APOE4: When Is It Too Late To Prevent Alzheimer's?

[0:00]It's not the gene that steals your years. It's the belief that it's too late to do anything about it. Hi, I'm Dr. Kevin tran I'm a doctor of pharmacy, and I'm an ApoE4/4 carrier I have two copies of this gene that this channel is actually built around. And the question I get more than any other from people just like you inside the Phoenix community or inside the comments on our socials, is some version of is it too late for me?

[0:31]Well, here is what the science actually says. The biggest prevention trials in the world didn't test this on 35 year olds like me. Or they tested it on people aged 60 to 79 and it actually worked. Measurable cognitive benefits two years in, including in carriers basically people with our gene.

[0:54]So the question is is it too late? The question is which lever do I pull first? So I'm going to be straight with you because I think you can handle it. And most channels or influencers online won't. If you're watching this, there's a good chance that you are around 50 to 75, give or take.

[1:13]And there's almost nine out of ten chance you watched a parent go through this. and there's a really good chance you're already doing the work. Basically the diets, the steps, the supplements. But underneath all of it, there is this quiet, ugly little voice that says, maybe I started too late Maybe the damage is already done I know that voice, the exact word change depending on who's asking, but the fear underneath never does.

[1:43]So if you type that question to someone or ask your doctor, or just whisper it to yourself at 2 a.m. this entire video is my answer to you. And here's the thing about that quiet voice. It's not the gene that steals your years is the belief that the window is already closed.

[2:00]as you might know, the best time to plant a tree was yesterday. And the second best time to plant a tree is today. So let's go kill the belief that it's too late with evidence. Here's what we are working out of this video with one The proof from real randomized trials that the risk reduction is achievable at the age you are right now two why it still works that late.

[2:26]So the mechanism and everything. Because once you understand this mechanism, the hope stops being just vibes. It becomes actual science. And then you have the certainty of it Which drives adherence and will drive your motivation as well. And three, the actual levers in priority order for an ApoE4 carriers because spoiler our list is not identical to everyone else's.

[2:52]There's one lever that may matter more for us than for non carriers. And I'll show you the study in this video. And four where I think the data is genuinely thin. So you're never relying on me to oversell you anything. So quick intro on who I am I'm a doctor of pharmacy I found out that I carry ApoE4/4 in December of 2024, at around 34 years old.

[3:17]I don't have a family history of Alzheimer's, which honestly made it weirder, not easier, because getting two copies with no warning shots was kind of difficult. And before all of this, I actually used to be a strategic consultant for pharma companies, and I worked in hospitals in the geriatric care So I was actually very aware of Alzheimer's, of the therapies that are around it and on patients with it coincidentally.

[3:48]So when I got my results, I didn't spiral. Well, actually I did for two months. But after that I became better and this is what I did. So let's get into chapter one. The part that should change, genuinely change how you feel about your ApoE4 Let's start with the headline, because I refuse to bury it right.

[4:08]There's a trial called finger. You might have heard like several times. Finnish randomized its control the gold standard 1260 people average age in the late 60s and into their 70s. All of them already at risk. They split them in two different groups. One group got a structured, multi-pronged lifestyle program.

[4:29]The other got general health advice, and that lasted for two years. The result? The active group improved on the overall cognitive battery by 25%, more than the control group. The executive function, which is your planning, your decision making. So 83% more improvement. And in terms of processing speed, it got 150% more in real terms the between group difference per year was very modest.

[4:58]0.022 on the Z score. That's not basically a miracle cure overnight unfortunately, but it's real. It's statistically significant. And that is the part most people miss. It compounds over time. A small slope run over years become a different trajectory entirely. A small slope run over years become a different trajectory entirely.

[5:16]The trials on conclusion, a multi-domain program could improve or maintain cognitive functioning in at risk elderly people. And it wasn't just the finger trial. In 2025, they ran the US pointer trial. Over 2000 people participated in the trial of five sites, and they were aged between 60 to 79 and it confirmed it.

[5:38]The structured group improved on global cognition by 0.029 standard deviation per year over the self-guided group and the way the trial framed it. The structured program was estimated to protect cognition from normal age related decline for up to two years. So this is not one quality finnish study.

[5:56]It's two continents, thousands of people replicated. Now, here's where you specifically lean in, because the average viewer of this channel is on asking, does it work for old people? You are asking, does it work for high risk people? Does it work for someone carrying the ApoE4 gene or two copies of it, like me?

