Optimal Aging

How to Help Prevent Alzheimer’s: Mayo Clinic’s Latest Research with Dr. Jonathan Graff-Radford

• Jay Croft

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In this episode of the Optimal Aging Podcast, Jay Croft speaks with Dr. Jonathan Graff-Radford, a Mayo Clinic neurologist and co-author of the new edition of the Mayo Clinic Guide to Alzheimer’s and Other Dementias. They discuss how Alzheimer’s disease begins 20 years before symptoms appear, what can be done to prevent or delay it, and what health and fitness professionals working with people over 50 need to know now.

Dr. Radford shares powerful new insights on early detection tools, lifestyle factors like exercise and hearing loss, and how fitness protocols can support cognitive health. You'll also hear how dual-tasking workouts, VO2 max, and neuroplasticity play a role in long-term brain health.

If you serve older adults in health, fitness, or wellness, this is a must-listen.

👤 Guest: Dr. Jonathan Graff-Radford

Bio:
Dr. Jonathan Graff-Radford is a neurologist at the Mayo Clinic and co-author of Mayo Clinic on Alzheimer’s Disease and Other Dementias. His research focuses on early detection, prevention, and treatment of neurodegenerative diseases.

Resources & Links:

🧠 Topics Covered

What Is Alzheimer’s Really?

  • Difference between Alzheimer’s and general dementia
  • Amyloid and tau proteins in the brain

Why Prevention Starts Now

  • Alzheimer’s can start 20 years before symptoms
  • 40–45% of dementia may be preventable

Lifestyle Factors That Matter

  • Exercise, diet, sleep, stress, and social connection
  • Hearing loss as a major (and treatable) risk factor

How Exercise Affects the Brain

  • Growing the hippocampus with aerobic exercise
  • VO2 max and brain resilience studies

The Role of Neuroplasticity

  • How the brain adapts and rewires itself
  • Dual-tasking in fitness for cognitive engagement

New Tools and Treatments

  • Blood tests with 90% accuracy
  • Two new FDA-approved drugs slow progression
  • Early detection through the Ahead & Trailblazer studies

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LinkedIn: https://www.linkedin.com/in/croftjay

🌐 Website: https://primefitcontent.com

📬 Contact: jay@primefitcontent.com

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Speaker 1:

Alzheimer's disease starts in the brain 20 years before the first symptom happens. So by the time you have that first symptom, you already have quite a bit of amyloid and tau pathology in the brain. And so we need to start moving towards earlier detection and earlier treatment. And there's ongoing studies right now. Right now One is called the AHEAD study, the other is called Trailblazer 3, where they're looking at removing the amyloid protein before any symptoms starts, to see if you could prevent or even delay Alzheimer's from happening.

Speaker 2:

Did you know that nearly half of dementia cases might actually be preventable? Did you know that exercise can help parts of your brain grow that are responsible for memory? Or that we now have blood tests that can detect Alzheimer's proteins with over 90% accuracy? Welcome to Optimal Aging the show for fitness, health and well-being professionals who want to grow their businesses with more people over 50. I'm your host, jay Croft, of PrimeFit Content.

Speaker 2:

Today's episode is part two of a two-parter on the Mayo Clinic's newly published, revised edition of its guidebook on Alzheimer's and other dementias. Two weeks ago, I had as my guest one of the co-authors, angela Lundy, and today I have her co-author, dr Jonathan Graff Radford, a Mayo Clinic neurologist, and he dives into the latest science, what it means for all of us, what it means for people over 50, and what fitness professionals and other in these related fields that we're all in need to know to help them stay healthy and strong and provide good care. It's fascinating stuff and I hope you'll go back and listen to the interview with Angela two weeks ago. If you missed that one, here's my talk with Dr Graf Radford. Dr Graf Radford, nice to see you.

Speaker 2:

Thanks so much for joining me today. Thanks for having me today. Yeah, it's my pleasure. It's a really interesting topic, powerful service that you and your colleagues at the Mayo Clinic have provided with your updated book and I'm looking forward to talking about some more. You know, we had your co-author, angela Lundy, on a week or two ago and it's just fascinating and it's such a complex thing. So I appreciate you helping us to understand a little bit more about it, to understand a little bit more about it.

