity index) More things we discussed: —A sleep foundation model that predicts 130 diseases —Impact of menopause on sleep —Getting to sleep vs staying asleep —Role of naps —Impact of interruptions of sleep —Sleep apnea and new interventions —Vagal nerve stimulation and sleep —Cerebrospinal fluid wave that occurs during attention lapse after poor sleep —cognitive behavioral therapy for improved sleep —Wearables, sleep scores, and effect on sleep —Any supplements that help sleep? —The rare genetically endowed short sleepers Thank you Jeoffry Gordon, MD, MPH, Dr. Sara Wolfson, Lynn L, Vau Geha, Bernie Newman, and more than 600 others for tuning into my live video with Yo-El Ju! Join me for my next live video in the app. ************************************************** Thanks to Ground Truths subscribers (> 200,000) from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026. +++++++++++++++++++++++++++++ I also want to thank the National Academies of Science, Medicine and Engineering for their recent recognition. Get full access to Ground Truths at erictopol.substack.com/subscribe

## Transcript

[0:00] SPEAKER_03: Great.
[0:00] SPEAKER_03: Thanks, Eric, for inviting me.
[0:02] SPEAKER_03: I'm super excited.
[0:03] SPEAKER_00: Yeah.
[0:04] SPEAKER_00: So let's get right into the topic,
[0:08] SPEAKER_00: the connection between sleep and neurodegenerative disease,
[0:14] SPEAKER_00: particularly Alzheimer's.
[0:16] SPEAKER_00: What's your overall perspective about how they come together?
[0:21] SPEAKER_03: Well,
[0:23] SPEAKER_03: I think there's two broad areas,
[0:25] SPEAKER_03: at least that I'm aware of,
[0:27] SPEAKER_03: in which sleep and neurodegeneration overlap.
[0:30] One is with Alzheimer's disease and how sleep or circadian
[0:34] disruption may have a
[0:39] SPEAKER_03: two-way direction with early Alzheimer's disease pathology,
[0:44] SPEAKER_03: where we know,
[0:45] SPEAKER_03: obviously,
[0:45] SPEAKER_03: once people get Alzheimer's dementia,
[0:48] SPEAKER_03: they have a very high prevalence of sleep problems.
[0:51] SPEAKER_03: But we now know that even in the preclinical stage,
[0:55] SPEAKER_03: meaning prior to any cognitive symptoms,
[0:59] people may have sleep disturbances that are detectable through
[1:04] a variety of means.
[1:05] Also,
[1:06] there's some evidence to suggest that having sleep disruption
[1:10] may promote or speed up
[1:13] SPEAKER_03: um,
[1:13] SPEAKER_03: the,
[1:14] SPEAKER_03: uh,
[1:14] the buildup of Alzheimer's disease-related proteins like
[1:17] amyloid plaques and tau
[1:19] SPEAKER_03: tangles.
[1:20] SPEAKER_03: So,
[1:20] SPEAKER_03: you know,
[1:20] SPEAKER_03: in the past,
[1:22] SPEAKER_03: say,
[1:22] SPEAKER_03: 15,
[1:22] SPEAKER_03: 20 years or so,
[1:23] SPEAKER_03: there's been a lot of data,
[1:25] SPEAKER_03: uh,
[1:25] SPEAKER_03: you know,
[1:25] SPEAKER_03: starting with mice in the Hultzpun lab here at WashU,
[1:29] SPEAKER_03: uh,
[1:29] SPEAKER_03: that have really looked at the,
[1:31] SPEAKER_03: uh,
[1:31] SPEAKER_03: interaction between sleep and,
[1:33] SPEAKER_03: um,
[1:34] SPEAKER_03: Alzheimer's disease proteins,
[1:36] SPEAKER_03: um,
[1:38] And I think as time has passed and as the biomarker field in
[1:44] Alzheimer's disease
[1:45] SPEAKER_03: has advanced,
[1:47] SPEAKER_03: we're getting more and more of these data in humans as well.
[1:50] SPEAKER_03: So that's one large area that's, I think, a concern to many of us.
[1:57] The other area in which sleep and neurodegeneration overlap a
[2:01] lot is in synucleinopathies.
[2:03] SPEAKER_03: And this is a group of disorders that includes Parkinson's,
[2:06] SPEAKER_03: dementia with Lewy bodies,
[2:08] SPEAKER_03: multiple system atrophy.
[2:10] We know that there's a specific sleep disorder called REM sleep
[2:13] behavior disorder
[2:14] that people who have that sleep disorder are at heightened risk
[2:19] of being diagnosed
[2:20] SPEAKER_03: with one of those synucleinopathies within 5-10 years.
[2:24] So we know that sleep can be a signal and sometimes a very
[2:29] specific signal as to
[2:33] neurodegenerative disease processes that may be ongoing in the
[2:36] brain well before
[2:38] SPEAKER_03: symptoms occur.
[2:39] SPEAKER_00: All right.
[2:39] SPEAKER_00: Well,
[2:40] so you made the link between the two most important
[2:43] neurodegenerative diseases,
[2:44] SPEAKER_00: Alzheimer's and Parkinson's.
[2:47] SPEAKER_00: But regarding the mechanism,
[2:50] SPEAKER_00: is this really related to the primacy of deep sleep,
[2:54] SPEAKER_00: the slow wave portion of sleep,
[2:57] SPEAKER_00: or is it really other phases as well?
[3:02] SPEAKER_03: So I'm a sleep doctor by training,
[3:04] SPEAKER_03: so I think that non-REM sleep and REM sleep are both important.
[3:10] SPEAKER_03: They're like my children, right?
[3:11] SPEAKER_03: They are important.
[3:14] SPEAKER_03: But when it comes to at least amyloid and tau,
[3:18] SPEAKER_03: we think that it is the slow-wave sleep,
[3:20] SPEAKER_03: which is kind of the deep part of non-RAM sleep,
[3:24] SPEAKER_03: that's important.
[3:27] One experiment that we did in my lab to really drill down into
[3:32] which specific part
[3:33] SPEAKER_03: of sleep is linked to amyloid
[3:36] SPEAKER_03: is we did a study where people came in and spent two nights,
[3:42] SPEAKER_03: at least a month apart,
[3:44] SPEAKER_03: and we set up a closed-loop system where after they fell asleep,
[3:50] SPEAKER_03: we were reading their brainwaves,
[3:53] and there was an automated system where once they started
[3:56] getting into deep,
[3:57] SPEAKER_03: slow-wave sleep,
[3:58] SPEAKER_03: they would get a little beep through headphones.
[4:00] And this beep would get louder and louder and louder every 10
[4:03] seconds until it
[4:05] SPEAKER_03: nudged them out of deep sleep into lighter sleep,
[4:07] SPEAKER_03: not waking them up fully.
[4:10] SPEAKER_03: And we did that one night.
[4:13] SPEAKER_03: And then on a different night,
[4:14] SPEAKER_03: we did a sham condition where we did not deprive their slowly sleep.
[4:19] And what we found out in that study is that when we look at the
[4:24] spinal fluid levels
[4:25] SPEAKER_03: of amyloid,
[4:26] SPEAKER_03: right,
[4:27] SPEAKER_03: which we measure through lumbar punctures the next morning,
[4:30] there's a very specific correlation between how much we're able
[4:34] to suppress
[4:34] SPEAKER_03: slow-wave sleep and how much amyloid beta increases.
[4:39] So there seems to be this very specific link between soluble
[4:43] amyloid beta and slow-wave sleep.
[4:47] SPEAKER_03: That's not to say other stages of sleep are important.
[4:50] SPEAKER_03: They are.
[4:51] REM sleep is very important for memory formation,
[4:54] for emotional regulation,
[4:55] and so on.
[4:56] SPEAKER_03: But when it comes to the actual...
[4:59] SPEAKER_03: amyloid beta levels,
[5:01] it seems like slow-wave sleep is the main part of sleep we
[5:05] should be concerned
[5:06] SPEAKER_03: about.
[5:07] SPEAKER_00: Yeah, so you've confirmed that, and that's a great set of experiments.
[5:10] SPEAKER_00: It's quite unique.
[5:11] SPEAKER_00: And,
[5:11] SPEAKER_00: you know,
[5:12] these people that went to two sleep studies and then had their
[5:15] lumbar puncture,
[5:16] SPEAKER_00: I mean,
[5:16] SPEAKER_00: well,
[5:16] SPEAKER_00: I give them a lot of credit.
[5:18] SPEAKER_00: Now,
[5:18] SPEAKER_00: P17,
[5:20] SPEAKER_00: which obviously has attracted lots of attention,
[5:24] SPEAKER_00: as well as these other neuroinflammation markers,
[5:27] Are there any data to show that the plasma blood level of
[5:32] pTau217 is affected
[5:34] SPEAKER_00: directly by deep sleep?
[5:39] SPEAKER_03: I don't know if anyone has done the specific slow-wave sleep disruption.
[5:47] SPEAKER_02: Yeah.
[5:48] SPEAKER_03: There are—tau phosphorylation is affected by,
[5:55] SPEAKER_03: for example,
[5:56] SPEAKER_03: giving a drug to increase sleep,
[5:58] SPEAKER_03: not necessarily slow-wage sleep,
[5:59] SPEAKER_03: but DORA,
[6:02] SPEAKER_03: which is a dual orexin receptor antagonist.
