Sleep Disorders

this program is presented by University of California television like what you learn visit our website or follow us on Facebook and Twitter to keep up with the latest uctv [Music] programs [Music] all right so you know we have three speakers and um we're going to try not to just Crush you with PowerPoint slides because I think the best part of these evenings is our Q&A so we're going to go through three talks we're going to try to stick to an hour and then the three of us will come up and uh and field questions so my name is Tom Nyon I'm in the department of Psychiatry and I've been in the the field of sleep research for over 20 years and uh with me tonight is Dr shelle Zach who's a sleep medicine specialist and Dr lisos k k georgu who is a behavior neurology fellow with a expertise in sleep and uh Shelly's going to lead us off and is going to give us sort of a PR of uh the basic wiring of sleep awake States um Alisos is going to talk a bit about aging and dementia and then I'm going to talk about insomnia and sleeping pills so why don't we get started Shelly great thanks Yik okay um so when I thought about doing this talk what is this too loud okay sounds pretty loud to me um I first thought about two very interesting anecdotes in sleep medicine that really outline how curiosity and creativity uh ended up leading to developments and sleep science however in order for you to understand them unfortunately you're going to have to learn a lot about the neurochemistry of sleep um it's going to it will be a bit dry but I'm hoping that it will prove to be interesting because by understanding the neurochemistry of sleep you'll be un able to understand the side effects of some common medications and understand why does benad make you sleepy um this will also form the basis actually for Dr nyan's lecture as he will be talking um a bit about or orex and hypocretin um in addition I'm going to end up going through um three compo um the components of sleep theories which involve clearly the neurotransmitters the Circadian and homeostatic processes which I'll explain um and we're going to enjoy the learning about the flip-flop switch which actually is probably better thought of as a teeter totter okay prior um to the early 20th century it was believed that sleep occurred just because you closed your eyes however a very bright um vienes psychiatrist um doc um Dr Constantine bonano who is shown here with his Aviator goggles because he also was an avid flyer um was working in the psych ward in Vienna and around 1917 so what's he seeing he's mostly seeing Soldiers with head trauma right but what starts to happen is he starting to see people who are incredibly sleepy they cannot maintain alertness they are awake for only 4 hours a day but when they're awake they're normal but they cannot maintain alertness conversely he's also saying people who are unable to sleep um and in addition these patients also some of them had some parkinsonian features the book Awakenings by Oliver saxs was his experience with people from this time period so it's going on now it's 1917 um this is the time of the Spanish Flu the Spanish Flu was an epidemic that went through Europe the United States um other parts of the world and was actually referred to as the Spanish flu because many of the countries that were affected were actually involved in World War I and this flu was affecting the soldiers and killing them um and so the military sensors were keeping it out of the press Spain was not involved and so it was coming out in the Spanish press and hence the Spanish Flu um it was an H1N1 flu such as what hit um in 2010 um more recently so vono called this en sephtis lethargica for obvious reasons he felt that there was an inflammation in the brain and it was making people sleepy now a number of these patients died and so vonic cono was able to do autopsies on them and in the process he delineated two parts of the brain that he was able to describe in terms of sleep a Sleep Center and the idea for awak center now um this is sort of a brain um this is the brain stem and Thalamus well this is the cerebellum you can think of the cerebellum as um I'm sorry let me back up this is the brain cut this way as if you take a chainsaw one so the cerebellum you can think of as controlling sort of it coordinates coordinates motion um stability essentially the brain stem is a very phenetically old part of the brain and so it has a lot of very very basic fun functions including res respiration in this case you can see he outlined the ocular motor nerve eye movements and all sorts of other stuff this is the thalamus which is where sensory information comes from the outside um up here that's not pictured but you're going to see it a little later is the cerebral cortex that's more what you think of when you think of brain that's the part of you that's thinking that's paying attention that may be sleeping um and so um tracks go from the brain down from things up but then right in here in this part of the brain stem leading to the hypothalamus the hypothalamus is a very interesting part of the brain it controls a lot of stuff it controls um it controls sleep which is what we're going to get into in gory detail um it controls temperature um feeding um growth hormone comes out of here cortisol is controlled in here so the hypothalamus is a pretty important part of your brain and so what he determined was that when he saw damage to this part of the this part of sort of the section between the brain stem and the hyp and heading up towards the hypo IC area these patients could not maintain alertness and so he posited that there were arousal systems going from here heading upwards that were being blocked similarly the patients who could not sleep the severe insomniacs had a lesion here and this is where he thought um that the center for um cells that controlled sleep were and actually this arrow is pointing to where he felt um probably narcolepsy which they were also seeing might have been controlled this is a prettier picture um and the now just a couple things I just want you to understand that when when you see this line here okay it's not going through there it's coming all the way up and in okay um this shows you the neurotransmitters that are involved in wakefulness um and I'm going to go through them in a little more detail in a second so you can imagine that if you put a lesion right there that all the processes coming here here are going to be blocked they're not going to be able to get up here um similar now if we look at these as all these all these congregations of um wake promoting nerves this is the VPO it's our friend for Sleep the ventrolateral preoptic nucleus don't worry about the name but the idea is that this nucleus produces chemicals that I'm going to go into gabang ginin that inhibit the Wake promoting cells so you can imagine that again if you put a lesion here you're going toe you're going to prevent the inhibition coming from the Wake promoting cells now let's just take a moment look at what the chemicals actually are so the Wake promoting neurotransmitters include histamine um acetycholine norepinephrine nor adrenaline it's an adrenaline type medication histamine is coming from here nor EP coming from here acetool coming from here and in here um serotonin here and also probably some down here dopamine my absolutely favorite chemical um and ereen which we're going to talk about about which is right around there um so knowing these chemicals that these promote alertness that explains why antihistamines that's why they make you sleepy okay they oppose histamine at least the ones that cross through the bloodb brain barrier the more recent antihistamines not doing so um anticholinergics it's a classic side effect of medications um more probably more classically seen with older anti-depressants you do see it with some of the newer ones but less frequently um anti-dopaminergic meds um when would you take an anti-dopaminergic Med well some of the anti- nausea meds and more more prominently probably the antis psychotics um some of the more recent ones like sakel even sometimes used for Sleep um and then the anti orexin which is what Dr nyan's going to be speaking about now in order to understand where the neurochemistry that controls sleep you need to understand a little bit about sleep um I don't expect you to be able to read sleep studies after this I just want you to get a visual picture of what's going on so this is the EEG tracing when you're awake with your eyes open this is awake with your eyes closed this is the EEG tracing when we see someone in drowsy what we would call N1 or very light sleep um this is N2 light sleep this is N3 deep sleep and this is REM which I'm going to talk about in a second but ignoring REM look at these patterns you can see that as you go deeper and deeper into sleep the brain waves gets slower and bigger now depth of sleep is defined by how hard is it for me to wake you up how loud a bell do I have to ring how much of a how much do I have to pinch you um and so as you're getting deeper what's really happening is that the brain is sort of getting deafferented um basically the thalamus where all these sensory stimuli are going is starting to have some of its more um inhibitory neurons the neurons that that um suppress f iring are starting to get engaged to prevent the brain from have from getting the the sensations now if you look at REM REM is really an interesting stage of sleep if you look at this EEG what's it look like it looks much more like the EEG of wakefulness some aspects of it look like the EEG of light sleep and in fact REM sleep is at a depth more akin to light sleep than actually deep sleep a lot of people think REM is deeper it's not actually deeper it's just different um REM sleep is also interesting and we're going to go over I'm gonna be talking about