Gut Health and Alzheimer’s Disease: Exploring the Vital Link with Dr. Jessica Caldwell

Podcast Transcript

Dr. Scott Steele: Butts & Guts, a Cleveland Clinic podcast, exploring your digestive and surgical health from end to end.

Hi again everyone, and welcome to another episode of Butts & Guts. I'm your host, Dr. Scott Steele, colorectal surgery and the president of main campus here at the Cleveland Clinic in beautiful Cleveland, Ohio. And I'm very pleased today to have Dr. Jessica Caldwell, who is the director of the Women's Alzheimer's Movement Prevention and Research Center at Cleveland Clinic. Jessica, thanks for joining us here on Butts & Guts.

Jessica Caldwell: Thanks for having me.

Dr. Scott Steele: So, for all our listeners out there, we always like to start out with a little bit about you, your background, where'd you train, how did it come to the point that you're at the Cleveland Clinic, and I believe you are centered in beautiful Las Vegas Nevada.

Jessica Caldwell: I am. I'm here in Las Vegas where I direct our Alzheimer's Prevention Center and I'm also a neuropsychologist. My background is, I trained in clinical psychology and neuroimaging at the University of Wisconsin, and I interned at Harvard and then did a postdoctoral fellowship in neuroimaging and neuropsychology at Brown. I came here to Las Vegas to follow this position for the opportunities that it included for research. Lots of interesting cohorts and really just a great place to work all around.

Dr. Scott Steele: Oh, fantastic. And as a fellow Badger, it's always good to have fellow Badgers here. So, today we're going to talk a little bit more about the relationship between gut health and brain health. And so to start, can you share a little bit more about your work with Alzheimer's disease or memory problems?

Jessica Caldwell: Sure. My work with Alzheimer's disease is primarily within the realm of sex differences and gender differences. My work focuses on the ways in which women may have some early resilience to disease processes and yet ultimately have vulnerability that causes them to undergo a steeper decline and to have higher rates of Alzheimer's disease overall. So, I look at a lot of risk factors and I also look at biomarkers. The other half of my research focuses on women who are at risk for Alzheimer's disease, and what may set them up at midlife to really have a body and a brain that might be ripe for Alzheimer's disease pathology to form. So, I work with women who have a variety of levels of stress across the menopause transition, and we look at both peripheral inflammation as well as neural activation, when women are trying to learn and remember new things. And our hypothesis is that that stress increase over midlife, combined with that estrogen decrease may be part reason why women have more rates of Alzheimer's disease.

Dr. Scott Steele: So, we hear a lot about cognitive disorders and Alzheimer's, and everything, but on a very basic level as Alzheimer's the same as dementia?

Jessica Caldwell: That is a great question. Alzheimer's disease is just one type of dementia. Dementia is an umbrella term that encompasses a clinical state when people change in cognition enough that they cannot independently do things like pay their bills, manage other types of finances and medications or drive safely. So, dementia is really a clinical term, but the way to get dementia is through a number of different factors, including the most common way, Alzheimer's disease, but also other types of neurodegenerative conditions like Lewy body disease or even things like stroke or head injury that's severe.

Dr. Scott Steele: So, let's circle back a little bit more about your research. You spoke about differences in sex and race, and how Alzheimer's affects that. Can you talk a little bit more about that?

Jessica Caldwell: So, when it comes to Alzheimer's disease, women are two-thirds of the current sufferers of Alzheimer's. And so there's a question about why that is. And decades ago, the answer really would've been a straightforward fact that women on average live longer than men, and so this is why women get Alzheimer's disease more frequently. But now the field has really exploded in terms of other reasons why women are at risk, and my work and others has shown everything from the rates of physical activity, which are lower in women can contribute to Alzheimer's risk, to genetic factors, having a bigger impact on women. For example, the most common risk gene for late onset Alzheimer's is the APOE-4 allele. And this allele, some studies have found if a woman has it, she's up to four times greater the risk compared to a man with that allele to go on to get Alzheimer's disease.

