Why APOE4 Carriers MUST Fix Their Sleep (And Exactly How)

[0:00]Here is something that should wake you up. And yes, there is a pun intended here. If you're an ApoE4 carrier, your REM sleep is very likely reduced right now. Even if you feel fine, even if you have no cognitive symptoms whatsoever. So there is a 2024 study in the journal sleep that found that ApoE4 carriers have significantly lower REM sleep percentage and duration.

[0:27]And here's the kicker I want you to remember, even in the absence of cognitive deficits. So you might not feel it, but your brain silently does this behind the scene. So today I'm going to show you exactly how to diagnose what is stealing your sleep, whether it's physical like mouth breathing or mental like stress.

[0:50]And then I'll give you the specific tools, supplements and devices that actually move the needle based on what worked for hundreds of ApoE4 carriers in the Phoenix community. So we are making more and more of these type of videos, where now we have enough members running experiments within Phoenix to be able to surface what works for ApoE4 carriers specifically and not the general population.

[1:15]So we layer that with clinical trials. We layer that with the research that is out there And on top of that, we have our own experiences as ApoE4 carriers as members. So as a matter of introduction, my name is Dr. Kevin Tran. I'm an ApoE4/4 carrier and the doctor of Pharmacy And I spent basically the last year diving deep into the research and building Phoenix.

[1:38]So let's get into it. Let's start with being extremely direct. If you're an APOE4 carrier with sleep problems, you are not just adding risk factors together, they basically multiply each other. So 2024 study in CNS Neuroscience & Therapeutics found that APOE4 as genetic risk factor could exacerbate the effect of sleep disorder on risk conversion to dementia.

[2:04]So we're talking about the synergistic risk not just additive So sleep problems plus ApoE4 equals faster cognitive decline than either factor alone. So the sleep plus ApoE4 plus group in that study had higher plasma NFL levels, which is a marker of neurodegeneration. So here's why this matters mechanistically I always like to understand you know the mechanics of it.

[2:29]And this gives you a sense of what is happening inside your body. So you can understand why we're doing certain actions. I believe that's very important. So during wakefulness your brain's waste clearance system, which is the glymphatic system, is reduced by 90%. So let me say that again 90%.

[2:44]So when you are awake, your brain is essentially running with its cleaning crew on a smoking break. It's only during the sleep time, particularly during deep sleep, that your brain actually clears out the metabolic waste, including amyloid-beta SWS enhanced the clearance of Abeta when compared to the waking state That's slow wave sleep. You know your deep sleep.

[3:05]Literally cleaning out the proteins associated with Alzheimer's. So I want you to first understand the different sleep phases. A quick primer, right? You have deep sleep, which is your brain's power wash. That's when amyloid gets cleared. Then you have the REM sleep, which is rapid eye movement sleep is where your memory consolidates.

[3:27]And this is where ApoE4 carriers are already deficient REM sleep is when you crystallize the memory of the previous day, and that's when you encode all that memory into your brain. So if you're only getting 10 to 12% in either phase per night of sleep, assuming you are sleeping, you know the total duration of 7 to 8 hours.

[3:48]It's a problem. And I can tell you 10 to 12% on REM sleep and deep sleep Each is actually already very high. Mine is actually lower, like close to 8% actually, I’ll give you the exact target in a moment, but I want you to remember the two sleeping stages that matter the most are REM sleep and deep sleep, what we call like light sleep.

[4:07]Or there are like different ways of calling that But if you have an Oura ring like me, they call that light sleep. We don't actually care about those that much. We want to maximize deep sleep and maximize REM sleep. And there are different strategies for each one of those.

[4:19]So in terms of metrics that you want to target for deep sleep, you want to have 15 to 20% of the total sleep. So that is quite a lot. We are looking at 1 to 1.5 hours every eight hours of sleep. So every night then the REM sleep you need even higher than that.

