"The Cost of Insufficient Sleep" Janet Mullington (12.09.2020)

December 14, 2020

ID6001

To CiteDCA Citation Guide

00:00Alright. So in 2014, the Sleep Research
00:08Society and the American Academy of
00:12Sleep Medicine got together too.
00:16At the encouragement actually of
00:19Michael Query, who is the head
00:22of the Center for Sleep Disorders
00:25Research at Heart, Lung and Blood?
00:29As the director of that? I.
00:35Component of heart, lung and blood.
00:38Michael Query had been asking for.
00:43Position paper on how much sleep is
00:47actually recommended so he he encouraged
00:51the societies and we got together a
00:56number of individuals to participate in.
01:00Uh. A consensus meeting there.
01:05There were many involved in this
01:09panel and the product of that work
01:13was published in Sleep in 2015 and
01:17it was really a landmark consensus
01:20piece and you can see here that there
01:25were several different areas covered.
01:28They reviewed a wealth of literature.
01:32From epidemiological to physiological
01:34data on the effects of insufficient
01:37sleep or hours of sleep on these
01:40different parameters,
01:41including general health,
01:42cardiovascular health, metabolic health,
01:44mental health, immune function,
01:46human performance, breast cancer,
01:48pain and mortality.
01:49Ann on all of these except for breast cancer.
01:54As you can see here,
01:56the hours of recommended sleep or the
01:59hours where there was most agreement.
02:02That that this amount of sleep 7 to 8
02:06hours was the optimal is shown here in green,
02:11so the consensus ended up stating
02:14that a minimum of 7 to 8 hours
02:18of sleep is recommended.
02:20As we can see over here,
02:23there is some disagreement
02:25in the higher range,
02:27but in epidemiological research at least
02:30we have seen that over 10 hours is.
02:35Is thought to be too much.
02:37However,
02:38comorbidities and age are
02:40important to factor in there,
02:42so in terms of the bottom line,
02:45one in three American adults doesn't
02:48get the recommended amount of sleep.
02:50And here you can see a prevalence
02:54map and you can see that.
02:57From 2024.3% all the way to 48.5%
03:01of the population in different
03:04counties across the country have
03:07insufficient sleep less than 7 hours
03:10of sleep on average per night.
03:14This has been monitored by the Center
03:17for Disease Control and there the
03:21Behavioral Risk factor surveillance
03:24questions have got some items on sleep and.
03:28Anybody can actually access those
03:31databases there and report from
03:342016 showed us more about the
03:37economic costs of insufficient
03:39sleep across 5 OECD countries,
03:42and you can see here that the gross.
03:49The GDP is influenced by
03:55insufficient sleep that 2.28%.
04:01Is the amount of GDP that's loss due to
04:05insufficient sleep according to this report?
04:09And this ranges from 1.35 in
04:13Canada to 2.9 in Japan, but.
04:161.2 million working days are lost.
04:20It's estimated each year
04:22in the United States,
04:24so this clearly has an impact on economics.
04:31In in our country and in
04:34other Western nations. She.
04:38Healthy Sleep Awareness program was
04:41actually a program that was developed
04:44in partnership with the Center for
04:47Disease Control and 2013 fourteen.
04:50They put out an announcement for
04:53a competition or excuse me for
04:57Grant to be supporting education,
04:59public education so the Sleep
05:02Research Society and the American
05:06Academy of Sleep Medicine got
05:09together as founding partners.
05:11Developed this education
05:14program with the CDC.
05:17And. This.
05:27This educational group put
05:30together they had a communications.
05:34A communications subcommittee that
05:36worked on these infographics together
05:40with the Academy and you can see here,
05:43from economic costs,
05:45through the importance of drawing of sleep
05:49for drowsy driving for cardiovascular health.
05:53Another one that was put out for sleep
05:57awareness around Halloween and then
06:00another that was developed for kids and.
06:05Particularly adolescents and these,
06:07together with some of the other so
06:11social media led to 4.2 billion clicks.
06:14And so this program was very effective
06:18in helping the educate the public
06:22about the importance of sleep.
06:25I wanted to talk now a little bit about some
06:29of the experimental work that we've done,
06:32so we have tried to do highly
06:35controlled experimental models
06:37looking at the effects of insufficient
06:39sleep and this is Monica hacks work.
06:42Monica is an associate professor
06:44in the Department of Neurology
06:46at our institution at Beth Israel
06:49Deaconess Medical Center,
06:50and she's done a lot of research looking at.
06:56The question as to whether or not
06:58we can adapt to insufficient sleep,
07:01and here you see, you know some plot that
07:04shows what somebody who's working too
07:07much might actually experience this is
07:104 hours of sleep followed by a weekend
07:13where they try and catch up sleep,
07:16and sometimes people can do this
07:18week after, week after week,
07:20and we think that we adapt to this, but.
07:25Monica wanted to look and see
07:27exactly how does this affect
07:29our Physiology in our health.
