← The Neuro Experience
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- [00:00]
Louise Nicola
People don't understand that this is the only disease that robs you of who you are. And every single memory that you have, every memory that you are building in your 20s and 30s and 40s can be taken away from you just like that because of the choices that you choose to make. Today's guest is Dr. Kellyanne Niotis, the.
- [00:16]
Podcast Host/Advertiser
First fellowship trained preventative neurologist.
- [00:19]
Louise Nicola
Currently, we have around 50 million people worldwide that have this disease. That number is going to triple by the year 2050. In my opinion, it's going to be the collapse of our health healthcare system.
- [00:30]
Dr. Kellyanne Niotis
We're about to hit a really big epidemic of neurodegenerative diseases.
- [00:35]
Podcast Host/Advertiser
In this episode, we uncover how Alzheimer's and other neurodegenerative diseases can be detected early and even prevented.
- [00:44]
Louise Nicola
What would you determine? High risk.
- [00:45]
Dr. Kellyanne Niotis
Everyone with the brain is at risk. If you die with Alzheimer's disease pathology in your brain, but you lived a perfectly happy, cognitively normal life, did you have Alzheimer's disease?
- [00:56]
Louise Nicola
No.
- [00:57]
Podcast Host/Advertiser
Expect a deep dive into genetics, hormones, biomarkers, diet, and the future of brain health.
- [01:03]
Dr. Kellyanne Niotis
Having biomarker positivity does not mean that you'll get Alzheimer's disease. You have to have symptoms and why.
- [01:11]
Louise Nicola
Prevention may be the most powerful tool that we have. If you were to tell the world, here are my. My top 10 things to prevent Alzheimer's disease. What are they?
- [01:20]
Dr. Kellyanne Niotis
I love this. Okay, put me on the spot.
- [01:22]
Louise Nicola
I'm Louise Nicola, and this is the neuroexperience. You're a neurologist? Board certified, but you are focusing on preventive neurology. What does that mean?
- [01:33]
Dr. Kellyanne Niotis
Yeah. Well, first of all, thank you so much for having me today. I am beyond excited to sit here and talk to you about this. I know we share this drive to get education out there and really, really make a dent in the onset and prevention of various neurodegenerative diseases, not just Alzheimer's, which I hope we'll get to talk about. But the whole field of preventive neurology is brand new, and it's analogous to the idea of preventive cardiology, which is identifying people at risk who do not have obvious clinical symptoms and applying early interventions to reduce the risk of developing various neurological conditions. In my particular niche, it's neurodegenerative diseases. So that includes things like Alzheimer's, Parkinson's, and Lewy body dementia.
- [02:24]
Louise Nicola
So why don't we do just a broad overview of all of this? Because we always hear the word dementia, and I think people still have a hard time differentiating between dementia and Alzheimer's disease and all of the other dementias. So why don't we just do a very quick overview of everything?
- [02:40]
Dr. Kellyanne Niotis
You know, we like to say dementia is this umbrella term. It encompasses neurodegenerative forms of disease, but also other forms of dementia, which can be from depression, for example, which is pseudo dementia. In our world, we' focus on sort of neurodegenerative diseases. We can kind of break that down into Alzheimer's, which is really the most common form of dementia. Then we have vascular dementia, Lewy Body dementia, and then a lot more atypical forms of dementia, like frontotemporal dementia, Parkinson's disease, dementia, and it keeps going, more and more rare from there.
- [03:18]
Louise Nicola
Do you believe that dementia is just for older people?
- [03:24]
Dr. Kellyanne Niotis
Absolutely not. We know that the pathological changes of these diseases occur years before the first obvious symptom. And in the research that I'm doing through the Institute for Neurodegenerative Diseases, we really are testing various biomarkers of neurodegenerative diseases in at risk patients, not just those who are impacted. And we've found pathological changes in people's 30s, which is shocking to think about, but it's real and it's present. And I view these people as prime candidates for prevention because I truly, truly believe that a large majority of these cases are preventable if we just know how to find them and know what interventions to apply at the right time.
