Got APOE4? A Vascular Surgeon’s EXACT Plan to Protect Your Brain

Got APOE4? Here’s the exact prevention strategy I would use to protect my own brain if I carried this gene.

In this video, I walk through the major modifiable dementia risk factors identified by the Lancet Commission — and how I would actually approach them in real life as a vascular surgeon specializing in cardiometabolic prevention.

We cover:
* ApoB, vascular disease, and why “brain health” starts in the arteries
* What you can do NOW without any clinical support
* Blood pressure, insulin resistance, exercise, sleep, and inflammation
* Hearing loss, social isolation, alcohol, smoking, and other overlooked dementia risks
* Which interventions matter most
* How I prioritize prevention clinically
* What people with APOE4 often misunderstand about risk

⏰ Chapters:
0:00 Almost Half of Dementia Cases May Be Preventable
0:24 APOE4 Is Not Fate
0:53 Why a Vascular Surgeon Cares About Dementia
2:05 Meet “Carol”: APOE4, Family History, and Fear
3:11 The Lancet Commission’s 14 Modifiable Risk Factors
5:29 Why APOE4 Carriers Still Have Real Hope
6:48 What You Can Start Doing Without a Prescription
7:08 Exercise: The Biggest Lever for Brain Health
8:49 The 4 Exercise Buckets I Recommend
11:56 How to Eat for an APOE4 Brain
16:49 Why I’d Keep Alcohol Near Zero
19:16 Loneliness, Social Connection, and Dementia Risk
21:29 When to Bring Your Doctor Into the Plan
22:11 Make Your Lipids Boring
24:47 Obicetrapib, pTau217, and New Alzheimer’s Biomarkers
29:58 Blood Pressure and APOE4 Risk
32:06 Sleep, Sleep Apnea, and the Brain’s Cleaning System
33:54 Insulin Resistance Is a Brain Problem
36:54 Hearing Loss and Cognitive Decline
38:39 The Shingles Vaccine Dementia Data
41:23 Bonus: Hormones, Homocysteine, and Dental Health
45:37 Why Supplements Are Part 3

APOE4 is NOT destiny. But it is a signal to get serious earlier, and there's so much you can do TODAY to head in the right direction.

Missed Part 1? Check it out here: 
https://youtu.be/y8vkJE_Zy7A

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___________________________
🧬 About Dr. Lily Johnston
  
Dr. Johnston is a double board-certified vascular and general surgeon in San Diego, specializing in metabolic and cardiovascular prevention. She’s the founder of CorSight Health and a passionate advocate for reimagining how medicine approaches chronic disease.

Disclaimer: This video is for educational purposes only and does not constitute medical advice or establish a doctor-patient relationship.

Transcript

SPEAKER_00 0:00

Almost half of dementia cases are potentially preventable. That's what the Lancet Commission says, and let's talk about it today. If you guys don't know me or you're new here, my name is Dr. Lily Johnston. I'm a board-certified vascular surgeon, but I also specialize in cardiometabolic prevention. So hopefully you never need me as a surgeon. If you carry an ApoE4 allele, when we talked about ApoE4 in the last video we did, and we'll link that for you here. If you carry an ApoE4 allele, you know that you are at increased risk for developing Alzheimer's dementia. But you also should know by now this is not deterministic, meaning this is not fate. This is an opportunity to modify and reduce your risk. Now, I get a lot of flack sometimes for talking about stuff that's not in my lane, like I'm a vascular surgeon. Why are you talking about dementia? Because dementia is partially a vascular disease. Alzheimer's is not, but if you saw our comment response recently, you know that up to 75% of all dementia cases on autopsy are found to have a vascular component. So the disease that I treat every day in the blood vessels in the neck does speak directly to your risk of developing dementia later in life. And as a personal aside, I have a family member whose brain does not work like it used to. And I have taken a real interest in trying to understand how to help this person in my family live and function better. So I do not profess to be an expert in this, but I have a very vested interest in knowing more, and I would like to share what I have learned with you. So let's talk about what you should do if you have an ApoE4 allele. Because again, this is not fate. This is an opportunity to get a head start on this risk and reduce it as much as we can. This video is all about the concrete steps you can take to make this happen. And what I want to do is talk to you about a patient because I actually see people in my clinic who come to me with this concern. So I'd like to introduce you to Carol. She is somebody that I saw in my office. Now, obviously, this is not her real name and this is not her real presentation, but this is a facsimile of patients that I see in my clinic. So this is a lovely woman in her mid-60s. She is postmenopausal. She has a genotype result that it's pretty new for her, uh, ApoE3 on one and ApoE4 on the other. But both of her parents had dementia, and she is fairly active. She takes a nice long walk most days. She does not smoke. She has a glass of wine most nights with dinner and had a lipid panel done a year ago that her doc said was quote unquote normal. And uh she comes in with her sister-in-law to say, I don't know what to do with this like test. I got this test, my parents had dementia, I'm really scared. Help me not get dementia if that's possible. What do we do? So let's go through what the Lancet says are the options because Carol doesn't have symptoms yet. She's functioning, she's living her best life, she's really happy, she's doing great, but she wants to know what the future might hold. And she wants to be informed about these risks and what the possibilities and options for intervention would be. So Lancet is a very big medical journal based uh in Europe, and they convene these commissions. So the Lancet Commission on Dementia published a very big paper in 2024, and