Research by Harvard scientists reveals that three specific blood-based nutritional biomarkers can predict a four-to-five-fold higher risk of dementia, with cognitive decline beginning decades before symptoms appear; this enables early detection and personalized nutritional interventions to protect brain health before cognitive decline manifests.
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A Harvard Scientist’s Nutrition Strategy to Protect Against Alzheimer’s Before Symptoms Show
Added:The brain doesn't age through one nutrient at a time. It's all about patterns. So you have to realize that the brain is exposed to thousands, hundreds of thousands of things all the time. You have a bloodb brain barrier that's, you know, protecting it's very selective. So the idea that a single supplement or a single nutrient is going to really have a profound effect on the brain, you should already be skeptical.
We've realized that through so many unsuccessful clinical trials in the space of Alzheimer's disease, you know, trying to prevent the progression of the disease, now that we have the tools to detect the pathology that's occurring in the brain before the symptoms of onset, we're realizing now that the pathology and the seeds for those conditions in the brain are seeding decades before the onset of the symptoms. Trans fats actually get into your brain cells. They actually get across the bloodb brain barrier. They get bound in there into the lipid billayer and they raise havoc.
When you give something like omega-3 fatty acids, there's a lot of things that happen. Those fats get broken down into other compounds that have anti-inflammatory properties. At age 70, you know, if you're cognitively intact, [music] that's fantastic, but there's probably an abundance of pathology brewing there. There is opportunity for nutrition at every stage, but I think ultimately you want as early detection and intervention as possible.
Traditionally, there's been a lot more bitter in our diet that kind of primes our gastrointestinal system to actually pull things out of the foods that we're eating and break these things down to improve absorption. One thing that really troubles me intraequely is that fluctuation in energy levels, [music] in mood, like this brain fog that I will sometimes experience for days on end.
What do we know about that and how to manage it?
>> It's probably a combination of several factors from the food perspective.
As our life expectancy continues to rise, one question is becoming more important than ever. How do we protect our brains against the onset of cognitive decline? Today's guest is Dr. Jean Bowman. He's a neurologist, Harvard physician scientist, and one of the leading researchers exploring how nutrition, metabolism, and lifestyle influences brain health and Alzheimer's disease. His work sits at this intersection of cuttingedge neuroscience and practical prevention, asking a question that affects every single one of us. What can we do today to reduce our risk tomorrow? Now, if you've ever worried about losing your memory, your executive function, your cognitive health in general, or watched a loved one experience symptoms of dementia or Alzheimer's, or just simply wondered how to keep your mind sharp as you age, this is a conversation you will not want to miss. So, without further ado, please enjoy this episode with Dr. Jean Bowman.
I think a good place to start would be take us back to the ' 90s and your time spent I believe in North Carolina in a cardiac ward where we were or you guys were doing >> things that were very helpful and efficacious for rehabilitating heart >> or and other organs but not so much the organ we're going to talk about today.
So let's start there and then give us the TLDDR as to how you got here.
>> Okay. Well, so uh so that period in my life, I was finishing up my undergraduate degree, uh and had to do an internship at a at a cardiac and pulmonary rehab facility.
And one thing I learned from that experience um was that people that we would see after bypass surgery or or a heart attack, some of them would come to our cardiac rehab program, stay for six to eight weeks and we would take them through an exercise, nutrition, stress management program, and they would come a couple times a week and it would last about an hour and we just had remarkable results.
So the people that did not come to our program, we would see them back on the ward and and I started to kind of put the pieces together of, you know, what what is so profound here, right? We're just talking about exercise and nutrition, things we kind of already know, >> but it was being packaged in such a way that they were just compounding on one another. Each of those modes of intervention >> um had profound effects on the vascular system and it was really clear to me. Uh so that that was a time when I began I was studying exercise physiology and sports medicine in my undergrad before I went to med school and I began to realize that you know lifestyle modification that's very targeted and precise can have profound results on the vascular system. Now, I ended up getting interested in neuroscience uh basically because I have this family gathering that we do once a year uh down in uh Oak Island, North Carolina uh where all the men in my family get together on Labor Day weekend and we play golf and hang out and do what guys do on a weekend.
>> And the oldest one of of my grandfather's generation uh was actually a physician at University of North Carolina. He was an eye doctor. He also was a backup uh running back at UNCC and he lived the longest, but he uh developed some cognitive deficits and really uh ended up with dementia, Alzheimer's type and you know I I just didn't understand this was why I was in med school. I couldn't understand how somebody so brilliant could end up with a cognitive disorder. So I started you know digging you know that kind of sparked my curiosity. I would see him every year and see the decline, see the lack of intervention, lack of any protocols that would help him. And I think that's really what sparked my interest in neuroscience and Alzheimer's disease research >> along with the lifestyle modification, particularly nutrition. And that kind of set my career on a path >> and I think we can all speak to examples like that in our own life. Right.
>> Right. And that feels very unfair. You know, that that very um apparent sometimes gradual but sometimes kind of steep cognitive decline that >> if we if we are fortunate enough to get to our you know seventh eighth decade and onwards that seems very frequent.
>> Yeah.
>> And so so you spark that thought process then then what happens?
How where do you start to try to solve for that? Well, I started thinking about myself, my parents, my own genetic risk.
You know, am I at risk for that same condition?
>> If I go to med school and I'm a doctor, I mean, okay, he was a running back. He had he took some blows to the head, obviously. Um, that doesn't help, you know. But then I I began putting the pieces together and realizing that, you know, my parents are at risk, I'm at risk. What can we do?
>> And I couldn't find any answers. there was very little. Uh >> why do you think why do you think that is?
>> I think it's just been a very difficult area to study. Yeah.
>> I mean we you know fast forward 20 years now we have neuroiming modalities where we can detect you know Alzheimer's disease pathology seeding in the brain. We even have blood based biomarkers now that just within the last couple years, you know, now with the blood test, we can get a pretty good indication if you have seeding pathology that's occurring.
>> So I think it's just been difficult to study the central nervous system and get into the skull and figure out how to to measure this other than cognitive function.
>> Yeah.
>> Same can be said for nutrition, for example. It's been very difficult to really assess nutritional status and dietary intake or diet quality outside of a questionnaire that somebody has to recall what they're eating.
>> Yeah. Self-reporting is just notoriously inaccurate, right?
>> Yeah. So I think that those two areas being able to understand how lifestyle or or nutrition um where somebody stands in terms of status um and then linking that to a condition like Alzheimer's disease that's also very difficult to study. I think over the last 20 years we've had profound advancements. So I think it is now's the time.
>> Yeah. You see now we have it's really the age of biomarkers and being able to identify nutritional status that's suboptimal. They can lead to cognitive decline or or dementias uh you know known dementia vascular dementia Alzheimer's disease type dementia. Um and so I think I you know having been in the in in the field and and being in academia and being in industry and then back to academia uh you know I I it's just very exciting time. I think there is so much more that we can do now than we could, >> you know, when I was seeing my great uncle, you know, uh, decline. And I think, you know, the idea of cardiac and pulmonary rehab and putting those pieces together, you know, I think we just need to do that. We need this kind of this mantra of kind of early detection, early intervention.
>> Yeah. And I think you know this particular focus this domain in particular so brain health cognition cognitive function I think if we are honest with ourselves is one of the most frightening things about aging is the concept of losing our sense of self or our memory or um you know our perception of the world around us. And I something I found remarkable that I've learned from working with you and Rudy as well >> is this idea that we can begin protecting against the onset of that that decline decades in advance of the symptoms.
>> That's right.
>> Could you could you explain that briefly to the listeners because I found that to be remarkable. Yeah, I think that's another profound breakthrough is that we've realized that through so many unsuccessful clinical trials in the space of Alzheimer's disease, you know, trying to prevent the progression of the disease, now that we have the tools to detect the pathology that's occurring in the brain before the symptoms of onset, we're realizing now that the pathology and the seeds for those conditions in the brain are seeding decades before the onset of the symptoms.
And now that we have these tools and can detect that, now we can identify people, you know, this early detection, early intervention, mantra can come to life.
>> Yeah.
>> Um through blood-based biomarkers. We have nutritional and metabolic markers that are doing a remarkable job of predicting those that go on to cognitive decline or have pathology um at autopsy. So we we we have ongoing studies that are showing that 10 years before somebody dies, we we have blood samples that can actually predict the type of pathology that they have in their brain after they die during autopsy.
>> And that's upstream of any symptoms.
>> That's right. That's right.
>> That's wild.
>> Yeah. You know, we talk a lot on the podcast about giving people agency, and I can't think of a better example than for cognition, and I think it's something that we've all been sleeping on. Like, we like when was the last time you had your executive function tested for or you looked for certain, you know, biomarkers in your blood for cognition itself? And that we weren't even talking about this as consumers at least even a few years ago, two three years ago.
>> Yeah.
>> And some of the biomarkers you've now we woven into our members experience are still very early, very new.
>> That's right.
>> Um but even upstream of some of this screening, some of like the preventative screening. Is that right? Am I overreaching there?
>> No, no, no. I think um I you know the things that you hear me talking about are are not readily available current and that's frustrating. Yeah.
>> Right. So that there's a piece of being being able to >> get this to the consumer as fast as possible and that's that's a discussion within itself.
>> Yeah.
>> But also it has to be based in the evidence, right? It takes a long time to develop the evidence base where someone like myself as an academic and say, "Yeah, I think it's I think this is something you should actually pay for and do." Right?
>> So I and I also think that the technologies are advancing. So we have blood-based biomarkers of Alzheimer's disease that we can measure in the blood. We also have comprehensive nutritional phenotyping >> that we're developing in the blood.