- [04:08]
Louise Nicola
We're going to focus a lot in this episode on Alzheimer's disease, because you said that's the most common out of all of the dementias. You know, what exactly is Alzheimer's disease from a pathological view?
- [04:20]
Dr. Kellyanne Niotis
There's a lot of debate now about how we define Alzheimer's disease. And this has really come to the forefront of a lot of experts in the field, because now, like I alluded to, we have blood based biomarkers where we can identify disease pathology in people who don't have symptoms. So how do we define Alzheimer's disease and how do we diagnose it? It's a clinical, pathological diagnosis. So. So you have to not only have pathological changes present, such as amyloid proteins, tau proteins present in the brain, identified, whether in the spinal fluid or the blood, but you also have to have the clinical symptoms for the disease, because if you die with Alzheimer's disease, pathology in your brain, but you lived a perfectly happy, cognitively normal life. Did you have Alzheimer's disease? No. And we theoretically can say that we prevented it. In that case, the pathological changes don't define the disease. It's the clinical symptoms.
- [05:28]
Louise Nicola
So it's both based on symptoms like. And you do this through imaging.
- [05:32]
Dr. Kellyanne Niotis
You do symptoms, but also imaging or biomarkers.
- [05:37]
Louise Nicola
Yeah. It's interesting because it used to be called the amyloid cascade hypothesis. Right. This is when we used to demonize amyloid. We're not still demonizing amyloid right now.
- [05:47]
Dr. Kellyanne Niotis
It really shouldn't be demonized. And I get a lot of messages and emails from a lot of people who, you know, rightfully feel that because of bad science and bad players in the field, that all the research that shows this association between Alzheimer's disease and amyloid is just fake and not real. And at the end of the day, we do recognize that amyloid is a pathological feature of Alzheimer's disease. Whether or not it's causative of Alzheimer's disease is a different discussion. I do believe these toxic proteins are involved and do trigger their own bits of neurodegeneration. But whether they're the exact cause, it's very debated. I personally think there's a lot of upstream changes that happen that trigger these changes. But regardless, amyloid and tau proteins are involved in all Alzheimer's disease. But only a third of people that have Alzheimer's disease follow that classic amyloid cascade, where it goes amyloid, tau, neurodegeneration, only a third.
- [06:55]
Louise Nicola
You know, we can both do a bit of a neuroanatomy lesson here, because I do think it's a network insufficiency, and especially when we're talking about amyloid, because that lives outside of the neurons in the CSF, different to tau, but we've got around 100 billion. And feel free to interject. 100 billion neurons, approximately. And they all have around 10 to 15,000 connections. And the way that they connect with each other is through these things, I call them legs, these little dendrites. And when this is how we communicate, how we think, and this is how neurotransmitters are going from one neuron to the next. But what ends up happening with amyloid is when the amyloid builds up, it messes with the communication between neuron to neuron, and that's where we start seeing those symptoms occur. We start seeing whether it's in the hippocampus, where I believe it's the first part to go during these diseases, depending on which one it is, you start to get memory loss. But then it's other symptoms too. Right.
- [07:53]
Dr. Kellyanne Niotis
You hit that. I mean, there's so many other effects that amyloid Triggers like we mentioned, activation of our neuroimmune cells or our glia cells, which causes a whole cascade of inflammation, which doesn't do well for memory and thinking and personality and so forth.
- [08:14]
Louise Nicola
So let's start from the start, because I'll tell you where I sit with the disease. I sit at the. The aspect of it's driven through inflammation. I know that that's just such an easy thing to say. It's so easy because inflammation, innate immune system, Innate immune system triggers amyloid, amyloid there as a protective molecule, if you will. And then it doesn't get cleared out and we just keep going through that cycle. It's like a. My broad overview. Is that wrong in saying that?
