Subscribe
Share
Share
Embed
Welcome to The Dr. Kumar Discovery, a health and wellness podcast hosted by Dr. Ravi Kumar, a board-certified neurosurgeon. This is the medical podcast for anyone who wants honest, evidence-based answers to the health questions that matter most. No corporate influence. Just a physician who reads the research, questions the dogma, and breaks it down in plain language so you can make better decisions about your own health.
Dr. Kumar is a practicing neurosurgeon who brings a surgeon's precision to topics most doctor podcasts only scratch the surface of. Each episode dives deep into the science behind metabolic health, cardiovascular disease, heart disease, hormones, nutrition, brain health, mental health, pain, inflammation, weight loss, aging, blood pressure, sleep, and longevity. Whether it's the truth about seed oils, the real data on GLP-1 drugs and weight loss, the science of cold water therapy, how light can heal the body, or why your testosterone is declining, Dr. Kumar goes straight to the peer-reviewed literature and tells you what the evidence actually shows, not what the headlines say. This is evidence-based medicine in plain English.
The show features three formats. Solo deep dives explore a single health topic from the ground up, covering everything from the biology to the practical takeaways you can use today. Expert interviews bring on leading researchers, clinicians, and forward-thinking voices in health and medicine for in-depth conversations you won't hear anywhere else. The Tribulations series tells the true stories behind medicine's greatest breakthroughs, from the discovery of penicillin to the invention of vaccines to a father's fight to save his son's life. These are the stories of the doctors, scientists, and patients who changed the course of medicine.
Topics covered on the show include testosterone and hormone optimization, sleep science, photobiomodulation and red light therapy, exercise with oxygen therapy, creatine, uric acid and gout prevention, gut health and probiotics, cardiovascular risk and Lp(a), cholesterol, PANDAS in children, PTSD and trauma, acetaminophen safety, glyphosate, foot health, and much more.
If you're tired of generic health advice and want to hear from a neurosurgeon who actually reads the studies, The Dr. Kumar Discovery is your podcast. New episodes drop regularly. Subscribe and join the discovery.
For show notes, references, and more, visit drkumardiscovery.com/podcast
Let me ask you something. If a gene were truly bad for us, how long do you think it would take for evolution to just get rid of it? Well, probably not long on an evolutionary time scale, because disadvantageous traits are ruthlessly cut and discarded by natural selection. And the reason why I'm asking you this question is because there's a gene sitting in about one in four human beings on this planet right now That is the single strongest common genetic risk factor for Alzheimer's that we know of. And if you carry one copy of it, your risk of developing Alzheimer's disease roughly doubles.
Ravi Kumar MD:If you carry two copies, it climbs closer to fivefold. And that gene is not a recent mutation. It's not some modern accident. It's the original version that we evolved with. So it's the oldest form of the gene in the human lineage.
Ravi Kumar MD:And every single one of our distant ancestors likely carried it. Natural selection had hundreds of thousands of years to delete it, and it didn't. So either evolution made a catastrophic mistake, or we're just looking at this genetic trait all wrong. The gene I'm talking about is APOE, and specifically the APOE four variant.
Ravi Kumar MD:My name is Doctor. Ravi Kumar. I'm a neurosurgeon in search of the causes of human illness and the solutions that help us heal and thrive. I want you to join me on a journey of discovery as I turn over every stone in search of the roots of disease and the mysteries of our resilience. The human body is a mysterious and miraculous machine with an amazing ability to self heal.
Ravi Kumar MD:Let us question everything and discover our true potentials. Welcome to the Dr Kumar Discovery.
Ravi Kumar MD:Welcome back to the Dr Kumar Discovery. My name's Doctor. Ravi Kumar. Today, we're doing a deep dive on a topic that's very relevant to all of us. We're talking about neurodegenerative diseases like Alzheimer's that take us, or people we love, away from the world during what should be the golden years of our life.