>> And that data is really pointing towards that there are distinct patterns in the bloodstream that can predict different aspects of deterioration of your cognitive function but also pathology in your brain. whether somebody is is on more of a vascular pathway, you know, breakdown of the small blood vessels inside the brain or they're on what we call an amalloid or a towel pathway where the you know, you have the plaque or the tangle pathology that's building in the brain >> um or breakdown in the the sheets around the the axon of the neuron like that speeds up the signal. So your speed of processing and so forth where you have a symptom of you know just speed of processing is kind of slow. Um so that that process and the biology there seems to be related to distinct patterns of nutrients in the bloodstream and and this has been under our nose this entire time. So we've started to develop these indices these index scores. we call them bloodbased nutritional risk index or brain nutrition index >> and we've landed on three initially uh that do a pretty good job. So, so if these are suboptimal, we've we've so there's been two studies so far, two observational studies, one in France, the multi-dommain Alzheimer's prevention trial where we measured this index score, and we found that people that had suboptimal levels on all three of these combined have remarkable cognitive decline over time. Those that have [clears throat] optimal levels on all three combined, they actually have cognitive enhancement over time because you do repeat testing on cognitive function. And every time that somebody has optimal metabolic nutritional status, they learn, they get better at the cognitive testing >> as opposed to people have suboptimal status, they get much worse over time.
>> Wait, let me let me just make sure I'm getting this right. There are three blood-based biomarkers that are dictated largely by or entirely by nutrition.
>> Yeah.
>> That if they are if one or more of them are suboptimal, you see a cognitive decline over time.
>> That's right.
>> If you optimize for all three with consistency, there's an increase in cognitive fun.
>> You can improve learning.
>> Huh.
>> Yeah. Over time.
>> Now, that was the first study. And you know, one study is just one study.
That's not convincing enough. So a separate group out of um the Netherlands looked in the Framingham cohort, a famous cohort of cardiovascular disease that also has cognitive and dementia incidents available. So they follow people over time and how many people end up with Alzheimer's disease. And they can predict that they ran the same three biomarkers and looked at sub-optimal levels versus optimal levels based on our our results.
and they see that people that have suboptimal levels on all three of these combined have a four to fivefold increase in dementia risk if you're 50 and older. That's a massive magnitude of effect. So what's convincing to us as scientists is consistency across studies.
>> The other thing is the magnitude of the effect, the association effect. How large is it? So we're talking four to fivefold increase. So then you start begin to think well [clears throat] what's the risk in running this test what's the risk of intervening based on this test and really there's no risk right so it it's it's a blood test you know these are things that are now you know are readily available in a sense it requires a blood test um but then these are things that you could if you're disciplined could modify through dietary modification and if you're not getting it done you can also supplement you can take a supplement a dietary supplement to to optimize these. It's just an example.
>> It's an example of understanding Alzheimer's disease and age related cognitive decline is really a metabolic issue.
>> Yeah.
>> You know where and it's not a there's no silver bullet, right? Like exercise or whatever it may be, one mode of exercise, there's not, right? It has to be wellrounded and it's all about the patterns that you have circulating in your bloodstream because that is the garden for your brain to actually vacuum these nutrients.
>> Hey Jean, this is going to sound naive but and I suspect I know the answer but I'm going to ask anyway because I think as a listener I would ask and that is why can't we all just have that test right now >> and know what those biomarkers are and then just make that change. You know, I think uh we're just at a tipping point [clears throat] where you have somebody like myself um and you have individuals with means to kind of translate these things >> and we just need to kind of collaborate and work out. So, we have these readily available. We've published it. From a [clears throat] scientific standpoint, one might ask, okay, well, you need to do a large clinical trial >> where you enrich people on suboptimal status on all three of those and then you optimize it through an intervention and see if it actually leads to the outcome that you showed in the observational studies. So, that's kind of the standard path.
>> Yeah. Yeah. Yeah.
>> But then at the same time, why not do that at the same time? It's just getting it out to the consumer that clinical trial and if we show that that's positive that's going to change standard of care for brain which is a long path and getting reimbursement from Medicare and you know these these take years if not decades to get involved. So, so then I personally as somebody that's that's you know discovered this this panel I asked myself okay well what's the harm what's the harm in doing okay so it's going to cost something you know so there's that but you can be transparent about that >> and then you just have to get the information out >> you know and and then you have to have you know primary care doctors or care providers and people educated enough to ask about it right We haven't done a great job with brain care. It's not part of standard of care and primary care to really assess brain health. And so we're trying to develop >> until you start noticing symptoms of the client.
>> Right. Until you start noticing symptoms and and and of course there's been a couple decades of disturbances at the bi biological level by that point.
>> Yeah. Do you know what I love about that? That's unique science amongst unique science in that the potential upside should we be able to prove that over you know a bigger um cohort is huge.
>> Yeah.
>> Lifechanging. Yeah.
>> And the potential downside almost doesn't exist other than an economic >> downside which I think everyone listening would be like I'd be willing to pay almost any amount to be to ensure the protection of my cognition, right? I mean, I certainly would, >> right?
>> Um, and and it doesn't sound like that amount would actually ultimately be that expensive as you scale this out given that we're already having these blood tests.
>> That's right. That's right.
>> Is that a fair assumption, would you say?
>> I think it's a fair assumption. I mean, I think the key thing is that we're not talking about, you know, one or two nutrients, right? We're talking about three. It's remarkable that these three have had, you know, had these strong links >> Yeah. to cognitive enhancement or cognitive decline.
>> Could there be more, do you think?
>> I think there's a lot more.
>> I think it's just, you know, it's the tip of the iceberg. Yeah. So to speak. I think we have now done profiling on 150 nutrient biomarkers. So we've done everything in the periodic table. So all the trace elements and minerals. We've done all the amino acids. We've done extensive fatty acid profiles from shorter chain length to the longest chain length. saturated versus unsaturated fats. All of those we've done the liposuble vitamins, the hydro, the water soluble and the fats soluble vitamins. Uh we've done particular pathways. So for example, the one carbon pathway. So this is the methylation pathway. These are this is a pathway that has co-actors for certain micronutrients to keep the pathway going and and the brain depends on that for methyl donation which basically turns genes on and off. It helps with the synthesis of certain neurotransmitters and protecting the the integrity of the the uh lipid layer around the cells. So all these biological things but it's like comprehensive. It's very very important we're not tapping into that pathway. But it what we've done in this these projects is that we've done comprehensive nutritional phenotyping.
And I think that's going to be the big change you see within the next 3 to 5 years in the Alzheimer's field is the availability of blood-based nutritional phenotyping that we can identify combinations of nutrients in the bloodstream and optimal levels that are related to certain pathways that lead to cognitive decline the underlying pathology whether it's a vascular pathway or the towel or the plaque pathway you know those aspects.
So I think that's going to be the big breakthrough. The question is where do we draw the line on how many we measure?
>> Sure. The thousands. Right.
>> Right. Yeah. There's there's so many.
But it it does appear that that the nutrients and what we're eating and how those foods are metabolized and the nutrients and and and bioactives that get into our bloodstream that they they appear to have a stronger influence on the vascular pathway which which would make sense because we're measuring in the bloodstream >> and then the vascular you know system that circulates the blood as it's moving through is what we're measuring in the brain at autopsy.
>> So it appears that there are a more broad array of nutrients that are important for vascular health >> than than there are for preventing for example the plaque and tangle. So the plaque and tangle seems to be very specific maybe like three to five nutrients for example whereas the vascular we're talking 20 to 30.
>> Yeah. Yeah. Yeah.
>> Yeah. And we could be testing for all of those and then essentially just manipulating our nutrient intake.
>> That's right.
>> And that could be an NF1, right? That could be specific to me. This is the dosage and volume of each of those nutrients that you would need >> to build armor against cognitive decline.
>> That's right.
>> Huh.
>> That's remarkable. I think we look back in 10 15 years at this field and say I can't believe we were not we didn't have more urgency about the prevention piece.
>> Yeah.
>> And I know we are like there's some remarkable people doing remarkable science but you know I think >> most of us I wasn't aware and I've been working in this field for 20 years now.
I wasn't aware of the impact that you could have on your future cognition so far upstream of having those symptoms.
>> Right?
>> And I think you know in the same way that we are all very familiar with the idea that if we do resistance training when we're younger or you know improve heart and lung function through >> exercise zone 2, zone three and so on that we are likely to retain that for longer as we get older, right? But we never think about sharpening the saw before it gets blunt for our brain.
>> Right.
>> And that's how we should be thinking about it. Right.
>> That is how we should be thinking about it. And of course, it's not just nutrition.
>> Yeah.
>> Right. It's also cognitive training, learning new things. Yeah.
>> You know, dealing with anxiety and stress, you know, taking the time that we need to kind of calm our minds.
>> But you have to have kind of the ground substance circulating in your bloodstream for those things to really work. Well, >> you always seem very calm, Jean.
[laughter] I'm kind of jealous of that.
>> You're calm.
>> I was going to say the same thing about you.
>> No, I'm on the edge of mental breakdown inside at all times.
>> I think having the and, you know, we use some of those tools and technology for the, you know, um, testing for executive function and working memory and short-term memory and even like things like peripheral vision and reaction time. And I think capturing data across those mechanisms of the brain >> is can only be beneficial. That's right.
>> One thing we still don't really understand, I don't think we understand in high science in general, is how do all of those interventions, whether that is nutrition or stress management or exercise, how do they impact the brain horizontally? Like what what is the most impactful thing for me to do >> today? Right?
>> And I mean, we suspect it's a bit of everything, right? But like the thing I'm most excited about is by capturing more of those data points, we will get more clarity on what works for me.
>> That's right. Exactly. I think you can think about it as kind of a multi- domain assessment. Yeah. Right.
>> Around stress management, you know, your movement and your exercise, the nutrition component. We've talked a lot about, you know, what supplements and medications you're taking. And then kind of the cognitive training piece. So you kind of assess an individual based on those factors and we do deep dive on some right like with the nutrition component or uh maybe the cognitive component something like that. But there' be some people that already have optimal nutritional status. So you don't spend a lot of time with that individual focus on that hey great job you're doing great there.
>> But then maybe they their stress management is the piece and it's really affecting their sleep right and these things. Or maybe you adjust the diet a little bit to kind of complement what you're doing to help with sleep or something along those lines.
>> Yeah.
>> It's such a marathon, isn't it? Like there is we're kind of all fighting this losing battle.
>> Yeah.