this a little later in that in REM sleep you're effectively paralyzed now clearly you're not totally paralyzed or we wouldn't have rapid eye movements right um also your diaphragm the bottom part of the lungs is moving or you wouldn't breathe um and finally there's a middle ear muscle that moves for a reason that I have no idea um but in any case REM sleep is characterized by brain waves that look closer to wakefulness but muscle that is effectively paralyzed with a few exceptions um and in fact in REM sleep we see that the brain is equally active as it is in Wake sleep now knowing that if you look here this is a hypnogram this is actually hypnograms are great um this is a timeline this is midnight 7 in the morning so we're looking at stages of sleep through the night and I think you'll see other examples of this later in the um in the evening um wake is always at the top and as we go lower we get deeper and deeper um this is older nomenclature S1 and S2 they're now N1 N2 N3 and four are combined so anytime you see a line here the the person is awake this is very light drowsy essentially light sleep and then these this stuff is deep um deep sleep here and then REM sleep which is on the bottom because it just looks good that way it's not really any deeper and what you can see is that you have Cycles between non-r r non-r r non-r r going throughout the night at approximately 90 to 120 minute intervals and the REM periods actually get bigger and the Deep Sleep gets less now I put that in so that you'll start to understand that not only I'm not even really going to talk about this but I sort of put this in for thoroughness sake um that the chemicals involved in rem um are not only those that promote REM which are essentially acline and glutamate but there's this back and forth between REM going on and then Rim being inhibited and going off and then Rim going on and going off and what's going on back and so this is you have your REM on cells and your REM off cells and REM on is acet toolin and glutamate and REM off is norepinephrine and serotonin now these name should sound a little bit familiar because aceto Coline or epinephrine serotonin these are all chemicals of wakefulness during this so acet Coline actually fires a lot when you're awake and then it goes down during um non-rem sleep and then it goes back up during REM sleep while these fire most during wake and then they damp down so looking at this um what's working for the REM so what's happening in nonr is that you have firing of right this part of the brain giving Gaba and ginin these are inhibitory chemicals and then when you enter REM you have the REM on cells firing the aceto Coline and glutamate and then they'll be followed by the REM off cells the norepinephrine and serotonin now Gaba Gaba is a great chemical it's a great receptor the most probably the one you're most familiar with alcohol where does alcohol work it works on Gab receptors um Gaba is sedate clearly Gaba helps you sleep so Gaba is sedating um up until recently most of these sleeping pills the sedative hypnotics worked through Gaba um anti-anxiety medications not all but many um work through Gaba and another favorite is progesterone wonder why pregnant women are so happy and relaxed Gaba um and then the REM the REM is the nor EPI and the um AET REM is acetol and glutamate and then inhibited by norian serotonin okay we actually are going to get to a cute story sorry about all of the science but it is the science of sleep um so there are two theories um of how we end up going from one one system to the other um You' think at this point it would be simplified it would be a single Theory it's always bothered me that there are two but this is where we still in the stain age are um the first one the Circadian Theory process c um the Circadian Theory talks about the biological clock you've probably all heard about it when it comes to sleep we like to think of it as a gate the gate is the gate opens when it's easy to fall asleep closes making it hard to fall asleep and so you can think of it as promoting wakefulness um this is the morning and early afternoon and then the gate opens and you and you get drowsy this is the cesta time time and then it's harder to fall asleep in the early evening and then as you get into the night time it becomes easier to fall asleep now this also explains why if you pull in all nighter you get sleepier sleepier sleepier so 5: in the morning you could just collapse but come 8 or 9 you feel worse you feel more tired but you try to lie down and you can't sleep that's this process the gate is closed now in addition to that we talk about process s s for sleep sleep specialists are just not that creative um and that refers to the homeo the homeostatic drive for sleep and that um was actually that's been around for a really long time um it was just oh I can't remember when but long time ago that if you took the spinal fluid from Sleepy dogs and you injected into wake dog awake dogs guess what they would do they'd go to sleep so that led to the belief in in somnogen that there are these chemicals floating around that produce sleep um we now have them a bit more defined adenosine prostag gland and D2 tumor necrosis Factor Alpha and interlukin one as well as nitrous oxide um so you can see process s is the is the homeostatic drive for Sleep the longer you're awake the more of these you make and it and it's pushing and and pushing you towards sleep and it's the it's where these two how these two processes are B balance that determines whether you're awake or asleep um and so we as sleep specialists when people come in and they're having trouble sleeping at night one of the first things we ask is are you taking naps because as you enter sleep your sagens fall down and so by taking a nap you will get rid of some of these and thus not have a high enough drive towards sleep when the gate is open so all of this is sort of some background to understand narcolepsy and what was a really fortuitous and clever clever Discovery um which are the Sleepy M the Sleepy mice that defined um one of the latest theories in not only sleep regulation but also narcolepsy or rexen um so narcoleptics you probably have seen in um discussions of it but basically narcoleptics are sleepy they fall asleep while talking they fall asleep um while eating driving which is what scares us but the main thing is forgetting they're sleepy the main aspect is they cannot maintain wakefulness conversely during the night they cannot maintain sleep there's sort of this disconnect they're going back and forth and back and forth and back and forth the balance is off one of the interesting other aspects of narcolepsy is that in certain in one VAR well probably the main one of it you have cataplexy cataplexy is the sudden loss of mus muscle tone provoked by a strong emotion um it can be anger it can be laughter in fact neurologists used to have um joke books so that they could try to induce a cataplectic attack in the office before we had better um studies for this um Consciousness is maintain it's a loss of motor tone I described for you how in REM sleep you lose your motor tone it's kind of akin to that and it can be manifest by a headd drop um total collapse of the body um Stamford is famous and we'll get into that in more detail these are the narcoleptic dogs um I don't know how to import a video but you can go on YouTube and you can watch the dogs and they're running around and then whoops they collapse because they got very EX excited um they'll be back up very soon it's very brief now the story behind narcolepsy began with the search for obesity in 1998 two two papers were published within a month of each other um delich and Koff were looking at proteins in the hypothalamus and trying to um purify them and figure out what they do so they knew they were working with the hypothalamus so they called their proteins hypocretin um they actually describ Pro hypocretin and then it's to byproducts um because it was from the hypothalamus and it looked like um a gut hormone called secretin the same time sakuray and yasawa were looking at what they called orphan receptors receptors that they didn't know what actually complex to them so they found a chemical and they injected it into rat brains and they started to eat so they called it or rexin for appetite okay so the next thing you do is you make an animal model so they made a mouse that didn't have any ereen and they videotaped these mice and somebody very cleverly um was watching them and notic that the mice kept collapsing during their active period which is nighttime and then they started to study them and they saw these rats these mice that were sleeping more during their active period than they should be and somebody went and just said you've got narcoleptic mice so this became the a second animal model for narcolepsy this was the discovery of or rexen hypocretin and its role in in and the fact that its absence will create Nar Y at the same time mino's Lab at Stanford who has they have their Doberman and they saw in in the Doberman not in people but in their animals that it's a problem with the receptor so in people they've shown that there's a 90% reduction in ere rexin producing neurons as well as little to no rexin being produced in the spinal fluid um this gets us very close to the end so now we realize that from looking for a model of obesity they found a model for narcolepsy and this ends up um going to the to the flip-flop switch Theory so the flip-flop switch is apparently a theory in mechan and Engineering that a St it's either one state or it's another you're not both you're going back and forth so they always talk about the flip-flop switch and they always show a seesaw but be that as it may that's the lingo and so the con the question was we have these parts of the brain that I sort of glossed over earlier that