Ravi Kumar MD:It's a scary, often helpless feeling disease, and we've been told that the gene variant APOE4 is a major culprit for it, and that it's practically written into our destiny. I myself carry one copy of APOE four, and honestly, the prevailing message about it just hasn't made sense to me. Not from an evolutionary standpoint, and not from a common sense one either. So I've been going deep into the literature for a paper that I'm writing, and the more I read, the more I realize that this is a story that I need to tell out loud, start to finish, and then share it with everyone. And that's why I'm doing this episode.
Ravi Kumar MD:So if you've had a genetic test done, maybe through 23andMe, or maybe your doctor ran a test, there's a reasonable chance that you already know your APOE status. And if you found out that you carry an APOE four allele, there's a reasonable chance that someone handed you that result with a grim look on their face and not a lot else. I've seen that happen, and it's a terrible way to receive information about your own body. So for anyone out there wondering about their Alzheimer's risk, or wondering how to interpret their APOE status, or the APOE status of someone they love, this episode is exactly for you. By the end, you're gonna understand what APOE actually does in the brain, why the APOE version, or variant, almost certainly helped our ancestors survive, and how the modern world became mismatched with the benefits of this gene variant.
Ravi Kumar MD:And even though there are some scary numbers around this gene, you'll realize that most people with this gene, even people with two copies, the highest risk people, do not develop Alzheimer's every time. It's not a straight line from gene to disease like we've often heard. It's much more complicated, and complicated is very good news, because that means there are levers you can pull, and by the end of this episode, you'll know what those levers are and how to pull them. One more thing before we dive in, it's just a quick disclaimer. I'm a doctor, but I'm not your doctor.
Ravi Kumar MD:This show is for informational purposes only. Everything in this episode is meant to empower you, so take this knowledge, ask better questions, and work with your doctor to build a more informed, healthier life. And just to be clear, this show is also separate from my role as Assistant Professor at UNC. Also, real quick, before we get started, I just want to talk to you about the show, because the show is growing really fast, and right now, the Doctor. Discovery reaches over 100,000 people every month.
Ravi Kumar MD:But a lot of the listeners aren't subscribed, so if you're enjoying this show, please hit subscribe and leave a review wherever you're listening. It dramatically helps the show reach more people, and reaching more people with good, honest, unbiased information is the whole point of what I'm doing. Alright, let's get into it. Let's start with what this gene even is in the first place, because APOE is one of those things that gets talked about constantly and almost never explained. APOE stands for apolipoprotein E.
Ravi Kumar MD:Its main job is moving fatty molecules around, like triglycerides, cholesterol, and phospholipids. You see, fats just can't float freely in blood or water, so they need to be ferried around by proteins like APOE. APOE is found all over your body, but specifically in the brain, it's the main lipoprotein, kind of like LDL is in the body. And this is an important concept because your brain runs its own fat economy. That's what I like to call it an economy because they're dealing in the currency of fat and energy.
Ravi Kumar MD:Lipoproteins from your blood can't cross the blood brain barrier, so the brain has to handle its own cholesterol and lipid transport internally. And APOE is the main truck doing all the hauling of those lipids. That matters enormously because your brain is a fatty organ, roughly 60% lipid by dry weight. So if you dried out your brain, 60% of the weight of it is lipids. And every cell membrane, every myelin sheath, every synapse that you rebuild, every time you learn something new, is built out of fat that has to get delivered to the right place at the right time.
Ravi Kumar MD:And APOE is that delivery truck. So most of your brain APOE is made by astrocytes. These are star shaped supportive cells that do a huge amount of housekeeping in the brain, and also made by microglia, which are the brain's resident immune cells. So already, you can see something interesting here. APOE sits at the intersection of fat transport and immune function.
Ravi Kumar MD:Stick that fact in your back pocket, because it'll play into the story a little later. Now, there are three common versions of the APOE gene in humans, E two, E three, and E four. The difference is extremely small. There's like one position where one amino acid can change, and the protein becomes a whole new variant. For example, E three, which is by far the most common version, has an amino acid called cysteine at that spot, and APOE four has an arginine in that spot instead.
Ravi Kumar MD:One swap, and it changes the whole shape of the molecule. The APOE protein has these two ends connected by flexible hinges, kinda like arms. In the E three, those ends are fully mobile and functional. In APOE four, that arginine swings a neighboring piece of the protein across and latches onto the back of the molecule. The whole thing folds in and basically grabs itself.