>> And so like it feels like there's always something we can be doing. I think the thing that gives me most hope is by getting more resolution through tests like these. Hopefully, we can claim back a bit more time through agency because you're like, I'm doing this thing because I know it's going to work and we're no, we're removing a lot of the guesswork. Right.
>> Right. And so, hopefully that should allow us more time to >> feel joy and do the things that we love doing rather than constantly feeling this anxiety about, you know, am I doing enough right >> or am I doing enough of the right thing, >> right? Having a plan, right? Having a plan in place, I think, >> and that's the thing I think becomes very scalable and very affordable.
>> Mhm. very soon actually. I mean, it's already happening, right? We're seeing that, >> right? You know, something else I've noticed about um the bloodbased nutritional profiling >> is that it's it's useful to motivate people, you know, people like, you know, it's kind of like the the lipid panel, right? Everybody knows about, you know, your lipids and are you at risk for heart attack and and these things. It's kind of the same thing, but specific for brain health. And it it helps motivate people to make the difficult changes in their diet to get away from the, you know, the ultrarocessed, you know, fried foods and so forth that are really the a person's eating that crowds out those healthy whole foods that are nutrient-dense that the brain needs those ground substance and substrates. now right as well because you know >> we have a bigger cohort of people now who are who have their weight under control >> right >> or or are getting their weight under control and if you remove that aesthetic >> um driver to >> you know eat well >> that's right >> then >> I think we need the cognitive motivation right because just because you're in good shape does not mean you're doing enough to protect against cognitive decline >> that's right that's right it's way beyond just the calories in your in somebody's weight, right?
>> I mean, these are really important things to think about. You know, it's not how many calories are in this meal that I'm eating. That's not really the question anymore.
>> Yeah.
>> Right. It's it's been driven into people, but you should be really thinking about are you eating healthy fats? Are you avoiding ultrarocessed foods?
>> You know, are you eating a low glycemic index type? You know, so getting your blood sugar under control. You know, often people are eating kind of these ultrarocessed high glycemic index meals and they're just, you know, they're they're on the edge of their seat and then they dive, right? And they can't think, they can't get anything done.
Inefficient processing and this and that and they keep pushing through, right?
The exhaustion.
>> Can we talk about that for a bit?
Because >> I think one thing that really troubles me intraequely is that fluctuation in energy levels in mood.
>> Yeah.
>> Like this uh brain fog, right, >> that I will sometimes experience for days on end, >> right?
>> What do we know about that and how to manage it? Because I think we all go through these cyclical periods of feeling like us at our best self and then we have days where you can't really put your finger on it, >> right?
>> But you just feel like >> Yeah. I mean, it's probably a combination of several factors. I mean I from the food perspective certainly again like these ultra high processed meals that are large meals >> and they're loaded with sugar those definitely are going to lead to some brain fog at some point right during during you know the postprandial uh period so I think again wait the post what period >> so after you eat so after you what did you call it?
>> Postprandial.
>> Prenial.
>> Yeah.
>> So anyhow [snorts] >> um so I think people um you know what are ultrarocessed foods, right? They're typically boxed, >> right? Frozen fried foods, things. I went to the Baltimore Orioles baseball game yesterday and I got stuck. You know, there was there were so few options. So I ended up with a hot dog and a barbecue sandwich and you know a pretzel and that's exactly kind of the standard American diet. Sure, right at a baseball game, >> you know. But again, >> uh, you know, the burden of knowledge knows that today I can't do that, right?
Today I had an I got a great salad here, right?
>> Yeah.
>> Mediterranean style salad.
>> How was it?
>> It was terrific. Terrific. I even had a little espresso. Okay. you know, so I mean the caffeine, you know, you know, a lot of the things that I'm talking about are, you know, so for example, just to back up on on the blood tests and those three factors. So if you go from suboptimal levels of those and then you optimize them, you may not feel an acute effect from that. So a lot of the things that we're talking about here are kind of more long-term effects, right? But there are some stimulants and things that that an individual can take and and people know about these, you know, caffeine and so forth and coffee and in tea. But if [clears throat] you really want kind of this acute effect, let's say you've got a podcast today and you want to be extremely sharp and, you know, four to six hours you want to, you know, do something to kind of make sure you're that that way. What should you do? So I think the evidence is probably strongest for for caffeine maybe with some elenine in there which naturally comes in green tea for example.
>> You might want to have you know um a small meal that's low glycemic index maybe with some berries. The polyphenolic properties within berries appear to add some attention and alertness um to cognitive performance. So these are kind of things that you can do and and foods to stay away from low glycemic index meal. So not a lot of sugar, refined sugars. Um so those things you would want to avoid. So a small low glycemic index meal with berries. Um something with caffeine and some alenine that >> What would you put with the berries?
>> Um so you could do yogurt. You could do something like that. You you could you could have berries on the side and have like eggs, >> something like that. Has a healthy kind of fat profile as well with some protein.
>> You also add some fiber, >> you know, you could add some like brown rice or something along those lines.
>> I'd have all of that actually.
>> Yeah, you could have some, you know, some flax seeds, some ground flax seeds.
Um, >> with caffeine, I mean, one of the most studied nutrient supplements in the world, right? um >> neuroprotective. I've seen some pretty promising data on caffeine in general and I hope that you say yes because I drink a lot of it.
>> Um but how how is that protecting our brains mechanistically?
>> You know, I'm not sure that it's that it's adding protection directly, you know, I think it it has a stimulant effect that ends up um you know, making us more alert.
>> Yeah. you know, whether or not it prevents degeneration, I don't see any evidence for that. You know, it's almost like it it squeezes the lemon a little bit. You get a little bit more out, right?
>> Yeah.
>> But over the long term, it's other things that you need to do to really protect your neurons and your brain cells. Are you seeing any data that would suggest the opposite like that there is a a ceiling to caffeine intake after which we see some detrimental effects?
>> Not really on the brain.
>> Yeah.
>> Yeah. So we've seen up to two to three cups a day. It seems to be some >> cut those numbers up. Two to [laughter] three a day. How much you drink?
>> So I'm I'm right one to three something like that. Yeah.
>> Yeah. Same.
>> Yeah. Yeah. So I'm I'm probably in that.
You know, the other aspect of caffeine is that it's one of the few bitters that we still have in our diet.
>> True.
>> And and the and the coffee. So, for example, coffee is the most common, right? And and with coffee, the question is, do you put cream in there or do you not? And it turns out that black coffee is really the most beneficial. And whether or not it's the caffeine in there or not, or it's the effect on the gut to add a bitter that stimulates the digestive system and the enzyme secretions. So for example, the pancreatic enzymes and the gastric enzymes that break down fats and proteins and carbohydrates, >> whether or not it's kind of an appetite, you know, before your meal.
um because we have so there traditionally there's been a lot more bitter in our diet that kind of primes our gastrointestinal system to actually pull things out of the foods that we're eating and break these things down to improve absorption.
Um so I think there's a couple different pathways by which coffee and caffeine could >> Do you drink your coffee with no milk?
Do you have it black?
>> I mix it up.
>> Same.
>> I mix it up. I rarely have it just black.
>> Yeah.
>> It's not very fun, is it?
>> If I I if I do uh so I I typically would do like a flat I make a flat white at home that I love. Um so I do that first thing in the morning, but if I have a second or third cup, it's always black and I'm typically just sipping it. I'm thinking just for the stimulation.
>> Yeah.
>> I'm reading I'm reviewing a research paper or I'm writing a grant or something where it's just very cognitively taxing. Um just something Do you cut it off at like earlier in the day? I mean, some people are kind of remarkable at that being able to still sleep when they drink later. My My dad like will have a coffee just before he goes like after his last meal, which >> I can't do that. Yeah, it it keeps me up for sure. Yeah. I mean, I think >> there's a couple things. I mean, um, you know, it it does have a diuretic effect.
they will you know make you produce urine and and through that you do lose some minerals and so forth like magnesium and potassium these things. So you know you have to be careful of that right those things that's why you end up with you know people drink a lot of coffee with arrhythmias you know where they have some heart flutter and things like that and and some people it's you know it's it's too too stimulating yeah in a way >> and also you lose your hydration right >> so you have to be careful not to get dehydrated you know because basically it's a you know it's like a diuretic um increases urine frequency and things like that so You're losing minerals there and you're losing water. And once you have it on board, it's not like you can just drink water, right? Because the diuretic's already on board. It's just going to end up >> making more urine, right? So, it's not actually going to get in the cells.
>> So, you have to let that effect die off.
>> And and caffeine has a very long halflife, right?
>> Yeah. Has a long halflife. And and so typically I encourage people to to drink a glass or two of water first thing in the morning after the overnight fast before you get the coffee going.
>> Right.
>> I think that's one of the greatest practical >> friction-free tips for health in general is yeah >> hydrate first thing.
>> Hydrate first thing after the fast. I mean that brings us to a whole another subject of how you combine foods.
>> Yeah. You know, we talk about ultrarocessed foods and they're the bad guys and high high refined sugar foods and they're the bad guys, but in terms of their effect on your biology, if you're eating those on an empty stomach, they're compounded.
>> So, if you're if you're having ice cream in the morning as your first meal or you're having a piece of cake or something or cookie, >> bigger issues if that's the case.
>> Yeah. Yeah. So, but you know there's kids. I mean, these are things that in school and and things that aren't >> it it's not common knowledge for everybody, right? So, a lot of the time you can get away with dessert and something sweet after you've had a meal, >> right? So, you have your bitter before the meal and you can have dessert after the meal on a full stomach where it mixes. The problem is is that if you have refined sugars, it's absorbed so quickly and and the blood sugar levels in your blood, your body doesn't know what to do with it. They just shoot out of the roof >> and so it doesn't know what to do. It just converts it to fat.
>> Yeah.
>> Or it has destructive properties on different organ systems over time.
>> We had Dar Mosafarian on um and his >> one great takeaway from him was skip the bread before the meal and have the ice cream after.
>> Right. Yeah, >> I thought that was a great strategy.