Speaker 1:

Yeah Well, thanks so much. It's delighted to be here.

Speaker 2:

Yeah. So, as you might know, this show is primarily for fitness and health and well-being professionals who work with people who are 50 and over. That seems like a nice sort of overlap with people who might be concerned about this. Developing dementia is one of the great fears that we all have. Before we get into some of the newest research, can you explain for us, for a general audience, in a, you know, fairly short version? We kind of throw these words around a lot dementia and Alzheimer's but they're not synonymous what's the difference and what does it do to our brains? You know we hear about plaque and there's actual things in our brain, but what does it do for? Again, for that sort of general audience?

Speaker 1:

Well, I'm glad you started with that question, because the terminology can be quite confusing. So, to take a step back, as you said, first we'll define dementia. So dementia is anytime someone has a memory and thinking problem that prevents them from performing activities of daily living independently. So what I mean by that is they have trouble paying their bills on their own, they have trouble driving, they may be getting lost while driving, they can't take their medications without supervision, and it doesn't have a specific cause. So it's an umbrella term and there's lots of types of dementia.

Speaker 1:

Alzheimer's disease is a specific subtype of dementia and it refers to when you have the presence of two abnormal proteins in the brain, one being amyloid protein, which is the plaques that you mentioned, and the other being the tau protein, which is neurofibrillary tangles. And so Alzheimer's disease is about 60 to 70 percent of dementia, but it's not all of dementia, even though the two terms are sometimes used synonymously. And I think it's really important because, if we take dementia as a global view, there's been a lot of work recently looking at what we can do to prevent it as a society, and a lot of people estimate that 40, 45% of dementia cases are preventable if we can do lifestyle behavioral changes, and that has a lot to do with health and fitness.

Speaker 2:

Right. So I want to hear about that, some of the new. If it's new, it's new. To me within the last few years, of course, that doesn't mean anything, but how much of it is new? How new is it? And then I want to help people understand that this is real. But we're not talking about oh, happy days are here again and everything's fine, and if you just go do this, you will never get dementia. That's not what we're talking about, right? So can you walk us through that just a little bit?

Speaker 1:

Sure, absolutely so. What's new? I guess I'll start with that.

Speaker 2:

Yeah.

Speaker 1:

Just this year, at the Alzheimer's Association International Conference, they presented a study called the Pointer Study, which was published in JAMA, which is one of our best medical journals, and this was a structured lifestyle intervention study. And so they took two groups of people. One of them they did an in-person detailed intervention that targeted exercise, vascular risk factors like blood pressure, diabetes. They did brain games with them, they gave them education around healthy behaviors and there was a socialization aspect as well. And then the other group, they did education and non-structured intervention and what they found is both groups actually improved cognitively at two years. But the group that had that structured intervention, that was adherent to their exercise, that got their vascular risk factors under control, had more improvement evidence that taking an at-risk group of people and doing a lifestyle intervention even in your 60s and 70s you can improve your cognitive performance, and we'll learn down the road whether this lowered the rates of dementia and cognitive impairment, but the initial study looks quite promising.

Speaker 1:

The second thing we've learned is we always knew that vascular risk factors and physical inactivity were associated with dementia, but I think what's come out more recently is boiling down to the specific lifestyles that can be targeted and understanding them one by one, and so what I mean by that is it's not just late in life. You need to start addressing this. It's really a whole lifespan of intervention. So even things like low education are associated with dementia risk, and that's something we need to start from an early age. And then we talk about vascular risk factors and physical inactivity later in life as well, and then even when we're in our older age. Those are important. But other things come up, like hearing loss, and it turns out that treating hearing loss is a big factor as well. That's being investigated for delaying or preventing dementia. But, as you said, just because you do these doesn't mean you won't get dementia. You're just lowering your risk and if you do have cognitive impairment, you're perhaps making the course of the cognitive decline slower.

Speaker 2:

Why is that? Why is exercise and stress management and a healthy diet and these other healthy habits? Why does this matter? What does it do to our brains that's good for us, and what kind of exercise are we talking about? Do I need to run marathons? Do I need to do, jane Fonda, aerobics, lift heavy weights? What are we talking?