07:31Health risk parameters,
07:33so we know that that stress affects the
07:38hypothalamic pituitary adrenal system,
07:41the immune system and the
07:45sympathoadrenal system.
07:47We know that cortisol inhibits
07:50monocyte production of aisle 6.
07:53We know that I'll six production when
07:57monocytes are stimulated it increases.
08:00We know that norepinephrine can
08:04also stimulate the production
08:07by a monocytes and I all six.
08:11Can cause a or an immune response.
08:14Causes cortisol to go up.
08:17So Monica was studying week after week.
08:20The effects of insufficient sleep
08:21and what you can see here is that
08:24the end of week one there's actually
08:27two nights of sleep recovery sleep.
08:29What you see is that from from baseline,
08:33which is actually not shown here.
08:35But there's three nights of baseline
08:37before this recording is done,
08:39so they've been sleeping 8 hours a night,
08:42or had that opportunity.
08:44These are normally 8 hours sleepers who
08:47we bring into the clinical Research Center.
08:49Um, then?
08:50What you see here is that
08:53for the first few nights,
08:56there's no significant.
08:58There's a drifting upwards,
08:59but no significant increase in
09:02the aisle 6 positive monocytes.
09:05Percentage and then what you
09:07see is that during the next.
09:10Bout of insufficient sleep this is the aisle.
09:136 positive monocytes are increased
09:15and then after you have that second
09:18that second week you're having
09:20recovery sleep on the weekend.
09:23Those levels are still elevated
09:25and again after the next week they
09:28are still elevated and recovery
09:30sleep is not really doing a good
09:33job returning it back to baseline.
09:35What you note here is that the
09:38cortisol is also increased so.
09:41Quarters all, as I said,
09:43should inhibit the monocyte product
09:47productivity production of the
09:49aisle 6 and it is increasing,
09:52so that's a counterregulatory if
09:55you will immune type response.
09:58And what you see here is that.
10:01The ability of the dexamethasone
10:07to dexamethasone being.
10:10Inhibitory steroid,
10:11the ability of this dexamethasone
10:15to reduce the production of IL.
10:186 drops so the glucocorticoid
10:22sensitivity is increasing in
10:24response to the sleep deprivation.
10:29Anet is not returning to baseline
10:33after a weekend of of sleep.
10:37So cutting back to half half the
10:41amount of sleep you need during
10:43the week and trying to catch up
10:47with just two nights of eight hours
10:50of sleep on the weekend is not
10:53doing it for your immune system.
10:56So Monica and Larissa and heart here,
10:59who is a postdoctoral fellow
11:01working with Monica currently in
11:04our lab has has been investigating
11:07these resolvins and resolvins.
11:08Are an active component of the
11:13immune system that actively tries
11:16to resolve the inflammation
11:19and stop the recruitment of.
11:23Immune.
11:28Immune factors. So here you see that
11:34edema is very quick and then this
11:38inflammation infiltration of white blood
11:41cells occurs within minutes and then
11:46this monocyte macrophage production
11:48of inflammatory signals and counter
11:52regulatory active resolution factors takes
11:55a longer amount of time, hours to days.
12:00These omega-3 fatty acid.
12:03Components are converted to specialized pro,
12:06resolving mediators that you see here.
12:10In these graphs there's RV,
12:13D3, RV D4, RV D5 and 17HD HA.
12:17These are all.
12:20Part of these resolving mediators,
12:23we're exploring them at this point
12:26and I've just selected three that
12:30for rather that are that are showing
12:33quite interesting patterns here
12:35of of stability with the control
12:39sleep and a drop in production.
12:44Associated with insufficient sleep,
12:47and this is showing insufficient
12:50sleep after 14 days of being in a
12:53protocol that involves fragmenting
12:55nocturnal sleep and allowing
12:58interdigitated recovery that that's a
13:013 three days of insufficient sleep,
13:04followed by recovery of one
13:07night and this is repeated.
13:10So this is a partial sleep deprivation model.
13:14That is a recurrent exposure
13:17to the sleep deprivation,
13:18and then when you allow after that sleep.
13:22What you seeing here is that this these
13:25rez resolving mediators are not jumping
13:28right back up to baseline levels,
13:31so it's taking longer for this resolution to
13:34occur in the context of sleep deprivation.
13:40So these models are based on pretty acute.
13:45God changes and we know that
13:48in cardiovascular disease,
13:50risk for cardiovascular disease.
13:52This is increased when CRP levels
13:56are even just mildly elevated,
13:59and so we were wanting to further
14:02examine the autonomic involvement.
14:05One of the hypothesis is that the
14:09inflammation that we see in shorter term.
14:14I sleep deprivation may be a stress
14:19response and may be related to.
14:23I. Two shear stresses,
14:27and so we wanted to look at vascular
14:31tone and to look at some of the.
14:35Inflammatory regulation mediators.