>> That's right. C >> can we talk about strategy a little bit here? Um, you know, I think there is there are two things that all of us would probably like to take from this.
And one is, you know, I think we've touched on already, like if I need to like an instant boost in cognition, focus, memory, attention, what does my day look like? And I think you've touched on that. um but maybe understanding the rest of the day not just that first meal. So that is the first part of my question. The second part is you know given that we know we can begin protecting against the onset of this cognitive decline particularly symptoms of Alzheimer's dementia.
>> Mhm.
>> Do those things match? Right? And if not what are the other considerations for how we should be eating as we go through our years?
>> Yeah. I'm not sure we have evidence to really draw strong conclusions about that. I mean, I think for, you know, the meals in the morning and the things that you do, you know, we've talked about this, but if you those are things that you can apply at any point in the day. Yeah.
>> Right. I think >> having the caffeine with maybe some some elenine is going to is is going to improve focus and attention. Um there's good studies on that. We've talked a little bit about the type of dietary pattern you might want to have, right? A relatively small smaller meals that are more frequent, >> okay, that that are nutrient-dense whole foods, right? And certain food groups you might want to focus on like berries that have, you know, these polyphenols.
Um, you know, we didn't talk much about healthy fats. those don't really have the acute response, but those over time are something that you want to kind of focus on. You know, you want certainly want to avoid trans fats. You know, so trans fats are something that most people know about. You know, these are the things where you have a trans fat infused muffin that you put on the kitchen counter and you go away for a month and you come back and it looks exactly the same, right?
>> It's a big boon for the food industry because of the shelf life improvement.
But those trans fats actually get into your brain cells. They actually get across the bloodb brain barrier. They get bound in there into the lipid billayer and they raise havoc. And it's really the worst thing you can do in very small amounts as well. So any food that has long shelf life, you know, you need to be skeptical of. Anything boxed, anything, >> anything boxed, >> long shelf life, >> any anything that survives in the fridge for a long time, >> you know, even processed meats >> and so forth, you know. So, uh, that's a whole another discussion, but I think, you know, the thing is is that there's no silver bullet. It's all about the patterns, whether it's in the bloodstream or the the dietary pattern.
If you put all the foods that you eat on the table and you're just looking at these, right, it's there's no real silver bullets out there. It's >> How do you feel about the new guidelines, the sort of reverse pyramid with specific regard to cognition?
>> That's funny you bring that up because this week is uh this next week we have uh the American Academy of Neurologies annual meeting and I'm doing an interview uh with the AEN on that specific issue. whether or not the new dietary guidelines are positioned well for brain health in general. No.
>> Right. In general, again, uh you know, for example, the red meat the red meat issue right at the top and whether or not that's really important and whether or not that's just an overcompensation for a kind of high carbohydrate Yeah.
diet, right? used to be stay away from fat, low fat, right?
>> Yeah.
>> And what happens when you have that public message, >> people stay away from those foods, but what do they replace them with?
>> Yeah. Yeah. That's so true.
>> And so this is the circular issue that we've been in.
>> You got to eat something, >> right? And now we're doing it again.
>> Now we're doing it again. Now we're pushing people towards red meat, which we know people that eat high red meat over time have cardiovascular events.
those vascular events can lead to strokes, you know, so it affects the brain, but it does it normally much quieter, right? And takes a little bit longer to to see it >> as opposed to like a heart attack, right? Or, you know, his heart conditions.
So, I think we're overcompensating again. So, I think we need to start doing more research on food combinations.
>> Yeah.
>> And the timing of when we're eating certain things. So I I think that's a it's an element it's very difficult to disentangle but it's somewhere we need to go you know we have the resources to do it now >> and and and I assume that this is all personalized as well right like very personalized >> it's very hard to say give these broad brush strokes of recommendations with something as nuanced as nutrition >> right >> do you eat red meat >> I do I do small portions though >> small portions and it's typically with you know some nutrient dense foods.
>> Yeah.
>> From a micronutrient standpoint, >> right?
>> So nutrients that you know, >> colorful vegetables.
>> Yeah. You can think about it as color.
Color is really interesting. You know, it's interesting in nature why there are >> these foods that have these remarkable colors. It turns out that these colors actually represent a certain profile of nutrients that were never really taught, right? It's, you know, I mean, you know, you walk around, it looks attractive, right? berry or a strawberry just or an orange so remarkable or an apple. All these things they're quite remarkable.
>> Yeah, it's it draws our attention to these things. But I think when you look down at your plate of food and you see very little color, let's say you see, >> you know, a brown black steak and you see uh mashed potatoes that are white and a piece of toast or something like that. You know, in general, you want to have a very colorful, you know, a ver variety of foods. I think the main thing is you want to stay away from ultrarocessed foods, high refined sugars, you know, stick with whole foods, things that are going to decay.
>> Yeah.
>> Over a relatively short period of time.
So, you have to eat them and get it done right.
>> And then I think it's just, you know, keeping things in relative moderation in a sense. And hydration, like you mentioned, is is really important.
That's something particularly as you age, >> particularly as you add exercise and caffeine and these things that are so common. Um >> I feel like a lot of my brain fog is is attributable to just not drinking enough water.
>> Yeah.
>> And like I suspect a lot of people are walking around just slightly dehydrated.
>> Yeah. Well, I think it's I think I think it's underemphasized and it's there's no gold standard for measuring hydration.
And again, we come back to kind of the biioarker, right?
>> Yeah.
>> We haven't made enough progress in kind of targeted nutritional therapies for chronic diseases because the tools haven't been available to us until now.
>> Yeah.
>> Same thing for hydration.
>> I've been looking for a tool that would be like a constant hydration tracker such that if you were slightly dehydrated, you would get a notification. And there are there are some. They're just not ready for prime time yet. I don't think >> anyone's listening and they have one.
>> No, there are some there are some that are looking promising. I say there's no gold standard, >> you know, but there are indicators of, you know, lower water intake, um, osmolality, you've got certain urine factors in the urine that you can measure. Um, you know, I typically encourage people to drink about half of their body weight in ounces.
lean body weight.
>> Yeah.
>> Yeah.
>> Yeah.
>> Huh.
>> Can I ask you about a study that I read recently about red meat being protective for APOE4 carriers?
>> Okay.
>> Did you see this?
>> I did not. No, I have not.
>> Seemed kind of counterintuitive to me >> from what I'd heard before. Maybe we would unpack that after the podcast.
>> Yeah. I'll show it to you, but I I'm not sure how good it was or >> Yeah, I'm not sure. We could take a look after the podcast. I mean, you bring up APOE for carriers, you know, so for our listeners that that, you know, >> yeah, maybe you could just explain that because I think that genetic component actually is a something that we don't truly understand. we as consumers I mean you you definitely >> I mean one one one thing that's clear okay so for in Alzheimer's disease we know and thanks to you know our colleague Rudy Tanzy and others um have pinpointed you know the key genetic factors that will cause Alzheimer's disease and that's that's in a a relatively small group that have the actual causal genes but the sporadic form of Alzheimer's disease okay the number One risk factor is APOE. APOE genotype. Apo lipoprotein E. If you're carrying one of those four alals or lo and behold two of them um two E4 two two E4 alles you're at dramatically increased risk. And we know that that APOE is involved in in lipid metabolism.
We ran a trial with omega-3 fatty acids, a randomized controlled placeboc controlled trial over three years. Turns out the omega-3s appear to work better in ApoE4 carriers. Okay. And it it appears to to improve uh neuronal integrity. So the integrity of the cells, the lipid layer.
>> When you give something like omega-3 fatty acids, there's a lot of things that happen. those those those fats get broken down into other compounds that have anti-inflammatory properties.
Sometimes they're not broken down and they get into the brain and they're incorporated in the lipid billayer that changes the the um how the cell works and how efficient it is in getting toxic products out and getting the good things in. So it's kind of an indirect effect.
So what we were able to determine with neuroiming with brain scans is that the integrity of the neuron is improved over time. So typically that breaks down over time. We were able to prevent that with the omega-3 treatment and it's amplified in APOE4 carriers. It if you're an ApoE4 carrier typically you struggle to get those type of fats into the membrane. So if you're giving it as a supplement it does work. So, and that's a randomized control trial. It's class one evidence.
So, again, that's something that's very tailored to the individual. Are you an APOE4 carrier? If you are, this might be something you do. So, there is a nutrient kind of gene interaction. It's very personalized. Right.
>> With with that in mind, then do you think that is because we can that test is readily available.
>> That's right.
>> Do you think would you recommend everyone does that test or is sometimes ignorance bliss.
>> I think again it depends. I think I think yes. I think if your omega-3 status is suboptimal and you're an ApoE4 carrier, yes, I think you need to address it >> and right away. Um I think do all APOE4 carriers need to do it? It depends on the omega-3 status.
So these kind of go hand inand but again it comes back to testing and coming up with a personalized approach on the individual both genetic and also your current status.
>> Yeah. But if you are an APOE4 carrier I would assume from your perspective the earlier you know that the better because we know we can begin right >> to like create a defense almost.
>> That's right.
>> Um but then some people might not want that knowledge. Do you think maybe I I >> you tell me what you think here. I I think that 20 years ago we would have said maybe not and now we can actually do things about it.
>> I think we're in a transition period.
Exactly.
>> I think um there's anxiety around doing the bloodbased biomarkers of Alzheimer's disease pathology because we need an answer >> to how to prevent you know that destiny for that individual. We haven't had great answers for that. Yeah. Now, we have a couple FDA approved medications, but in apoE4 carriers, >> it those therapies are problematic. So, we don't really have a standard of care treatment >> for APOE4 carriers. The omega-3 trial is one of the few that we've shown that there's an ampl amp amplified beneficial effect on the brain in APOE4 carriers that are taking the supplement.
>> So, I think that's something you could do.
>> Yeah.
>> You know, I think that that's very reasonable. I mean, there's no perfect evidence base, Sure. But again, you have to kind of weigh out the the riskto benefit ratio. And I think there that's that that one's pretty easy to answer.
>> And I think your destiny is not sealed by that >> that test alone, right? Like that's right. There are so many things that >> That's right. In in either direction.