are making um uh tn's got to be histamine I can't read histamine serotonin Ori um and then we have the other part of the brain that's making that induces sleep that's producing a lot of Gaba and the and so one's more active the other's more active what is actually controlling this this seesaw and the thought is that it may be orexin coming out of the lateral hypothalamus that during the day what is allowing you to maintain this wake State and not be dropping off every you know know every every couple hours during the day is the continuous prod um production of ere rexen during the day that actually then gets damped down at night and that it is allowing you to maintain the wakefulness state so basically um because of a very smart um psychiatrist we were able to figure out that sleep can that the control for Sleep involves the brain stem and the hypothalamus in different places and in different loai um this allowed the development of sleep wake networks running sleep wake networks running up and down the brain stem into the cortex the more thinking part of the brain that there are a lot of neurotransmitters involved that will explain some of the common side effects of common medications and that the biological clock along that the that the biological clock along with the development of the Sleep promoting factors the rise of these somnogen actually help modulate which way these these um systems are going and that it's you really think of it as sort of a flip-flop switch that's under the control not just of the biological clock and the homeostatic factors but that you have hypocrite and or rexin actually controlling it and that this discovery turned out at the same time sort of like the calculus um and that it was actually occurred because they were looking for obesity so um I thank you very much and now I think y Dr kajio is up so um I'm a behavioral neurologist I have an interest in uh sleep and dementia and uh what I'll try to do what I will outline first of all i' have no conflicts of interest and uh what I will try to do and outline is very briefly go over why we sleep and how we sleep and then Focus over uh what effects uh what changes happen uh in sleep over aging and then what changes we see in dementia uh patients as far as sleep is concerned and also will buil on a new um finding or new findings over the last few years where actually sleep changes can increase the risk of developing a degenerative disorder or degenerative findings in the brain um and then the more important part what can we do as um individuals and also what can our physicians do to help us so very briefly uh do we really need to sleep is there any practical purpose for anybody sleeping and uh there's two concepts two main Concepts as far as a neurologist is concerned on one hand you allow a restoration you your tissues through sleep get restored but also there's a very strong um reorganization that happens during sleep you get your synapses that reflect memory consolidation practically uh um uh remodeled throughout the Sleep uh cycle and there's also some ecological uh benefits potentially and we already talked about both the Circadian rhythm the C process and also the Sleep process the homeostatic process um and uh practically you have these two states in the brain while you're awake and when you're asleep and early on you as you are awake you start building uh different neurotransmitters adenosin being a prominent one and it eventually tells your brain or all right okay you're very very tired it's time that you fell asleep but as Dr Zach said well if you pull an all nighter in the early morning you can't really fall um fall asleep uh again because it's not just enough my cousin when we were five or six years old I told him hey it's 10:00 at night we've been uh up all day we're so tired why can't we sleep and he says hey it's not enough to just be tired you need to be sleepy and he was six and seven so if you understand it at that age you probably figure it out now and that's the second part how do you enter how does your brain get into that circadian regulation that internal clock and that is mostly controlled uh through um our internal um clock of the suprachiasmatic nucleus which gets information for light exposure that's why we tell our patients hey go out in the sun in the morning get that Consolidated and that will eventually block initially melatonin production but when Night Comes you see that melatonin starts to increase and that starts to give your body the sense okay it's now you're sleepy what's also interesting is that same nucleus indirectly also controls your body temperature and they're anti-correlated these two so when your body temperature starts to decrease is when you start becoming sleepy okay and uh practically you have this uh variation throughout the day where uh as your body temperature um increases you're fully awakened then as it starts to decrease you start becoming sleepy and so forth okay and each um we talked about the uh sleep architecture the that during your sleep you have Cycles through these Cycles you go through deep sleep deeper deeper deeper deeper and then you get a rem uh episode a rem period and then you have another cycle so each one of these uh uh use if you want is one of these Cycles um and we talked that each one is defined by the brain waves uh from the EG um what's important is that each one from uh memory perspective allows you to encode to consolidate memories uh better but specific types of memories so if you're in one of these deep cycles of the slow wave sleep as we say you encode episodic memories things that happen to you and you remember uh the next day and you say oh yeah I remember that but then when it has to do with procedural memories or emotional memories and that has to do for example how well somebody can shoot a basket a basketball into the hoop that's not something that you remember doing explicitly it's a process that you learn through several procedures and that's something important for ramle and just breaking it down uh same thing here just don't focus on everything there's just a couple of things I want you to focus here uh one is that during this period which is the ram sleep so in one cycle in the ram sleep one important neurotransmitter that's increased is the same neurotransmitter that's increased during wakefulness that's aetl Coline and I highlighted because when we talk to our patients we give when we treat our patients with that have Alzheimer's disease we give uh um medications that increase the levels of acetyl choline but that same neurotransmitter is low during other periods of the night and it has to be low to allow other types of um memory to occur and actually if you look at the brain which parts are active during the different periods of the uh night or the cycle the hippocampus the area that we have to be that has to be more active during um um memory encoding episodic memory uh is during non-rm sleep and vice versa the cortex uh and the frontal loes are more active during that uh REM sleep okay so classical thinking says that okay if I have a problem in my brain I will get some problem with my sleep if a specific Center that control sleep is affected I will have problems with uh sleep and uh thinking a bit before the full blown uh deficits happen is is there anything normal as far as aging and sleep is there something inherent to the aging process that okay it's expected that as you age you will change some aspects of your sleep some things that are um characteristic are first of all the Melatonin secretion which allows you to say which time of the night you will be more uh sleepy if this is a young adult and uh Mel is secreted between um whatever in the middle of the night let's say if you're a teenager this is a bit shifted so it's not weird that your teenage kids or grandchildren are actually up later they they are partying too but they're also having a melatonin secretion uh at later times but then as you age your melatonin starts to get secreted earlier and it is still the same amount of melatonin but when you also get into advanced dementia stages the the the sleep patterns really break down and also melatonin patterns uh start to break down and uh other aspects that are uh different as we age is that as a baby you you sleep as a baby like a baby you you go into that deep sleep an airplane maybe passing by the baby won't wake up but then as you're growing older and older and older you don't get into these deep stages as much and you you stay in those more lighter stages your R sleep is also smaller so you end somewhere in between Queen most of the night um and then there are some characteristic patterns that come up with aging in uh in populations that they were just observed people that didn't have any cognitive problems just observe for uh sleep patterns and they found certain characteristic uh uh changes so it's more likely that people nap during the daytime uh with aging but this also has an association to uh risk for having any type of mortality any type of risk of death being earlier by about 15 to 30% but if you have gone through an all nighter napping the next day is a good thing because it allows your body to uh recuperate also the breakdown that we um uh talked before uh does become more evident as we age and uh um actually this is one work over here by Christine Walsh where you do have a faster cognitive decline if uh um you end up having more um breakdown of your sleep patterns and also you are at increased risk of developing Alzheimer's disease what something that's very interesting over the past few years is there's several studies uh the biggest one by the wh show on how long you sleep so you have people saying okay I don't sleep long enough I'm tired all the time that makes sense on having poor uh cognitive function that's what these uh inverse U curve shows that if you don't sleep