[6:05] There was a human study here done by Brendan Lucey and
[6:09] colleagues where they gave
[6:10] SPEAKER_03: people that drug,
[6:11] and that seemed to alter the phosphorylation of tau measurable
[6:15] in the plasma.
[6:17] SPEAKER_03: In the slowly sleep deprivation experiment we did,
[6:22] SPEAKER_03: we do have plasma and CSF,
[6:24] SPEAKER_03: obviously,
[6:24] SPEAKER_03: from the next day,
[6:25] SPEAKER_03: but we have not tested the different plasma aged biomarkers.
[6:30] SPEAKER_00: Well, that'll be interesting.
[6:31] SPEAKER_00: We're starting a prevention of Alzheimer's trial next month.
[6:35] with 1,200 people,
[6:36] very high risk,
[6:38] with high P-tau-217 and other factors.
[6:41] And we're going to look at the effects of sleep on their
[6:45] P-tau-217 over the course of a year.
[6:47] So we'll have some complimentary data to what you get at,
[6:50] but it'll be really interesting.
[6:51] SPEAKER_00: I want to get back to the erection drugs in a minute.
[6:54] But this story about sleep is much bigger than just
[6:58] neurodegenerative disease and
[6:59] SPEAKER_00: health because what we've seen,
[7:02] SPEAKER_00: for example,
[7:03] SPEAKER_00: the remarkable relationship of sleep regularity,
[7:07] SPEAKER_00: the index,
[7:08] SPEAKER_00: And across the board,
[7:10] SPEAKER_00: cardiovascular,
[7:11] SPEAKER_00: cancer,
[7:12] SPEAKER_00: and neurodegenerative,
[7:13] SPEAKER_00: the three big age-related diseases.
[7:15] SPEAKER_00: How does this remarkable sleep connection,
[7:20] if you want to call it association or even if you want to
[7:24] consider possible cause
[7:25] SPEAKER_00: and effect,
[7:26] SPEAKER_00: how does it cut across all these different diseases?
[7:30] SPEAKER_03: Well, I guess I would add mortality to that as well.
[7:34] So all cause mortality is linked with sleep regularity and
[7:38] duration as well.
[7:40] SPEAKER_03: You know,
[7:41] SPEAKER_03: sleep is a foundation of health,
[7:44] SPEAKER_03: and getting insufficient sleep or irregular sleep,
[7:50] SPEAKER_03: we're throwing off,
[7:51] SPEAKER_03: you know,
[7:51] SPEAKER_03: what we're supposed to be doing to prevent
[7:55] SPEAKER_03: you know,
[7:56] to clean up from the day and to rest and restore our bodies and
[8:00] our brains,
[8:01] SPEAKER_03: you know,
[8:01] SPEAKER_03: that we're supposed to be doing for 30 percent of our time.
[8:04] So,
[8:04] it's not surprising to me that there's poor health outcomes
[8:07] associated with that.
[8:09] I will say,
[8:10] especially for neurodegenerative diseases,
[8:13] is that it can be hard to tease apart
[8:17] whether it's poor sleep that contributes to those poor outcomes
[8:22] or whether those
[8:23] problems are present to a small degree and if that is
[8:27] manifesting as poor sleep.
[8:29] SPEAKER_03: So,
[8:30] SPEAKER_03: you know,
[8:30] SPEAKER_03: I think,
[8:31] SPEAKER_03: you know,
[8:32] SPEAKER_03: it's becoming very clear that there is a very long preclinical phase of
[8:38] SPEAKER_03: Alzheimer's,
[8:39] SPEAKER_03: of
[8:40] SPEAKER_03: Parkinson's of all types of neurodegenerative diseases.
[8:44] So I think it's possible that some of these studies that have
[8:47] not followed people
[8:49] SPEAKER_03: for that long,
[8:50] that when they are doing cross-sectional analyses or following
[8:54] them for just a
[8:55] SPEAKER_03: couple years,
[8:56] SPEAKER_03: that they might be
[8:59] finding that people who have sleep problems,
[9:03] perhaps they already have preclinical disease.
[9:07] So I think it's important when we look at those studies that we
[9:12] keep in mind the
[9:12] SPEAKER_03: possibility that the relationship goes the other way.
[9:16] SPEAKER_00: Yeah.
[9:17] SPEAKER_00: Well,
[9:18] it's really interesting because this whole idea of your
[9:21] circadian rhythm and that,
[9:23] SPEAKER_00: you know,
[9:24] SPEAKER_00: before I was a terrible deep sleeper when I started to get it
[9:28] SPEAKER_00: monitored and I said, I got to work on this.
[9:30] SPEAKER_00: It was like averaging less than 15 minutes a night.
[9:34] Then the one biggest change I made was this regularity and it
[9:39] really jumped up from that.
[9:41] Of course,
[9:43] it's not easy to keep on a schedule,
[9:46] but it sure has made a big difference.
[9:49] SPEAKER_00: Is that related to keeping on our unique individual circadian rhythm?
[9:55] SPEAKER_03: So our circadian rhythms are separate from our sleep systems,
[10:01] SPEAKER_03: but they have a very close relationship.
[10:04] And I think of the circadian rhythm as the thing that sets the
[10:10] window for your best sleep.
[10:12] SPEAKER_03: So we've all flown a couple of time zones.
[10:15] SPEAKER_03: We're going to bed.
[10:17] SPEAKER_03: We feel tired, yet we can't get into good sleep.
[10:20] And that is because we're not sleeping aligned with our
[10:23] circadian rhythms when we have jet lag.
[10:26] SPEAKER_03: So if we are sticking to our own circadian rhythms and,
[10:32] SPEAKER_03: you know,
[10:33] SPEAKER_03: the majority of people aren't,
[10:35] SPEAKER_03: you know,
[10:35] SPEAKER_03: that off of,
[10:36] SPEAKER_03: you know,
[10:37] SPEAKER_03: typically sleeping at nighttime.
[10:40] If we go to bed and get up at a regular time that aligns with
[10:44] our circadian rhythm,
[10:45] SPEAKER_03: that's probably like the number one thing we can do to give ourselves the
[10:50] SPEAKER_03: opportunity to get good sleep.
[10:54] I will note that getting slow-wave sleep or deep sleep as
[10:59] measured by different
[11:00] SPEAKER_03: wearables,
[11:01] SPEAKER_03: that may not be the best metric to shoot for,
[11:04] SPEAKER_03: and it can get frustrating because those algorithms can change.
[11:07] Device-to-device differences in algorithms might end up showing
[11:13] different results.
[11:15] You know,
[11:15] people are actually very sensitive to the quality of sleep that
[11:20] they got.
[11:22] SPEAKER_03: So,
[11:22] SPEAKER_03: you know,
[11:23] SPEAKER_03: I encourage my patients or people who come up and ask me when they say,
[11:28] SPEAKER_03: how do I know if I'm getting good sleep?
[11:29] SPEAKER_03: And I say, well, if you're, you know,
[11:32] waking up in the morning and preferably without an alarm clock
[11:35] and you feel like
[11:36] SPEAKER_03: your sleep was refreshing,
[11:37] SPEAKER_03: you probably had good sleep.
[11:40] I think that sometimes we lose the ability to sense that and to
[11:45] sense the quality
[11:46] SPEAKER_03: of our sleep if we rely too much on wearables or other ways,
[11:51] SPEAKER_03: measurements.
[11:52] Well,
[11:53] while we're on the wearables,
[11:54] obviously there's several types here.
[11:57] SPEAKER_00: There's the rings, particularly Aura that's got a lot of popularity.
[12:00] SPEAKER_00: There's the various smartwatches and mattress sensors.
[12:05] SPEAKER_00: I mean, there's a lot of different ones.
[12:06] And have they been validated against the gold standard sleep
[12:11] lab for the different
[12:13] SPEAKER_00: metrics of phases of sleep and whatnot?
[12:16] SPEAKER_00: Yeah.
[12:17] So some have,
[12:21] but I don't know if they revalidate every time they upgrade
[12:26] their algorithms.
[12:27] SPEAKER_00: I see.
[12:28] SPEAKER_03: Yeah.
[12:29] SPEAKER_03: And in general,
[12:30] SPEAKER_03: for my research,
[12:31] SPEAKER_03: where we use actigraphs a lot,
[12:33] SPEAKER_03: which are motion sensors,
[12:35] we use research-grade ones that do have concurrent
[12:41] polysomnography or sleep study
[12:43] SPEAKER_03: data.
[12:44] SPEAKER_03: We generally don't use ones that are available over-the-counter,
[12:49] SPEAKER_03: shall we say,
[12:50] just because we simply do not know whether that algorithm has
[12:54] changed since
[12:56] you know,
[12:56] they gathered the original validation data or if it will change
[13:00] during the study.
[13:02] SPEAKER_03: So,
[13:03] SPEAKER_03: you know,
[13:04] SPEAKER_03: I think it's great if people use those devices to help be accountable to
[13:10] SPEAKER_03: themselves,
[13:11] SPEAKER_03: you know,
[13:11] SPEAKER_03: to get to bed on time or to,
[13:13] SPEAKER_03: you know,
[13:14] SPEAKER_03: to get up at a regular time.
[13:15] SPEAKER_03: That's great.
[13:17] But I think,
[13:19] you know,
[13:19] people should be aware of the limitations of using these
[13:22] devices.
[13:23] SPEAKER_00: Yeah.