>> That's right. There are APOE4 carriers that never end up with the disease.
>> Yeah. So it's not causal.
>> Okay. It just increases your risk.
>> It's the interaction with the environment, >> right? So if you have factors in your environment, we're talking about, you know, nature versus nurture, right? It's a it's it's a marriage between those two.
>> So the nature is you've got this genetic factor that you can't do anything about.
The nurturing is, you know, what about your environment? Can you change to nullify that effect?
>> Yeah.
>> The the bloodbased nutritional phenotype is going to change all that.
>> Meaning we're going to block all those poor genetic, >> you know, destiny factors. we can block it >> because basically we're we're going to change the nourishing lore that the brain has available to it and whatever those you know that that underlying mechanism that's disturbed in those APOE4 carriers we're going to come up with a remedy to nullify that. It may be that the omega-3 status for ApoE4 carriers is at a different level than for people that aren't carriers.
>> Yeah.
>> And that may very well be the case. And that's we have some data to suggest that.
>> So we'll be giving more power to nurture.
>> That's right.
>> Which we're seeing across every domain of science. That's right. Of >> I mean we're talking about brain health, but from this nutritional phenotyping this really applies across all >> disciplines >> and there is a apo2 people are ApoE2 carers, right? And that doesn't that seems to be protective protective. That's right.
>> That's right.
So there the metabolism related to the lipids for those carriers seems to be more beneficial. So the integration of certain fats into the neural membrane, the clearance of certain factors that are kind of metabolic waste is improved in those E2 carriers. So you know, so that's something that they're genetically endowed and that that's the gift they've been given, right, from nature.
>> Are you either two, three, or four? Are they the only three options?
>> Yeah. Okay. Y >> what's the percentage split? Do we know in the population or how rare is it?
>> Depends on the age.
>> Depends on the age. Um about 15% of the population is an E4 carrier in general, which is quite high.
>> Yeah. What about E2?
>> E if you're if you have two E2s is relatively rare. Most people most people are are three two threes >> or they'll be a 32 or a 34. Yeah.
>> Um, >> so if you're a 22, you're like an avenger.
>> Yeah. It's kind of like Exactly.
>> cognition >> in a certain sense. So, you know, your lipid pathways and your lipid metabolism seems to be you're endowed somehow.
>> Yeah. At least related to the brain.
>> But then the flip side of my concern before is if you do that test, you discover you're a 22. Maybe that will create some flippency.
>> Yeah.
>> In the way you approach.
>> That's right. Yeah. Well, it's it comes back to maybe that's something you don't need to focus on. Your lipid metabolism, you've been endowed there.
>> So, we focus on the methylation pathways and we focus on the other aspects that can be optimiz layers to that. So, >> that's right.
>> There's some there's some really um very promising data with some of these new blood tests like P the PALS, >> right?
>> 217 I think is one that Rudy specifically mentioned to us as as worth doing. What's your perspective on those?
Yeah, we're utilizing those. So, um I mean I think these have come, you know, just to step back, a you know, a bloodbased biomarker that reflects what's going on in the brain has been the holy grail.
>> Yeah.
>> Because it's readily available to everybody. Everybody's relatively used to having a blood test.
>> Yeah. Now more than ever, right?
>> Yeah. Most people. as opposed to having a brain scan, you know, where you've got to get into a machine and an MRI scanner and you've got to put your head in this >> completely. I think I've done them.
>> Yeah.
>> I think they're horrendous. I It was like I I can't like Right.
>> It's like you're >> So, it's either that or a lumbar or a lumb or a spinal tap or a lumbar puncture.
>> We don't We don't love those. Right.
>> So, so I mean even you know a robust individual is middle-aged, you know, is you know >> that's more of a me problem. I just don't like being like in one position.
But you're not alone, I guess, is what I'm saying. And so those those >> ways of detecting that uh there's not a lot of penetrance. So with the bloodbased biomark has been a big breakthrough. But again, we have to step back and say this has only been within the last couple years, >> two or three years.
So you know, we're still learning about what are the optimal levels of those or what are the levels that are really high risk. What are the key ones that are brain divi derived? So P27 is brain derived. Okay.
>> It will reflect Alzheimer's pathology very very very well. So it'll do just about as good as an amaloid PET scan. So an actual PET scan where you have an infusion and it binds on to the plaques and then you you measure the abundance and then you calculate how much is there in certain regions and you say, "Oh, this looks like Alzheimer's disease."
>> The blood marker does a great job almost as good. and it's just in the blood and it's a simple test. There's others though that don't that aren't quite as specific. You can look at the what we call amaloid beta 42 chain link to the 40 ratio.
>> Yeah.
>> And that's basically just metabolically how the enzymes inside the neuron are actually breaking down and cleaving the different trans proteins of this amaloid precursor protein that ends up getting washed out and you can detect it in the bloodstream. M >> and so if you're producing a lot of the 42 a beta 42 and it's high in the in the bloodstream that can actually be a good thing. That means that your your brain has the ability to actually clear it.
You're clearing you're clearing that toxic protein in rel in relation in relative to the 40 length which you really want. You want predominantly 40 length and you want to keep that a beta 42 soluble.
>> You don't want it to turn into a plaque.
So Rudy and I were working together to do clinical trials of combinations of natural products to actually improve these processes in the brain, but we're using strictly the bloodbased biomarkers as the primary endpoint.
>> So they're convincing enough where we're creating an entire clinical trial platform to test combinations of natural products focused on these bloodbased biomarkers.
And these natural products would be in the form of a supplement. I mean, we we work with some of these already and so I don't want to come across as as too naive here, but yeah, I think for the listeners, I think what's incredibly promising is that historically testing the efficacy of some of these interventions, whether it be through food or supplements, has been very difficult to actually prove, right?
Because that's right. of the like notoriously difficult space that is nutrition research but like self-reporting observational studies epidemiological studies very difficult to actually >> um squeeze any juice out of those lemons um and so I think that this is just such a great combination the bloodbased biomarkers and the development of actually figuring out what is working >> right >> it holds incredible >> it's a game changer it's a total game changer for accelerating are the whole pipeline for development of therapies.
>> I mean, I think these these blood-based biomarkers have been a big game changer.
>> Can we talk on that note? You know, we've spoken about good strategies for defense um both acutely and over the long term with the foods that you eat.
And we should add like a a TLDDR of that in the show notes. I'd love to have that as a resource for the listeners.
>> What about supplements, right? Because this feels like a complete minefield. I think one thing that I've probably repeated to the point where it's getting very boring now is that there is just so much misinformation in the longevity aging research space, but nutrition probably more so than any other.
>> Yeah.
>> Um and and I think we're we're led to believe that we should be taking 50 different pills a day. Um you know, I I take a number of supplements, not a huge number. I'm very bullish on omega-3. um primarily because I don't eat enough seafood >> um and you know vitamin D at certain times of the year and magnesium at certain times.
>> Yeah.
>> Um and creatine and some other little bits and pieces that I'm triing.
>> But you know I think one question I would love to hear your perspective on is if we were to eat the perfectly nutrient-dense balanced diet would we need any supplementation? Right? Is question one. And secondly, I don't think anyone is doing that >> 100% of the time, 100% as well as they could.
>> And if we did that, would we then be eating too many calories? Would we then be in a calorie surplus because we're trying to hit those, you know, to be optimal across those nutrients?
>> Yeah. And so I think that the answer is that we don't know for sure.
>> Yeah. Um the way to to if you're eating let's say you're eating the MIND diet and it's uh protein enriched like it has enough protein um you modify it a little bit. Let's say you're eating the neuroprotective diet.
>> Wait, can you can you explain what the mind diet is?
>> So the mind diet was developed by professor Martha Clare Morris who passed away in in 2021. She was a close colleague of mine. She's the co-founder with me of of the professional interest area at the Alzheimer's Association focused specifically on nutrition, metabolism, and dementia that we founded in 2014.
And um she had done a lot of observational studies on dietary patterns using subjective um uh questionnaires and identified diet patterns that are associated with dementia, Alzheimer's, and and rates of cognitive decline. and she called it the mind diet and and it's been tested in a good >> choice a good choice. It's been tested in a in a large clinical trial that that unfortunately she didn't see the end of it and it didn't seem to work in an intervention. So, it didn't get a lot of headline, >> but she's on to something there. And and I think that, you know, the dietary pattern is kind of the things we've been talking about, right? It's it's certain food groups that you eat and how frequently you eat those over time.
Includes berries, includes dark leafy greens, it includes seafood, >> nuts and seeds.
you know, certain types of protein sources. You know, she doesn't touch on the red meat factor, but you know, tries to stick with lean protein sources.
>> So, it's relatively similar to a Mediterranean style diet and also the DASH diet. It's like a hybrid of the DASH diet, which was specific for, >> you know, um reducing cardiovascular disease and and things. So, that's developed by Frank Saxs, Harvard.
So I think to come back to your question about if I'm eating the perfect diet, [clears throat] is it enough? We haven't had the tools to test that hypothesis.
Now we do, right?
>> So let's put people on a diet that's spec a feeding trial. Let's give people even if it's only for three months, two months, >> and let's see whether or not it optimizes the bloodbased nutritional risk index or not. It's associated with four to fivefold increase for dementia risk. If it does, then yes, >> why wouldn't it? There's a couple reasons of why a perfect diet would not deliver enough nutrients to the brain.
There could be other conditions, for example, right? So, we think about when we eat something, what are all the obstacles that those food components have to get through to actually make it to the brain? Yeah.
>> Turns out there's a lot.
>> Yeah.
>> You know, so it gets into your belly.
You've got the parietal cells releasing hydrochloric acid. It's trying to break it down. You've got, you know, amalayise, lipase, protease, all these enzymes being released to start breaking. Then it gets dumped into the small intestine. Then the pancreas has got to release enzymes and the liver's got to release bile. There's the microbiotin there. Whether or not, you know, somebody's on ultrarocessed food diet and then they transition to the perfect diet, >> they still have microbiome issues, right? They have encroachment from the colon of these species that is working their way up into the small intestine because they've been eating so much refined sugar and it's feeding all the bad bacteria and it's >> furious now. It's just vegetables.