[4:40]You need 20 to 25% of the total sleep duration. So assuming it's again eight hours, you are looking at 1.5 to 2 hours of REM sleep. And you also want to boost sleep efficiency, which means that you are not too much awake, that you're not hiding around in your bed, struggling to wake up and struggling to fall asleep so you won't sleep efficiency to be above 85%.

[5:02]That is basically the time you sleep again versus the time that you spend in the bed and the total sleep. For the big majority of people, it's 7 to 8 hours Another metric that you want to focus on is HRV And that metric is often overlooked. While talking about heart rate variability during sleep, HRV is basically your window into your own autonomic function.

[5:28]Low HRV correlates with poor sleep quality. Higher HRV complexity during sleep indicates a better parasympathetic activity, which is your rest and digest system actually doing its job. So you want to oppose parasympathetic and sympathetic system. The sympathetic system is when you are awake, when you are alert, is the fight or flee mode that you enter when you are relatively stressed, that is very useful to be awake, to fight diseases and so on.

[5:55]And then you have the parasympathetic system, which is when you relax. So if your HRV is consistently tanking overnight, that is telling you something very important. Remember HRV, the higher it is the better. So when you have low HRV you have either an issue with something physical that is disrupting your sleep or your nervous system.

[6:15]Your stress and so on is in overdrive. So it could be like for example, you overtrained in the gym or you run too much and so on. Or it could be that something is really stressing you out and you're under like, you know, heavy load. So in terms of diagnosing, first I'd say look at the physical issues.

[6:35]That is the mistake I personally made, because maybe that gives you a bit of an idea. Probably for the majority of you, you might not have these issues like me, but if you are part of the 5 10% of people who have unknown to you like these physical issues, that will help you a lot.

[6:53]I basically was a mouth breather. My entire life, and that's something that I realized very, very recently once I started optimizing my sleep a year ago. And I had no idea that that it was wrong. I used to sleep a lot, breathing through my mouth and only breathing from my nose when I'm running and so on.

[7:09]And this basically destroyed my REM sleep I only discovered that when I dug deep very, very deep into how I could improve my sleep and that cannot no doctors No one ever found it. So I noticed it because my REM sleep was really low, usually like 8 or 10% maximum when as I mentioned, it should be like 20 to 25%.

[7:29]I tried a lot of things like supplements and so on, but then somehow it didn’t go up. I actually went to an ENT to check it, and they discovered that the chronic nasal congestion, nobody ever flagged this. Like if I didn't manually myself decide to go to an ENT no one would have found it.

[7:48]And my entire life I would have gone with this REM sleep issues. So the main issue is you don't know what you don't know, right? I personally don't know how I agree with I thought everyone was doing the same thing. So now I'm using a Fluticasone which is a nasal steroid spray and then I'm using as well mouth tape So I taped my mouth shut.

[8:08]To be sure that I'm sleeping through my nose. And I also use like a nose dilator So you have like those that you stick on top that dilates your nose from the outside or from the inside. And the result has been dramatic. Like these three things that are very easy to do.

[8:23]Increase my REM sleep from 8% to 20%. So it's not like maximize like 25% as ideally, but it fixed it so fast. So that's why before you start on any supplements or any So that's why before you start on any supplements or any like devices, try to rule out if you have any physical issues linked to your breathing because your breathing will be linked to your sleeping.

[8:44]So does your mouthfeel dry when you wake up? Do you snore? Because that's something that is a very, very strong signal. You can either use, like for naps, like record you while you sleep. tons of them out there. Or if you have a partner sleeping next to you, they can also tell you you could have a Deviated Septum So see an ENT it's way more common than you think.

[9:03]You don't need to have had an accident as a kid to have a Deviated Septum Sometimes you're born like that. You can have like nasal congestion, like allergies, inflammation, chronic congestion All of those are very fixable, especially with nasal cortical Aids. And you might have Sleep Apnea we cover that in a lot of different videos.