- [08:43]
Dr. Kellyanne Niotis
I mean, you know, there's no right or wrong because we don't truly know the answer. I personally believe with all neurodegenerative diseases that there's really unlikely one pathway that explains the disease in everyone. I think different people may follow different pathways to disease, which is why I'm in the business of personalized and precision medicine. I think in some people, their brains have cholesterol homeostasis issues, which ultimately will trigger an inflammatory process. But other people might have metabolic derangements in their brain or energy utilization issues in their brain that are triggering that inflammatory process. So, like, I like to say that everyone's on their own unique path to this disease, and, and there may be multiple paths involved. And we have to think about this disease as really a multifactorial disease that involves different drugs, different treatments, lifestyle interventions that target different pathways of it.
- [09:48]
Louise Nicola
It's interesting because it's not a disease of genetics alone.
- [09:53]
Dr. Kellyanne Niotis
No, absolutely not.
- [09:54]
Louise Nicola
Which is still where we're getting a bit wrong when it comes to the general population understanding the disease. Oh, I'm not going to get Alzheimer's. I don't have the disease. I don't have the gene. And people still don't understand genetic mutations, risk genes. So let's start from that, because I want to approach this from a person who has no idea. And maybe they come to you and they're like, listen, I. My grandmother died of Alzheimer's, by the way. Who knows if she did or not? Because, I mean, that's another thing. Who knows what's actually on the death certificate? Was it frontotemporal? Was it Parkinson's? Was it dementia? Like, we don't know. More often than not, it's not Alzheimer's, it's not Alzheimer's, it's just dementia. Yes, it's like dementia with delirium it's like, okay, what does that mean?
- [10:36]
Dr. Kellyanne Niotis
Right.
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Louise Nicola
And that upsets me because it was the same with my grandmother. I'm trying to figure out, was it, you know, where did it say it was cancer? And it just says on the death certificate pancreatic cancer. But when we were there, I clearly remember it was something, a different diagnosis. So that's a whole new ballgame. But let's start with somebody comes to you and they're just scared of getting Alzheimer's. What do you do?
- [11:00]
Dr. Kellyanne Niotis
To start with, I do love starting with the family history because I think it provides so many rich clues about the person who's sitting right in front of you. That's, you know, the best way to get a look into what that person's risk could be. I like to ask really detailed questions about their family history. I don't ever accept that the diagnosis was dementia. I ask specifically about what symptoms they had, what age it started, what other medical conditions they had, how their life was, were they a stressed out person, did they live a pretty healthy lifestyle, did they have a fall? Like, how did the process and disease start? And again, what symptoms did they have? That really, really helps not only understand who in their family is at risk, how many family members are at risk, how high risk is the person sitting in front of you, but also what likely other processes might contribute to the person who's sitting in front of you's risk.
- [12:03]
Louise Nicola
If it's not a disease that's purely driven by genes, how important is the family history?
- [12:11]
Dr. Kellyanne Niotis
I still think that it's very important. I think that it's not purely driven by genes. That's true, but it is polygenic. And I think that there are the family history where whether or not they have one of the known high risk genes or a collection of smaller at risk genes that put them at risk, it still provides us a lot of information. We know that people with a first degree family member, whether or not they have a known gene, are at a higher risk of disease. So family history is really important.
- [12:45]
Louise Nicola
Yeah. And what's sad now, especially in the public system, is a patient history is taken within five minutes.
- [12:52]
Dr. Kellyanne Niotis
I know.
- [12:53]
Louise Nicola
So, okay, so we do family history and we find out, you know, maybe they don't know too much about how maybe their grandmother or their mother or father were affected, only if it was very prominent and they were the primary caretakers of that individual. But you go through family history and then what else would you start doing? Would you start doing genetic screening?
- [13:13]
Dr. Kellyanne Niotis
I don't think genetics are for Everyone. I am a huge proponent of certain genetic testing, specifically APOE testing. But I also really acknowledge and have a careful discussion with the person sitting in front of me about the risks and benefits of it, because there are emotional risks associated with it. There are long term risks in terms of eligibility for disability insurance and life insurance. So there are serious considerations. But it in some cases so changes the recommendations and what I think about a person's risk and how I would change the medications they're on, the supplements they're on, based on what I see in their genes.