long enough you don't perform as well on cognitive tests but there's these people that come to clinic and they say I sleep great I sleep 10 hours every night and when when you hear that you should go damn that's not good and and and actually that that is s even worse than sleeping less than uh 6 hours every night uh comparatively having insomnia is a bit of a mixed bag there are some features that could be good or non-c concerning and some other features that could be concerning but uh at this point we don't have a definitive uh answer as far as Dementia or aging I should say is concerned and risk for down the line dementia uh is involved a big part and I'm I'm sure you've heard of sleep apnea or sleep disorder breathing uh uh is um in aging is that and also in dementia eventually so there's uh these two big studies and these were done by Christine yaf here at UCSF and uh it's a big there are big population studies and they looked at women separately and Men separately but they really came up with the same result so they took women and men that either had sleep apnea or they didn't have sleep apnea what they found was that the ones that did have sleep apnea were more likely to develop dementia down the line either mild cognitive impairment or full-blown uh dementia it was more prominent in the men compared to the women the risk of uh having a dementia down the line if there was a sleep disorder breathing but both indicated that the mechanism was actually a hypoxide as you are not breathing well you don't get enough oxygen to your brain and recently there was a pathological verification so somebody cut down the brains of these people and found that there are micro infarcts in the in the brain uh and it's important because we can treat that uh sleep disorder breathing is something treatable uh whether you want a full mask or a nasal mask or other uh approach if you have milder deficits it is something treatable so something to consider uh and also our breathing as we enter these deeper our um brain perfusion the ability to for the heart to send blood to the brain during this deep sleep is uh uh decreased so you need to get more oxygen during that period of time otherwise you'll have more hypoxia more episodes so now the question is I've told you all these things that are risk factors for eventually developing the mentioned does it mean that if you see something if somebody has a problem they will develop uh degenerative problem so there was some uh very interest there are few studies um but uh one uh uh nice example is this one the sleep in America survey and what they did was they called people and they tried to identify what's the risk of having a um a sleep problem if you have another comorbidity and it could be anything and really what happened was that people that had had a sleep problem or we're more likely to have a sleep problem we're more likely to have more comorbidities uh so uh if you had more than one so let's say hypertension and high cholesterol you could have a sleep disorder by 40 40% chance you had a sleep disorder okay and there were some other studies that also indicate that so there is this evidence that really having um sleep problems as you age is not something that should be expected and anol Israel a prominent sleep and dementia researcher says that just having sleep problems alone uh just aging alone doesn't mean that you'll have sleep problems it's all the things that go with it the with the aging process that lead to the Sleep problems that can be illnesses it can be medications that you take as you age uh circadian rhythm disorders that uh uh you may have or primary sleep problems uh directly related to sleep so for me specifically as a behavioral neurologist I'm interested okay so I see people that are aging or they have a dementia and they say I have a sleep problem should I be concerned so there's uh should I be concerned for having a degenerative process that's advancing so there are there's this nice work by Ric Andel who works uh uh from the Netherlands who works also here at UCSF with Gil rabinovich and what's the interesting finding is that they took pictures of the brain with a pet scan and they looked at how much ameloid people have in their brains and they said okay if you have a diagnosis of Alzheimer's disease it is very likely that you have amalo in the brain and there are some other factors in that that with aging this probability is decreased however more importantly more interesting uh to me is that as you age even if you have no um cognitive deficits it's much more likely and that's that the black line to have um ameloid in the brain and amid is related to Alzheimer's disease so if you have a certain genetic uh Factor if you're um so you hear apoe4 for example and you're 75 years old the chance of having amalo of the brain is 50% it's much less if you're negative but this is important because if you are more likely to develop um to have amid pathology uh with the um as you age you start thinking okay what does that mean uh for the brain and what does it mean for sleep so when people come to me and say okay I have these problems with my cognition could be Memory it could be Behavior it could be orientation navigation seeing what I what I think is that okay depending on the pattern you give me I'm thinking of a different dementia it can be Alzheimer's it can be Parkinson disease or Louis body dementia it can be primary uh Progressive superclear PCY and I mentioned those three because those three early on in their um presentation affect the brain stem so we talked about all these nuclei that control sleep so if early on even before they hit the cortex those abnormal proteins go and reach those Central nuclei you would expect to have Sleep Disorders in people without having any cognitive deficits and practically this is one interpret ation of why as we age we see more frequent uh Sleep Disorders uh in people so putting it uh all together uh Sleep Disorders in uh healthy agers uh partially predict future uh dementia exactly because these centers are involved and there are specific not all the dimensions uh will have that pattern but the ones that do affect the brain stem early on and that does include Alzheimer's it does include Lou body dementia it does include Progressive superclear policy are more likely to also be associated with Sleep Disorders early on and they don't have to be extreme or out of proportion to what somebody would otherwise think for aging but if you do more detail evaluation you may be able to pick them up and some of them do have unique characteristics so you come to me and you say I'm really living the dream dog and every night my wife says that I'm uh throwing hoops or I'm beating somebody and yesterday even beat her and she was complaining but it's really you you you are going through a REM sleep you're having a dream a very Vivid dream and because the centers that make you paralyzed don't work anymore you end up uh acting it out um but that's a very unique case most of the disorders that we see that overlap the Sleep disorders that we see overlap in the dementias uh have to do with the sleep patterns The Napping the breakdown of the Circadian rhythm the Sleep Disorder breathing things like that that we uh mentioned before so practically now putting this trajectory from brain pathology brain degeneration to sleep disorders you have these Pathways where you have an incar alertness during sleep so you don't get into that deep sleep your your brain fires more and then you also complain of insomnia there's studies that show that even though we think somebody's sleeping there is EG shows that it's very fast it's as if it's a waking EG and we're not talking about well not fully waking but more active and uh uh it's not REM sleep and these people complain of insomnia even though we think they're asleep but what and they are right they are partially awake in their sleep um and that also they have lighter sleep and also they break down their sleep because it's easier to wake up it's also uh the the separation between the alertness center the wakefulness Center and the Sleep Center is not as complete the the there starts to be an overlap between the two so you end up having fragmentation entering uh in and out of sleep more what's the result you don't sleep well you don't rest well so you're sleepy during the day and you have one sleep disorder also if you end up affecting also the arousal centers and you don't send acetal coling as we said and other neurotransmitters during the day you end up being sleepy dur during the day that's why when we say okay take this medication for uh Alzheimer's disease we say take it during the day because it also stimulates you and perks you up also the early um the earlier the shift that we talked about that melatonin is secreted earlier as we age yes it causes an advanced sleep uh phase what happens then then uh people say okay I'm sleepy I may be tired but I want to stay awake I mean it's only a quarter to uh 8 and I want to hear listen to that talk I want to go eat afterwards I want to spend time with my grandchildren and then the Melatonin effect passes and then you're awake all night and or you sleep for a bit and then you're awake at 2 or 3:00 in the morning uh so that's another problem you have sleep maintenance insomnia but also in advanced dementia you end up seeing more people having Su Downing because you you have this sleepiness so you have these intrusions of sleep States even though you're awake wake and Sandown is I didn't explain it is an effect where uh dementia patients uh behave erratically if you want they are uh confused disoriented they may see things at times uh or talk gibberish uh and one of the explanations that uh you have intrusions of this sleep State during the wakefulness because it shifted okay but we talked about that there's recently a bidirectional