they looked through gobs, just reams and reams of papers, and came up with 14 modifiable risk factors. And together, all told, if you add every single one of them up, they account at the population level for what we think is maybe 45% of dementia cases globally. We will not cover all of them today, and modifiable is an interesting word. We'll talk about that in a second, but let me at least show you what they are and which ones we will cover in today's video. So, of the 14, education is one that is true in early life. Now, again, whether this is modifiable at an individual level or not, that's up to you to decide. We're not going to go through that today. Carol uh has a college degree, and her education at this point is pretty fixed. In midlife, the risk factors that Lancet calls out are hearing loss, high LDL cholesterol, that's new in 2024, depression, traumatic brain injury, physical inactivity, diabetes, smoking, high blood pressure, hypertension, obesity, and excessive alcohol use. And the risk factors they find in late life are social isolation, air pollution, and visual loss or vision loss. So again, air pollution is a modifiable risk factor, sort of kinda. Most people are not gonna pick up and move where they are later in life to change their air pollution risk. Um, most people are doing their best not to have traumatic brain injury above and beyond what's you know what happens to them in daily life. So, you know, if you do contact sports, I suppose you could stop that, but probably if you've had a TBI in the past, like that is what it is at this point. So we're not gonna belabor those points. We will talk about everything that is highlighted here and how I think about this in my practice. This is verbatim from the Lancet Commission paper, and it highlights what I have already told you. Risk is modifiable irrespective of APOE genetic status. Multi-component interventions addressing several risk factors potentially benefit individuals with either high or low genetic dementia risk. This means you, as an ApoE4 carrier, have a lot to gain from implementing these suggestions or these strategies that we're gonna talk about today. You might even benefit more than people who do not carry an ApoE4 allele. So this is not a reason to give up. This is a reason to double down and commit harder to all of the things that we're gonna talk about. And there have actually been a number of trials that did what we're gonna call these um multi-domain interventions. This means they did an intervention on nutrition, they looked at exercise, they looked at sleep, and they looked at a bunch of different components. They did all of these together as multidomain interventions. And if you combine the several trials that have happened like that, you find that the cognitive benefit is actually greater in people who have the ApoE4 allele than in those who do not. Okay? There is lots of hope to be had here. So we're gonna break this into two parts. The first half of the video are things that Carol can do absolutely on her own. She does not need anybody's permission, she does not need a prescription, she does not need a doctor. That means any of you watching can choose to do these things by yourself without any additional support. All right. Um, the first of these is exercise, movement. Move your body like it is a prescription. I will write it for you. We can post it somewhere, right? This is a really, really big deal. Movement is medicine. And we're starting here because I think that this is the single biggest lever for overall health and well-being. I mean, dementia for sure, but also your cardiovascular health and your mental health. This is enormous for all aspects of aging gracefully and well. So this is a big deal. And how would you say that this is related to ApoE4? We actually think that if you are sedentary, not moving enough, this is very costly for you if you actually carry this ApoE4 allele. So uh 2001, an older study, showed that the odds ratio for cognitive decline in APOE4 carriers was 3.7 times higher than in sedentary non-carriers. So being sedentary at all, yes, that doubles your risk of cognitive decline, even if you're not a carrier, but it's almost four times higher if you're in APOE4. And if you do exercise, we can show on imaging that you have an increase in brain volume. So aerobic exercise is a study from PNAS in 2011. Aerobic exercise training over 12 months grew the hippocampus. This is the part of the brain responsible for memory. And it grew by 2% in older adults, reversing typical age-related shrinkage because the control group actually lost 1.4%. So exercise is a big deal. If you're not exercising, it increases your risk. If you do exercise, we can improve parts of your brain responsible for memory. If I were talking to Carol about her exercise plan, we already know she walks. That's awesome. I bucket put that in the bucket of what we call low intensity, steady state. Some people like to call it zone two. Um, but let's keep it simple. Just say this is where you're walking, moving, you are anti-sedentary, your heart rate is higher than it would be if you were sitting on the couch, but it's not so high that you're short of breath. You're not necessarily sweating, but you're active and moving. And this should be sort of an all for you know, half an hour a day, every day, or 30 to 45 minutes multiple times a week. 150 minutes total of that per week is a great idea. And this helps with blood glucose. This helps with just not sitting on our butts and it gets us outside some of the time. Great opportunity. Number two, bucket number two, resistance training. Two sessions per week. This was actually included in the finger trial, which was one of those big multi-domain intervention studies. They included resistance training. Muscle is a metabolic organ. It helps dispose of glucose in our body. And we know from