- [14:05]
Louise Nicola
The APOE4 gene is really, it's a gene that I think people are so scared of, you know, and there's genetic counseling for those who are testing positive. I've met so many APOE 4 carriers. Obviously I've rarely met an E4, E4. I am envious for the E2, E3s. I'm a 3 3.
- [14:28]
Dr. Kellyanne Niotis
I'm a 33 2.
- [14:29]
Louise Nicola
Oh, really? Yeah. So we're. It's a null. It doesn't mean we've raised our risk or it's increased our risk. Why don't we just go through exactly what the APOE4 gene is?
- [14:39]
Dr. Kellyanne Niotis
Yeah. And I also want to know because it is a little bit unclear about how protective Apoe 2 is.
- [14:47]
Louise Nicola
Don't.
- [14:50]
Dr. Kellyanne Niotis
So, you know, we in general, on large population based studies, it does seem like people with the APOE2 gene are at a lower risk of Alzheimer's disease. They can and still do get it, but when they get it, it tends to be at a later age. People have better cognitive performance later in life. But there are some, there's a growing body of literature that actually shows they're at risk for some other diseases. One, frontotemporal dementia. And two is actually cerebral amyloid angiopathy, which is related to Alzheimer's disease. Instead of the Alzheimer's plaques being built up in the actual brain tissue themselves, they're building up in the blood vessels of the brain and leading to blood vessel friability, small bleeding in the brain, big hemorrhagic strokes if people have high blood pressure. So it's not all great to have APOE 2. It can still increase your risk for certain diseases. So that's just, just to be, just to be thorough there.
- [15:53]
Louise Nicola
Yeah.
- [15:54]
Dr. Kellyanne Niotis
But yeah, let's talk about APOE 4. Do you want to?
- [15:56]
Louise Nicola
Let's. Yeah, give me a full masterclass on it.
- [15:58]
Dr. Kellyanne Niotis
Okay. So, I mean, I have a love for lipids. I'm going to give out a shout out to Tom Day Spring. He's an amazing mentor of mine, and, you know, I feel fortunate enough to be able to pick his brain and have learned really alongside him so much. So. ApoE4, or ApoE, is a lipoprotein. It's involved in lipid transport throughout the body. It's made in the liver, but centrally, it's also made in the brain, specifically made in the astrocytes of the brain. And in the brain, it's involved in a lot of different processes. It is one of the primary lipid transport proteins in the brain. It helps shuttle lipids and fatty acids between astrocytes and neurons. Neurons actually aren't the main producers of cholesterol in the brain. It's the astrocytes. And the neurons are very dependent on these supporting cells to deliver cholesterol that they need for synthesizing neurotransmitters, maintaining the health of their dendrites or their little fingers, like you said, their cell membranes, communic cells, and so forth. So people with APOE4 have less efficient lipid transport between these two types of brain cells. And lipids can get stuck in places that we don't want them to, like inside the astrocytes. And when Dr. Alzheimer's back in the day described Alzheimer's disease, he described these lipid droplets on pathology inside the brain cells of patients, inside the astrocytes of patients. And could it have been. And we'll never know, but could it have been? He was really seeing this in our E4 patients who really had those lipids causing cytotoxicity or causing injury or death to the brain cells because they were getting trapped in there. So that's one pathway.
- [17:54]
Louise Nicola
Why were they getting trapped in there?
- [17:56]
Dr. Kellyanne Niotis
Because apoe4 can't transport the lipids. They have deficient lipid clearance and deficient lipid transport out of the cells. Okay, that's one pathway. ApoE4 may contribute to neurodegenerative diseases. We know that ApoE4 carri a lot. Or a robust neuroinflammatory response. It evolved as a protective gene. People who had APOE 4 were at lower risk for certain infections, diarrhea, illnesses, things that we don't die of nowadays. So it's not necessarily an evolutionary advantage today, but back in the day, it was. And these people mount very robust immune responses to infections, which may be another key contributor to these people may be more predisposed to the harmful effects of certain viruses. And we're seeing that more and more as. As some science unfolds.