14:41We conducted a study here you can see
14:44a four hour condition in an 8 hour
14:47condition in the four hour condition.
14:50The participants were kept awake until
14:533:00 o'clock and allowed to sleep from
14:563 until seven and this is a 22 day
14:59protocol an we studied heavy recording
15:02days are indicated here in the green
15:05and on these heavy recording days
15:08we did beat to beat blood pressure.
15:11And we also recorded continuous e.g.
15:15And we had vascular reactivity
15:19testing during the day.
15:22Following the last recording
15:26from each of these blocks.
15:30We also measured mediators
15:32before bed and after bed.
15:36So here you can see the blood pressure
15:39data and you see that that the control
15:43is shown here in the in the black line
15:46and the dotted or the hatched line.
15:49Here is the sleep deprivation.
15:51The partial sleep deprivation and these are
15:54showing the first block and second block,
15:57third block and 4th block and
15:59then the recovery.
16:00So what you'll notice here is
16:03that the systolic blood pressure
16:05is elevated and the diastolic.
16:07Blood pressure is elevated and
16:10the heart rate is.
16:12Is is elevated in the restriction
16:15condition and these are daily averages?
16:19I will show you some of the
16:23tracings but here you see the.
16:26This is the Porter press system.
16:29There's a block worn on the wrist,
16:32and the finger cuffs inflate and
16:35deflate at 15 minute intervals.
16:37We use so that it's reasonably
16:40comfortable and participants
16:41can be awake and performing or.
16:46Doing different activities in the day it is
16:49actually marketed as an ambulatory system,
16:51although I wouldn't want to try that.
16:54I we have people stay with this
16:56system in the lab and they can
16:59sleep with this through the night,
17:01and our hope is that we actually.
17:05Do not disrupt sleep as much as we
17:08would with something like spacelabs.
17:11We did do a little bit of a head
17:14to head comparison and didn't
17:17find a lot of difference in fact,
17:20but in any case,
17:22with this 24 hour blood pressure
17:24we did repeated repeated cycles.
17:27As you saw a moment ago and what we
17:30saw is that the sleep restriction
17:33led to elevation of blood pressure.
17:37When permitted to sleep in the
17:39short sleep condition,
17:40you can see here in the red
17:43bar at the bottom,
17:44the participants had elevated blood
17:46pressure compared to when they were
17:49allowed to sleep earlier in the night.
17:51So the slow wave actually was
17:54quite well preserved in the
17:56first part of the night here,
17:58but they did not get down as far
18:01as they did in normal sleep.
18:05And the recovery is here in the tracing
18:08at the bottom here in the green.
18:11So they go pretty quickly back to
18:14the range of where they were in
18:18baseline in the first recovery.
18:21This is actually the second recovery night,
18:23but I'll get into that later.
18:25But in any case,
18:27what I wanted to sorry what I
18:30wanted to show you here is the.
18:33Period from 8:00 PM until 3:00 AM
18:38and what you can see is that the.
18:43Later cycles the 3rd and 4th cycle of
18:46sleep restriction showed a decrease,
18:48so it starts the blood.
18:50Blood pressure tries to go down
18:52if you will eat earlier,
18:54and this is after the meal where
18:57usually you have and you can see
19:00a little bit of a peak here in
19:03the black and meal associated Pick
19:06peak here after lunch.
19:08But in the evening this blood pressure
19:11was starting to decrease at 8:00 PM.
19:13Long before they get into bed,
19:15they got into bed at 10:30 PM and
19:18lights were out at 11 actually.
19:20And So what you'll notice is that
19:23the blood pressure begins to
19:24decrease and then it at bedtime.
19:26It does go up and there is a
19:29pre sleep increasing in blood
19:30pressure that we see here as well.
19:33In this short sleep condition.
19:36We looked at that period between
19:388:00 and 3:00 and we found no
19:41difference in subjective sleepiness.
19:43We had thought maybe they were
19:45getting tired and that's why blood
19:48pressure was dropping early and
19:50we saw no increase in microsleeps
19:53we we had the EG and looked and
19:56scored through and didn't find
19:58that there were more microsleep.
20:00In the 8:00 to 8:00 PM to bedtime,
20:04whether that was eleven,
20:06there was no difference there,
20:09so that was 11 for the sleep condition.
20:15So we we looked at, I'm sorry.
20:21So we. We wanted to look at the recovery
20:26sleep also for homeostatic regulation
20:29of sleep and and autonomic involvement.
20:33So we have done additional
20:35studies and just to give you a
20:39little bit of the background,
20:42we all know that with the
20:45homeostatic regulation of sleep,
20:47there's increased sleep pressure
20:49and when participants are sleep
20:52deprived and allowed to sleep again.
20:55There's an increase in slow
20:58wave sleep and and Delta power,
21:01and there's one study only that showing
21:04only one study that looked at heart
21:09rate variability in the recovery.