part one that the brain does not use glucose well if you have an ApoE4 allele. It doesn't use it as well, for example, than if you don't have it. So using your glucose, maintaining insulin sensitivity, being exquisitely insulin sensitive. This is a function of how much muscle you have. So you gotta go build some. You've got to do resistance training and build the muscle. The third bucket, I would say, would be high-intensity interval work. So call it VO2 max, call it an interval workout, whatever you want to call it, getting your heart rate elevated and actually sweating and getting short of breath, moving the needle in your cardiorespiratory fitness at least once a week in that direction is helpful. We've done a video that shows it may actually even reverse plaque. So again, not only is this good for your brain, it may also be good for your heart and for your vessels everywhere else. I love for people to have kind of a workout in every bucket. The fourth bucket I talk to patients about is mobility and coordination. And a lot of different things fit in this bucket. It could be yoga, Pilates, dance classes, tai chi, martial arts of any kind, stretching and foam rolling, mobility workouts, anything in that category. There's, you know, people like to talk about the uh positive benefit of like paddle sports like tennis and pickleball and things like that. Part of that is just the coordination, moving your hands, moving your feet, keeping track of a ball, all of that stresses your brain in a good way and allows you to have higher performance in all areas of life. So we have four buckets. Two of them are aerobic, one of them is resistance training, and the fourth bucket is this coordination mobility bucket. That's one's pretty tenuous. But if we can diversify our exercise portfolio across all those areas, that is what I generally recommend for my patients. We are targeting at least 150 minutes a week of aerobic activity, but as much as you can stand, I don't think there's a ceiling for how high we can train unless you're not able to recover. Step number two, eat for an APOE4 brain. You don't need a physician to talk to you about how to eat well, but there is always the question of like, well, what does that mean exactly? And this diet is not actually one of the Lancet factors, but there are three things that are pertinent from the Lancet Commission that pertain to this LDL cholesterol, diabetes, and obesity. And these are the components that all could be addressed by a better nutritional strategy. And for APOE4, there actually seems to be a pretty interesting signal for how we eat. And there was a team at Harvard that did a study in uh 2025 published in Nature Medicine that asked: Does diet protect APOE4 carriers differently? This was a metabolomics study. So they looked at all of the different little proteins and markers that come from our nutrition and our gut, and they used the nurses' health study, which is over 4,000 women, and they actually followed this up with about 1,500 men from the health professions follow-up study. And they have like decades of follow-up for these individuals. So they started tracking them in the late 1980s, early 1990s, and they have data through 2023. They measured dietary patterns. Now, again, that is a little tenuous because that's a food frequency questionnaire, which, even though they're validated, if you have paid any attention in the nutritional epidemiology space, you know food frequency questionnaires are not the best data, right? It's hard to remember what you ate yesterday if you don't eat the same thing every day. And asking people what they ate in the last year or last month or last week is a little bit fraught. But they did measure a dietary pattern. They measured those blood metabolites that we talked about. They have ApoE genotypes for everybody, and incident dementia, meaning new diagnoses of dementia during the follow-up period. They're categorizing this as adherence to the Mediterranean style diet or a Mediterranean pattern. And what they mean by that is olive oil, fish, vegetables, beans, legumes, pulses, whole grains, fruits, and nuts. And this pattern they think is low in processed meats and refined sugars. They also incorporate red meat and call that the same as processed meat. We can quibble about that. Long story short, there is a very strong signal for benefit of a Mediterranean-style approach, again, based on food frequency questionnaires, but uh, in people who are ApoE4 homozygotes, they had a pronounced level of protection against dementia diagnoses when they had high adherence to this Mediterranean style diet. And about 40% of that is accounted for by these blood metabolites. And they don't see that impact in non-carriers, meaning if you didn't have an ApoE4 allele, adherence to a Mediterranean style pattern of eating was not necessarily all that helpful or protective for you against dementia. So what does this mean? If you have an ApoE4 allele, I think that the Mediterranean approach is a place to start. And then we consider other factors. Are we managing an excess of nutrition, right? Do you have excess energy? Do you have excess body fat that we're targeting? Or do we have any signs of insulin resistance? If either of those are true, we are gonna modify that Mediterranean-style low glycemic approach based on those other pieces. So again, we might choose to reduce carbohydrates if we have insulin resistance. Um, we know that ApoE4 carriers need to be maximally insulin sensitive. We are also, we just got done talking about exercise and muscle as a metabolic organ. We are gonna make sure that we're getting adequate protein to support our muscle protein synthesis. This is a number we can calculate based on somebody's body weight and their training volume, but we want to make sure that even if we're targeting fat loss, that we're not going to sacrifice