Ravi Kumar MD:A good analogy is like a person standing with their arms loose at their sides, versus a person who's got their arms folded tightly across their chest. It's the same person, but a very different posture, and that posture changes what the molecule can do. So let's actually walk through the mechanism of how APOE4 variants actually change your physiology. Okay, so first, people with APOE4 variants tend to have higher LDL cholesterol. And the reason is, is that VLDL particles, which are the large fluffy particles that eventually become LDL particles, have APOE4 in it.
Ravi Kumar MD:And because of that, they don't grip the liver's LDL receptors as well as VLDL particles that have APOE3 in it, if that's your genetic variant. So it attaches more loosely and lets go faster, so these particles, which eventually become LDL molecules, accumulate in the bloodstream. Second, after a meal, APOE4's other job, which is hauling big triglyceride rich particles, actually gets more aggressive, and those particles compete for the exact same liver receptors that LDL needs to get cleared out of the bloodstream and into the liver. So picture a parking garage with a fixed number of spots. The triglyceride rich particles get to pull in and take those first spots, and that leaves LDL circling the block longer before it can get pulled out of your bloodstream.
Ravi Kumar MD:That's very likely why APOE4 carriers tend to run higher baseline LDL levels, especially after fatty meals. APOE4 is also a less stable molecule generally. It's more prone to breaking into fragments, and in the brain, it's less efficient at delivering lipids to neurons that need them for repair. And it's also less efficient at hauling amyloid, which is a sticky protein that clumps together in the brains of people with Alzheimer's. It's less efficient at hauling that amyloid out.
Ravi Kumar MD:So people with APOE4 variants tend to accumulate amyloid, which then triggers a second protein inside neurons called tau to get chemically tagged in a way that makes it fall off of the neuron's internal scaffolding, which is the structure that the cell uses like train tracks to move nutrients around. So that process is called tau hyperphosphorylation, and the tangled, collapsed tau molecules form neurofibrillary tangles, and that actually chokes off the neuron and kills it. So amyloid plaques and tau tangles together are what we mean when we talk about Alzheimer's pathology. That's where you take a look at the raw tissue of the brain in someone who has Alzheimer's, and this is what you see under the microscope. So it's essentially the physical evidence of the disease process that's visible on a scan or under a microscope.
Ravi Kumar MD:But, and this is a big but, these findings are not the same thing as having dementia. Keep that distinction in mind because it'll make sense in a few minutes. Okay, so now you understand what APOE4 is, and how it works, and why it causes these problems. But now let's talk about numbers, and let's do it very carefully because this is exactly where a lot of the unnecessary fear gets created. A pooled analysis in the Journal of Alzheimer's Disease in 2021, drawing on 121 studies in roughly 389,000 people across 38 countries, found that about twenty four percent of people carry at least one APOE4 allele, and about two percent carry two.
Ravi Kumar MD:That varies by ancestry, so it's roughly nineteen percent to thirty seven percent, depending on the population. So a single global number is often misleading, but we can say this with certainty, roughly a quarter of humanity carries at least one copy of APOE four. When talking about risk, there was a classic meta analysis in JAMA back in 1997 that gave odds ratios of roughly 3.2 for one copy of APOE four and fourteen point nine for two, compared to people who inherited the common E3 version from both parents. Now that 14.9 odds ratio figure sounds pretty scary, and it gets repeated everywhere as though it means you're 15 times more likely to get Alzheimer's if you have two copies of APOE four. But that's not what the odds ratio actually tells you about your personal risk.
Ravi Kumar MD:It is a specific statistical tool, and it is not meant to be read the way it usually gets read online. The number that actually tells you something useful is your lifetime risk. Meaning, out of everyone with a given phenotype, what percentage actually go on to develop Alzheimer's by a certain age? So a study in molecular psychiatry in 2011 put real numbers behind this. By age 85, a man with two APOE four copies has roughly a fifty one percent lifetime risk of Alzheimer's, and a woman with two copies, roughly sixty percent.