[9:20]It's really critical. Get screened ApoE4 status interacts with sleep apnea to worsen Alzheimer's biomarkers So if you have both the interaction is way worse than either one alone don't skip this step I see like a lot of people buying like several thousand dollar devices where, you know, if you can just buy a $3 mouth tape, that would solve maybe your problem too.

[9:41]So just try with Then the second part, same thing. I'll tell you a personal story. I used to wake up at 3 a.m very randomly every day when I was like in San Francisco, I couldn't fall back asleep I was just lying there in my bed. My mind was racing.

[9:57]I was already thinking about work. It was kind of crazy. My HRV actually tank from 70 to 15 over a few months, and the line is actually quite straight down and my body was in full sympathetic mode, fight or flight mode when it should have been rested the reason why this is happening is because your cortisol spikes, because the cortisol awakening response is basically happening too early for you.

[10:23]So you have to know cortisol which is the stress hormone. have follows basically a predictable rhythm it peaks at your habitual wake time and gradually decreases through the day to its lowest point in the early night And when you are stressed, the pattern gets disrupted. Sleep restriction itself elevates late afternoon and evening cortisol, and then it becomes a vicious cycle So it doesn't matter if you go to sleep earlier or not.

[10:48]You get cortisol spike during the middle of the night and then you wake up. For me, I try to go to sleep at 9:00 p.m and then I wake up randomly at 11:30 or 12 a.m. and not be able to go back to sleep. So those if that happens to you.

[11:00]The key thing is really to control your cortisol control your stress levels and control your sympathetic system. I'll tell you more about interventions later on other things that I want to talk about is any signs of stress driven sleep problems that you might have because this is how you can identify that is happening to you when you are awakening very early morning, let's say 2 to 4 a.m.

[11:23]that's classic cortisol dysregulation. Your cortisol is spiking too early when you have low HRV. So if your HRV has been declining over weeks or months, you have a problem with your nervous system HRV. I would suggest to not completely look at the absolute number, but look at the trend.

[11:39]Usually that is a good indicator if you have a racing mind that night. You know when you are ruminating, when you are worrying, when you are planning all the time. These are also sympathetic nervous system behaviors that are not great. And the last one that is very, very easy to tell is when you feel tired but you are wired or you know you are exhausted, but you can't sleep.

[11:57]That's basically cortisol and adrenaline fighting your melatonin That's basically cortisol and adrenaline fighting your melatonin The fix will probably not be a pill, especially sleeping pill, because that degrades your sleep Architecture and your sleep patterns. So this is actually not that helpful. Even though you spend more time with sleep, you actually don't get the benefit of sleeping long.

[12:16]So for me, it wasn't that it was learning how to activate my parasympathetic nervous system before bed. So I want to emphasize that stress management is really not optional for ApoE4 carriers I used to be a strategic consultant. I used to work in corporate super high stress. Now as an entrepreneur building Phoenix, I would say my stress level is even higher than before, but I've learned how to control it and my stress is okay now, but I cover later on in this video, like specific tools.

[12:43]But the principle is actually very, very simple. You just need to know how to down regulate in nervous system before bed so you can do a lot of things like breath work, vagal turning, whatever works for you. Try different methods, lock them All right. In terms of tools and devices, what I've tried and what seemed to work for me is Vagus Nerve Stimulation So we had the partnership with Zenowell early on.

[13:05]We probably have a phase two that is coming out soon. So Phoenix members get a heavy discount And then we study the impact on ApoE4 carriers while the results are coming out very, very soon, which means I'll have another blog post on vagus nerve stimulation for ApoE4 carriers that are coming out.

[13:19]But if stress and nervous system. dysregulation is your issue. A vagus nerve stimulation tool is really worth considering. So the research shows that VNS increases HRV complexity during sleep, meaning better parasympathetic engagement when you need it most. The effect is actually very different during sleep versus wakefulness So during sleep, the complexity of HRV was increased, while at wakefulness it was decreased by VNS So you can both use it differently whether you want to fall asleep or not.