>> Yeah. Right. [laughter] So, so I think there's, you know, so there's a lot of obstacles in the absorption, the digestion, the absorption, you know, actually getting into the bloodstream, but then getting into the cells, which we call assimilation and then delivery to the brain. There's certain transporters at the bloodb brain barrier and and the blood CSF barrier specific transporters by how these nutrients get in. So, for example, if you have damage there, they may not. So, you make it all the way to that point and still not be able to get in there.
>> Um, so I think we need to do the studies to figure that out. I think that's a great study design. Actually, [laughter] >> it's exciting because there's so many unanswered questions.
>> Yes. I think the acute effect won't be there, but I think if you if you're eating a you know the perfect diet, eventually it's going to work.
>> Okay. I'm reframing the question, Jean.
Okay.
>> Do you take any supplements?
>> Yes, I do.
>> Can you tell us what they are? So, I mix it up. Um, I take a variety of things based on my blood testing. Um, so I think, you know, >> how frequently do you test your blood?
>> So, about every six months.
>> Okay. Oh, that's good.
>> Yeah.
>> Manageable.
>> Yeah. About every six months. Um, but again, I'm, you know, I'm I'm going to work every day and thinking about this, you know. Um, >> I hope so.
>> Yeah. there's there's an you know some individuals where you need to monitor a little bit more closely have more you know other conditions and things that are important to consider but um so I take a high EPA omega-3 supplement not DHA high EPA omega-3 supplement um a couple times a week at a dose of like 1.6 grams something like that same exact that we use in our clinical trial.
>> Yeah. And again, that's only when my dietary pattern I haven't had, you know, a serving of fish during that week, right?
>> Yeah.
>> I mean, optimally, you need about a 3.5 ounce of fish twice a week, it seems to be, you know, and most people are not doing that. Not even close.
>> Yeah, I can imagine.
>> So, and I'm not even, you know, meeting that most of the time. Uh, so that's the case. And then I I eat a whole foodsbased composite multivitamin mineral um that's extracted from whole foods.
So, it's not a synthesized entity.
[clears throat] >> So, there are companies that do that. Um I add on some zinc and magnesium at times uh you know during the winter, something along those lines and then I mix it with a slurry. I make a slurry from a powdered kind of potent absorbable form of some minerals and vitamin C combined.
And so I take them with that typically first thing in the morning. That's my first drink in the morning. Other things, you know, from time to time I'm feeling under the weather or if I know I'm really burning the candle at both ends, there's some other things that I do. I do do green tea with atheenine at times. Um, so but that's about all I do.
It's really based on the research findings that we're finding, right?
>> But now with this new these new re, you know, this profound, you know, comprehensive profiling, it's it's convincing me that, >> you know, we're not really >> getting close to these things.
>> We we are scratching the surface.
>> We're scratching the surface from, >> you know, the Olympian brain, right?
Like optimal performance. We're talking about we've been talking about slowing decline.
>> Sure.
>> But we're not talking about building the Olympian brain, right?
>> And that's ultimately what we what we want. I mean, that's going to save us time. I mean, what if we could do everything that we're doing in 50% of the time, right? I mean, think, you know, it's like the the human mind with AI attached or something like that.
>> But I think that's a really interesting thread to pull on that we don't talk about enough. How do we optimize an already healthy brain? Right?
>> Well, how much are we leaving on the table, >> right?
>> By just assuming that our seven out of 10, the way that [clears throat] we feel dayto-day is good enough.
>> Yeah. Well, I think that's um commonly overlooked. I mean, we we conducted a study called the Oregon Brain Aging Study where we studied um the oldest old population of exceptional health and we did nutrient profiling and we thought, you know, these people are exceptional health. We're probably not going to find any relationship to brain health because they're already kind of at the top aes >> super aes Yeah. And what we learned is that this was our some of our original work almost 15 20 years ago now.
>> We learned that we're not even close to calibrating or understanding the optimal levels of nutrients in in the bloodstream for optimal brain performance. These are these are super achievers cognitive performance way high. you know, they're out on the tail >> of the curve of of exceptionally cognitively endowed.
And we figured out that none of them had deficiency. Okay. There's very little deficiency how we define nutrient deficiency in the current state. And that's still pretty much the same.
>> Yeah.
>> Standards.
>> Just looking for deficiency. But we we found upper levels that were optimal, you know, two or three fold of the concentrations in the bloodstream for certain nutrients.
>> Are there any that stood out of those nutrients?
>> It's these. It's it's certain B vitamins >> like thamin and rioflavin, vitamin B1 and B2, >> vitamin B6, a certain form of folate, methyl tetrahydroofolate, vitamin B12. Yeah.
>> But again, none of these in isolation.
>> It's all combined. So if you take two of those and you do run a clinical trial and you try and prevent Alzheimer's, it's not going to work.
>> Why is it then that they stand out like that? Is that something to do with their the bioavailability for their biology or like their capacity to utilize that food? Because they can't all just be keeping some like crazy secret diet.
>> No, no. Well, it's not just those. So, it's it's those B vitamins, but it's also the antioxidants, vitamin C and E, >> vitamin D, which is predominantly synthesized from being out in the sun.
And, you know, you got fortified foods that have vitamin vitamin D.
>> Then you have the omega-3s, EPA, and DHA specifically, the precursor to DHA, EPA that's profound. So, it can dampen the microg GA release of cytoines like inflammation in the brain. So, it can cool off inflammation in the brain.
So those were the key and then two zanthopils which are like carotenoids called luteine and zigzanthin.
>> So if we peel all those apart we can't really determine somebody's trajectory over time but combined it's profound. So in the concentration call it baid pufil like a formula. So B, C, E, D, PUFAS, polyunsaturated fatty acids, omega-3s, >> and lutein and zeazanthin.
>> So those something on that combination.
So we we ran 30 biomarkers at that first study. Now we've done 150. Now we're putting together these these combinations that are related to vascular pathology and plaque pathology and tangle pathology >> and you know so we'll be able to kind of in the future understand that if somebody has genetic risk for vascular pathology in their brain we're already have a targeted panel available. It needs to be run in compliment and we know the dietary pattern that they can start with. They come back a month later, they're still sub-optimal in those and saying, "Okay, you're not getting the job done.
>> Yeah.
>> Then you got to start taking some supplements." Right? If you're not going to be able to make the dietary changes, we can't let these levels go for too long. I love this because at that point, you know, when we have that resolution in the genetic data and in the bloodbased biomarkers in real time, >> then it becomes a math problem, >> right?
>> Right. Once we understand >> where your deficiencies are, we could say, okay, here is optimal for your biology, right, >> across all of these different markers, right? And this is what you have to do to achieve it.
>> That's right.
>> And that would be you at 10 out of 10.
>> Yeah, >> I think >> that's right.
>> And that's coming, right?
>> Yeah, that's coming. that's coming.
>> Yeah. [snorts] >> Do you take creatine? The reason I asked that, there's there's a lot of talk in the media now about not just this we we know very well about its protective >> um properties for for lean tissue loss, but cognition is now becoming a big talking point for creatine at higher doses. Yeah.
>> Do you have a perspective on that?
>> Yeah, I think it's early. It's early. I think um I mean there are some intriguing studies for kind of shortterm effects and whether that's related to its you know what it's really doing in the brain. Is it is it is it because it's helping retain water or hydration factors and that's somehow leading to better you know plasticity in the brain.
So it's not entirely clear at this point the mechanism how how it's affecting >> I mean it's probably affecting mitochondrial function energy metabolism in the brain but the pinpoint the actual >> yeah process >> just needs more research.
>> Yeah. Yeah. And then to understand who we should be applying that to. There's no doubt that it's a bioactive that's having physiologic effects both on muscle mass as you know and building muscle mass and weight and uh those things. But in terms of the effects on some of these pathological aspects, it's just too early to really.
>> That's another example of something that I think very well studied. Again, one of the most studied of all time, >> right?
>> And if you are if you tolerate it well, which not everyone does.
>> Yeah.
>> With their gut. I don't see much downside in everyone taking.
>> Yeah. Yeah. I mean, it doesn't seem like there's much downside to taking that other than just the expense of are you taking something that's doing something for you? you know that there's always that, >> you know, nobody wants to pay for something that's doing nothing. But I think in that case and with the caffeine case, there's there's an abundance of evidence that it's having positive effects whether or not it's specific to the brain or other body, you know, organ systems. You know, it's definitely having effect on other organ systems with some potential for the brain. So, I think it, you know, it's something that is safe >> and it's not going to do any harm and it's worth trying. Jean, can we talk now about the things that don't work? And I mean that you can be completely frank here. Like any things that you're seeing that people are just completely overreaching with in the press, the media, the supplement game specifically. There's a lot of overreaching going on there. Do any of anything jump out to you that people should know about?
>> Yeah, I think >> if you're too harsh, we can cut it out.
[laughter] Well, I think you know here's the motto is that the brain in terms of brain health, the brain doesn't age one nutrient through one nutrient at a time, right? It's all about patterns, right? So, you have to realize that the brain is exposed to thousands, hundreds of thousands of things all the time. You have a bloodb brain barrier that's, you know, protecting it's very selective.
So the idea that a single supplement or a single nutrient is going to really have a profound effect on the brain should you should already be skeptical >> in those regards. Now there are some cases for example that an individual does have you know nutrient deficiency on one nutrient or something due to a metabolic condition or something along those lines. You optimize that and they feel better and they get more cognitively intact. You know alcoholics for example you know have to be very careful about their thamin levels you know vitamin B1 because to break down that alcohol requires a tremendous amount of vitamin B1.
>> Okay. If somebody doesn't address that they'll develop these white matter lesions in their brain and in a syndrome a brain syndrome that is devastating for the brain. It's like an alcoholic brain right? So there are some rare cases like that where a single nutrient or supplement might work. Thamin for example.
>> Yeah.