Ravi Kumar MD:With one copy, it was roughly twenty three percent for men and thirty percent for women. And in the general population, regardless of which APOE version you carry, lifetime risk of dementia by 85 years old sits around eleven percent for men and fourteen percent for women. Now think about those numbers, because this is the part I actually really want you to remember. Even with two copies of the highest risk version of this gene, APOE4, roughly four in ten men and four in ten women reach 85 years old without ever developing Alzheimer's disease. Two copies raises your risk substantially, but it does not decide your outcome, and that's the thing to sit with.
Ravi Kumar MD:So here's where we are. APOE is meant to move fat around your brain, and APOE4 is a slightly folded up version of that protein that's less efficient at several of its jobs, jobs that, when they go wrong for long enough, help drive the disease process of Alzheimer's. About a quarter of people in the world carry APOE4. It raises your risk substantially, but it does not determine your fate. And even people with the highest genetic risk can reach old age with their minds intact.
Ravi Kumar MD:Okay, so now that you understand the probabilities associated with APOE four, and hopefully you understand that it's not a determination of your fate, let's get back to the question that started this whole episode. If this gene is so horrible, why is it still here? Why wasn't it weeded out of the gene pool a long time ago? Well, here's the fact that puts it all into perspective. APOE4 is not the mutant.
Ravi Kumar MD:APOE4 is actually the original version of this protein. Gene sequencing work has compared the human APOE gene to the chimpanzee version, and the chimp gene most closely resembles the human APOE4 form. APOE3 and APOE2 are the newest versions, and that same research suggests that APOE three has been steadily gaining ground on APOE four over roughly the past two hundred thousand years, which is basically what natural selection looks like in slow motion. Something about APOE3 became more advantageous relatively recently in history, and that's why the change is happening. Which means the real question isn't why APOE4 is bad, it's what APOE4 was good for and what changed.
Ravi Kumar MD:And the best evidence comes from studying people who still live closer to the ancestral condition of the human being. And the richest source of that data is actually the Shimani, which are our forager horticulturalist population in the Bolivian Amazon who have been studied intensively for years. A study in 2017 looked at three seventy two Shimani, ages six to 88, and tested cognition against parasite burden. Among Shimani without signs of heavy parasite load, APOE four carriers actually performed worse, recalling about 16% fewer words on short term memory tasks. It's the same direction we see in the industrialized population.
Ravi Kumar MD:But among Shimani carrying a heavy parasite burden, that flipped. APOE4 carriers held their cognitive performance, while non carriers declined in their cognition when they had heavy parasite loads. So APOE4 wasn't a blanket advantage. It was an advantage under one specific condition, chronic infection. In a clean environment, having APOE4 cost you.
Ravi Kumar MD:In a world full of parasites, it actually protected you. Another study in 2021 looked at over 1,200 Shimani adults, and found that APOE4 carriers ran roughly 30% lower C reactive protein levels, which is a common marker of systemic inflammation. So they had lower resting inflammation, and in a population constantly fighting infection. And that tells us something very specific about how APOE4 modulates the immune system. And I think it's worth understanding.
Ravi Kumar MD:APOE4 carriers here don't run hotter all the time. If anything, their baselines run a little bit cooler. But what's different is how hard the immune system swings into action once a real threat shows up. Think of it less like a thermostat stuck on high and more like a smoke detector that's super sensitive. It's quiet when there's no fire, and it's the first to go off when there's just a whiff of smoke.
Ravi Kumar MD:So in a world of internal parasites and constant low grade infection, that's a great trait to have, honestly, because it's efficient at rest and protective and activated against something that could otherwise kill you, like parasitic infections. And there's also other evidence pointing in the exact same direction. Brazilian shantytown children who are living in unclean conditions and under long term surveillance found that among kids with heavy early childhood diarrheal illness, the ones carrying APOE4 did much better cognitively. So APOE4 in the ancestral environment is protective against infectious processes. And then there's another finding with APOE4 that I think was a big advantage, and I think it's actually the strongest of the whole set for explaining why APOE4 gene has persisted, and it has nothing to do with cognition.