relationship and we can uh we know now uh especially in animal studies but some human studies that if there are Sleep Disorders if you uh force your uh lifestyle to screw up your sleep you're more likely to develop a degenerative process later on so one uh for as a background there is evidence in mice that the more you uh uh you stimulate the mice either uh through tactile stimulation or you stimulate them chemically to be to have an active synaptic activity the more ameloid deposition happens at the synapsis so there is this Association where uh the neurons fire more and there's more ameloid deposition that's what this graph shows where uh the amount of ameloid increases with the amount of activity uh in this case it was stim represented through lactate now that leads to the obvious question okay what if I Mo modulate uh the sleep wake cycle of mice uh or humans eventually but will can I verify that if mice sleep longer or if mice sleep less that will uh translate to a an effect to the amount of ameloid in their brain and the answer is yes so over at wasu they took these mice that are more likely they're genetically modified more likely to develop Alzheimer's disease or Alzheimer's like pathology in the brain so they went through different manipulations in one state they said okay will increase their sleep they did actually through orexin mechanisms they increase that slow wave sleep and they found that from the situation where you would have a lot of amid all these black dots and reveal ameloid that amount was less comparatively uh when uh sleep was increased that deep sleep vice versa they took them and they said okay now you're awake and they again through manipulations they they forc them to remain awake and even though they they did develop um ameloid pathology in the um normal state if you want in the Sleep deprive state that ameloid deposition was more increased okay so overall that means that at least in my sleep is good for avoiding ameloid deposition so coming to humans now so across the bay there's a another campus called Berkeley and the people over there are actually doing some uh really nice stuff cool stuff uh and they took uh normal people and they said okay can we sort of see if sleep and ameloid deposition are related in normal people not in people that have Alzheimer's and they're advanc people that whose cognitive function is great or normal anyway uh so they took 26 cognitively normal participants and uh they had them do a task before they slept and a task uh the day after they also had images of their brain and that's the this top part of see how much ameloid each of these people had in their brain remember that curve that as you age it's more likely to develop ameloid so practically these people belong to different parts of uh a specific age so average age is 75 and some of them have more and some have less ameloid then they also looked at how much uh deep sleep do these people achieve and how is that translated what it showed was that the ones that had less deep sleep and those brain waves in that medial front Al area that we talked before in REM sleep that area over here that is more active during REM and less active during slow whip sleep that showed very consistently that um they were more likely to have uh increased ameloid pathology in that area also so there is this um relationship even in humans that getting into a slow wave sleep getting into that deep sleep can uh is at least Associated we can definitely say there's a causal effect yet but it is at least associated with less ameloid pathology uh and also the the cognitive test that they performed did show that these people also perform better the ones that were able to go into deep sleep also perform better the next day so what happens uh during uh the Sleep process through during sleep on ameloid so there's a few things that happen one one thing is that you uh during that deep sleep you can pick up more amid leaving the brain from your CSF your ceros spinal fluid the fluid that comes uh from the brain but also part of it leaves through your blood 60% leaves through your blood uh the other 40% leaves through other mechanism including the CSF now as you are uh as you don't have ameloid pathology in the brain that fluctuation where while you're awake you have less ameloid getting thrown out and uh during sleep uh you have more amid get you get rid of more ameloid that fluctuation that sinusoidal wave becomes less as you start developing ameloid plaqu this is mouse studies I should clarify that um so that ability to clear the ameloid uh from your brain becomes less uh prominent as you start developing am um ameloid plaques in the brain that's important because it also tells us that if we want to get rid of amid in the brain we have to hit the disease early because later on in the process we won't be able to clear the amid through these traditional mechanisms as easily okay and practically this brings us now to the full circle of how Sleep Disorders can add uh can lead to brain degeneration and the patterns we discussed was increased neuronal activity during your sleep leads to more ameloid deposition which is related to the generation but also the more ameloid deposition that we talked about leads to worse sleep because you don't sleep as deeply you have more neuronal activity so it's a vicious cycle there and uh just uh to clarify also that the Sleep Disorder breathing goes both ways you can have uh sleep apnea because the centers of the brain don't let you breathe deeply but you can also have uh sleep apnea because you're obese and uh the peripheral mechanisms don't let you D briefly so um the hypoxia that uh um accumulate or happens uh eventually can cause to degeneration both ways um so closing getting into the Practical aspects what are things that are uh important for us so first of all uh one thing uh I I always remember is uh I had this patient and she comes to me and she was 67 she says I'm okay uh my sleep is okay I wake up three times though in the middle of the night and I go pee I'm going okay so her prostate is enlarged and it didn't fully make sense so thinking about it uh and reading the literature what turns out is that as you have sleep apnea and you have hypoxia you send signals to your brain where you make your brain think it's okay to pee during the night uh and that's not what the brain normally does under sleep so you end up peeing during the night so as you if you uh and so if you end up peeing a lot during the night that's one thing to keep in the back of your mind do you have sleepapnea and indeed people that have been treated with a seap or with a surgery do improve as far as their brain saturation the the ability the oxygen saturation and also uh decreasing the amount of uh nighttime awaken is to PE um how about dementia and using the CPAP in dementia patients there's one good study on on that uh and uh it was in 52 Alzheimer's patients and uh giving CPAP did improve the Sleep qualities you people did enter that deeper sleep and also in one of their cognitive te or actually in a combined uh outcome measure that they looked at there was a positive effect to cognition they actually perform better as far as their thinking went um in overall analysis when you look at overall how does cognition improve how does our thinking improve if we treat sleep apnea uh the only marker that is really improve this vigilance so the ability to be alert during the day um just uh a couple of things for the Alzheimer's uh patients uh is that of the different studies that have been done on different medications that have been given for insomnia melatonin didn't work ramelton didn't work but trazodone has worked objectively probably melatonin could work but the studies were not uh tweaked in a way for that population to work but for TR it's a very uh safe drug and I don't get any money from them so but it's a very safe drug uh and it increases sleep by about 40 minutes at the lowest dose that we give it without any side effects the next day no sleepiness the next day in our population another thing we um touched on uh earlier was uh the acetal Coline so a common drug that we give to our patients is uh dzil or Exelon rasmin and so forth and when they your physician prescribes it or to your family members they may prescribe it at night because that's how their electronic medical records pops it up but actually we know that if you give it at night people don't sleep as well they have more insomnia not only that we know also that if you give a a calling at night the non-rem sleep is not as prominent so you don't consolidate that episodic memory so you give it in the morning you allow uh the body to have more acetal calling during the day which you do need for alertness you enod you do encode information during the day then you you have less amount of that during the night so you can go through your deep sleep and uh um consolidate memories as well and there are studies that show that that there is there is a benefit in giving it in the day so some uh last two slides first what to discuss with your uh physician so tell them um what's your the time to bed what time do you get up out of bed uh do you go to the bathroom at night how long do you sleep are you that great sleeper that sleeps 10 hours every night um and then if you're acting out your dreams are you really living the dream should you be uh looking for ways to treat because there are treatments for these things and discuss with your medic your with your physician exactly how you take your medication not only what medication you take but also what time you take it you saw badril uh has uh uh effects that can lead to sleepiness but it also affects memory for example we we really shy away from it in our our population of dementia patients and then ask for your physician if there's any questionnaires or sleep diaries that you can