Speaker 1:

Well, I'll tell you a couple of studies that have informed this. One is there was an exercise graded treadmill program where they just walked them on a treadmill with increasing intensity and frequency but they weren't running, it was a walk and the other group, they did a stretching intervention and what they showed was that the group that exercised actually increased the size of the memory center of the brain called the hippocampus, and one of the mechanisms by which they did that is they've showed that their brain derived neurotrophic factor, which is important for brain health. Growth of neurons was higher in the group that did exercise. So there was, it's thought to improve blood flow to the brain and release these important factors that can stimulate growth. And the group that did the stretching intervention, their memory center called the hippocampus decreased by about 1%, and that's normal aging.

Speaker 1:

It wasn't because of Alzheimer's disease, and so I think that's one mechanism by which exercise can specifically sort of make our brain healthier and more resilient to future changes. The second thing we know from Jeff Burns at University of Kansas is that people who have high cardiorespiratory fitness so he measured VO2 max, which is a measure of your fitness level, in people with Alzheimer's disease and he showed that they had larger brains, and they seem to have better preservation of their cognitive performance compared to Alzheimer's patients with a lower amount of cardiorespiratory fitness. And so we're starting to see that one of the mechanisms is sort of, you know, making the structure of your brain more resilient to changes by doing this sort of exercise intervention.

Speaker 2:

You mentioned some things that really stood out to me when I recently started learning more about this. I've worked with a few gyms who are introducing exercise protocols based on dual tasking, so I want to ask you about that, if that can be useful. But that's been my entry into this is trying to understand that, and so the idea is that you can grow your brain, that we can stimulate neurons, your brain, that we can stimulate neurons. I wonder if most people are aware of this kind of thing, because I remember I'm quite a bit older than you and I remember growing up in the 70s they told us, kids, you have a limited number of brain cells, you were born with them and once they're gone, you won't get any new ones. Now, maybe that was just what they told us, so we wouldn't drink alcohol. I don't know, but I don't think so. I think that's kind of a common thought among people my age that once you lose a brain cell, you're never getting another one. Well, you're right. You're absolutely right. That was dogma.

Speaker 1:

That was dogma in our field, for in the field of neuroscience for many, many decades, was that the amount of neurons are fixed, the amount of brain cells are fixed and you need to hold on to them because there's nothing you can do to, you know, increase them. But then we developed new methods to be able to measure new brain cells and found that wasn't true, that you could actually have neurogenesis later in life, and so what you were told was the thinking at the time and for sort of thought to be true until you know there were new advancements. So you're absolutely right and I think that is something we should dispel is that there's no changes in your brain that can happen and you can actually have new brain cells developed.

Speaker 2:

Hey, are you a fitness professional trying to grow your business with people over 50? If you are, then you need to know how to communicate with them, how to market to them and how to get them to trust you with their fitness, well-being and money. We're talking about millions of people who are a little older than the typical market that the fitness industry usually pursues. They have more money, more time and better motivation to make the best long-term fitness consumers you'll find anywhere. If you're not focusing on them, you should be. Prime Fit Content is the only content marketing company designed specifically to help you engage people in this group and to help you distinguish yourself from competitors in your community. It's effective, affordable and super easy to use. Check it out at primefitcontentcom. That's prime, like prime of your life, fitcontentcom. Back to the show. You use the term neuro. I can't pronounce it. Neurogenesis, there's that. I'd like you to define that, and also neuroplasticity, just for the folks out there.

Speaker 1:

Yeah, so neurogenesis is sort of the development of new brain cells that I described with that exercise intervention.

Speaker 1:

But neuroplasticity is really interesting and that happens often.

Speaker 1:

The way we think about it is after you have a brain injury like a stroke, your brain is really amazing in many ways and you can start to see it trying to compensate and rewire itself in some ways to make up for those deficits.

Speaker 1:

And so, for example, if someone has a language problem after a stroke and have trouble speaking, you can start to see the right hemisphere of the brain, which typically doesn't have much to do with language, start to activate more and try and take on some of those tasks of the left hemisphere. And that's an example of neuroplasticity and it's really profound in younger individuals. So there's some cases of younger individuals who, because they have a bad seizure disorder, have to have half of their brains taken out and they have almost normal neurologic development after that and that's the idea that your brain can compensate for an injury or change that happens. And so there's that aspect and it is thought that the more you practice and do things you can improve neuroplasticity. It's not something that just happens, you can actually instigate it and that's different than the growing of the brain cells, which is the neurogenesis that I mentioned.