Ravi Kumar MD:A study published in 2023 looked at seven ninety five Shimani women, ages 13 to 90, and women with one APOE4 allele had roughly 0.3 to 0.5 more children than women with no APOE4 allele. And women with two APOE4 alleles had somewhere between one point four and two point one more children. They started reproducing about zero point eight years earlier and had shorter gaps between births. And that study's been partially replicated in a whole another setting. In a study in PLUS ONE in 2017, looking at over 4,000 women in rural Ghana, split by pathogen exposure based on their water source, Among older women in the high pathogen group, each APOE4 allele meant roughly one additional child.
Ravi Kumar MD:Two alleles meant about three and a half more children, and in the low exposure group, APOE4 did nothing. Imagine what an evolutionary advantage that is. Natural selection doesn't care whether you're healthy and quick witted at 75. Natural selection is a numbers game scored on how many descendants you leave behind. A gene that gives you two extra surviving children spreads through a population very fast, even if the price of having that gene doesn't come due until fifty years later.
Ravi Kumar MD:So putting all this together, APOE4 is the ancestral human version of this gene associated with better fertility and better cognitive resilience under heavy pathogen load. It runs a quieter baseline immune system with a quicker and more effective immunological response pathogens. The payoffs for this show up early in life when reproductive success matters the most. So the genetic deal that our ancestors got looks something like this. APOE four helped you survive childhood infection and helped you have more children in a hard, pathogen rich world.
Ravi Kumar MD:In exchange, it sent you a bill decades later, and it was a bill that almost nobody lived long enough to actually receive and pay. Now, what happened to that deal as we transitioned into the modern world? Well, three things changed. Let's take them one at a time. The first is time.
Ravi Kumar MD:We live longer now. You'll hear people say that our ancestors died at 30, so Alzheimer's never had a chance to show up. And honestly, that's a misreading of the data. Life expectancy at birth in hunter gatherer populations was around 32 years old, so that is true. But that number is dragged way down by infant and child mortality.
Ravi Kumar MD:It doesn't describe an adult who actually made it past childhood. There's a cross cultural analysis that pulled together mortality data across forging societies, And the picture is very different. If you survived to 15, you had a good shot of reaching your fifties. If you made it to 45, you could expect roughly another twenty years. The single most common age of death among adults in these societies is about 72 years old, not 30.
Ravi Kumar MD:Our ancestors who made it through childhood often grew old. But here's the nuance that carries this whole argument forward. In 2002, there was a study of the Hadza, which is a hunter gatherer population, and they showed that for every 100 births, about twenty two people reached the age 70, about twenty five reached the age 65, and only eight people reached 80. Now compare that to now, where the overwhelming majority of us reach 65, and a very large share of people reach 85 years old. That's exactly where Alzheimer's prevalence goes vertical.
Ravi Kumar MD:So the accurate version of this whole argument is not that nobody lived long in these hunter gatherer populations. Some actually did. The argument here, or the explanation here, is that far fewer person years were ever lived in the late window of life, So natural selection had very little leverage there. A gene that hurts you at 80 is nearly invisible to selection when only eight out of one hundred people ever arrived at 80 years old. And of those people at 80 years old, they're no longer reproductively active, most likely.
Ravi Kumar MD:The pressure to weed it out was almost nonexistent at this point, while the pressure to keep it through fertility and infection defense operated at full strength on everyone all the time. That asymmetry is the engine of the whole paradox. Okay. So the second thing that's changed is our immune environment. And I think this is one of the most important.
Ravi Kumar MD:Remember how quickly APOE4 activated your immune system? Well, in a world of intestinal parasites, endemic infections, and no antibiotics, APOE4 had plenty of real fires to find and stay productively occupied. Now put that same sensitive detector in our modern bodies where most of us don't carry chronic parasitic loads. What we carry instead is visceral fat, metabolically active tissue pumping out inflammatory signals around the clock, insulin resistance, disrupted sleep, an out of balance gut microbiome, and constant chronic stress. The detector doesn't get less sensitive, it's still sensitive, but it thinks there's fires going on all the time.