fill out now some things for yourself just in general and and uh I include my myself in that is that what should I pursue like as we age since we know that keeping a good sleep uh pattern helps us prevent or likely helps us prevent uh uh brain degeneration what should we do so one thing is sleep hygiene and there's a lot of stuff in that um some uh important factors to consider are be exposed to light during the day and sleep consolidate your sleep during the night without having light exposure TV and stuff like that at night uh exercise during the day um have a a schedule during the day avoid caffeine or other stimulants after 2 in the afternoon no alcohol in bed near bedtime because it causes a rebound insomnia at in the middle of the night so you have that red wine right before sleep or a night cap and 3:00 in the morning you're wide awake and that screws it over um there's a trick in uh showering um about an hour or two before the desired time of sleep remember we talked about the the temperature the body temperature so if you bring up your body temperature by having a a warm shower a hot shower you come out and then your temperature starts dropping so you start feeling a bit sleepier it's not perfect but it's one way we can intervene especially for our dimension patients um and then think of medications uh and consider agents that can be avoided um so that's it thank you very much and uh we'll carry on okay all right all right so uh let's get started um so you know um these are the main Sleep Disorders you know that that that that a clinical sleep center will look at and I'm I'm just going to really focus on insomnia but but the big ones are sleep apnea which you've heard about narcolepsy periodic limb movement disorders we haven't gone into that much but it's l kicks in the middle of the night that have kind of a kind of a rhythmic quality to it almost like a metronome circadian rhythm disorders you know jet lag um night shift problems irregular sleep wake timing and then um my favorite insomnia um but you know the the the approach to this is sort of in some ways it's the same I mean you think about what is the problem is it sleepiness is it insomnia and this is sort of the kind of the basics of a good clinical assessment how long has it happened um when did it start when does it get worse uh what are the what what's the how's the person's General Health you know do they have any comorbid medical problems pain are they taking pain medications are they depressed have they had ever taken anti-depressants alcohol caffeine nicotine family history of sleep problems and of course of you know lifestyle and stressors uh and then of course you want you do want to rule out kind of major Sleep Disorders uh sleep apnea and periodically movement disorders um sleep logs are actually quite yell helpful you know the um and a variation of that are some of these Fitness to we weables that some people do and you get like a you get a instant feedback on your sleep and I actually think that to some extent that that that may be an intervention in its own right uh people tend to shift their behavior a little bit to maximize that that sleep score they're getting on their Fitbit or whatever it is and I don't work for the fifth bit people um but in the any event Diaries are very monitoring sleep in fact can change behavior of sleep um and of course the thing that we're interested in is the timing of sleep sleep onset how continuously you remain asleep during the night and whether or not you are a night owl or a morning person um so in any event this is what a sleep blog looks like and usually something when you go to bed at night you report on some some things about the day you know did you take any naps did you use caffeine and then in the morning when you wake up you fill out a report of how the night went how long it took you to fall asleep and how long you felt how how how long you felt like you slept when do you go to a sleep lab uh when do you go to see Shelly um so clearly if you're worried about sleep apnea um you know if you're worried about your bed partner having sleep apnea and that's usually what happens it's somebody who notices that their bed partner snores loudly and there and their breathing is you interrupted by loud gas um or if there's a you know leg kicks again it's usually the bed partner report gives you a pretty accurate diagnosis sometimes dangerous behaviors at night that people acting out their dreams uh or there's a certain percentage of people with epilepsy who only have seizures during the night um or if they have severe sleepiness that's a scary symptom because because the the risk is falling asleep while driving an automobile uh insomnia generally is not a a symptom that you refer people to The Sleep Center for uh except when theyve sort of when first line treatments have failed um and in which case you really start to worry that there is a an occult sleep disorder that you haven't picked up but in the absence of that sort of generic insomnia it's not really an indication to go to a sleep lab okay what are some of the insomnia comorbidities many many things uh heart disease pulmonary dis disease pain problems pain is a sort of a double-edged short pain will keep you awake and pain medications pain um alosa has talked about the these states where you're tired but not but not sleepy uh opiate pain medications can make you feel less alert but they do not make you sleepy and in fact there's actually been really nice studies show that that these that opiates actually all of them tend to have an activating effect on the EEG some people are actually subjectively aware of it themselves uh uh perky perets um so some some people are aware of the fact that the Opus have a stimulating effect most people don't most people feel as if they're under the influence and they're less alert but objectively they're actually their sleep is activated um endocrine problems both hypo and hyper thyroidism uh noctua is a big issue for fragmenting Sleep both in men and women actually actually uh I've already mentioned pain and of course in in my field Psychiatry depression and uh stress disorder are major causes of of chronic insomnia and then I've already mentioned these M these major Sleep Disorders so there are the first line treatment for insomnia is behavioral treatments um and I you can actually distill the essence of Behavioral treatment to a single phrase and that is spend less wake time time in bed so that means you only go to bed when you're sleepy it means that if you have trouble falling asleep and you're lying in bed awake you actually get out of bed if you if you get out of the if you wake up in the middle of the night and you can't fall back asleep you get out of a bed what you're trying to do is you're trying to eliminate the association with the experience of lying in bed with being awake so spend less wake time in bed and you do this by you know um you know sleep restriction is actually a big intervention there where you sort of limit the opportunity that you give yourself to be in bed and that actually is an interesting issue because a lot of people with chronic insomnia sort of develop a strategy of just spending more time in bed on the idea that if you have that much more time in bed you you're increasing the opportunity for sleep to occur but unfortunately what that does is that it sets up this linkage with lying in bed being in the sleeping environment and getting used to the fact of being awake for hours at a time so sleep restriction means you just don't limit that time you're you're in bed cognitive therapy is sort of addressing people's worries and anticipation of what might happen to them if they don't sleep uh that well that night you know idea is that you your brain won't work at all if you have a bad night of sleep you know sleep people um tend to speak out of both sides of their mouth when when they when they write a gr and they write a paper and they say sleep problems are killing us you know there are all these medical problems that occur with them and that's actually true but the real thing is to say that chronic sleep problems are associated with those morbid outcomes but intermittent insomnia is not going to kill you um and in fact your ability for your brain to work pretty well the next day is actually quite good and so the cognitive work of helping somebody with insomnia is to forget about tonight uh you're worried you want to change behavior that ultimately has an impact on long-term sleep awake habits but to forget about tonight get person less focused on am I falling asleep am I getting sleepy is it happening tonight is it going to happen I need to sleep tonight because I have this talk tomorrow um the more you're focused on sleep the more you feel to you try to willfully make it happen the less likely you're going to fall asleep you can't be there when you fall asleep right so so so so you have to give up the idea willfully making it happen so that's the cognitive work you actually have to get people to actually feel less frightened and frantic about occasionally having bad sleep because when it happens it's not that big of a deal all right um so uh relaxation training I actually think of that as something like playing a musical instrument it it helps if you have talent um and and then it's practice practice practice it's not something you can kind of flip on PRN you know you're flying to New York and you want to turn on your relaxation tape to fall asleep but if it on the other hand if you have a practice uh that involves some daily approach whether it's meditation or deep breathing or yoga whatever if it's part of a habitual practice pattern then it is very useful for sleep okay so um the you know here's the interesting thing the over-the-counter sleep medications are actually pretty toxic and and and and um you know you can kill yourself