[13:24] SPEAKER_00: I mean,
[13:24] SPEAKER_00: I've been comparing for now a couple of years,
[13:27] SPEAKER_00: a ring versus a watch,
[13:28] SPEAKER_00: an Apple watch and a
[13:30] SPEAKER_00: mattress sensor,
[13:31] SPEAKER_00: and the ring is the only one that seems to correlate with how I feel,
[13:36] SPEAKER_00: which is really interesting.
[13:37] And only recently did Apple introduce scores,
[13:40] and they were pretty primitive.
[13:42] SPEAKER_00: So the scores,
[13:42] SPEAKER_00: you know,
[13:43] SPEAKER_00: perhaps are not the best to rely on,
[13:45] SPEAKER_00: as you point out,
[13:46] SPEAKER_00: the changes in algorithms and different devices.
[13:48] SPEAKER_00: Now,
[13:49] SPEAKER_00: I want to get in,
[13:50] SPEAKER_00: come back to that in a bit,
[13:52] SPEAKER_00: but one of the people asked about sleep scores,
[13:54] SPEAKER_00: and I think it's an important question.
[13:56] But everyone wants to get better sleep who feels that they're
[13:59] sleep deprived.
[14:01] SPEAKER_00: And there are supplements we want to talk about.
[14:04] There's drugs that have been used characteristically that
[14:07] potentially make things worse.
[14:10] And then there's the erection drugs that you touched on,
[14:13] and we want to get back to that.
[14:14] Let's just talk about a few of these supplements like
[14:17] melatonin,
[14:18] magnesium,
[14:20] ashwagandha.
[14:21] SPEAKER_00: I mean, do any of them have any data to support their use?
[14:26] Um,
[14:27] so I guess I'll start with melatonin because that one I think
[14:30] is used the most.
[14:32] SPEAKER_03: Um, they're, um,
[14:36] SPEAKER_03: There is decent data to show,
[14:38] SPEAKER_03: you know,
[14:38] SPEAKER_03: in large meta-analyses that they do help,
[14:42] SPEAKER_03: and I believe it's in a subset of people,
[14:44] SPEAKER_03: and those are people who have delayed circadian rhythms,
[14:48] SPEAKER_03: meaning they're night owls,
[14:50] who take it a couple hours before their desired bedtime to
[14:54] shift their internal
[14:55] SPEAKER_03: clocks.
[14:56] SPEAKER_03: It does help them.
[14:59] SPEAKER_03: There was a meta-analysis for looking at melatonin in insomnia,
[15:06] SPEAKER_03: you know,
[15:06] SPEAKER_03: not related to being a night owl,
[15:09] SPEAKER_03: and it probably doesn't help them very much.
[15:14] SPEAKER_03: And,
[15:14] SPEAKER_03: you know,
[15:14] I think a problem with a lot of insomnia studies or drugs or
[15:19] things tested for
[15:20] SPEAKER_03: insomnia is that—
[15:23] SPEAKER_03: Even compared to other conditions,
[15:26] SPEAKER_03: insomnia is exquisitely sensitive to the placebo effect,
[15:32] SPEAKER_03: meaning even when measured by sleep studies,
[15:35] SPEAKER_03: the gold standard,
[15:38] SPEAKER_03: placebo has an amazing effect.
[15:40] It's probably responsible for about two-thirds of the effects
[15:43] seen in clinical
[15:44] SPEAKER_03: trials for sleep drugs.
[15:47] SPEAKER_03: So it's hard to beat placebo in insomnia.
[15:52] SPEAKER_03: So, you know, the bar is extremely high.
[15:55] SPEAKER_03: But overall,
[15:56] SPEAKER_03: when it comes to melatonin,
[15:58] SPEAKER_03: it does help for people who have delayed sleep phase or,
[16:01] SPEAKER_03: you know,
[16:02] SPEAKER_03: if they're night owls,
[16:03] SPEAKER_03: particularly if taken a couple hours before bedtime.
[16:07] SPEAKER_03: But for people who want to take it for trouble sleeping,
[16:11] SPEAKER_03: I think it's reasonable to try because it has a generally,
[16:15] SPEAKER_03: you know,
[16:15] SPEAKER_03: benign side effect profile.
[16:18] SPEAKER_03: But if it doesn't help,
[16:20] SPEAKER_03: then people should just,
[16:22] SPEAKER_03: you know,
[16:22] they shouldn't keep taking it with some belief that it'll like
[16:25] build up over time
[16:26] SPEAKER_03: and help them.
[16:27] SPEAKER_03: It doesn't.
[16:29] SPEAKER_03: You know, I think if it's going to help, it'll help.
[16:32] SPEAKER_03: Otherwise, people can throw in the towel.
[16:35] SPEAKER_00: What about magnesium?
[16:38] SPEAKER_03: So magnesium helps sometimes.
[16:41] I think some of this is related to some insomnia actually being
[16:49] a symptom of restless legs.
[16:52] And so some people report that their restless legs is better
[16:57] with magnesium.
[16:58] SPEAKER_03: And so I think it may help in those cases.
[17:02] SPEAKER_03: I have a lot of patients who take magnesium.
[17:06] SPEAKER_03: They're not quite sure if it helps, but they still take it.
[17:10] I think the main potential side effect is it can cause diarrhea
[17:14] or stomach upset.
[17:16] SPEAKER_03: So if it doesn't hurt them, I say, go ahead.
[17:22] SPEAKER_03: but I have not been, you know, similar to all supplements.
[17:26] You know,
[17:26] if they worked really great,
[17:27] I think they would make them prescription.
[17:30] SPEAKER_00: Yeah, yeah, really.
[17:31] SPEAKER_00: Well, we'll talk about prescription in a moment.
[17:34] SPEAKER_00: There's,
[17:35] what about the ashwagandha or anything else that is worth
[17:38] mentioning about on this
[17:39] SPEAKER_00: long list of putative supplements that help?
[17:43] SPEAKER_03: So I don't think any of those, you know, have, you know, randomized
[17:50] double-blind controlled clinical trials where I've been really
[17:55] impressed that it beats placebo.
[17:58] On the other hand,
[17:59] I do know that some people say it has really helped them.
[18:04] SPEAKER_03: So I say, if it helps you and it doesn't harm you, go ahead.
[18:08] SPEAKER_00: Yeah.
[18:08] SPEAKER_00: Yeah.
[18:08] SPEAKER_00: Well,
[18:08] it's really interesting that you mentioned about the placebo
[18:11] effect because even in
[18:12] SPEAKER_00: studies,
[18:13] SPEAKER_00: when you tell the person it's a placebo,
[18:15] SPEAKER_00: it still works.
[18:17] SPEAKER_03: Yeah, and it is especially so for insomnia.
[18:21] SPEAKER_03: It's great and it's also not great for clinical trials.
[18:25] SPEAKER_03: But,
[18:25] SPEAKER_03: you know,
[18:26] seeing a half hour or even 40 minutes of increased total sleep
[18:30] time on objective
[18:31] SPEAKER_03: polysomnography is very common in insomnia drug trials.
[18:36] SPEAKER_00: Now, recently there was a paper about Ambien.
[18:40] SPEAKER_00: Of course,
[18:41] SPEAKER_00: it was in the experimental model,
[18:43] but it showed that instead of the washout of toxic metabolites
[18:47] from the brain,
[18:48] SPEAKER_00: Ambien led to a backflow.
[18:51] SPEAKER_00: That is, it made things worse.
[18:54] SPEAKER_00: Is that accepted now that don't take Ambien,
[18:58] SPEAKER_00: which I never thought was a very good drug anyway,
[19:01] SPEAKER_00: but that it actually can make your sleep worse,
[19:03] SPEAKER_00: quality worse?
[19:05] SPEAKER_03: So I think that in general,
[19:11] we should be cautious in having people take drugs to increase
[19:17] their sleep because I
[19:20] SPEAKER_03: think the best sleep is the kind that people can get on their own.
[19:28] SPEAKER_02: Right.
[19:28] SPEAKER_03: Right.
[19:28] SPEAKER_03: So most people's brains have the ability to fall asleep every night.
[19:35] SPEAKER_03: Right.
[19:36] So if people are having problems sleeping where they need to
[19:43] they're asking for
[19:44] SPEAKER_03: medication to help with their sleep.
[19:47] SPEAKER_03: I think sometimes we kind of,
[19:49] SPEAKER_03: or in medical practice,
[19:50] we can jump to giving the drug without maybe looking for why
[19:55] people are having
[19:55] SPEAKER_03: problems sleeping.
[19:56] SPEAKER_03: Sleep disorders are extremely common.
[19:59] SPEAKER_03: For example, sleep apnea, probably, you know, 20-30% of them.
[20:04] SPEAKER_03: American population, middle-aged or older, has sleep apnea.
[20:09] SPEAKER_03: But,
[20:09] SPEAKER_03: you know,
[20:11] SPEAKER_03: most doctors who prescribe,
[20:14] SPEAKER_03: say,
[20:14] Ambien or any of the sleep drugs probably are not screening for
[20:18] and testing for
[20:19] SPEAKER_03: sleep apnea or other sleep disorders before they prescribe them.
[20:23] SPEAKER_03: So I think we do need to be cautious about,
[20:25] SPEAKER_03: well,
[20:25] SPEAKER_03: who are these people who are taking medications,
[20:29] SPEAKER_03: right?
[20:29] SPEAKER_03: So do they have a sleep disorder?
[20:31] Do they have some other reason to be having the sleep problems
[20:36] in the first place?
[20:37] SPEAKER_03: So it may not necessarily be the drug.