>> And people have different forms that are more absorbable and these things and and some of that is quite true. So, but these things that that you see, you know, televised that, you know, that works for cognition, you know, to sell those things, you you have to stretch the truth. And they're stretching the truth, right, from the evidence standpoint. Now, you're talking to somebody that, >> you know, I'm on the far side of like what is truth and what is false in in a certain regard, right? Yeah. just because of, you know, my, you know, my calling or whatever.
>> Yeah.
>> You want to call that. Um, >> so I think there's opportunity for a supplement or program to work, but it has to be tailored to the individual.
It has to be an individualized nutritional therapy that's targeted. So it needs to be based on some kind of diagnostic test that gives the individual, the care provider some or the consumer some >> context >> context to then >> decide exactly what you need.
>> And the thing is you're with with dietary supplements and diet too, you're saturating tissues.
Okay? Once you've saturated the tissue with a supplement or something along those lines, it's done.
>> You've already saturated the tissue. You don't need to keep taking it.
>> Yeah.
>> Right. You have to rotate. And so that's another important feature. So if you're taking some kind of bioactive, eventually the dose is going to be high enough where your tissue levels are are well in the therapeutic range and you don't need to keep taking it for the rest of your life, right?
>> Hopefully, you're making the lifestyle adjustments, you know? So, it's it's temporal, meaning you're taking a dietary supplement for a certain period of time based on some type of test showing that you're suboptimal. Yeah.
>> And again, we already talked about >> that the levels in our bloodstream are not calibrated >> currently on standards for brain health.
>> Yes, >> that's what we're working on and we're figuring that out.
>> And we figured out the different thresholds, the cut offs. What's the cut off, >> you know, for cholesterol levels? Is it 200 or high? You know, do you address it? LDL cholesterol at a certain level.
If it's at that certain level, you address it. Same concept there.
>> Huh. That's kind of the frightening thing. I think that we're led to believe that these um normal thresholds are good or optimal.
>> Right. Right.
>> HBA1C I think is a great example of that. Right. There's no lower threshold to where you should be.
>> But suddenly you get 0.1 within >> right >> good and you're no longer in danger. And that's not how biology works. Right.
That's right. That's right.
>> That would be really incredible, I think, for all of us to have, you know, what does great look like, >> right, >> for me as an individual. And if we can do that, and it sounds like you it's coming.
>> Yeah.
>> I think that's so >> Yeah. And I think that's that's probably the reason that a lot of these these dietary supplement clinical trials and stuff have failed. they've they've applied them in a population where that supplement was not really well suited >> because they didn't really have a blood test, for example, to understand what their current status was.
>> And then the other component is that the magnitude of the effect of a single or just a few nutrients is so small.
>> Yeah.
>> That it's so hard. You'd have to study a 100,000 people over five years to see that effect over, you know, a fiveyear period or something like that. So it it it's using nutrition in a conceptually flawed fashion. Yeah.
Right. There's synergy, right? There's synergy. None of us have just one or two nutrients circulating, right? It's thousands of them, >> right? And they're they're interacting.
That's how nutrient nutritional metabolism is. There's there's an interactive effect. Now, we've built models to appreciate that and we're seeing profound results.
>> So, it's a major breakthrough. And we can also determine, you know, so for different cognitive faculties, there are patterns that are more optimal for executive function and intention and processing and things like that. But again, these are all temporal, right?
You address it, you get to the optimal level, you see that, then you move on to something else and you just you're kind of stable over that time >> and then you retest.
>> So we could effectively then in the not too distant future actually then test for those different faculties.
>> Yeah. like within our own unique biology like so I could understand okay if my executive function is suboptimal this is how I would address it through nutrition at least >> to this and this is the effective dose >> that's right >> of each of these different nutrients how >> that's right so you can go either way you could do the cognitive testing and each of those domains you you would have some hint to what nutrients you need to have addressed based just on the cognitive testing >> or you could do the bloodbased nutr nutitional risk index and say that these are suboptimal and you know that if you that if you don't address those you're going to end up with that cognitive domain.
>> Yeah.
>> That declines over time.
>> Yeah.
>> Wow.
>> Yeah.
>> That's that's going to be remarkable.
>> Okay. Sounds like that is coming. Right now as a consumer I can't do all of those things to the degree in which I would love to.
>> Yeah. So, let's round off the the episode with some sort of practical takeaways and then I'm going to hit you with some quickfires.
So, [laughter] for someone in their let's do 20s, 50s, 70s.
>> Okay.
>> Okay. What would be your number one piece of advice for each of those age groups to protect against cognitive decline?
Well, I mean what research has shown in terms of brain aging for example is that you have a period of neurode development and then you have a static period and then you have a period of kind of decline just in general. Okay, >> so 20s, 50 and 70s, okay, in the 20s you're still in that neurodedevelopment phase and that peaks around age 30. Then you're in the static phase, right? Late 40s, 50s is where you really start to see kind of the decline. Some people would argue it happens as early as 30.
Okay. And so what we're talking about there, we're talking about building up neural networks and brain volume.
>> And then over time you have brain shrinkage atrophy. Yeah. Okay. In general, certain areas of brain atrophy and shrink faster than others depending on your genetics and the environment that you're exposed to. In Alzheimer's disease, we know it's the hippocampus and temporal temporal parietal loes. You know, certain loes of the brain specifically get the pathology early on >> and we see changes there over time.
>> So, at age 20, you know, would be the ideal window. Ideally, you're starting in early life because we know the biology for Alzheimer's disease is happening decades before. So if you start in midlife at age 50, it's certainly not too late, but certainly you could start earlier, right? I mean, we don't we know that you can make changes. So for example, those that we ran the nutritional risk index, 50 and older in the Framingham study that um the group in the Netherlands ran, you know, that was in people aged 50 and older, right?
>> And they're the ones who improved over the >> That's right.
>> four was four years, I think.
>> Yeah. So we so we see that that in the Framingham study, those that have optimal and all three of those, you see very little change and they don't end up with dementia 20 years later. So at age 70, you know, if you're cognitively intact, that's fantastic, but there's probably an abundance of pathology brewing >> there. Um, however, we've done studies in the oldest old that are exceptionally healthy. um and we see variability there. So I think there's opportunity for nutrition at every stage, but I think ultimately you want as early detection and intervention as possible.
Yeah.
>> Meaning the mold the mold is already set at age 70, right? So there's very little, >> you know, there's inert tissue there.
There's there's stuff that you just can't change, right? When you're young, everything's relatively vibrant, you know, and in middle age, you're somewhere in between depending on your lifestyle and the life that you've lived.
>> Yeah.
>> So, I think there's an opportunity at each stage, but regardless, we need to identify, we need to establish the essential nutrients for cognitive health with aging.
>> Yeah.
>> And we need to establish not only what the nutrients are, but what their optimal levels are >> and what their optimal levels are for you as an individual. That's right. I assume as well.
>> That's right. Yeah.
>> But so my my takeaway from that monologue was um uh that start earlier.
>> Yeah.
>> Would you agree?
>> Yeah.
>> The earlier you can start the better.
>> If the earlier you can start, the better.
>> Yeah. Don't hesitate. Don't hesitate.
Because the scary thing about cognitive decline is that if you ever have experiences where you're just not as sharp or you have a family member, you know, a parent or something uh that develops Alzheimer's or or dementia, >> you begin to realize how quickly it can slip.
>> Yeah. Yeah. It's heartbreaking.
>> And then you don't have the cognitive abilities to address it. Somebody else has to do it for you.
>> Yeah. So if you know at age 20 you're not aware of those things. Age 50 you are. Most people are.
>> How do you how do you create enough urgency before you experience any of these symptoms? That's the thing I think is just incredibly challenging.
>> I think you have to provide people tools to identify risk factors and we just haven't had those. We have not had those that are specific for brain health until until >> Make it easy to do it. make it easier to do it. The bloodbased biomarkers, whether it's the nutritional index, the brain nutrition index, or >> it's these Alzheimer's disease pathology markers, all of those can be measured in the blood. Now, >> so understanding your risk early on and and incorporating a healthy lifestyle, >> you know, the metabolic patterns that we're identifying related to cardiovascular disease and now brain health and neurodeenerative disease are quite similar.
So these disturbances in those metabolic pathways um you know are going to probably help a lot of different organ systems outside of the brain, right?
>> Yeah.
>> Well, look, Jean, this is both exciting and sounds very expensive. [laughter] not not so much the uh the the tests themselves, but to get to a point where we I say we I mean you you guys stand collectively around the science, right?
>> And you know, we work with with a number of um council members on the board who who I know you're you work closely with >> and we're trying to figure out how to >> move that forward. Um, one question I would have in the meantime is, okay, it's clear that two questions actually. It's clear that we know there are some very simple, straightforward, accessible, preventative measures we can take through our nutrition.
>> What would you say is the number one red flag thing to avoid, habit to avoid when it comes to nutrition and your cognitive health? I've got a couple of guesses, but I'm gonna >> Yeah. I mean, I think >> Yeah. The the most detrimental things in our study have been higher levels of trans fatty acids. Yeah.
>> Okay. So, the trans fat, it's got to be out cut out of the diet. I mean, it looks like a neurotoxin and at relatively low levels. So, it's getting into the brain. It's associated with brain atrophy, total brain atrophy, >> and poor cognitive function on almost every domain.
>> Okay?
>> You know, sold. So, that's one. Um, the other thing is these ultra processed foods, right? You know, bread is a is a good example of an ultrarocessed food.
It's hard to go out into nature and find a piece of bread on a tree, right? Or or growing from the ground.
>> Yeah.
>> Um, so those are kind of key things. And then you know part of the reason that we developed this nutritional risk index um and have done such comprehensive profiling and just tried to reduce it down to just three or two or four is because it's easy to measure.
>> You know it's not overwhelming for people and it's relatively inexpensive.
So I think you know optimizing your omega-3 status, your one carbon metabolism status, we measured homocyine, that's only one factor within that pathway. Um and then your vitamin D levels and optimizing all of those simultaneously is something you can do today and it's readily available now.
>> Love.
>> So you could measure those. We know the thresholds. We have the publications already. can't guarantee that it's going to prevent, but you position yourself just like the people in the study.