Speaker 2:

Right, and then the hippocampus. It's fascinating that there are again I'm coming to this from someone who might have never learned the first thing about their brain health that there are parts of our brain that are associated with different functions and some of them are related to memory, and that exercise is good for the development of those parts of the brain. They can grow, they can get bigger, and one of the easiest ways for someone like me to wrap his head around that is exercise sends blood throughout our bodies. We know that it also sends blood up to our brains, right?

Speaker 1:

Exactly right. Yeah, you definitely improve blood flow to the brain with exercise and just something that simple can be very important.

Speaker 2:

Exactly right, yeah, you definitely improve blood flow to the brain with exercise.

Speaker 1:

And just something that simple can be very important. Exactly, and it's not just we mentioned exercise, but there's a really famous study where they looked at London taxi drivers and you know they really this was in the early 2000s and you know if you've been to London you know there's a lot of complex traffic patterns that you have to navigate and they found that these London taxi drivers who spend all day navigating these complex patterns actually have larger right hippocampus which is your visual memory compared to people who aren't taxi cab drivers. And the thought is that may make them resilient to atrophy or shrinkage of the hippocampus later. So it's not just you know cardiovascular exercise that's doing it, but you know other complex activities can also sort of improve brain structure as well and because that visual representations in that right hippocampus you can see that anatomical difference in you know that group as well.

Speaker 2:

So I often hear older folks. My mother used to say this she and her husband they're both have recently passed and not related to dementia, but they liked to do the crossword and play Scrabble because they someone told them that it would help prevent dementia and it was good for their brain health and tell us why. It's a little more complicated than that.

Speaker 1:

Yeah, there's been a lot of epidemiologic studies that have looked at does doing brain games lower your risk of cognitive decline, and they consistently see that people who engage in things like crossword puzzles, scrabble, those sort of interactive Sudoku puzzles have a lower risk of cognitive decline.

Speaker 1:

But there's a major confounding variable in there is that if you're developing cognitive problems, you may stop doing those tasks because of the cognitive problems, and so there's always been. You know, the chicken and egg problem with these cognitive tasks is, you know, are people doing these and they're preventing cognitive decline, or does the cognitive decline start manifesting with decreased interaction with these activities? That being said, there is pretty consistent evidence that you get a mild benefit in things like cognitive speed not necessarily memory, but definitely cognitive speed and processing speed if you do engage in these brain games, if you will, and crossword puzzles being a great example of that. So I do think there probably is a small benefit to doing it, but there is always. That question is how much of it is just related to the fact that people are disengaging as they develop cognitive issues.

Speaker 2:

I mentioned dual tasking a minute ago. What's the thinking on that?

Speaker 1:

Yeah, so you know that's been an exciting area.

Speaker 1:

There's been a lot of interest in dual tasking, not only for neuroplasticity and rehabilitation but also in cognitive decline. So it's sort of simultaneously performing not only a motor task but adding a cognitive task to that and there's all sorts of paradigms that people have tested to do that. And you know, I think we're just starting to scratch the surface on dual tasking. There's a lot of people using it diagnostically. So if you have, you know you may not detect that someone has a cognitive problem, but when you put them through a dual task paradigm then their cognitive problem starts to come out more and that may be an early sign that they're going to be at risk of developing a cognitive problem. And then there's the intervention aspect of dual tasking. Is working on that to help with neuroplasticity to, you know, be an additional way to train the brain. So I think a lot's going to come out in the next five or 10 years and I've just seen a lot of interesting paradigms to test both the diagnostic and the intervention aspect of it.

Speaker 2:

So could there be a real value to gyms investing in learning excuse me, learning about dual tasking and how to design protocols around that and buying equipment that helps them do these sort of interactive? They're better than video games, but they remind me of the Chuck E Cheese things that you take your kids to Chuck E Cheese except they're very high tech and more elaborate than that, but where you're learning patterns and you're moving your body at the same time. Do you see a lot of potential in that for helping with these kinds of disorders?

Speaker 1:

I think it's very forward thinking.