[6:15]Well, when they went back into the finger trial data and split it by genotype ApoE4 carriers versus non carriers, basically the intervention effect in carriers was 0.037 in a year. And in non carriers it was 0.014 So the point estimate was bigger in carrier which may make you think that carriers think more right.

[6:40]Well not quite because there is a nuance here. The difference between carriers and on carriers was unfortunately not statistically significant. So the confidence intervals overlap. So I'm not going to stand here and tell you carriers benefit more as settled fact. But the science actually supports rock solid. Is this carrier benefit at least as much as everyone else.

[7:03]And there is very good evidence that we might benefit more from interventions from other trials. So the high risk gene does not exempt you from the payoff. And I think that is a very important takeaway. The characteristics of the gene may make you think that no matter what you do, it won't help. It's not true.

[7:22]It might actually help more than non carriers very objectively. So the researchers say plenty healthy lifestyle changes may be beneficial for cognition in older at risk individuals, even in the presence of ApoE related genetic susceptibility to dementia. And the pointer trial back this up from the other direction.

[7:43]In that 2025 American trial, 30% of participants were carriers, and the researchers reported that the structured intervention benefit was consistent for ApoE4 carriers and non carriers in plain English. Statistically, the gene didn't blunt it at all. So what do you do with that? Chapter one today. Honestly the first action is internal.

[8:06]You have to update your belief the data does not support. It's too late. The data supports that. It works at your age. For people like us. And the way I made that belief stick for myself was by turning it into a scoreboard. I started with lifestyle interventions for myself, I picked levers, I measured the biomarker before I checked it after, Like reviewing a journal in Phoenix.

[8:30]That's literally a feature. You log your baseline in bloodwork, you run a structured experiments. You see if the number moved. That's how our entire Phoenix app was developed for. That loop is what converts. I hope this helps into. I watched it help, and when you get the confidence that something works, then you get the certainty and you get the motivation to keep doing it because you have this like great feedback loop that is happening.

[8:55]But here's the question that broke my brain when I first read these trials, and I need to answer it before any of these feels real to you. How can a two year program possibly move the needle when you are 70 and the disease has supposedly been brewing inside your brain, inside your head, for decades?

[9:13]If the damage starts that early, why isn't it too late? Well, that's chapter two, and the answer is the most hopeful piece of biology that I've seen lately. All right. So there are two ideas. Get these and the whole too late fear collapses. Idea number one dementia is decayed in the making.

[9:32]The pathological, the plaques, the tangles. They start accumulating 15, 20, sometimes even more years before you'd ever notice the symptom and adjust carriers. It actually starts even earlier than non carriers. Now when I first learned that I really read that's bad news right? Great. It already started I'm cooked.

[9:51]But actually if you flip it if the process takes decades, that means a 56 year old or a 70 year old is acting inside the window, not after it. You are not late to the party. You are actually early enough to change how the rest of it goes.

[10:07]The long fuze is the bad news and the good news. You have a lot of time to intervene. idea number two is my favorite thing I've learned from all of this. It's called cognitive reserve and it's basically your brain's version of a savings account. Here's the image. Take two different brains.

[10:24]Same disease, same amount of dementia. Community. One person stays sharp for years longer than the other. Not because the disease isn't there, it actually is, but because the brain has more of a buffer before things tip over into symptoms. Yaakov Stern who defined these concepts, calls it exactly that a threshold you have to cross before decline shows up.

[10:47]More reserve means the threshold is actually higher, and that reserve is a buffer you can build. And here's why that matters for the two late question, the single most important sentence in this chapter Stern's review says experiences at all stages, even in late life, can impart such reserve.

[11:07]So you can actually build the buffer late. That's the whole thing the exercise, the learning, the social engagement. That's you at 56, 66, 76, actively raising the threshold the disease has to cross. It's a mechanism with a published schematic. We're not just talking about blind hope. But with that said, reserve delays the onset.

[11:30]It doesn't make you immune. And once that threshold is finally crossed, decline can move faster. So it's not like a false field protecting you, right? It's time, but it's years of good function you would otherwise lose instead of declining early on. You actually leave a great healthy life for longer and then in decline faster.

[11:49]And this is what we can best hold for all of us, right? So for me, for someone who wants to be sharp, for the people I love as long as humanly possible, years is the entire game. So that's the answer to your question. It works late because you've got a long runway and a buffer.