[20:40] It could be whatever is going on that is causing them to want
[20:44] or need the sleep
[20:45] SPEAKER_03: drug in the first place.
[20:47] SPEAKER_03: I don't think necessarily the NBBRAs,
[20:51] SPEAKER_03: you know,
[20:51] SPEAKER_03: the class of drugs that Zolipidem is in,
[20:55] SPEAKER_03: I don't think that they're necessarily bad.
[20:58] You know,
[20:58] I prescribe it in a small number of patients if it's
[21:03] appropriate.
[21:04] SPEAKER_03: But really,
[21:05] SPEAKER_03: for any sleep drug,
[21:06] SPEAKER_03: we want people to be taking it on a temporary basis as short as possible.
[21:13] SPEAKER_03: I think that...
[21:17] SPEAKER_03: permanent,
[21:18] SPEAKER_03: you know,
[21:19] SPEAKER_03: never-ending daily use of a drug to improve sleep,
[21:25] SPEAKER_03: I don't think that's healthy.
[21:26] SPEAKER_00: Okay,
[21:27] SPEAKER_00: so next,
[21:28] SPEAKER_00: the medical community isn't yet really aware,
[21:31] SPEAKER_00: even though it's been available for some time now,
[21:34] SPEAKER_00: on the erection group of drugs,
[21:36] which are supposedly ideally suited if you're going to
[21:42] prescribe a medicine to help
[21:44] SPEAKER_00: sleep.
[21:45] SPEAKER_00: Can you talk about those?
[21:47] SPEAKER_03: Sure.
[21:48] SPEAKER_03: So DORAS,
[21:49] SPEAKER_03: which stands for Dual Orexin Receptor Antagonist,
[21:52] SPEAKER_03: they came on the market a few years ago.
[21:56] SPEAKER_03: There's now three of them, Suvorexin, Lemborexin, and Doreorexin.
[22:02] SPEAKER_03: And these all work by blocking the action of orexin.
[22:06] SPEAKER_03: Orexin is also called hypocretin.
[22:09] SPEAKER_03: When hypocretin is low, that's what causes narcolepsy.
[22:14] SPEAKER_03: So orexin is a wake-promoting pathway.
[22:19] So it's a new class of sleep drug in that all the prior ones,
[22:23] basically,
[22:24] they increase sleep.
[22:26] pathways,
[22:27] whereas this was the first one to tamp down a wake-promoting
[22:32] pathway.
[22:33] SPEAKER_03: So it's a new class of drugs in the past few years.
[22:37] It does have objectively measured improvements in total sleep
[22:44] time and sleep
[22:45] SPEAKER_03: efficiency compared to placebo.
[22:49] SPEAKER_03: And they've been available.
[22:52] SPEAKER_03: I think the uptake has been kind of sold because they are expensive.
[22:56] And,
[22:56] you know,
[22:57] in the U.S.,
[22:58] we are very limited by what insurance covers.
[23:01] SPEAKER_03: And it is unfortunate that,
[23:04] SPEAKER_03: you know,
[23:04] SPEAKER_03: while drugs are on patent,
[23:07] SPEAKER_03: the drugs can be out of reach even for people with good insurance.
[23:11] SPEAKER_03: So they've been on the market.
[23:14] SPEAKER_03: And,
[23:14] SPEAKER_03: you know,
[23:15] SPEAKER_03: I think it really kind of depends on the person,
[23:18] SPEAKER_03: whether they respond better or compared to,
[23:22] SPEAKER_03: you know,
[23:22] SPEAKER_03: any of the other sleep drugs or other insomnia treatment methods.
[23:28] SPEAKER_03: But I have noticed that, you know...
[23:31] SPEAKER_03: it tends to help people kind of say,
[23:33] SPEAKER_03: I can't turn my mind off,
[23:34] SPEAKER_03: you know,
[23:35] SPEAKER_03: if that's the issue,
[23:36] SPEAKER_03: you know.
[23:37] SPEAKER_03: But, you know, it's not 100%.
[23:38] SPEAKER_03: And like all drugs, you know, they have different side effects.
[23:45] SPEAKER_03: But they did have good clinical trials.
[23:50] And I'm curious to see what the long-term data look like as
[23:55] there's more widespread usage.
[23:58] SPEAKER_03: You know, so far, I think the safety data look
[24:00] SPEAKER_03: pretty good.
[24:01] But,
[24:02] you know,
[24:03] Zolpidem and the other NBBRAs also looked pretty good when they
[24:06] came out.
[24:07] SPEAKER_03: It took some time for that data to accumulate.
[24:09] SPEAKER_03: So I am curious to see,
[24:11] SPEAKER_03: you know,
[24:12] what happens in the next 5-10 years as we get more experience
[24:15] with these drugs.
[24:16] SPEAKER_00: Yeah,
[24:17] SPEAKER_00: no,
[24:17] SPEAKER_00: this is,
[24:17] SPEAKER_00: I think,
[24:18] one of the reasons that I think a lot of people are not aware
[24:21] of this class of
[24:22] SPEAKER_00: drugs.
[24:23] SPEAKER_00: You point out they're expensive, not covered by insurance.
[24:26] SPEAKER_00: The one thing you mentioned earlier,
[24:29] SPEAKER_00: about lowering P-Tau 217.
[24:31] SPEAKER_00: That's really provocative.
[24:33] And I assume they do promote a higher level of slow-wave deep
[24:37] sleep than placebo.
[24:41] SPEAKER_00: They also are touted not to be habit-forming or addictive.
[24:45] SPEAKER_00: I don't know if that's true.
[24:46] SPEAKER_03: I don't know if that's true either.
[24:49] SPEAKER_00: Yeah.
[24:50] Anyway,
[24:50] people should at least know about them because it could be
[24:53] helpful.
[24:53] SPEAKER_00: Now, there's two parts of the sleep
[24:56] SPEAKER_00: difficulty,
[24:57] SPEAKER_00: not sleep apnea,
[24:58] SPEAKER_00: which we'll talk about in a moment,
[24:59] SPEAKER_00: but getting to sleep and staying asleep.
[25:04] SPEAKER_00: And they seem to be very different.
[25:05] SPEAKER_00: Of course, you just mentioned
[25:08] SPEAKER_00: uh,
[25:08] SPEAKER_00: um,
[25:08] SPEAKER_00: you were all about the,
[25:10] SPEAKER_00: uh,
[25:10] SPEAKER_00: mind wandering racing issue,
[25:13] SPEAKER_00: which could be related to both.
[25:15] SPEAKER_00: You wake up for some interruption and then you just are minds moving,
[25:19] SPEAKER_00: uh,
[25:20] SPEAKER_00: at a high velocity and you can't get back to sleep.
[25:23] Are there differences the way you look at as a sleep medicine
[25:26] physician about how
[25:27] SPEAKER_00: do you deal with those two categories?
[25:30] SPEAKER_03: Uh, yeah.
[25:31] SPEAKER_03: So, um,
[25:33] A lot of times people who have problems falling asleep,
[25:37] it may be their sortadian rhythm.
[25:39] SPEAKER_03: So I'm a night owl,
[25:41] so I have great sympathy and empathy for other night owls out
[25:44] there where,
[25:45] SPEAKER_03: you know,
[25:45] SPEAKER_03: you have trouble falling asleep,
[25:46] SPEAKER_03: but once you get to sleep,
[25:47] SPEAKER_03: you can stay asleep okay.
[25:52] SPEAKER_03: Especially among younger individuals,
[25:55] SPEAKER_03: that's probably the most common reason why they can't fall asleep.
[25:58] SPEAKER_03: Yeah.
[26:00] When people are coming in with awakenings in the middle of the
[26:03] night,
[26:03] that 2,
[26:06] 3,
[26:06] 4 a.m.
[26:06] SPEAKER_03: is a very difficult time.
[26:09] SPEAKER_03: That's probably the most anxious time for everyone when they're awake.
[26:15] SPEAKER_03: And it can also be hard for people to get back to sleep,
[26:18] especially if they've used up that sleep drive that helps put
[26:22] them to sleep at the
[26:22] SPEAKER_03: beginning of the night.
[26:25] SPEAKER_03: And it can be trickier to treat, especially with medication.
[26:29] SPEAKER_02: Mm-hmm.
[26:31] SPEAKER_03: because,
[26:32] SPEAKER_03: you know,
[26:32] you obviously don't want any hangover sedation because people
[26:35] are going to have to
[26:36] SPEAKER_03: get up in a couple hours,
[26:37] SPEAKER_03: drive to work,
[26:38] SPEAKER_03: you know,
[26:38] SPEAKER_03: be at school and so on.
[26:41] So we have kind of different medication strategies if we decide
[26:46] to go with medication.
[26:48] SPEAKER_03: But regardless of the time that people are having problems sleeping,
[26:54] SPEAKER_03: I try to identify,
[26:56] SPEAKER_03: well,
[26:56] what is actually causing you to have problems sleeping or
[27:01] what's waking you up to
[27:02] SPEAKER_03: try to address that?
[27:04] SPEAKER_03: And then also our first line treatment for insomnia,
[27:09] SPEAKER_03: it should be CBTI,
[27:11] SPEAKER_03: which is Cognitive Behavioral Therapy for Insomnia.
[27:14] SPEAKER_03: So it kind of doesn't matter when the insomnia is.
[27:18] SPEAKER_03: We do try to identify,
[27:20] SPEAKER_03: you know,
[27:22] SPEAKER_03: the sleep hygiene things we can improve,
[27:25] SPEAKER_03: any bad habits people are engaging in,
[27:27] SPEAKER_03: like having coffee or caffeine late in the day.