Speaker 1:

I think that's a lot's coming down the pipeline and, I think, one of the questions. So the answer is yes, I think that is a very important area of future and ongoing research and intervention today, and I think what we need to do is understand which are the best paradigms to use. It may be a different paradigm that you would use for diagnosis than to treat, and so we just have to get more and more of these trials done to really figure out which are the best ones to help, and it may be individualized right. It may be that one person would benefit from this type of dual task and another from a different one. So I think the answer is yes, but we need to learn a lot more too.

Speaker 2:

I'd like to ask you about some of the advances in early testing and treatment. Your book talks a lot about those, and I think it's really important to reveal to people some of the things that are new just in the last five years since the previous edition of the Mayo Clinic's book on this.

Speaker 1:

Well, there's a couple of important things to realize. One of the reasons we went 20 years between drugs being approved in Alzheimer's disease is it turns out that a clinical diagnosis alone was not that accurate. In fact, in some of the trials in the mid-2000s, about 25 to 30 percent of people enrolled in an Alzheimer's specific trial didn't have Alzheimer's disease, and so you can imagine how can you end up with a positive trial if you're diluting the effect with all of these people who don't have Alzheimer's disease. So the first thing that came out is the ability to measure the amyloid and tau proteins in the brain that cause Alzheimer's disease during life, not just at autopsy. Initially that was done with PET scans and doing spinal fluid exams, where you had to stick a needle in someone's spinal fluid to measure their amyloid and tau. But what's happened more recently is the blood test technology has gotten so good we can now measure those proteins in the blood pretty accurately, and blood tests are over 90% accurate for detecting the amyloid protein, for example, and so that's really been a game changer for us, because PET scans can only be done at some centers, are expensive and hard to get at scale. Not everyone wants a spinal fluid exam, as you can imagine, but blood tests are easily accessible, so the ability to measure that has been a big improvement for us.

Speaker 1:

And then the other thing to recognize is that Alzheimer's disease starts in the brain 20 years before the first symptom happens. So by the time you have that first symptom, you already have quite a bit of amyloid and tau pathology in the brain, and so we need to start moving towards earlier detection and earlier treatment. And there's ongoing studies right now. One is called the AHEAD study, the other is called Trailblazer 3, where they are looking at removing the amyloid protein before any symptoms starts, to see if you could prevent or even delay Alzheimer's from happening, and those will read out in 2027, 2028. And so we'll have those answers. But it's just been these series of advances in first being able to detect these changes with biomarkers, then making those biomarkers more accessible by making them in the blood, and now testing this paradigm of prevention for them. So I think all of that's happened and so a lot of progress with that early detection, now able to do trials in that space.

Speaker 2:

There have recently been two I think the first two medications approved, two after diagnosis. Is that correct?

Speaker 1:

So we had medications approved for symptomatic treatment. These were the cholinesterase inhibitors and memantine and those sort of masked symptoms. They modestly helped mask symptoms. But yeah, you're right, for 20 years we had no new medications, and then just in the last two years we've had two new medications approved which modify the disease for the first time. And so what I mean by that is they actually slow down the disease progression.

Speaker 1:

And so these two medications both target the amyloid protein, their antibodies. You give it by infusion and they remove the amyloid protein from the brain. You give it by infusion and they remove the amyloid protein from the brain, and by doing so you can slow down the disease once it's started by about 30%. But they're only effective in early Alzheimer's disease, meaning when you have mild symptoms. They're not necessarily effective later and they require infusions and they have important side effects. So because they're removing that amyloid protein, they can develop inflammation in the brain and 12% of people who get these drugs can get inflammation in the brain and they can also cause some microbleeding in the brain, which has led to some hesitation in them being deployed widely. Fortunately, these side effects are often asymptomatic and can be managed by doing MRI scans. But they are an important step in the right direction for us to start to slow down the disease progression with Alzheimer's disease.

Speaker 1:

But what they don't do is they don't stop the disease and they don't reverse it. So, to use sort of a baseball analogy, they're kind of like a single. You know they're important, you know they're, it's necessary we get these new treatments for Alzheimer's disease, but they're not enough. They're not where we need to be moving forward and they're just targeting one aspect of the disease, and it may be we need to target multiple aspects. So you can imagine using these drugs with a lifestyle intervention as well. Maybe you would get a bigger effect. Or using these drugs with another drug that improves vascular brain health, you might get a better outcome. And that's a lot of the discussion in the field of where things might move next.