muscle much to do that. Okay. And again, carotenoid-rich foods, these are the brightly colored fruits and vegetables that you'll hear talked about in like all of the major nutritional spaces. This was particularly helpful, we think, in these ApoE for carriers. There are some data using ketogenic style approaches for patients who already have a diagnosis of Alzheimer's dementia. Um, those are case reports. They are not big series. We don't have any randomized controlled trials for me to report back to you about the use of ketogenic dietary therapies for people with ApoE4 or for the prevention of dementia. That is a popular topic and question, but we just don't have the data for me to answer that for you today. What we do know is that a Mediterranean style approach, for all that that is a little bit fraught based on how the study was designed, is what is our evidence base today in 2026. All right. Factor number three that you can do without anybody's permission, alcohol. So excessive alcohol intake is for sure associated, but I actually go a little further and I think that people should default to quote unquote near zero. And we have to talk about the right reasons for this because what we know is excessive alcohol intake is bad, right? So reduction of excessive alcohol and sustained light drinking is associated with a lower dementia risk than excessive alcohol. Duh. That's not like we don't need to write home about that. There is lack of clear evidence that not drinking alcohol increases the risk. Meaning, if you don't drink much now, should you start as a heart protection or as brain protection? No, you should not. We have no evidence that starting drinking, if you have not been drinking already, will help you. Here is why I personally default to a slightly lower permission for alcohol for all my patients, but particularly for Apo E4. Because what the Lancet Commission says is, well, this is just the population pattern. But what I notice in my practice is that if you have insulin resistance, if you have excess adiposity or excess body fat, or if you have any issues with your sleep, alcohol will make all of those things worse. And those are separate factors, right, that are counted differently in this Lancet Commission. They are counted differently in other studies, but alcohol does not help with any of those things. So if you're gonna come to me and ask about weight loss and you're drinking every night of the week, we're gonna talk about just a source of empty calories. If you are insulin resistant and struggling, even though your nutrition, you know, you're not eating either a large number of excess calories from fat or a large number of excess calories from carbs, but you're still drinking a couple of drinks every night, your body has to process the energy from alcohol before it can process either fats or carbohydrates. So your alcohol is stalling your fat loss. And if you are struggling with sleep at all, even though you may think that alcohol allows you to fall asleep better, most people will report if you wear a whoop or you wear an aura ring that the quality of your sleep is degraded. Your heart rate will go up, your HRV, heart rate variability will go down. Not everybody, most people. So it certainly for me made me uh think twice about how much alcohol I drink within several hours of going to bed. So for most people, alcohol is a treat. It is something you can do once in a while socially. It does not need to be complete abstinence, but I would say uh if it's every night, perhaps that's not serving you. All right, item number four, stay socially engaged on purpose. Loneliness is a measurable, modifiable risk factor for dementia. And unfortunately, I told you I have uh a family member who has a brain that doesn't work like it should. And I think part of my dad's problem is that he is pretty socially isolated. Now, we have to distinguish because loneliness and social isolation are not the same. And when they are measured separately, it is loneliness that actually seems to be the risk factor, not just social isolation. I don't know if my dad would identify as lonely. He certainly is socially isolated, meaning he doesn't have friends that he goes and hangs out with. He does not have a regular social group and he doesn't seem to want one, and he's hard to get out of the house and hard to encourage him to go do those things. Uh, and he's just not engaged in a community in the same way. So, whatever community you have, build it, nurture it, and lean into that. So, whether that is church, whether that's your pickleball group, your bridge club, I don't care. Pick some friends, go make a new friend, get a hobby, be out about and engaged in the world. Go meet some people at your coffee shop and just chat with them, make a book club, whatever it is that means something to you, go find those people. Because persistent loneliness in women is almost a two-fold increase in incident dementia over eight years. And in a meta-analysis, we can see even up a 60% increase in risk for dementia in people with a poor social network. So staying engaged and having your community is a really big deal. And you'll remember that Carol didn't actually come to my office alone. She came in with her sister-in-law, and I actually took this as an enormous positive sign for her. They are really good friends, they hang out a lot, they go walking together most days. And it is one of the things that makes me very optimistic that Carol is able, going to be able to, you know, enact this part of our recommendations pretty, pretty easily. And you may not even realize that this is a big deal for you, but um, in some ways, it's one of the most enjoyable prescriptions I can write as a physician, even though you don't need one. So we've gone through a bunch of things that you can do all by yourself, and you have no need for a physician involved in any