Some of what we're doing in my work now has really focused on what women have going on early that might prevent them from getting a timely diagnosis or might give them some resilience. This is something that we're currently working on in my group. This is led by my postdoctoral fellow, Dr. Levine. And what our group has found is that women have a memory advantage over men on average when it comes to verbal memory. And this advantage actually persists almost into mild cognitive impairment. But at the same time, that advantage can really be a detriment to women because it means that if you test women's memory, even if she has changes in her memory, she may not be picked up by the tests that pick up men pretty well.

Along with that memory advantage, we've also found that there's an advantage or a stability for women in hippocampal volume and cortical thickness, compared to men who have a more linear decline. Ultimately though this doesn't save women from getting the disease, it leads to a steeper slope of decline later. When it comes to race, this is such a good and such a needed question because almost all of the findings in the studies that my group has done in the past and groups across the country have done are based on nationally available cohorts of participants who are almost all non-Hispanic white. So, there's a big question as to whether people who are not non-Hispanic white have these same patterns of risk and resilience.

Dr. Scott Steele: That's fantastic. We hear people say flippantly in some cases they forget something and say, "Oh, I must have Alzheimer's," but what are the signs of Alzheimer's and what should we be looking out for?

Jessica Caldwell: The signs of Alzheimer's disease can be similar in some ways to signs of normal healthy aging. So, for example, one of the most common complaints about normal healthy aging is folks misplace something or folks can't come up with a word when they want it. At the same time, those things are normal. What demarcates normal from maybe not normal is how often those things are happening. So, one time losing your keys, not a big deal, losing them multiple times per day on multiple days, that could be a big deal. And then beyond frequency, the other piece is severity. So, what kinds of things are you forgetting? Is it the name of somebody you met when you were working 20 years ago, or is it the name of a family member? So, finding yourself in a situation where you're noticing memory mistakes or word-finding mistakes frequently or for important items, that's when you could have a concern and really need an evaluation.

Dr. Scott Steele: So, you mentioned some of the genetic things earlier. So two questions. Is it known what is causing Alzheimer's disease? And second, is it hereditary?

Jessica Caldwell: Another great question. Alzheimer's disease, the best that we can say at this point is that it's multifactorial. Alzheimer's disease does have genetic or family history-based contributions. So, folks who have that risk allele, APOE-4 are at greater risk than people without. And people with a family history of Alzheimer's disease are at greater risk than people without. But there's also evidence that shows that up to 40% of current cases of Alzheimer's could have been prevented if we had just known decades back about how impactful lifestyle is. And when I say lifestyle, I mean factors like not smoking or drinking too much, avoiding diabetes and hypertension, and also getting a good education, finishing high school, staying socially active and treating depression. These are all factors that also play into why many people do get Alzheimer's.

Dr. Scott Steele: So, let's circle back to the reason we're here today and it's the gut-brain connection. How does the gut health come into play with regards to Alzheimer's?

Jessica Caldwell: Gut health is one of those things that has been not recognized for quite some time as the important player it is in brain health. At this point, we usually, or the public usually would think about Alzheimer's disease is a brain disease, but we know now that the gut and the brain are interconnected. It's why we talk about things like the gut-brain access. And the way that the gut health comes into play is that in the gut we have what's called the microbiome. It's the collection of all the genomes of what lives in our gut. So, bacteria or viruses or fungi and all that microbiome is important for maintaining a healthy blood-brain barrier. It's important not just for our bodily health, our heart health, but also for our brain function. Many people don't really think about it, but the products of that microbiome include even things like neurotransmitters or signaling molecules. And when we don't have the right complement of those signaling molecules and of those healthy products, we wind up with not only, not very well functioning gut, but also can be at risk for brain changes.

Dr. Scott Steele: So, we see on TV all the time about take this activated, this pill, whatever, it's going to change your microbiome and activated cultures, like I said before. So, can a person change the makeup of their gut microbiome and either add bacteria or remove those bacteria that are associated with Alzheimer's disease? So, what are some ways a person can either improve or affect their microbiome?