21:11In sleep during recovery sleep
21:15following the sleep deprivation and
21:18Glos and colleagues showed that
21:21the low frequency high frequency,
21:24so this is showing the
21:28sympathetic predominant.
21:33The increase of parasympathetic predominant.
21:41Heart rate variability
21:42following sleep deprivation.
21:44So during recovery sleep there is an
21:47increase and you can see that very nicely
21:50here in jurist as beautiful illustration,
21:54showing the sleep histogram here with
21:57slow wave sleep and REM sleep and
22:01what use notice here is the Delta
22:04power coinciding with this low.
22:07Obviously with the slow wave sleep,
22:09but the high frequency Spectra
22:12of of the heart.
22:14Rate the high frequency is shown down
22:18here on panel C and it is coinciding
22:22it with actually the Delta power
22:25and the peak in the high frequency,
22:29the autonomic.
22:32Parasympathetic peak,
22:33if you will, is in advance of
22:36the Delta power by a little bit.
22:39The Delta Power does show an
22:42increase here in advance of that,
22:46so clearly there is a regulation
22:49with the sympathetic parasympathetic
22:52balance and those sleep stages.
22:55So we wanted to look in the recovery
22:59sleep following the short sleep
23:02boats and look for any rebound.
23:05We did not have a recording on
23:09the 1st Recovery Night because
23:12as I showed you earlier,
23:15we were recording the heavy
23:17recording was done on the third
23:20night of the deprivation throughout
23:23these cycles and then.
23:26The first recovery night was always
23:28without EG to give participants a
23:30break and then we did the full each
23:33G and beat to beat blood pressure
23:36monitoring again on recovery
23:37night 2IN Recovery Night 3.
23:42And we were interested in looking at
23:45the spontaneous cardio, vagal BRS,
23:48Barros reflect sensitivity,
23:50an we used a sequence method,
23:53and we were looking at the up
23:56sequence so when the up up sequence
23:59when blood pressure goes up the
24:02heart rate should come down and when
24:06blood pressure goes down the heart
24:10rate should go up the RR interval.
24:14Response to the blood pressure and what we
24:18saw is that the normalized high frequency.
24:22So this is the parasympathetic
24:24response to sleep loss in that second
24:28recovery night we see here quite a
24:32pronounced increase this these data
24:34that I'm showing you here on this slide
24:38are from the first hour of sleep.
24:42On the baseline and then the recovery sleep.
24:47Not the recovery sleep.
24:49Sorry the third night of sleep deprivation.
24:52And then finally the second recovery night.
24:55So we would expect that these
24:58first nights of.
25:00Partial sleep deprivation that
25:02these nights of partial sleep
25:05deprivation might show a rebound.
25:08So I'm very interested to know what the
25:12first recovery full night would look like,
25:15but what we see is the recovery too.
25:19Has the increase in the high
25:22frequency and also the BRS down down.
25:26So when the down the the blood pressure.
25:30Is going down there.
25:32Heart rate is more more responsive here
25:36and also the Delta power is increased on the.
25:42On each of those nights, as one would expect.
25:46This shows you the correlation and
25:48the correlation for the baseline night
25:51as well as the recovery nights shows
25:54a very tight correlation between the
25:56high frequency and the slow wave sleep,
26:00just as seen here in the juristic data.
26:04So what what is it about?
26:08Restoration, Ann? Can we?
26:11Can we further understand the recovery
26:15sleep by looking at subjective
26:18indices and we know that 20 to 30%
26:22of patients seek attention in primary
26:26care settings for significant fatigue
26:29and over 700 million office visits
26:32per year in the United States.
26:35Are are with presenting concerns
26:38about fatigue and sleep.
26:40Is sleepiness and fatigue as we know
26:44are produced by insufficient sleep.
26:48We we decided to compare the data
26:50that I was just talking about
26:53with the four hours sleep.
26:55Three nights of insufficient sleep
26:57followed by recovery repeated four times
26:59and then three nights of recovery sleep.
27:01Compare that with another protocol
27:03where we gave 4 hours of sleep,
27:06but we spread it out and this is again.
27:09This is 3 cycles and we're comparing
27:11the the three cycles first three
27:14cycles in the four hour condition
27:16and what we did here was allow.
27:1940 minutes of sleep and
27:2120 minutes of wakefulness,
27:23so the total amount of sleep is
27:264 hours here and is also four
27:29hours in the upper graph.
27:34What what I'm showing here is the visual
27:37analog scale ratings of sleepiness.
27:40You can see that that each cycle
27:43of insufficient sleep causes an
27:45increase in sleepiness as we expect
27:48the consolidated short sleep.
27:50The four hours of sleep is shown here,
27:54and the fragmented 4 hours are shown here.
27:59What you'll notice is that there's an
28:02increase in the base in the baseline.
28:05This is after recovery sleep.
28:07There is still an elevation
28:09of sleepiness the next day,
28:11and this is showing fatigue.