of this. And if Carol did all of those things and stopped right here, we know she would already be so much better off than when she first walked into my office. She would be cutting her risk for dementia in a very meaningful way. But we don't have to stop here. We actually have a bunch more things that we can do together as a team to help her reduce her risk for ever-developing dementia. So the next Few things are things that I think are helped by having your physician on board or your clinician of any kind help you out if you need some additional testing or access to additional tools. And number five is to make your lipids boring. We talked in part one about how APOE4 in the brain in particular is a lipid taxi service. It is a delivery fleet. Its job is to move lipoproteins and other stuff like amyloid beta through this highway network in the brain and take junk from where it doesn't belong and keep it from building up and making the cells toxic. So making your lipids boring is an important thing. And again, 7% population attributable fraction in the Lancet Commission for high LDL cholesterol. Let's look at the data because you might not want to hear this. But high cholesterol raises risk for instant dementia in midlife, and lowering it seems to bring the risk down, at least in large cohort studies. Let's look at the first part of this. If you have for every three millimole increase, or sorry, for LDL greater than 116 milligrams per deciliter, which is three millimoles, then you have a 33% increased relative risk for dementia. And the younger you are when you have elevated LDL cholesterol, the stronger this impact is. This makes sense, right? Because we always are now talking about exposure over time. So if you start having elevated LDL cholesterol in your later life, like not until you're 60 or 70, you're not going to have as much impact as if you've been living with this since your 30s and 40s. What about lipid lowering therapy to actually improve this? We see a 32% reduction in Alzheimer's risk in patients who are on statin therapy from cohort studies. So we actually don't see a big effect in the randomized controlled trials that have been done with statin therapy. We can talk about why that might be. Perhaps it is that the follow-up isn't long enough. Perhaps it is that the patients are too old when we're starting therapy. All kinds of possibilities exist. But when we look at bigger cohorts of just all comers, we do see this 30-ish, 32% reduction in risk. Now, what I really want to draw your attention to is that the effect in ApoE4 carriers seems to be larger, meaning ApoE4 carriers seem to get more benefit from being on lipid lowering therapy and statins in particular. So we see a in these cohorts a reduced risk for all-cause dementia, about 20%, and um for 32% for Alzheimer's in particular. Now we're going to talk about a little bit of a new kit on the block. This is a sub-analysis of the Broadway trial. Broadway is looking at a new drug called obacetropib. This is something called the CTEP inhibitor, cholesterol ester transfer protein. Now, you may have seen some of my other videos where we talk about the CTEP inhibitor class of medications and why this was a historically a colossal failure in the cardiology research space. CTEP inhibitors are not new. We've tried them before. And originally their attraction was because they raised HDL cholesterol in a lab panel. So cholesterol ester transfer protein, CTEP, its job is to take cholesterol away from HDL and put it in LDL, meaning it can go the wrong direction. So if you inhibit CTEP, then HDL cholesterol goes up and LDL cholesterol should go down. For all kinds of reasons, the multiple drugs that were tested in this class all failed. Several of them were harmful, some of them didn't really help that much. And this was part of the story that helped us understand that just raising HDL cholesterol without really understanding why it was going up or whether that was effective in reverse cholesterol transport wasn't really helping patients and wasn't moving the needle. And this is why we no longer believe that raising HDL just in and of itself is all that helpful or protective. But obaceptrapib is a new CTEP inhibitor that is in clinical trials right now. And there was a substudy released from this Broadway trial, and they looked very specifically at the biochemical markers for Alzheimer's disease. So we now have a blood test you can get that measures something called P Tau or phosphorylated Tau 217. Now, this is not really prime time yet. I'm not testing people for this in my clinic because it's very new and we are not quite sure how to interpret it in people who are not symptomatic yet. Nevertheless, there is now a blood-based test that can measure this marker that is highly associated with Alzheimer's disease. We have a couple of other ones that we measure as well. All of them were measured in this study, and the TLDR of it is that this molecule, this obacetropib drug, reduced P tau to 17 in ApoE4 carriers a lot. Okay, so we actually had the PTAW levels fell 7.8% in the ApoE4 group, and they rose 12.7% in the placebo group. So over time, PTau tends to accumulate, right? And these are the tau tangles, the fibroid tangles that happen, and over time that just goes up. But in the opacetropib group, it went down in ApoE4 carriers. They also saw a 17% decrease in the neurofilament light or the NFL in the homozygotes, ApoE4-4. They fell 10% on the drug and they rose again in the placebo group. This is the first trial where an oral molecule is reducing the markers for Alzheimer's dementia. We do not have cognitive outcomes yet. We do not have a diagnosis for Alzheimer's in any of these patients. So we don't know if moving the biomarker is enough. We don't know whether this will be clinically helpful. And for to be very clear, like this drug is not really