Speaker 2:

Okay, things might move next. Okay, For ordinary folks out there listening to this, what's the takeaway? Stay informed, read this book, make sure your doctor's up to speed or be sure you're managing your health and lifestyle. Is there anything that we can tell people? And I know this isn't again, I don't want to reduce everything to be so simplistic that it's silly, but is there anything that you can tell people?

Speaker 1:

Two main takeaways. One is a lot of dementia risk is preventable. A lot of dementia risk is preventable, and so you can do things throughout your lifespan to lower your risk of dementia. It may not prevent it it may not, but you do have an ability to do that. These include things like getting all your vascular risk factors under check, so that's blood pressure, diabetes, smoking, avoiding physical inactivity and staying physically active. Those are big ones, and even ones that are emerging, like hearing loss, where, if you're starting to notice hearing loss, don't ignore it. Go ahead and get evaluated and get treated, because that's an emerging risk factor for dementia. So you want to make sure you're covering your bases there.

Speaker 1:

The second thing I think takeaway point is if you are having cognitive problems, don't ignore them, because early diagnosis is important. There are drugs available for treating people with early Alzheimer's disease, but it's also helpful for you to know that you can start to do maybe a more aggressive lifestyle intervention. If you're starting to have cognitive issues, you may be evaluated for these new drugs if it is due to Alzheimer's disease, but there's also things that mimic Alzheimer's disease that are reversible. We sometimes see people who have poorly controlled sleep apnea, having memory problems and treating that can make their memory better. Or B12 deficiency, for example, can cause memory issues, and so getting checked early to make sure you can identify some of these reversible causes as well is another take-home point.

Speaker 2:

Maybe it's just me, maybe it's how other people might be seeing this too, but through all of this it seems that it's important to realize that the brain is a part of the body and that what's good for the rest of the body is good for the brain. Get enough sleep, don't drink too much, don't smoke cigarettes, eat a healthy diet, exercise your body all these things that contribute to good blood pressure, good body weight, good cholesterol levels they all build on each other. You can't pull one apart. So it's not like well, if I just manage my cholesterol, I won't get dementia Not really. I wonder if it's more useful for some people to see it as part of the big picture, or maybe I'm again making it too simple. I don't know.

Speaker 1:

I think you summarized it really well. It's pretty consistent that what's good for the heart is good for the brain, and following those straightforward principles will get you a long way, absolutely.

Speaker 2:

Wonder what people out there listening to this who are in fitness and health and wellbeing fields, what can they do? How can they help their clients? Just stay more informed or, you know, work with the doctors in the area, or what can they do?

Speaker 1:

Well, I think one thing is is, as you're working on their exercise program, for example, I think, talking about the other associated risk factors that are good for the brain as well.

Speaker 1:

So we're going to, you know, get you moving, we're going to get your, and that's going to help your blood pressure, that's going to help your cholesterol, but it's important to get those checked as well because they may need additional support and intervention outside of the exercise and that's going to support your brain health and be important for you over the next couple of decades. So I think being aware of these associations between these risk factors and brain health will be one important thing. But I also think it doesn't hurt when a lot of times, you're with a trainer and they may be talking about some memory concerns or other things and saying you know, I've heard that there are things that can be done if you're having some early cognitive impairment. Go ahead and get evaluated. I've heard about and get evaluated. I've heard about new blood tests, I've heard about new treatments, and I think it makes sense for you to be proactive about it and not wait for something to come up. Go talk to your doctor about it.

Speaker 2:

I also want to encourage them to get this book that you have co-authored the update of the Mayo Clinic's Guide to Dementia and Alzheimer's and it's readable, it's accessible. I'm not a doctor, I don't know anything about any of this, and I'm able to read it and understand it and get a lot out of it. So I will put in the show notes how people can get a copy of that and I'll encourage them to take a look at that.

Speaker 1:

Thank you so much.

Speaker 2:

Doctor, thank you for joining me. This has been really illuminating. I'm very excited by all of this, and maybe that's premature, I don't know, but the key thing is that we have some glimmer of hope. There's something we can do. We're not just sitting ducks. So thank you very much for all your important work.

Speaker 1:

Thanks for having me.

Speaker 2:

Have a good day.

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