28:13This is the fragmented sleep,
28:15and this is the consolidated short sleep.
28:18And these are the levels of eight hours of
28:22of sleep that you see in Gray at the bottom.
28:27Of particular interest, I think,
28:29is that if you compare what
28:32happens on the day after,
28:34so this is showing the baseline and then
28:37what about one night of recovery sleep
28:40following either the fragmented short
28:43sleep or the consolidated short sleep?
28:46What you'll see here in the red?
28:49That the fragmented short sleep leads to
28:52a much greater impairment the next day,
28:55so this is in all of these.
28:59I'm showing you what it looks like after
29:01they've had recovery sleep subjectively,
29:04so they're reporting elevated
29:06levels of subjective sleepiness
29:08even after recovery sleep.
29:11Following the fragmented but not
29:13the consolidated short sleep.
29:15So they're feeling much worse,
29:17and this is persisting even
29:19after the second night.
29:21It's not significant anymore,
29:23but you still see some elevation.
29:26However,
29:27with fatigue,
29:27and this is showing this same thing
29:31with the fatigue self report the the
29:34fragmented short sleep causes an
29:37elevation in fatigue that persists even
29:39on the third night after recovery sleep.
29:44So the fatigue and sleepiness here
29:48which you'll notice is that they
29:52are separable in in the post.
29:55Deprivation exposure when they
29:57are recovering. They they are.
30:00Separating fatigue and sleepiness and
30:03the sleepiness system more quickly resolved.
30:08So what about translational?
30:09I wanted to talk a little bit about
30:12translational opportunities for the field an.
30:15We've done a study,
30:17so I've been talking with you about,
30:20you know the effects of.
30:23Insufficient sleep on blood pressure.
30:26Can we help people with hypertension
30:29by increasing their sleep duration?
30:32And this study is ongoing,
30:34but.
30:36I just want to show you a little bit of
30:40preliminary data and I can tell you we don't.
30:43We're not unblinded yet,
30:45so we don't know which.
30:48With the data I'm going to show you,
30:51we don't know which condition
30:53that that the participants are in,
30:55but we randomized to a sleep
30:57extension or asleep timing and we're
30:59hoping to look at sex differences.
31:01Covid has really had an impact on
31:04our ability to run this study,
31:06so we won't have as many subjects
31:08as we had hoped,
31:10but we're still hoping to look at
31:13sex differences as well. Alright.
31:18We are.
31:21We advertised for individuals who had
31:25hypertensive hypertension and this
31:28is not a high level of hypertension.
31:32We're looking for participants
31:35with less than Stage 2 or 160 / 100
31:40and yet still over the 120 / 80.
31:46So in the in the pre hypertension and stage
31:50one phase one hypertension if you will.
31:55We we. Determine what their regular time
32:00is based on a couple of weeks of sleep.
32:04Log in, act graph and we then design.
32:10What is an increased amount of time
32:13for them by an hour or we maintain
32:17the time that they most usually?
32:20They usually would go to bed and get up.
32:25So we either maintain or we extend.
32:28But in both cases it's based on their
32:33circadian placement and duration of
32:36time prior to coming into the study.
32:39So I'm going to show you as I said some.
32:43Preliminary data,
32:44but essentially we have that evaluation
32:46phase with the screening visit and
32:49then they do an overnight stay where
32:51we do beat to beat blood pressure,
32:54an EEG recording.
32:55Then they go home and they are
32:58on a wait list.
32:59This is a wait list control for this study.
33:03They come back and repeat the same thing.
33:06We did this because we were concerned
33:09that maybe being in a study,
33:11maybe the adaptation to the.
33:14Stressful condition within the being in
33:17clinical Research Center might have affects,
33:20so we're interested in
33:22this overnight stay too,
33:25as well as the overnight stay 3 where
33:29we evaluate whether the sleep extension
33:33or the sleep timing condition improves.
33:37New blood pressure and this work
33:40that I'm going to show you has been.
33:44Can analyze Dan process by.
33:49Quan Yang and Michael Vasquez,
33:52who are shown here.
33:56And here I'm showing you the blood pressure,
34:01beatbeat blood pressure and the
34:04heart rate tracings.
34:06And with the Valsalva maneuver what we
34:10what we do is instruct the individual
34:14to take a deep breath and this is
34:19the early phase here early phase two
34:23where the individual is holding their breath.
34:27It's inspiring and holding their breath.
34:32And then when they released their breath,
34:35we see a drop in blood pressure
34:39corresponding with the peak in the ECG,
34:42and then as the blood pressure
34:45comes back to normal,
34:47then the heart rate goes back down.
34:50We see we're in phase four here and
34:54we look at the the responsibility
34:57of the part to this.
34:59These changes in blood pressure.
35:02So we're looking at the baroreflex
35:04sensitivity in the data that I will show you.