intended, or at least it wasn't originally designed as an anti-dementia drug. It's designed as a cardiovascular drug. But uh just based on how they're designing the trials, I wouldn't be surprised, depending on how things end up, if they might also seek an indication for this for the dementia prevention side. That's pretty exciting. So we'll see, right? This is very early days. We do not have outcomes yet, but an interesting story. Stay tuned on this one. In terms of Carol, what we're gonna do is we're gonna check an advanced lipid panel. We'll check an Apo B, we will check her LDL particles, we will check in lipoprotein little A, and we're gonna have perhaps a more aggressive target for her. This will be done in conjunction with, you know, some imaging to see what her vessels look like. Does she have any plaque, all the rest of her risk factors, right? None of this should ever be managed in isolation, and it's all done as a risk-benefit conversation with Carol. But I would say you could be potentially um, you would be within reason to have slightly lower lipid targets if you're an ApoE4 carrier based on the data that we've shown you so far. How would you do that? Again, you can use statin therapy, that has been shown. You can use a zetomide. Uh, we've talked about that recently in a video. You can use PCS-K9 inhibitors. The trial data from PCS-K9 inhibitors did not show any reduction in cognitive design. And the current PCS-K9 inhibitors are monoclonal antibodies. They are injection drugs, it's two out of the three. And best we can tell, they're not going to cross the blood-brain barrier. So I'm actually not sure if I would use a PCS-K9 inhibitor for the sole purpose of reducing lipid burden in the brain. This is an interesting question. It's a data-free zone, but that's just my two cents about that. All right, let's talk about blood pressure. Carol really needs to have normo tension, normal blood pressure, 110s through to 120s. Why is that? Because for every millimeter of mercury above 140, there's an increased risk of Alzheimer's disease. And the amyloid plaque buildup in the brain goes up in ApoE4 carriers who have high blood pressure. So the buildup was four, four and a half times higher with high blood pressure than in people who don't have an ApoE4 allele. And if we get blood pressure down, we reduce the risk of cognitive impairment or dementia by 14%. That was the Sprint Mind trial. It's important to recognize that the combined endpoint was significant. Dementia by itself was actually not. But overall, the importance of blood pressure control is a good idea, whether you're thinking about dementia, stroke risk, heart attack risk, kidney disease, all of them are good reasons to be very intentional about your blood pressure control. The most important thing about this is probably getting a blood pressure cuff for yourself and having it at home and checking your blood pressure at home twice a day. If I had a dollar for every time somebody has high blood pressure in my clinic and they swear to me that they don't actually have high blood pressure most of the time at home, but they don't have a cuff at home. Yeah. So I white coat hypertension is a thing. A lot of doctors' offices do not take the time to measure blood pressure correctly with two feet on the floor after somebody's been in a nice quiet space for five minutes, right? That's just not the average doctor's office. I get it. But the best thing you can do for yourself is to really know what your blood pressure is and just get a blood pressure cuff, have it at home, check your blood pressure appropriately, and keep a log and chat with your doctor about that. Um, you need, if you're an APO-A4 carrier and you have hypertension, I strongly recommend making that a priority for yourself. A lot of it can be done with lifestyle, but you may need pharmacologic support. I would not sit on this for six months or 12 months while you hope and pray that lifestyle interventions alone are going to get this number down in a good place for you. Number seven is sleep. Okay. The brain cleans itself during sleep. It actually goes in there and sweeps away all the garbage and takes out the garbage at night. This is through something called the gymphatic system. Not lymphatic with just an L, but there's a G on the front of there. Glimphatic system. The brain cleans itself. It's amazing. But it has to sleep to do it. And if you are not getting high-quality sleep, your brain is not going to be able to re-get those toxins out of there. And perhaps the biggest sleep problem I see in my practice is undiagnosed and untreated sleep apnea. The Lancet Commission does not call this out specifically as a risk factor, but they do mention therein that in fact there is a 40% increased risk for dementia in multiple studies in patients who have sleep apnea. Well, that's nice, but does treating sleep apnea actually make it better? We think so. We think so. We don't actually have a randomized controlled trial for this. So this is observational and the quality of the evidence is weaker. But for patients who have disordered breathing, sleep breathing problems, and wear a CPAP, their onset of dementia in a big study population was 10 years later than those people who had sleep disordered breathing but did not treat with CPAP or other devices. So give or take, about a 10-year delay in dementia onset, I would take that. So if you have sleep problems, if you snore, go get a sleep test. Okay. I also want you to prioritize your sleep hygiene, right? Nice cold, dark room. Plan for seven to nine hours a night. And if there is any concern about your sleep quality, go get a sleep test. Number eight, treat insulin resistance like it is a brain disease. Because if you're an ApoE4 carrier, it is. I know we already talked about nutrition. We're putting it again here as insulin resistance because diabetes is consistently one of the single biggest drivers of dementia. And while I do believe that a lot of people are able to manage this with nutrition and exercise alone, some of you are going to need a little additional support, at least initially, to get this under control. And again, even though I am such a huge believer in the power of your lifestyle to manage this, and many of my patients are able to do this independent of supplements or drugs, we don't have a lot of time if you're coming to me in midlife with an ApoE4 allele or even two to get this fire suppressed. We really need to work together to get this under control as quickly as we can to keep your brain in great shape. Because patients with diabetes have a huge amount of additional amyloid plaque on their brain imaging, right? 