[12:07]You can still grow, which leaves exactly one question standing. What do you actually work on first? So in 2024, The Lancet Commission, which is basically the most authoritative body on dementia research, updated their big report and their headline number stopped me called. Roughly 45% of dementia cases are potentially preventable.

[12:29]That's insane 45 Almost half not through medication, not through some future cure, through 14 lifestyle and health factors you actually have control over. Now, I want to be precise about what these 45% means because it's easy to misread it. It's not saying you personally can eliminate 45% of your risk You have to understand that this is a population level number, meaning across everyone, nearly half the total burden of dementia traces back to things people could have changed.

[13:00]So that's a massive number. And it means the gene you carrying is not the whole story. It's not even close. So here is the mental model. I want you to have split your risk into two different buckets. The first bucket age, the gene family history. Nobody can touch that.

[13:18]That's the cards you were dealt when you were born. the second bucket is where the whole game is played, and the 2024 update added some things worth flagging for us. Specifically, high LDL cholesterol in midlife now accounts for an estimated of 7% of dementia cases. Untreated vision loss in later life about 2%.

[13:40]These are not huge numbers on their own, obviously 7 and 2%, but they are very actionable. You can measure them, you can move them. The other thing the 2024 reports makes clear is that these factors don't all hit at once. Some matters most in early life, some in midlife, some later.

[13:58]Now, lifestyle is a useless word. The thing that works isn't one heroic change. It's a stack, a stack of intervention run at the same time. And this is what that stack looks like. Number one, your diet mind Mediterranean style. Number two exercise. You want to combine Arabic and strength training.

[14:22]Number three, you want to do cognitive training challenging the brain. Number four, you want to have social engagement a lot of human connections. And number five, you want to have vascular and metabolic monitoring. So great blood pressure glucose lipids with a lot of clinicians check ins that you can do at least yearly.

[14:41]So the last one monitoring your blood pressure, your glucose, your lipids, that's the part most people skip and it's the part that turns, I'm trying into I know. It's also the part Phoenix is built around, because I built an entire app to help you track everything from your blood work, your cognition, your brain fog on a daily basis, your energy levels, your sleep, all of that.

[15:06]And we tie it back to the interventions that you actually do. So you understand which interventions leads to which effect. Then again, you can keep doing these interventions whether there are supplements, sports, what you are doing to improve your sleep and so on so let me make one lever very concrete, because it's the most actionable for someone who feels behind, food.

[15:27]Food is so important. So you have the mind diet Mediterranean plus Dash, basically a brain targeted eating pattern in the cohort study, people in the top tier of mind adherence decline slower. The difference was equivalent to 7.5 years younger cognitively. So I have to label that one carefully.

[15:47]Mind diet studies like this are observational. There could be other things confounding factors about diligent eaters driving it. And the later randomized trial found smaller effects. But here's the part that lowers the bar beautifully for you. Even moderate adherence was linked to lower Alzheimer's incidents. You do not have to be perfect partial credit counts, and the highest tier had the hazard ratio of 0.47, but the middle tier already showed benefit.

[16:16]Okay, so here's where I answer the question. I opened the entire video with which lever First for a career who just wants to get started. And I know there is a lot of you out there because I received tons of questions like that. So for carriers, start with your metabolic health.

[16:33]Now let me show you why there is a 2025 analysis that it's something really interesting. You know how we just talked about that list of things you can actually change the diet, your exercise, your blood pressure, your blood sugar, and so on. They took that list. And as does it look the same for carriers as it does for everyone else.

[16:49]Are the same things most dangerous for us? And the answer was actually no for non carriers. The biggest one on that list was hearing loss for carriers. It was actually midlife diabetes problems with blood sugar, insulin resistance and how your body handles energy. So that findings lines up with something researchers have suspected for a while that for carriers, specifically, the brain relationship with insulin is especially important.

[17:18]Some even half jokingly call Alzheimer's the type three diabetes. It's very early data. There are a few conferences analysis, so I'm not overstating it, but it's consistent enough that if you ask me where to look first as a 4/4 metabolic health is my answer, now I have to flag something.

[17:35]metabolic health is my answer, now I have to flag something. The same study had a genuinely kind of weird result. Midlife hypertension appeared to reduce risk in carriers so that again, hypertension reducing risk in carriers. I'm not going to touch that as an advice at all, and neither should you.