[13:46]That's why you have like different modes. That works. The second thing that work for me is Photobiomodulation something we have to study with Neuronic This is like red light therapy it’s really fascinating this Near-infrared light therapy during sleep may enhance glymphatic clearance. And research indicates that photobiomodulation improves the clearance of fluid and toxic substances from both the periphery and from the brain.

[14:09]In animal studies photobiomodulation we use beta amyloid brain accumulation more effectively during the sleep and we also have a study running with Neuronic The result is coming out in June, which is probably when you’ll have this video So again, a blog post is coming about the Neuronic red light therapy devices on ApoE4 carriers.

[14:30]So stay tuned on the blog. ApoE4 other links will be below. In terms of sleep trackers, because you want to maximize sleep, but you also want to know and to track what is working, what is not working. And the best way for that is to have a tracker, whether you're using a smartwatch or an Oura ring let me cut through the marketing because I've benchmarked that extensively Oura ring that I have here, and we are not affiliated with that, but I love it.

[14:59]It's very easy to wear. It's like way more comfortable than any smartwatch, and it's also the most accurate for sleep stages. So there was a 2024 validation study that found oura was not different from PSG in terms of wake light sleep, deep sleep and REM sleep estimation. So we are looking for the gold standard here and that's an Oura ring The Whoop bracelet that I don't have is excellent for HRV.

[15:22]You get like 0.99 correlation with ECG which is basically essentially perfect. So if HRV is your primary focus, whoop delivers the Oura ring also delivers on the HRV it’s probably less accurate. But again you want more of the delta between two values. So the trend rather than the absolute value.

[15:39]Other than that, the Apple Watch is great for total sleep time, but it might overestimate light sleep by about 45 minutes on average, depending on the studies, and it under estimates deep sleep by 43 minutes. So again, it might be fine for trends, but don't trust the absolute number to much on sleep stages if you have an Apple Watch.

[16:00]Meaning that all the metrics that I gave you before you know the 20% or 25% that you need to reach for REM sleep and deep sleep early on, make sure that the way you are measuring it is not full of noise, and you actually get enough of that sleep.

[16:15]Except it's not tracked properly. So my recommendation is you have several ways you can have multiple devices to see if there is a delta or not. If multiple devices measure more or less the same values you already know that works. The second one would be to actually focus on the trend.

[16:32]You know that you want to do whatever you can to boost your REM sleep and your deep sleep. So whenever device you use, if it sees that you are increasing your REM sleep and deep sleep, you're on a good track. And maybe that's the only thing that matters In terms of other type of optimization for sleep, there is a lot of studies that show that side sleeping tends to win.

[16:53]It's very simple the end. And because research on glymphatic transport found that it was most efficient in the lateral position compared with the supine or prone position. So side sleeping is literally optimizing your brain waste clearance, which I try to do that. I feel like that's a very easy, quick win.

[17:08]And then the researchers also concluded that the lateral position during sleep has advantage with regard to the removal of waste products, including Abeta So sleep on your side If you are back sleeper, consider a body pillow to train yourself to sleep on the side. In terms of temperature, this one is relatively easy.

[17:23]If you have a aircon, colder is usually better. So for older adults And this data is from a study of 11,000 nights of sleep The optimal range is 20 to 25°C, which is 68 to 77°F. For younger adults, you can actually go colder. 65 to 68°F is often recommended, and the key finding is that sleep efficiency drop 5 to 10% when temperature rise from 25 to 30°C.

[17:52]So an 8-degree difference cause a 10% drop in sleep efficiency. So if you can keep your bedroom cold, your body needs to drop its core temperature to initiate and maintain sleep. You have a few devices that help you reduce the temperature of your bed like eight sleep that is available, I believe, quite worldwide.

[18:12]Now at least I know it's available in North America, which you can check on their own website. It's relatively expensive, but it seems like it's worth it now in terms of supplements. I know you guys love supplements. I love supplements to the few that I would recommend is Magnesium L-Threonate.