3.6 times more likely to have amyloid plaque on imaging than those without diabetes, even independent of your ApoE4 status. Um just a huge increase in risk if you have diabetes. So we need to know your insulin resistant status, and some labs will help us know this. So you need a fasting insulin, a fasting glucose, and an A1C. We'll get a Homo IR from that. You should have a triglyceride to HDL ratio, right? We already talked about lipids, but this is part of it. And if you are interested in understanding how your own personal nutritional strategy is serving you, I can absolutely recommend a month with a continuous glucose monitor to see what's going on for you. Because I have had a lot of patients who just don't read the textbook, and some things spike their blood sugar that really shouldn't. Other people have a completely flat curve with things that would spike my blood sugar. You have to get data. Get some data and figure this out. Okay. We have a lot of targets here. These are general suggestions. They are optimal in my practice, but everybody will be a little bit different in terms of exactly where you need to be on this. And if and when, for some patients, lifestyle is not enough, or it's not enough soon enough. We have additional tools that are available. Okay, metformin, berberine, acarbose, these are options for the right patient. The GLP1 receptor agonists are also very, very interesting. And there is some signal in cohort studies that they may help prevent or delay the onset of dementia. Interestingly, they do not seem to be helpful once dementia is already present. Also, maybe a conversation for another day. I don't know why that is. I have a theory, but we can talk about it another time. Nevertheless, if you don't have dementia yet and you're having an insulin resistance issue of some kind or excess inflammation from excess body fat and need a little support to manage that as the lifestyle comes into alignment, these are good options to talk about with your physician or your clinician. Number nine, hearing. Hearing, okay? Get your hearing tested. And if you need hearing aids, get some hearing aids. There is a huge prevalence of hearing loss in especially older patients. And this is absolutely associated with an increased risk of dementia or at least an increase uh in the manifestations of it. And there are some indications that if you fix the hearing loss with a hearing aid, you will improve your outcomes. Okay. Um, the achieve high risk subgroup had a 48% reduction in cognitive decline. Overall, there was actually a low, like the whole Achieve study was not a high-risk cohort. And in that particular overall population, there was not a significant finding. But I would say ApoE4 qualifies as high risk. So if you have an ApoE4 allele, please get your hearing checked. And if you need a hearing aid, please wear one. So I know, right? Nobody wants to wear a hearing aid in their 50s or even in their 40s. But if you have an occupational exposure that's major hearing loss, a problem, then this is something that you need to try to make peace with. Don't let the stigma of wearing a hearing aid stop you. And um I wish that I could convince my dad to wear a hearing aid. He absolutely has occupational exposure-related hearing loss from jet engines, and uh shouting at him is getting really old. And he has been dead when audiologist, and he just won't wear them. Just won't wear them. Okay. This one is gonna throw you guys for a loop. Get a shingles vaccine. Get a shingles vaccine. I'm not talking about everything, we're not talking about flu, we're not talking about anything else. Shingles. Why are we talking about this? It's not even in the Lancet Commission, but there have been two studies that came out in the last few years that are almost as close to a randomized controlled trial of dementia prevention as we have ever had. And the results are kind of astonishing. So in Wales, there was this experiment that happened. There was this cutoff, there was a birthday cutoff, and everybody before the cutoff did not get a vaccine. Everybody after the cutoff did get a vaccine. So this is a random date in time. And they looked after seven years of follow-up, and there was a 3.5% absolute risk reduction in new dementia diagnoses. So this means your number needed to vaccinate is 29 to prevent one dementia diagnosis in seven years, and the effect was a little bit stronger in women. Okay, well, maybe that's just whales, like maybe they're weird. No, we replicated this finding in Australia, and it was a very similar trial design. They had a cutoff date before which people did not get vaccinated, after which people did get vaccinated. Populations were largely equivalent, and again, it wasn't quite as large a reduction. It was 1.8% absolute risk reduction over seven and a half years of follow-up. So that's a number needed to vaccinate of 56, but we're still well under 100 and we are preventing diagnoses of dementia. Now, why does this even make sense? Shingles is the reactivation of the herpes uh virus, and it's in the central nervous system, right? Herpes