>> Yeah.
>> That did that had reduced risk.
>> So, if that's enough for you, >> then go for it.
>> Yeah.
>> You know, >> I can tell you within the next year or so, >> we're going to have some profound publications that are really going to shake the field around this this blood-based nutritional phenotyping in the Alzheimer's space.
>> That's gonna be part of that.
>> Yeah.
>> Yeah.
>> I'm genuinely excited.
>> Okay. I'm going to wait. The second part of that question was if you could get the magic number amount of funding right now to actually go ahead and do as much as you need to to get to a point where we can all benefit from from that. Have you is there a number >> in case there's some incredibly generous benefactors watching?
>> I think it depends on how we want to roll that out.
>> Yeah. So, had I not seen the data that I've seen right now on the 150 biomarkers and the patterns that I'm identifying, if we were just with the nutritional risk index version 1.0, Um, I would say, you know, we're depends how you want to roll it out, but if we wanted to roll it out, for example, here, >> I think we could do it for under5 million dollars, something around the, you know, but what we're beginning to see is that Alzheimer's disease, pathology, and vascular pathology in the brain appears to be a metabolically driven disease, which is a from a scientific ific standpoint is a very strong statement, right?
>> Yeah.
>> So, it's going to take time for the scientific society to accept that my peers >> because I haven't published any of this additional data. So, I think there's an opportunity for other versions, version 2.0 and 3.0.
What it will take to develop that um I need help. I need help to figure out how to translate that and how much it's going to how much it's going to cost.
I'm so inundated in the science right now and figuring out the combinations for specific features.
>> Yeah. that how to roll that out and how to reduce it to just the right number that makes it readily available or right I mean literally live right like I mean like tomorrow I'm going to go back to this data and you know so it's happening every week >> we're going to go and unpack that over some blueberries and green tea after this podcast. [laughter] >> Okay.
>> Yeah. Yeah. Let's let's go on to some quick fire questions and you only have 30 seconds tops to answer these.
>> Okay, >> we can do another episode. I think there's so many questions I want to ask you about this topic.
>> Um, but I'm mindful of your time. So, first one is you can pick one food that you have to eat every day for the rest of your life.
What would it be?
>> Dark leafy greens. Anyone specifically?
>> Kale. You choose. Anything that's a dark green leafy.
>> One food that you c that you should not eat every day for the rest of your life.
Just eliminate altogether. What would it be?
>> Frozen fried foods.
>> It's very blanket statement.
>> Yeah.
>> Okay. I'm taking it.
>> Yeah. [laughter] Anything Anything that's that's frozen and fried.
>> Okay.
>> Yeah. So, anything that's in the freezer, >> even if it's frozen fried kale.
>> Even if it's frozen fried kale. I mean, I think Yeah, you still end up with those specific fats and trans fats that really look neurotoxic. So, yeah.
one thing that you see in the press, media, even amongst your peers that you wish you never had to hear again about nutrition and cognition.
One thing you just like stop, please stop talking about this because it's not you got any credence to it.
>> That the effects of diet and nutrition are are very very are small.
I think I think we have not appreciated the magnitude of the effect of nutrition on the brain because we haven't had the tools not because it's not there.
>> Huh.
>> And I think we have the tools now to do that. Can I come back to the food one?
>> Sure.
>> Because I want if this is for the public. I think the other thing is um like soda, >> right? Beverages >> like >> Yeah. Yeah, I mean we we consume so many >> energy drinks. This sugar like look at how much sugar is in some of these drinks and it's in liquid form. And if you're doing that on an empty stomach, which most people are because they're thirsty, >> right? So they think, "Oh, this is this is my water. It's actually an energy drink." So they're low energy, right?
Because they're eating ultrarocessed foods, refined sugars already. Then they get the brain fog and they want an energy drink loaded full of sugar on an empty stomach.
So that that is setting up the terrain.
>> Diet, soft drinks, yes or no?
>> I'd say no.
>> Okay.
>> I say you stay away from soft soft drinks and soda al together.
>> If you weren't >> stick to clear fluids.
>> Okay.
Or coffee.
>> Or coffee. Yeah. Or tea. Yeah.
>> Okay. If you weren't studying nutrition science or the brain or cognition, would there be a what would be your next field that you'd be most excited to to be involved in?
>> Probably a business, probably a startup company, >> not science.
>> Well, science-based.
>> Okay.
>> Yeah. So, like biotech or something along those lines or a theagnostic company, something like that. something where I could move faster, make decisions quicker, and and have the horsepower behind me to to really touch people's lives quicker.
>> Yeah.
>> I thought going to Nestle, from academia, from Oregon >> to Lance, Switzerland, and working with Nestle, I thought I would be able to touch people, the consumer, quicker in that path.
>> I was wrong.
>> There's there's challenges even in that type of environment >> the business as well, >> within a large food and beverage company. just different challenges. Now I'm back and I joined Rudy and you know now we're at Harvard and Mass General.
We're like ground zero for kind of medical research. So let's see. I think you know I think this is a the probably the best environment I could be in from an academic standpoint to move things forward. But >> yeah, >> for the people who listening when we keep saying Rudy, by the way, [laughter] >> it might be worth just explain Rudy Tanzy is um I mean maybe you do it >> uh he's on our council as well.
>> Yeah. So, Professor Rudy Tanzy is um a famous neurogeneticist uh >> and musician >> at Harvard and and is a fine musician.
He plays uh the ham in Oregon and piano.
uh and he um hodge podgees with celebrities uh but but when he goes to work with us he's a brilliant scientist and um is an advocate for lifestyle you know modalities >> and has been at Harvard for over 40 years and um he uh and colleagues identified the the genes that cause not only Huntington's disease but also Alzheimer's disease and has really built a foundation for um the mechanisms that are involved in the pathology over time around the the am what we call the amaloid hypothesis which is really been the dominant hypothesis of Alzheimer's disease for the last 20 20 30 years.
>> Yeah.
>> Which now has FDA approved medications that to address it. So it's come full circle and uh he's also my mentor. Yeah.
>> You know on the >> he's tireless as well. Yeah. has been for so long.
>> Yeah. Yeah. He's a great He's just on a personal level, he's a great great dad.
He's a great husband. He's a great >> colleague and uh >> great go around. We We'll have him on soon.
>> Yeah. Yeah. Have him on soon. Yeah.
Yeah. Have him on soon.
>> Um >> Okay. I'm going back to your quick fire.
>> Okay.
>> You got three more questions.
If you could have any amount of funding to answer any question within your field right now, endless funding, not all the resources you want, and it can't be something you've already mentioned, what question would you answer?
It would be setting up an intervention based on the nutritional phenotyping, >> the blood-based nutritional risk index, and proving with class one evidence that identifying people that have nutritional risk using this blood test and then addressing that nutritional risk strictly on the blood test, meaning you go from suboptimal to optimal and then showing the effect on the Alzheimer's type pathology. I think that would be groundbreaking for the field. That would really prove the point um to peers and and be the cascade for public health.
>> Um >> I think I think there's there's other ways to get about that, you know. So you could do it in a in a more kind of public like pragmatic trial where you know where you do it for example here in the clinic you do it at another clinic >> and you do different things at each clinic and see which one works best. So that would be another one.
>> Um but I think these could be like shortterm trials right this could be something you do for just three months.
>> Yeah it could be a dietary intervention with a new neuroprotective diet. We're working on a review paper that actually is going to look at what we call a neuroprotective diet because not the mind diet or the DASH diet. You know, none of these are perfect and there's gaps. But if we want to if we're thinking about the Olympian brain optimal cognitive performance, we want to take the best from all those diet and create a neuroprotective diet and that should really be the guidelines for brain health.
>> Love that.
>> Yeah, that's coming. that's coming.
>> Okay. Penultimate question.
When you look at how quickly the technology, research, computational biology, quantum comput, all of these things are evolving so quickly now. Do you think when you look forward 30 years from now that we even have to solve for these issues?
>> That's an interesting question.
>> Yeah. I mean I think we've done a lot of datadriven modeling of these biomarkers for example to look at how they interact with one another which ones are kind of interacting and which ones are distinct from one another.
I think AI could have done that in a fraction of the time.
>> So we spend a lot of time and resources doing manual models and so forth to do that. So I think accelerating that you know it if used the right way could accelerate a lot of the churning that we do in the lab. Um I think even in communication you know disseminating the information. I think AI can help with doing that at a large scale and very quickly. Um so those are also things that you know over time we may look back and say god I mean Rudy you know wrote a book about you know decoding darkness like when he was doing genetic work you know 40 years ago the methods were quite different than they are now the amount of time that it takes >> the cost of everything very similar concept um so I think >> you know to answer your question what 30 years It's so hard to tell. Things are moving so fast. If you if you look ahead 30 years, I can hardly imagine. But I can also imagine as a kid being told, you know, by this time, >> you know, by 2010 or by 2020, we're going to have cars that are flying around. Yeah, that's true. And that hasn't happened either. So, I think >> there's there's interference in their progress.
>> Air taxi today. Yesterday, back from JFK.
>> Okay.
>> So, >> so there we go. 2026 2026 missed it by 16 years.
>> Yeah. So I you know it's it it's hard to predict like the trajectory of things over time because there's interference in things. It could be administration, it could be policy, it could be war, you know, war, you know, like things we don't really can't you can't know like these compounding variables.
>> Last one. Where do you see yourself in 50 years time?
>> In 50 years. lay nuance question.
>> Oh, that's a good one. I see myself in a lot of different arenas.
Um, but the first thing that came to mind is is um hiking somewhere in the Alps, maybe in Switzerland.
Um, >> love that.
>> And reviewing, you know, just kind of recalling my work life and, you know, the things that I have with me on my hike are some of the technologies that we've developed. you know, a finger stick for the bloodbased nutritional risk index and then I have a bar in my bag that will address that while I'm hiking.
>> What a time to be alive.
>> Yeah. Or something along those lines.
>> Jean, it's a pleasure and a privilege as always.
>> Yeah, likewise.
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