35:10Alright, so here what we're looking at is
35:13the slope and you see that the early phase.
35:17So this phase over here.
35:20Over sorry over here the slope is not
35:24changing between state one and State 2,
35:28but then with stage state three is increased.
35:34And the blood pressure maximum
35:36is decreasing on Stage 3.
35:39Not a lot of difference
35:41between stage one and two,
35:44but the blood pressure Max during
35:47the early phase is decreased on
35:50stage three and the phase four.
35:54So the responsiveness the slope
35:57is increased through each state.
35:59The most important for our study will
36:03be stay two to stay 3 and you see there
36:08is still an increase showing here,
36:12but it's not reached
36:14statistical significance.
36:15This is, as I said,
36:18a combination of both conditions were
36:21not unblinded yet, so we don't know.
36:25Who's in what condition?
36:27But we can see that there is a
36:31signal also with the BP Max dropping,
36:35so the the system is getting more
36:39responsive with the sleep conditions and.
36:43It it we consider the stabilization
36:45of sleep as an active control.
36:48So the fact that we are seeing
36:50anything here is encouraging.
36:52And if we have a difference between our
36:56conditions that will also be important.
36:59Of course for the sleep extension we
37:01expected to see a greater effect,
37:04but having any effects here compared to.
37:08Overnight stays one in particularly
37:11overnight stays.
37:12Two will will be of interest for
37:15sleeping circadian scientists.
37:17So what about future directions for
37:19behaviorally based interventions
37:21to improve sleep?
37:22Well,
37:23we know there's a lot of work that has
37:27been done and more to be done with CBT eyes.
37:32Cognitive behavioral therapies for insomnia.
37:34Sleep extension we've,
37:36we,
37:37and others have been working with.
37:40Some studies have started to look at
37:43more at breathing and meditation,
37:46and this is just showing you Juan
37:50Yang and Michael Goldstein,
37:52who one is an instructor in our group.
37:56And Michael Goldstein is a postdoc who's
38:00recently joined us and they applied
38:04for and were awarded Oscher Center
38:07grant to look at slow paced breathing.
38:10And mindfulness,
38:12they are trying to differentiate the.
38:17Effects on.
38:18On blood pressure with slow paced
38:21breathing or mindfulness trying
38:23to tease apart these effects so
38:26people will be doing mindfulness.
38:29Yoga's yoga,
38:30breathing plus mindfulness or just
38:32the slow paced breathing and they're
38:35hoping to tease apart the effects
38:38on blood pressure with these three
38:41different usually if court with
38:43these three different approaches.
38:45Usually of course we see apps in a lot of.
38:49Advertising too.
38:52To combine these and it's not
38:54really known what is the relative
38:56contribution of each,
38:57so I'm looking forward to seeing
39:00the results of those studies.
39:02I've, I think that there's it's an.
39:05It's an ideal time to do research
39:08in the home,
39:09and Tele medicine has really taken off
39:11even even more during the pandemic,
39:14and I think that it is developing
39:17some opportunities for us in the
39:19field to do more research in the
39:21home with ambulatory monitoring methods.
39:24Tele medicine. As I said,
39:26I think can augment augment
39:28some of that so we can do some.
39:34Work in interacting with participants
39:37with through Tele medicine and OPT based
39:41interventions have been and are being
39:45developed now and can integrate then the
39:48sleep log and sound or motion detection.
39:51To be able to create different interventions
39:55that may be helpful in improving sleep,
39:59consolidating sleep.
40:00For insomnia, for instance,
40:03maybe even helping to reduce blood pressure.
40:07So I wanted to just acknowledge that
40:10our team and our our funding sources.
40:14This is Monica Hack and she is doing a lot
40:19of different models as I've shown you.
40:24Looking at sleep affects and immune function.
40:27Michael Goldstein is a clinical
40:30psychologist who's working.
40:32With us, and as I showed you,
40:34is going to be starting to do
40:37those that Oshir grant.
40:38Looking at mindfulness
40:39and breathing and sleep.
40:41And blood pressure and Larissa Angert
40:44doing a lot of work now on the resolvins.
40:49And she's fellow,
40:51who's with us now from from Germany.
40:54And this is 1 Yang who is an
40:58instructor in neurology in our group,
41:02and she has currently a HK early
41:06career investigator and Sleep Research
41:09Society grant to look at some of the.
41:13Um?
41:15Some of the renal aspects of blood
41:18pressure control and sleep deprivation,
41:20so thank you very much for your attention.
41:24I will.
41:26Stop it there and I just need to.
41:35Sorry, I should stop sharing the screen
41:37I guess. Thank you Doctor Millington,
41:40this is under the truck.
41:41This was a really long talk,
41:44not really, only just we all know
41:46that sleep deprivation is bad,
41:48but it's really impressive to see
41:50the specific mechanisms by which they
41:52lead to disease and importantly,
41:54some of the mechanisms
41:56for potential recovery,
41:57especially with the sleep extension.