on two week supply of Benadryl that's sort of the shocking thing and um so you know the benad dril and the Sleep over-the-counter drugs they do make you sleepy there's actually a lot of drugs that make you sleepy and in some ways you you have to kind of turn the problem upside down the you don't as Physicians we're not trying to make people sleep more we're trying to make them feel more alert and attentive and functional during the day and once you adapt that attitude it really change your thinking about what treatments are acceptable uh for sleep you know because there's a lot of sedating drugs out there a lot of them have inappropriately long half-lies including the antihistamines Dien hydramine and you know they're especially not well tolerated in in older people uh they they can actually has significant cognitive problems so all right um these are most of the insomnia treatment medications and there's Kind of a Funny Story here a lot of the these are benzidines these are the older School sleeping medications um the the decision of a drug company to go for to make their benidipine a hypnotic drug as opposed to an angiolytic or anxi drug that was entirely a marketing business decision and it had nothing to do with the pharmacologic properties of the drug actually so um some of these drugs actually aren't as uh lipophilic don't go into brain as rapidly as some others and some but the big issue here is this these drugs are just so long acting um and again if your Strate if what you're really trying to achieve is to is to improve daytime alertness and and daytime Co cognition these old schooled hypnotic drugs uh florapan which is deline um and in fact there's a metabolite of delain that has a halflife of about 200 hours it's almost like a a Depo hypnotic drug it's just it's something that's just in your body for a long time now the newer drugs these so-called Z drugs zulm uh ambian uh zaplan Sonata ESOP Lunesta you know In fairness to them they actually do have more appropriate half-lies you know that they're they're not as long acting that's a good thing um but the idea that they're sort of somehow a much cleaner drug than the the older Bodines is not necessarily that true um so can I ask for a show of hands how many people here either themselves or know a person have had ever had had a funny behavioral experience on ambian so you know maybe about 20% of the people here it's not a trivial amount um so okay so anyhow there's a couple issues here and I'm going to come back to the ambient story is that I worry a lot about half-life of these drugs because the same property that promotes sleep at night is the same property that diminishes alertness and vigilance during the day that's not what we're trying to achieve in clinical medicine um all of these drugs U all of the benzodi aines and the Z drugs are going after Gaba now you we showed you pictures of the Sleep awake centers and there there was one Center called the ventrolateral preoptic nucleus this is where Gaba is well unfortunately Gaba is in a lot more places than this one nucleus it's in fact it's everywhere it's in the cerebellum it's in the brain stem it's throughout the entire cortex and the problem with giving a gap hgic drug is that you are under the influence when you have that drug on board it affects motor coordination affects arousal affects memory cognition so um what's this um this is a picture of a small platoon in um Eastern Afghanistan and featured right here is a 19-year-old named Zachary Boyd and this Photograph um when went viral on the New York Times years ago in part because he's wearing boxer shorts that say I love New York um but what what what this what this story is about is that Zachary had been asleep for two hours um when they had incoming Fire And so there's there's Fire coming in and he immediately gets to work he puts on his body armor and he gets to work so the defense department has recognized for decades that people deployed in a war zone are not sleeping well and people who aren't sleeping well make errors they make mistakes uh and they make errors of omission errors of commission and they've actually decided that in the risk benefit calculus it's actually better to give sleeping pills to soldiers who are deployed in a war zone because sleep loss from sleeping in a hostile environment leads to operation problems so they use ambient in a war zone so so I asked this question about how many of you either you personally or know somebody have had an unted experience on ambient that's because this is be increasingly recognized as a problem you give these drugs they're under the influence for you know ideally six hours sometimes eight so much longer but if you give somebody who's if you take a medication every night some night it's going to happen the phone is going to ring at 2 o'clock in the morning or the fire alarm is going to go off and you're going to have to act while you're under the influence so more and more attention is paid for the fact that the acute cognitive effects of these drugs really are important so um let's talk about you recognize this uh this this this slide here so um I mentioned Gaba Gaba is everywhere you know everywhere anywhere I point here there's Gaba that's inhibiting areas of the brain but then there's this area this so you know I I you know I mostly work at the VA hospital so I tend to think like this or rexen works almost like the federal government so so so a lot of the circuitry of sleep wake behavior is organized around wake and and but wake comes in lots of different flavors it comes in these different there there are different Wake On centers and you can kind of think of these big Wake On centers are like the large states you know we've got New York down here and we've got you know Pennsylvania and Ohio and we've got Texas and then Shell's favorite neurotransmitter doping which of course is California and and and and so what re rexen does is that it actually ensures that all of these Wake On centers and the different flavors of wake act in Tandem and in coordination and when you lose that coordination that gives you the fragmented weight wake States during the day and then fragmented sleep States at night that you see in narcolepsy so but the interesting thing is that if you antagonize or rexen with an antagonist you you you do make people sleepy but the interesting thing is that animals given these erex and antagonists when you awaken them like Zachary Boyd they're non a taxic they seem to perform pretty well on mazes and different sort of you know tests of animal cognition so we were interested in actually testing the same thing uh we this was funded by the defense department because they're actually keenly interested in this issue and we were comparing um two different doses of an ereen antagonist versus a standard benzodiazapine receptor agon zulum versus placebo and we are dosing people in the afternoon because we're really just testing the acute cognitive effects and we were looking at measures of cognition before dosing and immediately after and the idea is that we thought that zulum would be have a much more acute effect on cognition but that the ereen antagonist would be less problematic because again the big States erex you know histamine and coleric centers and nephrine they're not antagonized with an ereen antagonist so we dose people at 3:00 in the afternoon 100 milligrams was a standard hypnotic dose for alar 200 milligram was double that dose and zulm is a is a you know standard dose of ambian versus placebo and I'm going to just cut to the chase we had about 203 people a lot of UCSF graduate students thank you very much healthy normal people ages around 26 and so here's the punchline here so this is looking pre-dose and this is looking post and this is comparing ambient this is the lower dose standard hypnotic dose this is the higher dose versus placebo and if you looked at the continuous performance task where higher scores are worse um that you saw a big effect of zulum and not on the the two doses of orx ant antagonist if you look at lapses and vigilance or reaction time you can see that there's a bigger effect of zulum less so on the 100 milligrams a little bit of an effect of 200 milligrams of Alm rexen or PBO again this is just higher Peak on this curve is bad in terms of number of cognition um and another mean Reaction Time same same issue here IDM is not so good uh standard hypnotic dose not so bad at all double the hypnotic dose you know you can see an effect less no effect of placebo so and then here's the here's an interesting feature all those things I just showed you involved an active task where they had to do something they had to react to something being presented to them however if you ask them to try to stay awake in a completely dark environment lying motionless on a bed semi-recumbent um in a darkened room and you gave them these doses it turned out they that you see a hypnotic effect and so in the absence of an external test demand you see evidence of sleepiness on these drugs so just to summarize for most cognitive measures performance under the standard sleeping pill zome was quite bit worse than an ereen antagonist or Placebo there were performance DEC decrements for the ereen antagonist so you don't there's no such thing as a perfect sleeping pill but they were quite a bit better than Zulo and but greater than Placebo and then finally cognitive measures demonstrated a dose effect so this is the time for our Q&A so so the question was uh how does the use of smartphones and just having screens in the middle of the night uh change uh are sleep patterns and also behaviors and I suspect you also imply uh other problems that come down the line as a result of these uh sleep problems and uh since it is more recent yes we don't have a lot of prospective data but we do know that if you do uh turn off your uh uh