Ravi Kumar MD:It just runs out and tries to put them out all the time over and over in... Over decades of life, and this leads to chronic inflammation. And in the brain, we call that neuroinflammation, which is the basis for Alzheimer's disease. Okay, so I hope that's pretty clear. APOE4 is fantastic at pulling the fire alarm and getting things going from an inflammatory standpoint, But when you're constantly inflamed through all these modern lifestyle signals, that can basically cause APOE four to run constantly, leading to systemic and brain inflammation.
Ravi Kumar MD:Okay. So the third thing that changed, and I think this is very important, is our food. Ultra processed food now makes up nearly 58% of the calories the average American eats in a day. It supplies almost 90% of the added sugar we consume. There's a real change historically for most of human history and for essentially all of time that this gene has existed.
Ravi Kumar MD:Nobody was eating like this. And here's why that matters. Eat that way constantly, and your blood sugar and your insulin spend a lot more time elevated than your body ever knew or evolved to handle. This is what I talk about all the time in this show, and it's called metabolic syndrome. You become fat and inflamed from the constant deluge of glucose, which eventually leads to prediabetes and diabetes, and all these chronic diseases associated with chronically elevated glucose and insulin.
Ravi Kumar MD:And the connection between metabolic disease and dementia has been very well clinically established. A pooled analysis of over 2,000,000 people found that type two diabetes carries roughly sixty percent higher risk of dementia. So I think it's pretty clear that metabolic disease and Alzheimer's disease are heavily connected, and now we're in this world where our food is driving us into metabolic syndrome, and it's wrecking our brains. Okay. So the next question is, now that we know what's changed and how this has led to APOE four becoming a liability rather than an asset, is this.
Ravi Kumar MD:Is there anything that we can do that reduces our risk of dementia, even in the setting of APOE four? Well, luckily, there is a lot we can do. I like to call these interventions levers because you're essentially pulling a lever that changes the physiological machinery in your body leading to a different outcome biologically. I think it's a great metaphor, and I use it all the time in my podcast, so I'm gonna go with it on this one too. Lever one is sleep, and there's real good human evidence on this.
Ravi Kumar MD:A study in 2018 kept 20 healthy adults awake for one full night, and scanned their brains before and after. Amyloid, that sticky protein that we talked about earlier that's not well cleared in APOE4 carriers, rose by about 5% in the thalamus and hippocampus after just a single night of sleep deprivation. Separately, a study in JAMA Neurology in 2013 and nearly 700 older adults found better sleep consolidation substantially blunted the effect of the APOE four allele on Alzheimer's risk and on neurofibrillary tangled density at autopsy. Remember, the neurofibrillary tangles are those tangles of tau proteins that actually kill the neurons. There's a proposed mechanism behind all of this, and it's called the glymphatic system, which I love talking about.
Ravi Kumar MD:When you go to sleep at night, your brain pulses cerebrospinal fluid through your brain tissue, and it flushes out the toxins, the waste molecules, and the beta amyloid particles that often accumulate in APOE four genotypes. So if you carry APOE four, sleep, and especially deep, slow wave sleep, isn't a nice to have. It should be treated like the best medication you can take. I've done a whole podcast on optimizing your sleep, and if you haven't listened to it, just go back through my library and take a listen. You'll be really glad you did.
Ravi Kumar MD:Okay, so lever two is metabolic health, specifically insulin sensitivity. The single clearest gene environment interaction in the literature is diabetes. A 2002 study found that type two diabetes plus an APOE4 carrier carried a relative risk increase of 5.5x compared to having neither. So protecting your insulin sensitivity isn't a general wellness goal here. It's one of the most important levers you can pull.
Ravi Kumar MD:The third lever to pull is midlife cardiovascular health. Controlling your blood pressure is probably one of the most important things you can do in this realm. A 2001 BMJ study followed nearly 1,500 people for decades and found that high blood pressure in your 40s and 50s roughly doubled later Alzheimer's risks. That holds up consistently, so keep it controlled in midlife, full stop. Now, as far as your cholesterol goes, that's much messier.