[27:30] Or,
[27:31] you know,
[27:32] we try to identify what's actually causing insomnia because it
[27:36] is different.
[27:37] SPEAKER_03: There's no one size fits all.
[27:38] SPEAKER_00: Right, right.
[27:39] SPEAKER_00: Now,
[27:39] that's an important distinction and how you got to dig deep to
[27:44] potentially figure
[27:45] SPEAKER_00: out what is linked.
[27:47] SPEAKER_00: Recently,
[27:48] SPEAKER_00: there's the idea that you could stimulate the vagal nerve,
[27:52] SPEAKER_00: these external devices,
[27:54] SPEAKER_00: and that would just help you sleep.
[27:57] SPEAKER_00: Is there anything to that?
[27:59] SPEAKER_03: Well, I mean, I think there's a lot of devices and
[28:04] SPEAKER_03: strategies,
[28:05] SPEAKER_03: shall we say,
[28:06] SPEAKER_03: to try to help people sleep and,
[28:10] SPEAKER_03: you know,
[28:10] SPEAKER_03: to get a better sleep score or to increase their slow-wave sleep.
[28:14] And for all of these,
[28:16] I think that it kind of feels sometimes like people are trying
[28:23] to,
[28:23] like,
[28:24] build a big skyscraper but they don't have a foundation you
[28:29] know like you know the
[28:31] the basics actually do a lot you know keeping a regular wake
[28:35] time and sleep time um
[28:38] you know avoiding bright lights in the evening which will
[28:41] suppress um your own
[28:43] SPEAKER_03: endogenous melatonin um
[28:47] You know,
[28:48] exercise,
[28:49] which has enormous benefits on sleep and specifically slow-wave
[28:53] sleep.
[28:55] SPEAKER_03: You know,
[28:55] there's just so many things that we can do to actually improve
[28:59] our sleep that
[29:03] SPEAKER_03: sometimes I wonder whether some of these fancy things that we talk about,
[29:08] I don't know if anyone would actually ever need them if they
[29:12] had the foundations in
[29:13] SPEAKER_03: place.
[29:15] And you're bringing up this critical topic of the
[29:17] interdependence of sleep with
[29:20] SPEAKER_00: physical activity and with diet,
[29:23] SPEAKER_00: and that includes beverages,
[29:24] SPEAKER_00: but also when you eat,
[29:28] SPEAKER_00: what you eat.
[29:29] SPEAKER_00: I mean, it's not just sleep, of course.
[29:32] SPEAKER_00: It's a multivariate equation that's coming together.
[29:37] SPEAKER_00: Now, recently there was a really interesting paper
[29:41] SPEAKER_00: that when people have a tension lapse during the day,
[29:45] actually that they're getting some washout of these waste
[29:49] products from their
[29:49] SPEAKER_00: brain.
[29:50] SPEAKER_02: So I thought it was pretty cool.
[29:59] SPEAKER_03: It was a very sophisticated protocol in that they used fMRI.
[30:06] SPEAKER_03: They did psychomotor vigilance testing to look for attentional lapses.
[30:10] SPEAKER_03: They had EEG.
[30:12] SPEAKER_03: It was very cool.
[30:15] I think we need to be a little bit cautious in thinking of
[30:22] sleep as just like a
[30:23] SPEAKER_03: time when we washed away toxins.
[30:27] SPEAKER_03: Because the glymphatic system,
[30:31] SPEAKER_03: right,
[30:31] which is a system that was described involving glia and the
[30:35] perivascular spaces and
[30:37] SPEAKER_03: the clearance of solutes in the interstitial fluid,
[30:41] SPEAKER_03: that's very different from,
[30:44] SPEAKER_03: for example,
[30:44] SPEAKER_03: what was studied in that study,
[30:47] SPEAKER_03: which is the movement of cerebrospinal fluid across the fourth ventricle.
[30:53] So,
[30:53] you know,
[30:54] just the scales of the size of spaces are very different in
[31:00] those two models.
[31:02] SPEAKER_03: And it is very appealing for me to think of,
[31:05] SPEAKER_03: oh,
[31:05] SPEAKER_03: when I'm sleeping,
[31:06] SPEAKER_03: it's like a big old dishwasher and I'm getting everything cleaned out.
[31:12] SPEAKER_03: And,
[31:13] SPEAKER_03: you know,
[31:13] SPEAKER_03: if thinking of it that way helps people,
[31:16] SPEAKER_03: you know,
[31:16] SPEAKER_03: maintain regular sleep schedules and to prioritize their sleep health,
[31:21] SPEAKER_03: I say great.
[31:23] SPEAKER_03: But I think we should also remember that there's...
[31:29] you know,
[31:31] the cells in the brain are putting stuff into the interstitial
[31:35] space,
[31:36] right?
[31:36] SPEAKER_03: So there's the creation of solutes and putting,
[31:40] SPEAKER_03: you know,
[31:40] the amyloid beta and all the other waste products need to get
[31:43] into that space
[31:44] SPEAKER_03: somehow,
[31:45] SPEAKER_03: right?
[31:45] SPEAKER_03: And that happens when people are awake.
[31:48] So I think that there is both a change in production or release
[31:53] of those things,
[31:54] SPEAKER_03: as well as a change in clearance.
[31:58] SPEAKER_03: during sleep.
[31:59] So I think we need to be careful about not being too simplistic
[32:03] about how we think about sleep.
[32:06] SPEAKER_00: Yeah, no, I think it's, I found that paper fascinating.
[32:09] SPEAKER_00: We'll link to it when we put the post up,
[32:11] SPEAKER_00: but the fact that,
[32:12] SPEAKER_00: and it's a different wave of fluid,
[32:14] SPEAKER_00: as you point out,
[32:15] SPEAKER_00: but it's the cerebral spinal fluid,
[32:17] but that time when you feel that you lose your attention span
[32:23] and that your brain
[32:24] SPEAKER_00: is trying to compensate for the poor
[32:27] SPEAKER_00: or inadequate sleep the night prior.
[32:30] Now,
[32:31] another recent piece appeared in the New Yorker about the short
[32:35] sleepers.
[32:36] SPEAKER_00: And we've talked about this for a number of years.
[32:38] I think it was UCSF first case with these people that have
[32:42] these rare variants that
[32:44] they can sleep three or four hours and they have just perfect
[32:49] performance as if
[32:50] SPEAKER_00: they slept eight hours with lots of deep sleep and REM sleep and whatnot.
[32:55] Is there anything we can learn from these people that everybody
[32:59] could only have to
[33:00] have four hours of sleep and be just as sharp as the people
[33:04] with the rare endowed
[33:06] SPEAKER_00: gene variants?
[33:08] SPEAKER_03: Well, one, they're extremely rare.
[33:10] SPEAKER_03: I think a lot of people wish that they came from one of these families.
[33:17] SPEAKER_03: I do as well.
[33:19] SPEAKER_03: I don't know whether it would actually be that useful to try to
[33:26] SPEAKER_03: copy whatever molecular or genetic mechanism is going on because,
[33:33] SPEAKER_03: one,
[33:33] SPEAKER_03: these are extremely small numbers of people,
[33:37] SPEAKER_03: right?
[33:38] SPEAKER_03: They're all within one or two kindreds.
[33:41] SPEAKER_03: So I don't know if it's worth trying to copy that or...
[33:47] whether we'd be better off just doing the things that we know
[33:50] help a lot more.
[33:52] SPEAKER_00: I guess what I'm saying is,
[33:57] SPEAKER_00: you know,
[33:58] SPEAKER_00: if that pathway,
[33:59] SPEAKER_00: the biologic pathway is known and you could,
[34:02] SPEAKER_00: replicate that with a pill or even a genome editing approach someday.
[34:08] SPEAKER_00: We spend a third of our time approximately in sleep.
[34:12] SPEAKER_00: If you could only spend a much lesser proportion, a sixth of our time,
[34:20] SPEAKER_00: You know, look at the productivity.
[34:23] SPEAKER_00: You don't even need AI.
[34:24] SPEAKER_00: You just get productive.
[34:27] Speaking as a sleep physician scientist,
[34:32] even if that pill were available,
[34:34] I would not use it.
[34:36] SPEAKER_03: I think sleep is really valuable,
[34:38] and there's a lot of things that occur during sleep that are
[34:43] mysterious and
[34:44] SPEAKER_03: probably can't be boiled down into a pill that,
[34:47] SPEAKER_03: at least in my lifetime,
[34:48] SPEAKER_03: I don't think I'd want to take such a pill.
[34:51] SPEAKER_00: Well, I like your answer.
[34:52] SPEAKER_00: I tend to agree with you,
[34:54] but I think it's provocative at any rate because now it's
[34:58] almost like use your
[34:59] SPEAKER_00: imagination of what's going to happen next.
[35:03] SPEAKER_00: Now,
[35:03] SPEAKER_00: going back to a more mundane but a very important topic,
[35:06] SPEAKER_00: as you said,
[35:06] SPEAKER_00: at least 20% of the population has sleep apnea.
[35:11] SPEAKER_00: And all these years we were relying on CPAP machines or BiPAP machines.
[35:19] SPEAKER_00: Have we ever gotten out of that?
[35:21] Have we ever progressed from these machines that people have to
[35:24] carry around when
[35:25] SPEAKER_00: they travel and
[35:27] SPEAKER_00: make a lot of noise.