42:00So now the forms open to questions,
42:02so please use the chat to ask your questions
42:05and there's a couple in there already,
42:07so I might ask him to you right after that.
42:10And so first question is,
42:12is there data of recovery,
42:14sleep and disease states such as sleep
42:15apnea or other medical conditions?
42:19Um so so we have lot done.
42:26We have not investigated apnea.
42:31Um? We haven't done any of
42:34these studies with apnea.
42:37I think that that would be a very interesting
42:42and important line of of work to do look.
42:46At in more detail.
42:48I mean there there is some data
42:51looking at see pop effects Now, yeah,
42:54but I haven't seen any studies that have
42:58done these sleep deprivation in apnea.
43:01I would expect them to be more sensitive,
43:05and we have actually been looking at
43:09AT and we will be looking at some.
43:13Responsivity in insomnia population.
43:15So I think that's an important area
43:19that that we're starting to move into,
43:22but I think it's definitely.
43:25Relevant often, particularly in shift work,
43:28where there is increased incidence
43:31or increased prevalence of of of.
43:35Uh, you know diabetes and cardiovascular
43:38disease associated with insufficient sleep.
43:41I think, definitely,
43:43it's important to pursue that.
43:46He I I'd like this say something here,
43:50Andre.
43:50This is Mayor Krieger and I I'd
43:54like to remind Janet that the
43:56very she she presented a paper at
44:00the Canadian Sleep Society when
44:02she was a student.
44:05And she got an award and I was
44:08very pleased to give her an award.
44:10What seems like many, many years ago,
44:13and it was a copy of my textbook and Ann.
44:17And who knew that years later you
44:20would be a professor at Harvard.
44:22Anyways, congratulations on a great career.
44:24Thank you so much.
44:26My thought was really very, very nice.
44:29You know, I actually when I got that award
44:32it was really a very special for me.
44:35And that had been work that I did with
44:39a lot of data that Roger Broughton had,
44:42and I did my as you remember,
44:45I did my PhD work with Roger Broughton
44:48that was on the timing and placement of
44:51napping in narcolepsy and circadian aspects.
44:54And I actually got a call from Roger out of
44:58the blue on the weekend this past weekend,
45:01so he's over in France,
45:03sheltering in place and doing.
45:06All. Nice to see you, yeah.
45:10Great thank you.
45:11Thank you for the kind comment.
45:13Merona reminder at that.
45:14Encouragement early on it can be
45:17very meaningful at lead to success
45:19and so so there's a couple of other
45:23questions and so one question is,
45:25in this sleep extension protocol
45:27that you mentioned is the
45:29sleep extension just extending
45:30the opportunity to sleep?
45:32Or are you providing some
45:34sort of interventions to
45:36actually extend sleep?
45:37And yes, we are we.
45:39We give them instruction
45:41that are behaviorally based,
45:42so it's really around sleep hygiene.
45:45We're not doing CBT,
45:46but we we actually do coach and
45:49we have a psychologist working
45:51with us who calls them checks in
45:54with them weekly asking them how
45:56they're doing with it and giving,
45:59giving them some assistance
46:00with following their times.
46:02So they are just given those times.
46:05But they are also given a set of
46:08recommendations for good sleep hygiene.
46:10No blue light before you know
46:12computer screen time and blue
46:15light before bed and.
46:16No caffeine in the afternoon
46:19and keep your exercise and.
46:22Food in consumption not just before bed for.
46:27Sleep hygiene and
46:29all the wonderful things that we
46:31intend to invite patients to do,
46:33and so are the patients asleep
46:35for the entirety of that
46:37sleep extension protocol. Or
46:39are you measuring that in some way?
46:42Yes, we are, so they have.
46:44They have actigraphy for the whole time,
46:46and we have looked,
46:48and they we are not blinded,
46:50but they are wearing their active
46:53graphs and so we have just looked
46:56and so I cannot tell you how long.
46:59Currently with that protocol,
47:01but I actually have preliminary data from
47:05a pilot study we did that did show that
47:08we were able to increase about 35 minutes,
47:11the sleep duration,
47:13and that was measured with actigraphy,
47:16so we're monitoring that again.
47:18They're coming in,
47:19so they start wearing the actigraphy,
47:22and they wear it until they're completed,
47:25which is usually it's taking.
47:29You know three months or so,
47:31so we have a very large data set of
47:35actigraphy on these participants,
47:37as well as they get into the protocol
47:40of and and into the treatment arm.
47:44We are monitoring all of that
47:47and what is interesting we can,
47:49we can tell you that.
47:52The variability of sleep duration
47:55there variability decreases when
47:57they come into the study and that
47:59I think is pretty interesting.
48:01So just by knowing that there they
48:04haven't gotten any instructions yet,
48:07they've just been asked is keep
48:09asleep blog and where in actigraph
48:12and between just over the course
48:15of time until they are randomized
48:17we see this kind of.