Jessica Caldwell: What I like to remind people who ask about the microbiome and supplements when they come into clinic is really that, it's not as simple as saying, for the most part, that there's good things that you can put into the microbiome. There's bad things that you want to take out because most of the time no one prebiotic, which would be something that can help your microbiome grow the right kind of bacteria or a probiotic that really helps them to thrive or post bacteria in the gut make naturally, no one of those things is all good or all bad. So, a single supplement is unlikely to be the answer to totally revamping gut health. At the same time, there are a lot of things that we can do that we know support a more healthy and less inflammatory stomach and gut-based profile.

And those are things like avoiding processed foods and having a diet that has a lot of plant-based dietary fiber, and really thinking about whole foods that support not only your heart health, but also really support the complement of products that your gut would need in order to do what it does for the brain.

Dr. Scott Steele: Truth or myth. Following the DASH or Mediterranean diet may help protect brain from some cognitive decline?

Jessica Caldwell: This is a truth with some caveats. We know that the Mediterranean diet and then the mind diet, which is combining Mediterranean with the DASH diet, which is designed to reduce hypertension or stop hypertension, has the best evidence from a nutritional standpoint, an interventional standpoint on nutrition for supporting brain health for the long run and reducing risks of dementia or cognitive decline. These are not things that can guarantee prevention or risk reduction for Alzheimer's disease. But we know that this type of diet, which emphasizes what we are just talking about, whole foods, healthy fats, leafy greens for that plant-based dietary fiber really do support brain health as well as gut health, as well as heart health. So, this kind of a diet, it really has both those direct effects, gut-mediated effects as well as heart-mediated effects because these diets will also keep your circulatory system healthier.

Dr. Scott Steele: We've talked a lot in the past about just the role between gut health and inflammation in different parts of the body. So, can inflammation also impact the brain?

Jessica Caldwell: Inflammation indeed can impact the brain, especially the type of inflammation that is chronic and unrelenting. This type of inflammation is the type that can really be caused, it has other potential causes, but one is a diet that's pro-inflammatory. So, not having as many of those good prebiotic, probiotic, whole food, dietary fiber-based diet and having a lot of processed foods or red meats, whole fat dairy products, for example, can cause low-level inflammation that's chronic. And when there's chronic inflammation throughout the body that can actually induce brain-based inflammation. And brain-based inflammation is the type that we really would like to avoid to keep our brain healthy as possible.

Dr. Scott Steele: So, let's dig in a little bit more about brain inflammation here. Is it the same type as other inflammation, meaning I got a great workout in the gym and I'm sore and my muscles got swollen all up, is brain inflammation the same type of that?

Jessica Caldwell: It is not exactly the same type. And the key here is that there are good types of inflammation too. So, inflammation after a workout, that's short lived and it actually will lead to better muscle strength. There's also the type of inflammation that might come with having an injury or being ill, and that inflammation has a great purpose. It's attacking something that's not healthy for your body and then it leaves. But chronic inflammation, especially when it's in the brain, it's not something that you will feel, like you feel in your muscles. But what it is something that can really facilitate other processes like building up a pathology that relates to Alzheimer's disease, if it's just chronic. Because it's not then serving the purpose that it would be initiated for typically, which is keeping the brain healthy. It's actually having a paradoxical bad effect on brain cell health.

Dr. Scott Steele: So, let's circle back to something you mentioned earlier, and that's the. Blood-brain barrier. Can you tell us a little bit more about that and how it comes into play here?

Jessica Caldwell: Sure. So, the blood-brain barrier is really designed to keep our central nervous system, our brain healthy and to really protect the neurons, the glia, to make sure that things that are going on in our bloodstream aren't also just having free access to our brain. So, it's a protective barrier. It's not a complete barrier. So, there are certainly still things that can pass from the blood to the brain, things like signaling molecules. However, at times in which there's a very unfavorable profile going on in your blood, and when I say unfavorable, what I mean is if you have an unhealthy microbiome, is one way this could happen, you have products that are not needed for brain health floating around, you have things that are pro-inflammatory, you may actually wind up damaging some of that blood-brain barrier.

And now because you have this complement of unhealthy factors in the blood, you can actually have some of that passage through, whereas many of those should never get to the brain. Now they can. And again, this is a different way that we can think about the gut-brain axis really being a continuous section of health versus the brain sits on one side, the body on another, and they don't interact.