[35:28] SPEAKER_00: Are there better solutions for sleep apnea?
[35:31] SPEAKER_00: Besides,
[35:31] SPEAKER_00: of course,
[35:32] lose loss of weight with GLP-1 drugs that we've seen some real
[35:36] impressive results.
[35:40] SPEAKER_00: One, is there a better approach?
[35:41] Two,
[35:42] does fixing the apnea spells really change the natural history
[35:46] of a person's health?
[35:49] SPEAKER_03: So there are other treatments.
[35:53] I think it depends on the individual whether they would
[35:56] consider them better.
[35:57] SPEAKER_03: At least among my patients, I feel like they really split on path.
[36:02] SPEAKER_03: They either love it or they hate it, right?
[36:04] SPEAKER_03: So for the people who love it, I say great.
[36:07] SPEAKER_03: I think,
[36:08] SPEAKER_03: you know,
[36:08] SPEAKER_03: in the past 15,
[36:11] SPEAKER_03: 20 years,
[36:11] SPEAKER_03: there's been continued improvements in mandibular advancement devices.
[36:16] So these are like mouth guards that people wear that push the
[36:18] lower jaw forward.
[36:21] And more recently,
[36:22] there's been the emergence of hypoglossal nerve stimulators.
[36:27] SPEAKER_03: These are like pacemakers.
[36:28] SPEAKER_03: They're implanted.
[36:29] SPEAKER_03: They stimulate the hypoglossal or 12th cranial nerve.
[36:33] SPEAKER_03: So it increases the muscle activity at the base of the tongue.
[36:37] And so that helps hold the upper airway open and prevents it
[36:41] from collapse.
[36:42] SPEAKER_03: So that's pretty cool.
[36:44] You know,
[36:44] they have an implanted stimulator that prevents them from
[36:47] having apneas.
[36:49] SPEAKER_03: So, you know, that's been on the market for a few years now.
[36:54] SPEAKER_03: So,
[36:54] SPEAKER_03: you know,
[36:55] SPEAKER_03: now we have a substantial number of people,
[36:57] SPEAKER_03: at least at our sleep center,
[36:58] SPEAKER_03: who are treated with that.
[37:00] SPEAKER_03: But, you know, it's not perfect.
[37:02] SPEAKER_03: It's not like you walk in as a day surgery and you're done.
[37:06] SPEAKER_03: You know,
[37:07] because the devices have to be implanted and then the settings
[37:12] need to be titrated
[37:13] SPEAKER_03: during sleep,
[37:15] SPEAKER_03: You know,
[37:15] SPEAKER_03: it can take,
[37:16] SPEAKER_03: I would say,
[37:16] a good 9 to 12 months to get someone actually properly treated
[37:23] with that method.
[37:23] SPEAKER_03: So there's no magic pill yet for sleep apnea.
[37:29] SPEAKER_03: I'm glad you mentioned GLP-1s.
[37:32] SPEAKER_03: I think for the first time in my career,
[37:35] I've actually had a significant number of patients cure
[37:40] themselves of sleep apnea
[37:41] SPEAKER_03: by losing weight.
[37:43] Previously,
[37:44] it was extremely rare where people were getting gastric bypass.
[37:50] SPEAKER_03: A very small number would actually lose through diet and exercise,
[37:54] SPEAKER_03: but I mean,
[37:55] SPEAKER_03: I can count them on one hand.
[37:58] SPEAKER_03: So in the past year or two,
[38:00] SPEAKER_03: I have been able to discharge patients from my clinic because they lost a
[38:06] SPEAKER_03: substantial amount of weight,
[38:08] which also involves losing fat in the tissues in the neck and
[38:12] upper airway.
[38:13] So I think the GLP-1s have really changed options for people
[38:20] with sleep apnea in
[38:22] SPEAKER_03: that substantial weight loss is a potential real solution,
[38:28] SPEAKER_03: where it was kind of a hypothetical one before.
[38:31] But now we're actually seeing real numbers of people lose
[38:35] substantial amounts of weight.
[38:37] And what's interesting is some of the effects of these drugs
[38:40] are independent of
[38:40] SPEAKER_00: weight loss,
[38:42] SPEAKER_00: cardiovascular and
[38:44] SPEAKER_00: liver,
[38:44] SPEAKER_00: kidney,
[38:45] SPEAKER_00: you know,
[38:46] the benefits are occurring even before there's any weight loss
[38:50] and reduced
[38:50] SPEAKER_00: inflammation being particularly in the brain and the body.
[38:54] SPEAKER_00: But here, it looks like it's more a weight loss function.
[38:58] SPEAKER_00: Now,
[38:59] SPEAKER_00: recently,
[39:00] James O and colleagues at Stanford published a very remarkable
[39:05] Sleep Foundation
[39:06] SPEAKER_00: model where they had 65,000 people out of their sleep labs.
[39:10] SPEAKER_00: So you probably have even more in WashU, I imagine, in your lab.
[39:13] SPEAKER_00: But
[39:14] they were able to predict 130 diseases from one night of sleep
[39:19] where they took all
[39:19] SPEAKER_00: the different sensor data and everything and were able to say,
[39:23] SPEAKER_00: this person's going to have a heart attack,
[39:25] SPEAKER_00: this one's going to have Parkinson's,
[39:26] SPEAKER_00: this one's going to have heart failure.
[39:29] Do you think there's a lot encoded in that physiology of sleep
[39:33] that someday we all
[39:34] should have a formal sleep study and help us prevent the
[39:38] diseases that we're at
[39:39] SPEAKER_00: risk for?
[39:41] So there is so much information in the data that we collect
[39:46] during an overnight
[39:48] SPEAKER_03: sleep study in the lab.
[39:51] SPEAKER_03: A big change in sleep medicine in the U.S.
[39:54] has been that a lot of sleep studies have shifted to these home
[39:58] apnea tests where
[40:00] we're not actually seeing the data that we used to on people
[40:05] being studied for
[40:06] SPEAKER_03: sleep disorders.
[40:07] SPEAKER_03: So I think that has been a major loss.
[40:09] We can get a lot out of,
[40:11] you know,
[40:11] say the EEG signals,
[40:13] the brain wave signals.
[40:16] SPEAKER_03: We also get a lot of cardiovascular information,
[40:20] SPEAKER_03: you know,
[40:21] SPEAKER_03: like heart rate variability,
[40:23] SPEAKER_03: resting heart rate,
[40:23] SPEAKER_03: if they have arrhythmias and so on.
[40:26] So there's just a ton of information that we're collecting that
[40:30] right now we use to
[40:32] SPEAKER_03: stage sleep or to diagnose sleep disorders.
[40:35] But I think it would be fantastic if we could upcycle those
[40:39] data and get some real predictive
[40:43] information about patients so that we could help direct them to
[40:48] more confirmatory
[40:49] SPEAKER_03: testing or treatment if the diagnostic accuracy is good.
[40:57] SPEAKER_03: One of the main projects I've been working on for the past few years,
[41:01] SPEAKER_03: which I hope to finish up soon,
[41:03] SPEAKER_03: is developing markers that we can pull out from the brainwaves,
[41:08] SPEAKER_03: the EEG,
[41:09] so that we can hopefully identify who has preclinical
[41:14] Alzheimer's disease.
[41:16] SPEAKER_03: You know,
[41:17] SPEAKER_03: this is all,
[41:18] SPEAKER_03: you know,
[41:19] non-invasive data that we collect during a sleep study that's
[41:22] otherwise kind of
[41:23] SPEAKER_03: discarded and never used again.
[41:25] SPEAKER_03: So if we can actually narrow down the
[41:29] the pool of people that we'd want to follow up with testing
[41:32] with a plasma biomarker
[41:33] SPEAKER_03: or imaging,
[41:35] SPEAKER_03: I think that would be great.
[41:36] Especially now that the biomarker field has developed so much
[41:41] in Alzheimer's
[41:42] SPEAKER_03: disease,
[41:43] SPEAKER_03: I think that we need to kind of
[41:46] SPEAKER_03: think more about, well, how are we going to bring this to the masses?
[41:48] SPEAKER_03: We can't have 100% of people getting their plasma AD biomarkers tested.
[41:54] We need to be able to narrow the pool more to use our resources
[41:58] efficiently.
[42:00] SPEAKER_00: Yeah.
[42:00] SPEAKER_00: No,
[42:00] SPEAKER_00: I think it's really intriguing,
[42:02] SPEAKER_00: especially because there's always been the sense that,
[42:05] SPEAKER_00: oh,
[42:05] SPEAKER_00: these sleep lab studies are non-physiologic.
[42:08] SPEAKER_00: Now, just do it at home or don't do it at all.
[42:12] But there's something that is captured with all this exquisite
[42:15] continuous data
[42:16] during the night that is really fascinating how it could be
[42:19] predictive of health
[42:20] and someday may be part of a way to assess a person's risk and
[42:26] to change that.
[42:28] SPEAKER_00: Now,
[42:29] SPEAKER_00: some of the questions that have come up along the way,
[42:31] SPEAKER_00: by the way,
[42:32] SPEAKER_00: thank you for some people who have been saying how helpful,
[42:35] SPEAKER_00: useful the discussion is as we're talking.
[42:37] SPEAKER_00: Oh, thank you.
[42:39] SPEAKER_00: Yeah,
[42:39] one is about menopause and the concern that with menopause that
[42:45] this leads to sleep
[42:47] SPEAKER_00: issues.
[42:48] SPEAKER_00: Do you have any solutions for that problem?