[17:52]It's one observational study. It's counterintuitive. And the last thing I ever do is tell a carrier to ease up on blood pressure. So keep treating your blood pressure for sure with your doctors and flagging that finding for honesty, not turning it into a protocol. But I want you to understand that these observational studies can create like results that are a bit weird like that But instead, I'll point you to the metabolic markers that you want to optimize.

[18:19]So for example. So for all of these values I'll give you the Phoenix optimal, which is based on all the literature that is out there crunched by our AI to look at the one signals that have the highest probability. Of being right for ApoE4 carrier. So for hba1c the optimal for us is between 4.5 and 5.2%.

[18:41]Fasting glucose will be between 75 and 85mg per deciliter, Fasting insulin will be between 3 and 8 micro IU per milliliter. Those three together tells you almost everything about whether your metabolism is working with your brain or against it And remember, for carriers, early and preliminary data points to metabolic health as a high leverage level.

[19:06]Diabetes was the top modifiable factor associated with carrier risk So here's what I actually do. Not what you should do, what I do, and you still what fits your lifestyle and your preferences. Remember the number that made me exhale my ApoB Well, ApoB is the single best marker of the atherogenic cholesterol particles that drives heart disease.

[19:29]And the LDL cholesterol those particles carry is per the new Lancet update now a recognized midlife dementia risk factor too I don't go on statins. It's just not my route for now because I'm young enough, I believe, to be able to control it other ways. I went after it with ezetimibe at ten milligrams.

[19:46]I have another video about ezetimibe that you can watch on my YouTube channel and plus diet plus a genuinely stupid amount of exercise close to 15 hours per week and ApoB dropped 39%. So the Phoenix app optimal is between 40 and 70mg per deciliter for ApoB And after all these interventions, it wasn't just lipids my VO2 max went up 31% after exercising crazy and running like a rabbit, my hba1c was down 8%, my body fat down 43%, and I started this at 34.

[20:21]I know I'm probably earlier and younger than you. I have more runway. I won't pretend otherwise, but every one of those numbers is proof of the thing. This whole video is about action moves the markers after you start the trials. Proved it for 70 year old. My own blood work proved it to me.

[20:41]The way you do this without losing your mind is one lever at a time, so it's not too overwhelming. And you want to measure everything to get that motivational loop, to see that you have results afterwards. The great thing with having lower body fat and better VO2 max is you actually feel it right?

[21:01]Once you start exercising, you'll be out of breath less. When you look at yourself in the mirror, you actually look much better, so you have tons of actual benefits. You'll probably feel much less brain fog, more clarity. You'll sleep better. All of those actually compound. And the great thing about all these interventions is you really see the results within like 1 or 2 months actually. So in Phoenix, basically these interventions are what we call an experiment.

[21:28]You pick a lever, you pick an intervention, you set a window and you track the marker in blood work or through your wearable or through qualitative questionnaires that we send you every day. That takes a 30s or less to fill And you basically read the result as a session with you.

[21:46]And that's. Chapter three of this video. But before you run off and do all of it at once, let me tell you where I think this evidence is softer than the internet pretense, because that's how you avoid wasting effort on the wrong lever So let's move on to chapter four, the honest part.

[22:02]So I promise you the truth. And I feel like that's super important out there, including telling you all the inconvenience bits. And here it is, four of them very fast. One the effect sizes are relatively modest. Fingers per year difference was 0.022 pointers was 0.029 These are not reversed or decline overnight.

[22:25]It takes effort. It takes time. They are more like bend the slope type of numbers. The magic is the compounding and the stacking of all these different interventions together because they synergize together, right? Having better sleep, better diet, exercising, having more activities. All of that work positively, each one of those individually, but also together they have a synergistic effect Remember that anyone selling you a grammatical jump, an improvement in cognition is probably selling you something.

[22:57]And the great thing about these interventions is all of that is basically more or less free, Number two, there's a lot of diet evidence, the mind stuff. So it's observational associated with not proven to cause. The later randomized trial showed smaller effect. I still eat that way. It's really a lot of salmon and fishes.

[23:20]And I try to really reduce my carbs And I'm usually cycling with a keto low saturated fat keto diet because the downside of that is zero. It's well, I actually miss pizzas, baguettes, branch and so on, which I indulge in when I'm traveling, but 90, 95% of the time I stick to that diet and the benefit, the cognitive benefit, the benefit in terms of energy is really worth it.