- [18:55]
Podcast Host/Advertiser
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- [20:11]
Louise Nicola
Our energy, our mood, our fertility, our.
- [20:15]
Podcast Host/Advertiser
Metabolism, how our brain ages, our sleep. The list goes on. I know when mine feel out of balance because everything feels off and I'm quite cranky. That's why I started using Glow by Beam. It's a once daily hormone balancing blend with 18 active ingredients, pure electrolytes that support metabolism, immune health, collagen production and more. I literally add just one scoop into water and it becomes the easiest, most delicious part of my routine. I've noticed better skin and it doesn't taste bad, it actually tastes good. My favorite flavor is the blue raspberry. Over 40,000 women trust Glo and now it's your turn. So visit shopbeam.comtne and use code TNE for up to 35% off. Shopbeam.comtne Everyone has two genes, one from.
- [21:11]
Louise Nicola
Two alloys, one from mum, one from dad. So can you just describe what it means if you're an E4E4, E4, E2, E4.
- [21:18]
Dr. Kellyanne Niotis
Yeah, let's like go really basic. So everyone has two copies of the APOE4 gene as you are. APOE gene as you said, you can have a 2, a 3, a 4 and you get one copy from your mom, one copy from your dad. And us scientists and doctors call that a genotype. So the most common genotype, as you said, is APOE 33. More than half the population has that. It doesn't increase our risk for Alzheimer's or Lewy Body Dementia directly. But of course understand that people with this genotype still can and do get these diseases. I think they probably just follow a different pathway than people with the higher risk genes. And then you can have a combination of any of these 2, 3, 4 together. So you could have an APOE 2. 3 and APOE 2. 4 and APOE 3. 4 and an APOE 4. 4. I'm always really hesitant to give exact numbers by which ApoE4 increases someone's risk.
- [22:18]
Louise Nicola
Because right now, currently, from what I'm hearing is the general consensus is if you've got one copy, it raises your risk three times.
- [22:25]
Dr. Kellyanne Niotis
You know, if you look at these big population based studies, it's somewhere between two and fourfold.
- [22:30]
Louise Nicola
Okay, so three times is probably approximately. Right.
- [22:33]
Dr. Kellyanne Niotis
And then four, four, somewhere between eight and twelve fold. And what does that mean exactly? Like, what does that actually mean?
- [22:41]
Louise Nicola
Did you read that study which. I was actually traumatized when I actually spoke about it openly on a podcast. It was this study where they saw. I think it was. Was it in Africa? I won't exactly say exactly where it was, but it was a large population of individuals there have the E4 E4.
- [23:02]
Dr. Kellyanne Niotis
Oh, yeah, I know the study you're talking about, the large pop. The one that said that essentially E4, E4 was deterministic, a genetically deterministic form of Alzheimer's disease.
- [23:14]
Louise Nicola
Because what they found was that just because they were E4E4 carriers, raising their risk of getting the disease 10 to 12 fold, but they had a very low population actually getting Alzheimer's disease even with the E4 E4.
- [23:27]
Dr. Kellyanne Niotis
This goes back to what we were speaking about in the very, very beginning. Alzheimer's disease is a clinical, pathological diagnosis. And the harm of using just biomarker positivity to diagnose Alzheimer's disease is. Is real. That caused so much undue stress and worry. I see a lot of people who have the APOE4.4 genotype and some of them have completely normal biomarkers in their 60s and 70s. It's a biased population, a biased pool that that study really came from. And again, having biomarker positivity does not mean that you'll get Alzheimer's disease. You have to have symptoms.
- [24:15]
Louise Nicola
It sounds the same as perimenopause just because your hormones are phenomenal and on track. But if you've got the symptoms, then that's a different story. It seems like the same thing.
- [24:26]
Dr. Kellyanne Niotis
Similar.
- [24:27]
Louise Nicola
Now there's also other genes involved in this disease we've got the amyloid precursor protein presenilin 1, presinellin 2, which we can talk about, but there's also another 70 genes as well.