smartphone at night and you follow these sleep hygiene patterns where it includes also not watching TV in bed and not being exposed to the screen and not eating in bed and other stuff like that you do consolidate your sleep better and the theory is that you you achieve that you avoid all the other stuff that are related to poor sleep uh patterns yeah yeah there there there this was uh all over the New York Times and I I think the punchline of that study was that so so the question was that people who uh like a hunter gather group was study and sleep and um it the results the punch time was that there was fragmentation of sleep an average duration of sleep around 6 and 1 half hours um less than what was sort of reported where we say as a as a as a society we are sleep deprived at our counterparts 120 years ago slept an hour and a half more than we do now it was it was somewhat of a contradictory finding saying that it may be that 6 and a half hours in such a scandalous amount of sleep can I I actually want to make a comment because this is this is actually a general um misconception there isn't an amount of sleep you need you need the amount of sleep you need to feel refreshed we sort of talk about averages sort of around somewhere between seven and eight but and we talk about sort of pathologic ranges um but for any individual you need the amount of sleep you need so don't get worried like when there was when there were these big campaigns oh you need to have eight hours of sleep a night and I literally had patients in my office doc I sleep 7 hours what's wrong with me um and the answer is there's nothing wrong with you as long as you're feeling alert during the day so we really need to focus much more on the quality of our sleep than on the quantity of our sleep so the question is how do we manage sound Downing uh and the answer is first it's very difficult uh the second is it uh there are ways you can address it and you have to think of what causes it so so one thing is are there medications that do uh add to sound Downing because uh you have somebody who is not fully alert and they enter this sleep state are they let's say on badril or other medication that just old age no well that's what my my thinking is that if somebody's sundowning so sown means that um as it's closer to nighttime uh traditionally uh people start having abnormal behaviors and and it's not just that they're tired it's that they are really disoriented they are they could be combative they could be uh confused they can't process information properly so this one Theory says that because you have shifted when you um secrete melatonin uh you end up having being awake but not asleep uh being awake with high melatonin levels and the different networks of the brain the sleep and the wakeful networks overlap so you have elements where you won't be you while you're asleep you're not fully aware you're not attentive so that affects your performance uh during that period of time that you're awake so what do you do you try to shift on one hand if you need to you try to shift the Melatonin secretion it's not uh always possible uh and you can do that by light exposure uh and the timing of the light exposure plays a role if what time of day you do it um the studies that uh we discussed on if you give melatonin does it actually help the the answer is early on it probably uh well there is a study that says that it doesn't uh and the theory behind is that melatonin uh Administration makes sense if you're trying to bring somebody earlier into sleep uh or if they are lacking amounts of melatonin but really early on uh people have a good amount of melatonin it's just the timing of melatonin shifted so you can do tricks especially the lighting is a a huge way of achieving that um um exercising during the day um timing the stimulant the coffee let's say or whatever you're taking appropriately and then making sure that there are no other medications that can add to Sund Downing as an effect you see people in hospitals and uh they they completely they have screens on they have lights on they have a benad dril rather than another hypnotic and and so forth so as a physician it's it's a more U what I would say simply is um talk to the physician in charge address and and and somebody who knows how to think of these things and have these things addressed as a whole not just one thing that's my question um uh restless leg syndrome is my absolute favorite sleep disorder to treat um so I'm going to poetic so you're going to have to try to stop me on that restless legs syndrome is the subjective discomfort of the urge to move the legs that has a circadian rhythmicity so it's going to be worse in the evening than it is in the morning it is um and that can be all it is just some discomfort you know sitting trying to watch television it can also be associated with insomnia with fragmented sleep during the night when we do sleep studies on those on people with Restless leg syndrome we see these periodic limb movements of sleep which are these very periodic leg jerks Dr Nan described it beautifully like a metronome like yep every 20 seconds generally on average but there is a range so as most people with restless leg syndrome I never want to say everybody but it's essentially everybody will have periodic limb movements of sleep however there are people who have only the periodic limb movements of sleep without the daytime discomfort without that urge to move that creepy crawly feeling the feeling like their a like their ants crawling or electricity in the legs some of those people just have periodically movements of sleep it's an incidental finding we did the sleep studyo isn't that cute some of them have actually fragmented sleep in association with those leg movements at that point it's called a disorder and that's periodic limb movement disorder so Dr nylan brought it up because it can be an ult it can be a very subtle thing to diagnose in cases of insomnia because these aren't people coming in saying ooh I have this weird feeling in my legs I just have to get up and Pace I can't sleep these are people who just they have nothing in the evenings they're fine but they but they have difficulty sleeping they wake up un refreshed and they're kicking a lot during the night so that's what periodic Lim movement disorder is so it is actually separate but it's an Allied D it's an Allied condition with with people with breastless leg syndrome I have sometime um just sort of as one more aside from that there are certain medications that can cause periodic movements of sleep but very frequently if I'm seeing them as an incidental finding on a sleep study and somebody who's not on a medication that can cause it they often will have a family history of restless leg syndrome and so they're they're totally asymptomatic I'm treating their sleep apnea but I see this incidental finding and I almost wonder if it's a form fru or if it's going to develop into restless leg syndrome so they're Allied but not identical so the question is what's the long-term effect of taking ambient for so uh the answer actually isn't welln I mean there's there's been a handful of studies that have looked out at 12 months um and in general people so the surprising thing is that there's usually you know sustained efficacy even though people real you know the idea of Tolerance has been a big part of the clinical lore both for benzidines and ambient um but there's no known long-term sort of you know Progressive decline that's shown with an chronic ambient use uh but um I as I was saying before if you kind of think of it as just um like a probabilistic term that you're if you take something where for six hours you're under the influence um at some point over a year or several years you're going to have to do something in the middle of the night you know try to drive somebody to the emergency room and that's that's the scary part yeah all right I'll run with that so you know there there's a whole world of what's called um lucid dreaming where you have you're in a you're a dream state probably rapid eye movement sleep and you have the subjective awareness of the fact that you're sleeping and you're dreaming um and people like that idea because they like to feel like they could have some executive control over their dreams or whatnot but the fact is if you're in that state and you're aware of it you're you're also going to be aware of the fact that you can't move because your skeletal muscles are paralyzed um so I mean it could be that people have experienced this and sort of brief fragments at various issues but the the dream of I I'm being chased and I feel paralyzed and I can't move is almost ubiquitous it's such a common you know scary dream and you think it is connect that's my guess yeah the thing about dreams is that you can't directly measure them all you can do is wake people up and get them to write down what they're experiencing but we can't we can't really directly measure Dreams yeah you know that's a great question so you know um insomnia is there isn't a single definition of it you typically it's seen as you know trouble falling asleep trouble staying asleep but it's actually not a problem unless you can actually yoke it to some actual daytime imp pyramid you just don't feel rested you don't feel feel like you're alert enough um a certain amount of fragmentation of sleep at night is actually kind of normal you know it's normal they have Awakenings across the night it's only a clinical problem when people feel as if they're not getting a sufficient amount of sleep and they don't feel attentive during the day all right well thank you all for listening [Applause] and [Music]

Channel: University of California Television (UCTV)

Views: 80,625

Keywords: Sleep Apnea, Narcolepsy, insomnia, aging

Id: 7bfpI0YZLVA

Length: 89min 5sec (5345 seconds)

Published: Wed Feb 03 2016