[23:49]And we see that in our community. People going on it have usually reported exceptional results, not even looking at long term. Right. Even in the next 1 or 2 months when they swap the diet, they feel much, much better, much healthier as well. But again, I won't overstate the certainty of these trials.

[24:10]You'll have to try for yourself. Remember one thing everyone is unique, so try interventions and see if it fits you your genetics, your habits, your blood work, your biology. Number three, I know that it's exciting to talk about how carriers benefit more than non carriers, but remember those are relatively preliminary.

[24:30]The authors usually say that themselves the bankable claim where we are 100% sure is we benefit at least as much as non carriers. and number four. This is the spine of everything on this YouTube channel. Risk is not destiny. Having ApoE4 even two copies like me means your probability of developing Alzheimer's is higher.

[24:53]It does not mean it's certain it is still a probability. Those are two very different things, and I want that distinction to actually land for you. Think of it this way if I told you a particular road has a higher chance of accidents, that's useful information. It means you will drive more carefully.

[25:09]You pay more attention. It doesn't mean that you are guaranteed to crash if you go drive on that road. So the gene is basically that float. How you drive still matters enormously And this isn't just me being optimistic. The researchers who study this gene specifically say that lifestyle changes may benefit cognition, even in people with ApoE related genetic risk.

[25:30]It, they didn't say might help a little. They say benefit. So that's the science talking, not just the wellness, blah blah. So there are plenty of carriers, including 4/4 like us who never develop Alzheimer's disease. As we say, the gene loads the gun It does not pull the trigger.

[25:48]One last honest truth about sustaining everything because none of these matter if you quit in two months time. So here's what I've learned. Watching our community, watching all the data that goes through our app. Consistency beats intensity every single time. You don't want to go on the hardcore interventions, diet do tons of sports and then give up because your life is just too miserable afterwards, right?

[26:16]Remember the person who managed to walk 8000 steps a day for ten years destroys the person who does a harrowing 90 day sprint and burns out. So the thing that keeps people consistent is not just willpower, it's usually other people. So in Phoenix we run this in pods, which are small groups of 2 to 4 carriers doing the same experiments, checking in, keeping each other honest.

[26:41]We match carriers together every month based on your targets, your goals, and based on your biology and also your time zone so you can meet each other in real life. That's actually a new feature, and they are actually 550 plus carriers in there right now, all running their own version of the experiments and sharing back the result with the community.

[27:04]So you are genuinely not doing this alone and you should not try to. That's the whole reason why I built Phoenix. Once I started in this journey, I felt so lonely. No one understood what I was going through. That's why I built Phoenix and that's why it's called the Phoenix Community.

[27:20]That's the whole point of having a community. Instead of just dropping a PDF and disappearing. So let me now bring this home back to the whole question I took away from you at the very start of this at the top. I said the question is it too late?

[27:34]Is completely wrong as a question to ask, and I ask you to trade it for a better one. Which lever to pull first? Now you've got your answer and it's not too late. The trials that proved it enrolled people aged 60 to 79. And it worked for them.

[27:51]It worked for carriers at least as much as anyone, if not more than non carriers. You've got an extremely long runway and a buffer you can still build no matter your age, and nearly half the risk is sitting in a bucket marked yours to change. So here is your quick start list.

[28:09]You have four moves. Take them now in. First you want to get your baseline labs right. Do ApoB do your hba1c do your fasting insulin. We actually have a guide for blood work that I'll put in the link below in the description. It's a free PDF that you can take to your physician to know what to test for.

[28:28]Second, you should pick at least one metabolic lever first. Early preliminary data suggest it may be a high leverage starting point for carriers. Then three you want to build the stack over time your mind style diet, Mediterranean diet, aerobic and strength training, cognitive challenges, social connections. You want to fix your sleep.

[28:49]And number four, you want to run all of that as an experiment. I know experiment can sound daunting, but it's not. You can either do that in an Excel sheet, or you can join Phoenix and do it with our app that is completely guided. So you want to measure change one thing and then remeasure.

[29:05]again, if you want to do all of that with a part of carriers doing it, along side you with an entire community who is on the same journey, that's what I build Phoenix for. The link is also in the description of the video below. Pick one lever this week and I'll see you in there by.