- [24:40]
Dr. Kellyanne Niotis
Yeah.
- [24:40]
Louise Nicola
That we never hear about or speak about.
- [24:42]
Dr. Kellyanne Niotis
Trem1 is one of them. Clue.
- [24:45]
Louise Nicola
Oh, clue. Yeah. Interesting.
- [24:47]
Dr. Kellyanne Niotis
There's so many. And again, aside from these very deterministic genes like app that you mentioned, these diseases are multi or polygenic. There are so many genes that increase or decrease our risk and there are probably synergistic effects between the genes that you know, just because you have APOE4, you might have inherited, for example, a Clotho gene that protected your APOE4.
- [25:12]
Louise Nicola
I want that. You've said the word biomarker quite a few times and I know that you have a strong interest in biomarkers. Why don't we talk about what that is and what you're discovering right now?
- [25:23]
Dr. Kellyanne Niotis
This is an area that's exploded. It's become possible to get these tests yourself. The issue is that these biomarkers haven't been robustly studied in at risk populations.
- [25:39]
Louise Nicola
Specifically for Alzheimer's disease.
- [25:41]
Dr. Kellyanne Niotis
Specifically for Alzheimer's disease. So what we know about some of these FDA approved biomarkers, for example, the new one that came out or the new one that was recently FDA cleared was the Lumipulse G P Tau 217 over Amyloid Beta 42 ratio. That again is for a specific age range of people, people over 55 with cognitive symptoms. And the same is true for other commercially available biomarkers like Preciviti AD2 test which again tests Amyloid Beta 4240 and P Tau 217. These are for people over the age of 55 with cognitive symptoms. Because we know, and what we're really interested in studying at IND is what are the normative values or ranges of these biomarkers in different groups of people, different ages, different biological sexes, because they are different. And in people who don't have clinical symptoms, what's normal in that group of people? It hasn't been formally established. So that's an area that needs a lot more research. And unless you are working with a clinician who really understands these biomarkers, I don't recommend people getting them tested on their own because it has, and I've seen it firsthand, led to so much undue stress and anxiety, not to mention that, you know, the way that these biomarkers are handled and processed really impacts the results. For example, amyloid proteins are so, so sensitive. If they're Left out at room temperature, the amyloid will get stuck to the sides of the test tubes and you'll get false results.
- [27:33]
Louise Nicola
So how did that even get FDA cleared?
- [27:35]
Dr. Kellyanne Niotis
It just has to be handled really properly and put on dry ice or negative 80 and sent really appropriately. But you know, if you're mass doing a lot of these things, you can imagine, especially in the summer, how things can kind of not the quality can suffer.
- [27:53]
Louise Nicola
So you're saying that people at high risk, what would you determine? High risk?
- [27:57]
Dr. Kellyanne Niotis
If you have a high risk gene and a significant family history, meaning more than one family member with the disease, you're at high risk. But everyone's at risk for these diseases. We're at risk despite having APOE 33. The APOE 33. Everyone with the brain is at risk.
- [28:18]
Louise Nicola
Especially those who live in Manhattan.
- [28:20]
Dr. Kellyanne Niotis
Absolutely. People who live in Manhattan are at risk. Pollution, stress, all the things.
- [28:25]
Louise Nicola
So these biomarkers actually can be exactly the same. I read, as getting a PET scan.
- [28:32]
Dr. Kellyanne Niotis
In someone who is cognitively impaired, they have a high correlation to CSF or PET positivity of biomarkers in people who are cognitively impaired.
- [28:46]
Louise Nicola
There's so much discussion around why two thirds of Alzheimer's disease patients are female. And there's two branches, as I see. One is the because of menopause and estrogen. Then there's the other one. Well, women just live longer.
- [29:01]
Dr. Kellyanne Niotis
Yeah.
- [29:02]
Louise Nicola
And two thirds of caregivers are female as well. So females are really taking a hit right now with this disease. Can we just talk first of all about the gender differences?