Dr. Scott Steele: So, we talked a little bit more about the gut-brain connection in the pre-phase or hopefully in the preventative phase of Alzheimer's disease. But let's take it from the vantage point that someone has Alzheimer's or any neurodegenerative condition. Would a change in diet help? And if you're a caregiver, are there changes in diet that we should make? Or is it just too late once Alzheimer's or other neurocognitive disorder sets in?

Jessica Caldwell: When someone has Alzheimer's disease or dementia or even mild cognitive impairment, it's not too late to make dietary changes that can support brain health. So, the way that I think about this when I'm talking with patients is that having something unhealthy that places a burden on your brain is only going to facilitate or impact Alzheimer's in a way that Alzheimer's likes. So, if you can take that off, that burden off the brain, off the body by changing diet, that can actually improve things for some time. It's not a cure again, but it's well worth it. The one exception to that that I would say is when we're looking at folks and caregivers who are providing care for someone with quite advanced dementia in the moderate or severe range, what I would say is that caregiving has to focus on whole quality of life and whole health. So there may be some times where there are trade-offs.

If someone has advanced dementia and they really do get quality of life from a treat that might not be the best brain healthy treat, there's still a reason to have that sort of treat in the life. So, I think for caregivers, this is a very difficult position to be in, and it's all about balance.

Dr. Scott Steele: So, are there any advancements on the horizon when it comes to this relationship between gut health and Alzheimer's?

Jessica Caldwell: I think that the advancements that we will see in the coming years are really coming from studies that have taken into account not just the microbiome in terms of what's there, but the microbiome in terms of how different pieces interact with each other and how we might be able to look at almost a profile of different interactive viruses or bacteria or products in a way that helps us to understand how to change things, to reduce Alzheimer's risks or even treat the disease. I think that there's a lot we still don't understand about receptors that are present in gut, and that targeting those with some really effective bottom-up strategies for finding them can really be something that's going to produce big results and suggested treatments in the coming years.

Dr. Scott Steele: So, now it's time for our quick hitter. It's a chance to get to know you a little bit better. First of all, what was your first car?

Jessica Caldwell: My first car was a 1989 Oldsmobile.

Dr. Scott Steele: Fantastic. And what are you, salt or sweet?

Jessica Caldwell: Sweet.

Dr. Scott Steele: Give me a trip that you're looking forward to taking or something on your bucket list.

Jessica Caldwell: I am very much looking forward to going to AASC in a couple of weeks, which is in Philadelphia, a city I really enjoy because they have the best oysters, my favorite kind.

Dr. Scott Steele: Are those cooked or raw?

Jessica Caldwell: Raw.

Dr. Scott Steele: Fantastic. And so finally, if you could go back in time and give yourself a little bit of advice, what advice would you give yourself? Maybe pretend that you're going into college. What would that be?

Jessica Caldwell: I would tell myself to really just be open to different paths your life and career can take. There are so many ways that a person can be happy and they might look very different all within the same person, different possibilities. And that openness, I think is something that's hard to have, at least it was for me at 18.

Dr. Scott Steele: Super. And so give us a final take home message for our listeners about this gut-brain connection.

Jessica Caldwell: The take home that I think is most helpful is really the gut and the brain are not living in separate worlds. These are connected entities, and if you want to best support your brain health, you have to think of your entire body health, and diet and nutrition are very, very critical for that. This is a habit to start early if you can.

Dr. Scott Steele: Fantastic. And so to learn more about the work being done at Cleveland Clinic's Lou Ruvo Center for Brain Health in Las Vegas, or to schedule an appointment, please call 702.483.6000. That's 702.483.6000. You can also visit our website at clevelandclinic.org/nevada. That's clevelandclinic.org/nevada. And for more information on Women's Alzheimer's Movement Prevention and Research Center at Cleveland Clinic, is at clevelandclinic.org/wamprevention. That's clevelandclinic.org/wamprevention. Dr. Caldwell, thanks so much for joining us on Butts & Guts.

Jessica Caldwell: Thanks for having me.

Dr. Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.