[42:52] SPEAKER_03: If I had a one-size-fits-all solution, then I would be a rich woman.
[42:59] SPEAKER_03: So,
[43:00] SPEAKER_03: you know,
[43:01] SPEAKER_03: as people go through perimenopause and then menopause,
[43:07] SPEAKER_03: sleep issues become much more prevalent.
[43:11] SPEAKER_03: So I don't want to...
[43:15] SPEAKER_03: overbear on sleep apnea, but that is actually a big part of it.
[43:21] So women have about half the prevalence of men in terms of
[43:26] sleep apnea before menopause.
[43:29] SPEAKER_03: After menopause, they've caught up.
[43:31] And so this means that around menopause is when a lot of
[43:36] people,
[43:36] a lot of women,
[43:38] SPEAKER_03: develop and are diagnosed with sleep apnea.
[43:41] So I think that is actually a big chunk of it that we don't
[43:44] talk about very much.
[43:47] SPEAKER_03: Also, women have hot flashes.
[43:51] They also just have awakenings for no apparent reason sometimes
[43:57] during menopause.
[44:00] SPEAKER_03: And,
[44:00] SPEAKER_03: you know,
[44:00] this probably has to do with how our hormones help regulate our
[44:06] sleep continuity
[44:08] SPEAKER_03: and sleep quality.
[44:09] SPEAKER_03: So it's not inevitable, but it is very common for people.
[44:13] SPEAKER_03: for women to have a decline in their sleep during menopause.
[44:19] And at least if someone is having sleep problems bad enough
[44:23] that they're coming to
[44:24] SPEAKER_03: see me at a sleep center,
[44:26] SPEAKER_03: I always test for sleep apnea because common things being common,
[44:30] SPEAKER_03: we do need to look for that and treat it as a serious sleep disorder.
[44:34] SPEAKER_00: No, that's helpful.
[44:36] SPEAKER_00: Now, alcohol.
[44:38] SPEAKER_00: We didn't talk about that.
[44:39] SPEAKER_00: Do you have antibodies to alcohol because of its interference with sleep,
[44:46] SPEAKER_00: or is that a very individual,
[44:48] SPEAKER_00: variable thing?
[44:49] SPEAKER_03: So, I...
[44:53] SPEAKER_03: Do I have antibodies to alcohol?
[44:55] SPEAKER_03: No.
[44:57] SPEAKER_03: So we know that alcohol is not good for your sleep.
[45:00] So obviously,
[45:01] alcohol can have sedating effects because of its effects on,
[45:05] say,
[45:05] GABA.
[45:06] SPEAKER_03: It can also, you know, help people fall asleep initially.
[45:10] But I always discourage people from using alcohol for sleep
[45:16] because there's a very
[45:18] rapid physical tolerance where people will need higher and
[45:22] higher doses to help
[45:23] SPEAKER_03: them fall asleep.
[45:25] SPEAKER_03: Also, alcohol wrecks sleep.
[45:27] SPEAKER_03: in the second part of the night.
[45:29] SPEAKER_03: It suppresses REM sleep in the first half of the night.
[45:32] SPEAKER_03: And so then you have to catch up in the second half of the night.
[45:36] SPEAKER_03: But then there's a lot of awakenings as well.
[45:38] SPEAKER_03: And so a lot of times people will have those awful 3 a.m.
[45:44] awakenings where they feel anxious and sweaty and waking up in
[45:48] these awful dreams.
[45:50] SPEAKER_03: So when people come to me and say, I'm waking up at 3 a.m.
[45:53] SPEAKER_03: feeling anxious, I can't get back to sleep, I'm all sweaty.
[45:57] SPEAKER_03: My first question is, do you drink alcohol?
[46:00] SPEAKER_00: Right.
[46:01] SPEAKER_03: because it's so common.
[46:03] SPEAKER_03: And then as people age, their tolerance goes down.
[46:07] SPEAKER_03: So,
[46:07] SPEAKER_03: you know,
[46:07] even people who routinely had one or two drinks in the evening
[46:11] and slept fine,
[46:12] SPEAKER_03: you know,
[46:13] SPEAKER_03: they're almost indignant.
[46:14] SPEAKER_03: Like, this is what I do.
[46:16] SPEAKER_03: Why am I having problems sleeping?
[46:17] SPEAKER_03: And I say, well, our bodies change over time.
[46:21] SPEAKER_03: And,
[46:21] SPEAKER_03: you know,
[46:22] you may not be able to have a whole drink or you may need to
[46:25] just save it for,
[46:26] SPEAKER_03: save alcohol for once in a while.
[46:29] SPEAKER_03: when you're willing to sacrifice your sleep that night.
[46:32] SPEAKER_03: So alcohol is terrible for sleep.
[46:35] SPEAKER_03: I say never use it for sleep.
[46:39] SPEAKER_03: And this is especially because we sleep every night,
[46:43] meaning we don't want to use an addictive substance every night
[46:47] to do something
[46:48] SPEAKER_03: because then,
[46:49] SPEAKER_03: you know,
[46:49] obviously there's a risk of abuse and dependence that we don't
[46:53] want to encourage.
[46:54] SPEAKER_00: Yeah.
[46:55] SPEAKER_00: I want to circle back to
[46:57] SPEAKER_00: the one thing that you mentioned that's very helpful for many people,
[47:00] SPEAKER_00: and that's the cognitive behavioral therapy,
[47:03] SPEAKER_00: which you could get digitally.
[47:05] Is there any one app or path that you recommend for that,
[47:08] or are there many choices?
[47:12] SPEAKER_03: There are some apps.
[47:14] I mean,
[47:14] I think obviously the best data are for in-person,
[47:18] you know,
[47:20] with a human therapist.
[47:23] SPEAKER_03: So, you know, that's what I recommend for, say, you know, my patients.
[47:26] SPEAKER_03: We have two psychologists at our sleep center who do CBTI.
[47:31] SPEAKER_03: You know, that's primarily what they do for their practice.
[47:35] SPEAKER_03: So that's my top choice.
[47:37] SPEAKER_02: Wow.
[47:37] SPEAKER_03: that's not always affordable or feasible for people,
[47:41] SPEAKER_03: in which case,
[47:43] SPEAKER_03: you know,
[47:43] SPEAKER_03: there's a variety of different apps.
[47:46] SPEAKER_03: And nowadays there's like AI-assisted apps or programs.
[47:51] SPEAKER_03: It can't hurt to try.
[47:53] You know,
[47:54] I think there's decent data on some of these app-based ones
[47:58] compared to CBTI.
[48:01] But,
[48:01] you know,
[48:01] I'm like,
[48:02] well,
[48:03] you should still do the real CBTI if you can.
[48:06] SPEAKER_03: Otherwise, I think it's always reasonable to try an electronic version.
[48:12] SPEAKER_00: Okay.
[48:13] SPEAKER_00: So no comments about particular electronic digital ones.
[48:17] SPEAKER_00: There's not one that you think has helped people particularly?
[48:23] SPEAKER_03: Not necessarily.
[48:24] SPEAKER_03: And I've had different patients use different ones,
[48:26] so I don't think there's any one that jumps out in my memory as
[48:30] being particularly
[48:31] SPEAKER_03: more effective.
[48:32] SPEAKER_03: And sometimes it's just like with a therapist.
[48:35] I think sometimes there's just a better fit between the person
[48:38] and the app.
[48:41] SPEAKER_03: And it can take multiple tries.
[48:43] So this is what I tell patients a lot is don't give up after
[48:49] the first try,
[48:50] right?
[48:50] SPEAKER_03: You can always try again.
[48:52] SPEAKER_03: Take a break and try again.
[48:54] SPEAKER_00: They vary.
[48:55] SPEAKER_00: I mean,
[48:55] SPEAKER_00: some are just like for reducing your level of anxiety,
[49:00] SPEAKER_00: calm,
[49:01] SPEAKER_00: talk space,
[49:02] and others are really trying to get at this issue in more depth
[49:06] and specificity.
[49:08] SPEAKER_00: What about naps?
[49:09] SPEAKER_00: What's your sense of?
[49:11] SPEAKER_03: What do I think about naps?
[49:12] SPEAKER_03: So naps are great if you are a good napper.
[49:17] SPEAKER_03: So we say keep your naps before 3 p.m.
[49:21] SPEAKER_03: so that it doesn't interfere with sleeping at night.
[49:26] SPEAKER_03: And then you want to avoid getting sleep inertia.
[49:30] That's that groggy sensation where your brain is still like a
[49:34] little bit in
[49:34] SPEAKER_03: molasses when you wake up.
[49:36] SPEAKER_03: And that tends to get worse the longer you've been asleep.
[49:39] SPEAKER_03: So you really want to try to end your nap by 30 minutes.
[49:43] So I tell people,
[49:44] set an alarm so that you don't get into real deep sleep and get
[49:49] sleep inertia.
[49:50] SPEAKER_03: I would say in general, people are either good nappers or bad nappers.
[49:55] SPEAKER_03: And by good nappers, I mean they fall asleep and they wake up.
[50:00] easily so i am a bad napper so i don't take naps because i
[50:04] can't fall asleep and
[50:05] then if i do i feel real groggy right so most people kind of
[50:09] know if they're good
[50:09] nappers or bad nappers so people who are good nappers if
[50:13] they're able to keep those
[50:14] naps brief before 3 p.m and it's not interfering with their
[50:18] nighttime sleep it's
[50:19] great it's good it'll help boost their cognitive function you
[50:23] know they've done
[50:24] SPEAKER_03: studies looking at
[50:25] SPEAKER_03: um, uh, cognitive functioning.