- [29:14]
Dr. Kellyanne Niotis
Another area that I'm really, really fascinated by. I think biological sex impacts these diseases in ways that we have yet to really learn. On the other hand, we know men are at one and a half times higher risk of Parkinson's disease and why. And when we say the hormone thing, which is. Well, we know estrogen is protective for the brain, so women are at a lower risk for Parkinson's because they have estrogen. But then we also say women are higher risk of Alzheimer's disease because, you.
- [29:47]
Louise Nicola
Know, estrogen fall off and estrogen is protective against Parkinson's.
- [29:51]
Dr. Kellyanne Niotis
It is, yes. We do understand that estrogen is neuroprotective.
- [29:55]
Louise Nicola
Yes.
- [29:57]
Dr. Kellyanne Niotis
The idea behind, you know, this hormonal shift in this opportune window when women seem to be more predisposed is really that perimenopausal period where there's rapid fluctuations in female sex hormones that put women disproportionately more at risk. We know that there are estrogen receptors in the brain, and the brain will upregulate these estrogen receptors during that time to truly try to soak up as much estrogen from the blood as possible. But you know, there's so many other changes that happen during that midlife period for women that happen alongside menopause. Body composition changes, changes in their lipid panels, changes in their metabolic health. All downstream impacts of are all things that can contribute to Alzheimer's disease risk later in life. Poor sleep, increasing anxiety, mood changes, all things that really impact risk.
- [30:57]
Louise Nicola
So would you say that having bioidentical hormones would be protective against this disease?
- [31:03]
Dr. Kellyanne Niotis
I in general am a proponent of using hormone replacement therapy. Of course, you know, the right answer is that we need really robust studies. Right? Of course that's the right answer and I would love that. I would love if we had really robust studies using bioidentical hormones, but we don't. So what do we do now to help our patients? I think using hormones and the right person at the right time is beneficial. Not only short term for their cognition, not only do they start to sleep better, not only do they start to feel.
- [31:36]
Louise Nicola
Cognitively feel like a human again.
- [31:37]
Dr. Kellyanne Niotis
Yeah, More cognitively sharp. But in our own research in women who we've started on hormone replacement therapy, we're actually seeing really promising biomarker changes in those women who we put on hormones. So I think used at the right dose, in the right woman at the right time, there's a potential there.
- [31:57]
Louise Nicola
Yeah, I read a really great study and I actually tracked it because I'm going to do a single episode on it. It was on testosterone, something that we don't speak about because it's all about females estrogen. But we have more testosterone than estrogen, especially in our 20s and 30s. And I'm telling you, I'm telling you, people are going to turn around in 20 years and we're going to know we're going to have robust studies that proves that testosterone has a correlation, low testosterone to dementia and Alzheimer's disease. And people are going to be like.
- [32:28]
Dr. Kellyanne Niotis
Ah, Louisa was right, progesterone too. We don't talk about progesterone.
- [32:32]
Louise Nicola
No, we just talk about estrogen, we.
- [32:33]
Dr. Kellyanne Niotis
Just talk about estrogen. But like, like progesterone is the mood hormone, like give some women progesterone and it's like anti anxiety, calming, soothing. Of course it's involved in how our brain works. Of course it is, but we just don't know as much about it. And that's why I said the right answer is we need more Studies?
- [32:49]
Louise Nicola
Yeah. How do you feel about testosterone?
- [32:51]
Dr. Kellyanne Niotis
I don't personally use testosterone in my clinical practice, although I've seen a lot of women come to me on testosterone who have reported major cognitive benefits on it. Also benefits in terms of their body composition and their libido. The studies that we do have are all in men, and we see short term cognitive improvements in men. We see correlations in men between higher levels of testosterone and lower risk of Alzheimer's disease. But whether or not that's causative, we don't really know.
- [33:25]
Louise Nicola
You've said the word body composition, and it reminds me of the risk factors for dementia or Alzheimer's disease. I've got to really start, you know, differentiating between the two. What do you think about those? Do you think they should be updated?