Ravi Kumar MD:The same study found that high midlife cholesterol also doubled risk, and both together more than tripled it. But how cholesterol relates to brain health depends a lot on when in life you're looking at the cholesterol levels and what else is going on metabolically, which is a longer conversation, and I've gone very deep on this in past episodes. But for now, just get your numbers checked with your doctor, and don't panic over one cholesterol number in isolation, especially later in life. Separately, a 2005 BMJ study following over 10,000 people for twenty seven years found midlife obesity, which is part of metabolic health, by itself was associated with a seventy four percent higher risk of later dementia. So get your metabolic health, and your weight, and your muscle mass, and all the things that lead to a metabolically healthy diet, which I've talked a lot about on this show, get that all locked in.
Ravi Kumar MD:Okay. So lever four is structured movement and mental engagement. Aerobic exercise several days a week, resistance training, a Mediterranean style diet, and cognitive and social engagement. These are all super powerful lifestyle changes. There's not one heroic intervention here.
Ravi Kumar MD:It's actually a bundle of lifestyle factors that lead to overall better health and resilience. I've talked a lot about these on my show. You can go back, search Mediterranean diet, search resistance training, look up sleep, look up metabolic health. It's all there, and it's all just waiting for you to implement it. It's free, and it will make you a better person and give you a lower chance of Alzheimer's disease later in life.
Ravi Kumar MD:Okay. So those are the four main levers I tell everyone to pull. But there are other significant things that you can do to reduce your dementia risk, whether you have APOE4 or not. The Lancet commissioned a report in 2024 that listed 14 modifiable risk factors across a lifetime, estimating up to forty five percent of dementia cases worldwide could theoretically be prevented if every one of these were fully eliminated. That's a population statistic, and it tells you what happens across millions of people, not what happens to you personally if you actually have one of these risk factors.
Ravi Kumar MD:So let me give you some numbers that are actually useful. I'll tell you how much higher your risk runs if you have one of these risk factors. And the reason I'm telling you this is because each one of these may be potentially fixable, which reduces your dementia risk later on in life. Okay. So let's start with hearing loss.
Ravi Kumar MD:The commission's own pool data puts it at roughly a thirty to ninety percent higher individual risk of dementia if you have uncorrected hearing loss. But if you combine the estimates, it comes out at approximately thirty seven percent higher of dementia if you do not correct hearing loss. And here's the part I find really exciting, because most of what I've told you today is correlation with caveats attached to it. In this one, it's different. A randomized trial called Achieve, published in The Lancet in 2023, gave older adults either hearing aids or a health education program and followed them for three years.
Ravi Kumar MD:In the group already at higher baseline risk, hearing aids cut the rate of cognitive decline by roughly half. That's not association anymore. That's a controlled trial showing a fix that actually works. So if you have hearing loss, see your doctor and get hearing aids. It could make a massive difference in your brain health.
Ravi Kumar MD:Okay, so the next risk factor is social isolation. Social isolation and loneliness track with roughly fifty five percent to sixty percent higher individual risk of dementia based on a 2015 meta analysis of over fifteen thousand people. We don't normally think of social isolation as a disease state, but it really is. It affects your brain, it affects your cardiovascular system, it affects your overall health, and affects your happiness. And often, people who are depressed or their health is failing become more socially isolated, which feeds into a vicious cycle.
Ravi Kumar MD:So if you or your loved one is isolated, find ways to get out and talk to people. You need to interact. It's some of the best medicine you can take. Untreated vision loss is the newest identified risk factor for dementia. Dementia runs about thirty eight percent higher in people who have uncorrected vision loss.
Ravi Kumar MD:We don't have a clinical trial here like we had with the hearing loss study, but a large study on cataract surgery specifically found that it was associated with a meaningful lower risk of Alzheimer's disease afterwards, meaning they fixed people's cataracts, helped them see better, and they had lower risk of Alzheimer's afterwards. The next risk factor, and one that's very clear, is smoking. Current smokers run about a thirty percent higher risk of dementia than people who have never smoked, and people who quit don't carry the same elevated risk that smokers do. I know I say this all the time, but smoking does nothing but tear you down. If you smoke, just stop.