virus travels and sits and rests dormant in the nerves. Shingles is a disease where it reactivates in a dermatomal distribution, meaning the nerve that goes to a certain section, whether that's right around your eye or right up of your neck or right on your shoulder, there is a whole nerve that just innervates that one section of your body. And the virus just preferentially activates right in that one nerve. So this virus is laying dormant in our brains, in our central nervous system. It might make sense that in some way getting shingles creates a bunch of inflammation in the brain. We don't know exactly why this works, but it's kind of powerful. And I am impressed by these data. So Carol is of age to be eligible for the Shingrix vaccine series. And even though it's not yet on the Lancet list, I would strongly encourage you to at least consider getting vaccinated for shingles if you are interested in maximal risk reduction for dementia. So that is kind of the big list. There are three more things that I talked about with Carol in our appointment, and I'm going to walk you through them really quickly just for the sake of completeness and because I think they're fun. They are not on the Lancet list and they are not necessarily anything that will move the needle for Carol, but because we talked about them, let's talk about them here. The first is hormone replacement therapy or menopausal hormone therapy in APOE4 women. There are some very interesting data about the use of MHT from the EPAD cohort in 2023. ApoE4 users had better delayed memory and larger brain volumes in patients who were started early on menopausal hormone therapy, meaning within a few years of the menopausal transition. However, in the UK Biobank, we saw the opposite effect. ApoE44 women had smaller brain volumes and then never users. Okay, so is this the timing hypothesis? Meaning, does this impact when we're starting menopausal hormone therapy? Does it matter? It probably does matter. Carol is in her 60s and she has not been on menopausal hormone therapy for the 10 years or give or take since she went through menopause. Does that mean we can't start it? No, but it means we have to be careful and not start it for the wrong reasons. We are not going to start it for dementia prevention in Carol. We are going to start it potentially to help manage any menopausal symptoms that she may have, and that's a whole other conversation. But I don't think that starting it for her in her 60s is helpful for dementia prevention. Timing matters for menopausal hormone therapy, no matter the indication, if we're thinking about preservation of function. Okay. So I would offer it to her to treat a very specific symptom. I would not offer it to her because of her ApoE4 status or to prevent dementia. Homocysteine, this is a marker for your body's ability to convert inactivated forms of B vitamins into the activated forms. And there is some interesting evidence for homocysteine in stroke reduction risk. And there's also some interesting evidence for elevated homocysteine in dementia prevention, like the Vitacog RCT, where use of these vitamins slowed brain atrophy by about 30%. And that was even higher in people who had a high baseline homocysteine. In general, I think it is a pretty low risk intervention. So I don't know what Carol's homocysteine is, but you bet I sent one. We checked it. I'll let you know. The last thing is dental health. You may have heard me talk about this in other videos, but you can find the plaque from The bacteria in your mouth in the plaque in your brain. You can find it in the plaque in your arteries. We think that inflammation in your mouth is probably a bad thing for your blood vessels, and it's probably a bad thing for your brain. So if you are not brushing your teeth twice a day, if you are not flossing or using a water pick, like maybe daily, maybe multiple times a day, then I would strongly encourage you to do that. We do not have high levels of evidence that say that it will prevent a stroke, prevent a heart attack, or prevent dementia, but it's a good idea. You should just do it. So I am going to leave you with those as the big things. This is the summary of what we've talked about today and what I had started off with for my patient Carol. Let me know in the comments below what you think about all of this, what makes sense to you, what I missed. And I just want to point out again that if you are APOE4, you get more, potentially more benefit from doing these things. And you have a lot of hope here. Okay. Your risk is modifiable. We talked about part one. Knowing is a head start. So Carol is here and doing things very intentionally and on purpose. So if you are concerned about your family history, go talk to your doctor, see about getting tested, and work on your modifiable risk factors. If you want to go check out part one, we will link that for you here. If you're interested in other genetic components to cardiovascular disease risk, I also have a series on lipoprotein little A that you can check out. We will link that for you below. In the meantime, take really good care. So we in part one promise to talk about supplements for those of you who have an ApoE4 allele and perhaps even more broadly, the use of supplements for brain health and protection. We have just gone through 45 minutes of the most important 95% of what I think really moves the needle for you if you have an ApoE4 allele or you are worried about brain protection. The supplement piece is important, but it was too much to tack on to the end of this video. So welcome to your promise for part three, where we will get into the EPA DHA, the omega-3 fatty acids. We'll maybe talk about lithium orotate. We'll talk about all of the things that people are using for supplementation with ApoE4 and for brain protection. Stay tuned for part three for more on supplements.