48:22Decrease in variability,
48:23so I think they become more aware
48:26of the importance of sleep or they
48:29become more sleep sensitized and
48:31that doesn't influence which is
48:33part of why we wanted to do this.
48:38Wait list control approach because on
48:41our pilot study we didn't have a wait
48:44list control we we measured them and
48:47then sent them on their way for eight
48:49weeks and had them come back and.
48:53And evaluated again, but we thought,
48:55you know, it might also be that now this
48:58is the second time in the lab and you
49:01know it might be a regression to the mean,
49:04so we wanted to add this wait list
49:07control so I'm glad I'm glad we did
49:10because I think looking at at the
49:12second and third overnight stay
49:14is going to be most important.
49:16Yeah, that's a really nice
49:18way to address that challenge
49:19or regression to the mean,
49:21and so there's a couple of more questions.
49:24Methodological, less.
49:25I'll just group them together and
49:27so the other one is your recovery.
49:30Sleep period was eight hours and
49:32often the patients tend to sleep
49:35much longer on the weekends,
49:37trying to make up the sleep, and
49:39so does the greater sleep
49:41extension change their response.
49:43We we can't say, but I think that's a
49:46really important question we we needed
49:48to draw the line somewhere and we rather
49:52than have participants have different.
49:54Durations of sleep.
49:56We decided to go for what might be more.
50:00Commonly experienced,
50:01many adults don't have the opportunity.
50:04Certainly I think you're right with
50:07early adulthood and teens they might
50:10be more likely to extend their sleep,
50:13and we know that early adulthood,
50:15those people in their late late teens
50:19early 20s can sometimes extend sleep.
50:23To an unusually long duration of 12 hours
50:26and even 14 hours that's been reported.
50:30So rather than deal with the.
50:35Large variation in in ad Lib sleep.
50:38We decided to cut it off at 8 hours,
50:41which might be more typical of
50:43people who are working and have
50:45to do other things or take care of
50:48children during their day times.
50:50But I think that's an interesting question.
50:53Can you actually sleep it out if you
50:56allow extended sleep rather than just
50:58the 8 hours of recovery as we chose?
51:02Great, thank you. Let's see.
51:04Then there's there's several other
51:06questions, and so I will have to.
51:10Focus a little bit on the kind
51:11of clinical end of things and so.
51:15My question is, do you think that
51:17the so-called short sleepers without
51:19any symptoms are biologically
51:21protected from potentially harmful
51:22changes of sleep restriction?
51:25Right, well I can. I can tell you that.
51:32Well, we don't know with regards to the
51:34Physiology, and I think that's a really
51:38important and exciting area to do.
51:40To study. We do know that.
51:46That people who claim to sleep shorter
51:49with regards to their performance,
51:51like if you look at Psycho motor vigilance
51:54tests, we do know that they are.
51:57Also they are impaired when
52:00they don't get adequate sleep.
52:02So there might be some.
52:05Definitely I.
52:06I think that there are different
52:09degrees of vulnerability to sleep loss.
52:13We have a lot of data on the
52:18neurobehavioural and to show that,
52:20but I do believe that there are also
52:24different degrees of sensitivity to
52:27sleep loss that system specific.
52:30So you might have more metabolic
52:34vulnerability than neurobehavioural.
52:35Vulnerability or you may have
52:39more autonomic vulnerability.
52:41So I think it needs a good systems approach.
52:46He's not one apart.
52:49And the last question that's here
52:51is an interesting one. It's in.
52:54Is there any information on sleep
52:56restriction and migraine headaches
52:58that you are familiar with?
53:02So Rami Burstein at our institution has
53:04done some work in Susie Birtish has
53:07done some work on migraine and and.
53:12I think that the the actual
53:15research in the area is still
53:19pretty pretty new and there are.
53:22There's some different findings clinically.
53:25I know that patients with migraine
53:29often complain of. You know of.
53:34Sleep loss bringing bringing
53:36on migraine and if they can get
53:40to sleep at an early point in
53:43the process there is anecdotal.
53:46Evidence if you will,
53:48that that sleep can actually turn
53:51it around for some patients,
53:53so prevent the full blown migraine
53:57attack if they get sleep at and
54:01at a critical point in time.
54:06But that's that's anecdotal.
54:09Great, thank you very
54:10much well the commotion.
54:11Thank you very much for a
54:13wonderful talk and answering.
54:14All these questions are fully and
54:16thank you everybody for attending
54:18yet another excellent addition of
54:20the Joint Seminar Series and Hope
54:22you guys have a great holiday and
54:24we will resume the joint seminars
54:26in January with a special guest
54:29James Nestore who is an author and.
54:31I will discuss his recent book
54:33Breathe The Science of the Lost Art.
54:38And then great. Good luck with
54:40the pipeline development.
54:42Obviously you guys are doing a great job.
54:46Super. Bye bye thanks very much.