Ravi Kumar MD:Ask your doctor for help. There are great drugs like varenicline that can make quitting completely possible if you previously thought that it just wasn't. Okay. So the next risk factor is depression, And depression is a massive risk factor for dementia. It doubles your risk and needs to be addressed no matter what stage of life you're in.
Ravi Kumar MD:Depression can actually damage the brain over years, and it can also be an early symptom of dementia before any diagnosis shows up. That's exactly why treating it can be very high yield. I've done a two part podcast on understanding and treating depression. If you or someone you love is suffering with depression, please listen to that series. Go back through my history, find it, and listen to the part one and part two.
Ravi Kumar MD:It'll help you understand depression and help... And give you hope that you can get over it because it is fixable and curable. You can also download a roadmap off my website, which is linked to in that podcast. Okay, so alcohol is the next risk factor, and it's more nuanced than the other ones. First, I wanna say that alcohol is by definition a neurotoxin.
Ravi Kumar MD:There are no redeeming chemical qualities to alcohol in your body. Hard stop. But light to moderate drinking has not shown clear excess risk for dementia. Heavier midlife drinking, more than about two drinks a day, tracks with somewhere around twenty percent higher risk of dementia. And diagnosed alcohol use disorder, the clinical far end of the spectrum of alcoholism, was linked to more than triple the risk in a French National Registry study, covering over thirty million people.
Ravi Kumar MD:So it's safe to say that heavy alcohol use is a great way to wreck your brain. Ask your doctor for help if you plan to quit, as alcohol withdrawals can be dangerous. Okay, so the last risk factor I want to talk about is air pollution. And this is not one that most of you would think about, but it's a real risk for dementia. And it works on a sliding scale rather than an on and off switch.
Ravi Kumar MD:Each increase in fine particulate exposure nudges your risk of dementia up a little each time, and it adds up over a lifetime. So if you are exposed to chronic air pollution and you have a way to modify it with indoor air filtration or just moving to a cleaner environment, this is well worth the change when it comes to your dementia risk and your overall health. Okay. So that was a lot. Let me sum it up for you.
Ravi Kumar MD:And here's what I want you to walk away with. APOE four is not a defect. It's a well designed piece of biology tuned for a world of infection, scarcity, and early reproduction, and it now runs inside bodies like mine living in a world of abundance, sterility, and eighty year lifespans. The gene didn't change, but the environment did. And that reframe matters, because a defect is something you have and can't really do anything about.
Ravi Kumar MD:A mismatch is something that if you understand, you can actually modify your environment to better fit that mismatch. Okay, so there was a fact that I mentioned early in the podcast that I asked you to hold onto, and it was this. Nearly every person with two copies of APOE four develops the Alzheimer's pathology in their brains. Remember, that's the amyloid and the tau with the neurofibrillary tangles. You see it under the microscope, you can see it on scans.
Ravi Kumar MD:But about half of them still reach the age of 85 years old without any dementia. Their minds are clear and strong. Something is protecting these people. Some of it's lifestyle, and some of it's other genes that we just don't fully understand yet. But much of what prevents dementia in those otherwise high risk people, like me, are lifestyle factors that we just talked through, and none of that requires a prescription, except for maybe the hearing aids and the glasses.
Ravi Kumar MD:So if you've been carrying around an APOE four result like a diagnosis, I hope this episode loosened its grip on you a little. It's a risk factor, but it's not a verdict or a destiny. And it also tells you something useful, which is exactly where you can aim your lifestyle interventions. I myself am an APOE four, E three heterozygote, and I'm not scared of dementia. I'm doing the things now and into the future that will keep me metabolically healthy and resilient for a lifetime of healthy cognition.
Ravi Kumar MD:So if you take just one thing from this episode, it should be this. The most powerful tools we have against this disease are still sleep, movement, food, and metabolic health. That's not a disappointing answer, folks. That's an empowering one, because every single one of those is fully modifiable by you. Okay, folks.
Ravi Kumar MD:Cheers. I'll see you next week.