[18:28]This has actual randomized clinical trial evidence. 2024 randomized trial found that Magnesium L-Threonate significantly improved versus placebo deep sleep score REM sleep score and light sleep time and activity and readiness parameters. So we are both looking at deep sleep and REM sleep. Exactly what us ApoE4 carriers we need one gram per day was the dose use so go for it.

[18:51]Magnesium L-Threonate very low risk type of intervention. The second one is Glycine So take three grams before bed. It basically walks through the NMDA receptor activation promoting hypothermia So it helps your body cool down for sleep. As we mentioned before, you need to cool down your temperature to fall asleep and stay asleep.

[19:12]The last one is L-Theanine so you're looking at a little bit less than 500mg or something between like 200 and 500mg. It appears safe and effective for sleep on set and overall sleep quality. Those are the supplements are recommended. A quick word on Melatonin because this comes very often, here is something specific to us.

[19:33]ApoE4/4 carriers have approximately half the CSF melatonin levels of those with one APOE4 allele so we may be naturally deficient. No clinical trials are specifically tested, this in ApoE4 carriers yet, but it's worth considering a few things you should also know because I personally don't take chronically Melatonin I only do that when I'm traveling, when there is jet lag, when I'm trying to recalibrate to a different time zone, or if I have something to do, like very, very early in the morning, I need to go sleep because there are some studies that might show that melatonin, the more you're taking it Exogenously like a few pills, the less your body is able to produce it by itself.

[20:14]It's not 100% confirmed and you have to check, but if you manage, not take it continuously and only for specific occasions, I would suggest you do that Now we talked about tracking using devices. I think what matters is to link everything that we mentioned together. Right. You want to link your interventions like if you are doing, you know, like cooling your room or if you are taking supplements with whatever data is coming from your Oura ring and so on.

[20:43]And this is how you know if something is working or not. I'd say it's very, very difficult, almost impossible to think and try to have a sense of. Or I've tried these supplements and these improve my sleep or not over time, because your memory will change. It will not be able to track all of that, especially when you have the sleep disruptor.

[21:02]Maybe one night you have very late dinner, maybe this and maybe that, and then it's very hard to actually correlate if your interventions are working or not. And that's why we build the Phoenix app, where you can track everything together. You know, we have like daily check ins with sleep quality rating through the wearable as well.

[21:19]We pull that data directly from Apple Health or Google Health. And on top of that we ask you how you feel, because that is so important to correlate how your metric is shown in a wearable and how you actually feel, because sometimes you might feel actually very tired and your wearable is showing you that you had great sleep or vice versa.

[21:37]And then we also track all the interventions that you do. Did you use like a mouth tape Do you use magnesium? Was your room cold? And we use our Phoenix AI that has been trained on ApoE4 data from all the members and from all the studies We have like 90 plus monthly active users.

[21:54]Everyone is extremely active on top of the community and posting things. So if this is of interest to you, please join us. You have the link in the description below this YouTube video Cool. The takeaway. Now let me recap this diagnosis first framework. First, you want to rule out all physical issues mouth breathing, nasal congestion, sleep apnea.

[22:14]These are often the lowest hanging fruit with the biggest impact if you have them. Not a lot of people will have them, but if you have them highest impact, then you want to address any mental and stress issues. If your HRV is tanking, if you're waking up at 3 a.m., your nervous system needs attention.

[22:28]So Vagal toning, stress management, parasympathetic activation all of that will help. Then you want to optimize it. So side sleeping cold room evidence based supplements like magnesium L-threonate Because sleep isn't a luxury for us ApoE4 carriers. It's when our brain cleans house. So our glymphatic system needs all the help it can get Remember the combination of sleep problems and ApoE4 is synergistic.

[22:50]We can't ignore this, but the flip side is that optimizing sleep might be one of the highest leverage interventions we have. and if you want support with this, you know, tracking your sleep, testing interventions, connecting with others ApoE4 carriers who are figuring this out All together that's exactly what we do in the Phoenix community.

[23:06]All right. I'll see you in the next video. Bye.