[50:28] SPEAKER_03: And also,
[50:28] SPEAKER_03: uh,
[50:29] SPEAKER_03: for athletes,
[50:30] SPEAKER_03: it can help athletic function,
[50:31] SPEAKER_03: uh,
[50:31] SPEAKER_03: to,
[50:32] SPEAKER_03: to take a nap before,
[50:34] SPEAKER_03: before a competition or something.
[50:36] SPEAKER_03: So if, if people can, can nap well, then, then great.
[50:39] SPEAKER_03: But, uh, the naps can't be too long.
[50:42] SPEAKER_03: Um, I will add that unintentional naps are not good.
[50:46] So people who are,
[50:48] uh,
[50:48] dozing off in the evening in front of the TV,
[50:51] that is not a good nap.
[50:53] SPEAKER_03: So, you know, I kind of think of, um,
[50:55] SPEAKER_03: That kind of sleeping is like junk sleep.
[50:58] SPEAKER_03: It's like eating junk food.
[51:01] That is bad because it uses up your sleep drive so then you
[51:06] don't get good sleep at night.
[51:11] And the quality of sleep that people are getting when they're
[51:15] kind of drowsy off
[51:16] SPEAKER_03: and on is not good.
[51:18] SPEAKER_03: They're not getting into high-quality slow-leaf sleep when they doze off.
[51:23] SPEAKER_03: So people who are finding that they are dozing off unintentionally,
[51:27] they really need to take measures to get adequate quantity or
[51:32] quality of sleep at
[51:33] SPEAKER_03: night.
[51:35] And if they really want or need,
[51:37] they can add a scheduled nap during the day.
[51:40] SPEAKER_03: But an accidental nap is not a good nap.
[51:43] SPEAKER_00: Those are really good tips on naps.
[51:44] SPEAKER_00: I love that.
[51:45] Now,
[51:46] one last question I have for you before I was opening up,
[51:50] finish up,
[51:50] but interruptions.
[51:52] SPEAKER_00: So during the night when you have these monitoring,
[51:55] SPEAKER_00: whether it's in sleep lab or with wearables,
[51:59] SPEAKER_00: you're awake a lot more than you know.
[52:01] SPEAKER_02: Mm-hmm.
[52:03] SPEAKER_00: Sometimes these are very brief.
[52:05] SPEAKER_00: Sometimes they're longer and maybe you do know then.
[52:08] SPEAKER_00: And so the person that says,
[52:11] SPEAKER_00: oh,
[52:11] SPEAKER_00: I went to bed and I slept eight hours,
[52:13] they may actually have only actually been asleep seven hours or
[52:17] lesser a number,
[52:18] SPEAKER_00: seven and a half hours.
[52:21] SPEAKER_00: Are these interruptions meaningful?
[52:23] SPEAKER_00: I mean,
[52:24] SPEAKER_00: if you have a lot of deep sleep and REM sleep and whatnot,
[52:29] SPEAKER_00: does it matter if you have these short bursts of interrupted wakefulness,
[52:35] SPEAKER_00: I should say?
[52:37] SPEAKER_03: So it's normal to wake up several times during the night.
[52:40] And we actually have a word for it,
[52:44] AFNAR,
[52:44] which is arousal for no apparent reason.
[52:48] SPEAKER_03: So they're normal.
[52:49] SPEAKER_03: AFNARs are normal.
[52:50] SPEAKER_03: Arousals and awakenings are normal.
[52:53] SPEAKER_03: So during a normal night,
[52:54] SPEAKER_03: we go through several rounds of having non-REM sleep and then REM sleep.
[53:00] SPEAKER_03: And then there's a small awakening at the end of that.
[53:03] SPEAKER_03: That is completely normal.
[53:05] SPEAKER_03: And in fact, if someone tells me that they never wake up, I...
[53:10] SPEAKER_03: think they are the abnormal ones.
[53:13] SPEAKER_03: So waking up several times is completely normal.
[53:17] And if people get back to sleep within a few minutes,
[53:21] again,
[53:21] that's totally normal.
[53:22] SPEAKER_03: That's just normal human sleep.
[53:26] SPEAKER_03: So, you know, I think trying to
[53:30] SPEAKER_03: you know,
[53:30] take whatever measures necessary or taking medication or doing
[53:35] whatever to try to
[53:36] SPEAKER_03: get rid of those awakenings,
[53:37] SPEAKER_03: I think that does more harm than good.
[53:40] SPEAKER_03: You know, you can imagine that from an evolutionary standpoint,
[53:45] SPEAKER_03: we do need to wake up a little bit once in a while.
[53:49] SPEAKER_03: So if predators are taking care of babies or other people,
[53:55] SPEAKER_03: we do need to be able to wake up in our sleep.
[53:59] SPEAKER_03: That's what separates it from, say, a coma.
[54:02] SPEAKER_03: So in normal healthy sleep,
[54:04] SPEAKER_03: there are normal awakenings and arousals,
[54:08] SPEAKER_03: and we just leave them alone.
[54:09] SPEAKER_03: If people are getting,
[54:11] SPEAKER_03: you know,
[54:11] SPEAKER_03: between seven and nine hours of sleep,
[54:14] SPEAKER_03: they wake up,
[54:14] SPEAKER_03: they feel good,
[54:16] SPEAKER_03: that's fine.
[54:17] SPEAKER_00: That's great.
[54:18] SPEAKER_00: I love this AFNAR.
[54:19] SPEAKER_00: I have to say I wasn't familiar with it, so it's a new acronym for me.
[54:23] SPEAKER_00: Okay.
[54:24] SPEAKER_00: We've covered a lot of ground, Professor Zhu.
[54:27] SPEAKER_00: I mean, you're a gem.
[54:28] SPEAKER_00: You're a resource of great information.
[54:31] SPEAKER_02: Thank you.
[54:32] SPEAKER_00: A lot of this is so practical, too, not just the science of sleep.
[54:36] Did I miss anything that you think is worth reviewing for the
[54:40] people that joined us?
[54:43] SPEAKER_03: Well,
[54:44] SPEAKER_03: I would say from a public health standpoint,
[54:46] probably one of the things we can do to improve our sleep
[54:50] health and our overall
[54:52] SPEAKER_03: health is to get rid of daylight savings time.
[54:55] SPEAKER_03: So it's coming up in a couple of weeks, which has reminded me.
[55:00] SPEAKER_03: But,
[55:01] SPEAKER_03: you know,
[55:01] there was a study that came out last year that looked at the
[55:04] public health toll of
[55:08] SPEAKER_03: the time switch.
[55:09] SPEAKER_03: And especially the spring one is awful for us.
[55:12] SPEAKER_03: You know,
[55:13] we have a lot more strokes and heart attacks than we need to in
[55:16] this country
[55:17] SPEAKER_03: because of this random hour time switch.
[55:21] So whatever people can do locally at the state level to get rid
[55:26] of daylight savings
[55:28] SPEAKER_03: time,
[55:29] SPEAKER_03: please do so.
[55:30] SPEAKER_00: Yeah,
[55:30] SPEAKER_00: I've never understood the resistance to keeping this,
[55:34] SPEAKER_00: even though there's a tremendous outpouring of public to not have it.
[55:38] So maybe someday,
[55:40] you know,
[55:41] maybe someday,
[55:42] but it sure is taking a long time to get it on track.
[55:45] SPEAKER_00: Yeah.
[55:47] SPEAKER_00: Well, what a joy to have this conversation with you.
[55:51] We really have hit the goal for expert on this topic,
[55:56] which is so central.
[55:57] SPEAKER_00: There are so many people in this crazed world we live in that's
[56:01] SPEAKER_00: have a lot of anxiety and stress,
[56:02] and people don't feel like they're getting adequate sleep
[56:05] quality and sleep health.
[56:06] SPEAKER_00: And I hope everyone has got the sense how important it is.
[56:11] SPEAKER_00: And it's not just for neurodegenerative diseases across the board.
[56:14] SPEAKER_00: So thank you, everybody, for joining.
[56:16] SPEAKER_00: We're going to keep following your work.
[56:20] I'm going to be following your PTAL 217 and neuromarkers on the
[56:24] people you've
[56:25] SPEAKER_00: already studied to see the influence of sleep on that directly.
[56:29] SPEAKER_00: That'll be fascinating.
[56:31] And we'll look forward to hooking up and discussing our
[56:35] Alzheimer's prevention
[56:36] SPEAKER_00: trial with you in the times ahead.
[56:39] SPEAKER_03: Well, thanks so much for inviting me, Eric.
[56:42] SPEAKER_03: This was a lot of fun.
[56:43] SPEAKER_00: Yeah, and thanks everyone for joining.
[56:45] SPEAKER_00: We had over 600-some people here live.
[56:49] SPEAKER_00: Thousands more in the archive.
[56:52] And it's just because it's such a big topic and we,
[56:55] you know,
[56:56] really got such a great expert.
[56:58] SPEAKER_00: And if you've got sleep questions, now you know who to refer to.
[57:04] SPEAKER_00: I learned a lot.
[57:05] SPEAKER_00: Thank you.
[57:06] SPEAKER_03: All right.
[57:06] SPEAKER_03: Thank you, everyone.
[57:07] SPEAKER_03: Thanks.
[57:09] SPEAKER_03: Bye-bye.

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