- [33:37]
Dr. Kellyanne Niotis
I'm just grateful that we put together this list finally and that more people are recognizing that 45% of dementia may be preventable. I absolutely think that that's an underestimate. Like, I truly, truly believe that a large majority of dementia cases are preventable. I wouldn't be doing this if I didn't. So I'm one just grateful that that message is getting out there from a really credible medical journal and people are believing it because when we first started.
- [34:07]
Louise Nicola
Down this pathway, smoking and obesity, go figure.
- [34:10]
Dr. Kellyanne Niotis
Yeah. Nobody, like everyone is like, what are you talking about? These diseases aren't preventable. I mean, the work that I was doing was dismissed as fluff and I was, I was told by a colleague that all I do is tell people to eat blueberries. I was like, yeah, okay.
- [34:25]
Louise Nicola
I don't know if you're talking about the study that I read on blueberries, but let me tell you, it was funded by the blueberry industry. Yes. So that makes it an epigenetic disease for sure.
- [34:36]
Dr. Kellyanne Niotis
And, you know, going back to APOE 4, we do know that APOE 4 carrier, APOE 4 carriers are more susceptible or more vulnerable to the harmful effects of some of these risk factors, like diabetes, like dyslipidemia, like obesity. So it's like they're predisposed and then put them in the wrong environment. And those genes really do the bad, do all the bad things for them.
- [35:01]
Louise Nicola
Okay, so I've been getting a lot of hate on Instagram lately because I have spoken highly about, especially people with the APOE4 gene, that a lot of the data points towards having an LDL Less than 70 is ideal for long term brain health and staving off Alzheimer's disease. How do you feel about that statement?
- [35:23]
Dr. Kellyanne Niotis
This is such an interesting area first and foremost, and I would love again to have a perfect answer for this. So LDL C apob. I'm sure you've talked about the this distinction plenty of times. APOB is probably better because it's telling us more about the atherogenic potential of LDL particles. But. But you know, neurologists and the people or the Lancet Commission is pulling on a lot of neurology journals and neurologists check LDL C. So all of these studies are based on what we've done in medical practice for years and years and years. So we just don't have as much data about apob. That's a long story, but important distinction. Even though it's a better metric, what is the ideal target for somebody? In my opinion, again, it comes down to personalized care and precision medicine. Are we seeing that somebody has a lot of evidence of microvascular changes on their brain, mri? In that case, we probably should be pretty aggressive in how we lower apob. Ldl, treat their insulin resistance, treat their blood pressure, do they have changes or coronary calcium plaque building up like that? All changes how, what our target should be, what is the ideal target? I think you're probably right. An APOB less than 70, less than 70 is probably right. But again, we don't really know what the ideal answer is there. And lower might be better, but again, we just don't know.
- [36:58]
Louise Nicola
But that then brings into question statins, which I'm all for because we can see the correlation. If we're going to reduce LDL C and APOB with a statin, then that's going to be a positive thing for sure.
- [37:12]
Dr. Kellyanne Niotis
And again, no one size fits all. What should somebody be on? It really depends on their risk factors, their biology. In general, statins have shown that they lower risk for dementia. And we do know that elevated LDL C is a modifiable risk factor for dementia. So we got to address it without a doubt. And how we do that, what medication we do that with is we're still studying it. I wish I can say there'll be really robust data that says statins are the best thing to use, or Zetia is the best thing to use. I don't think we'll ever have those studies. And again, it's so individualized, in my opinion.
- [37:53]
Louise Nicola
Why do I get messages from people saying, hey, Louisa, my mom was told by her doctor that she needed to take a statin. But I heard that raises your risk of getting a diagnosis, getting dementia. I'm like, here's a study, here's a study, here's a study that shows that it lowers the risk. I even put it out on Instagram and I'm getting so much hate for it.
- [38:12]
Dr. Kellyanne Niotis
I get a lot of hate for it too.
- [38:14]
Louise Nicola
And I don't know how many times I have to tell people that serum cholesterol is not getting into the brain and crossing the blood brain barrier. I will take it to my grave. And do you know how many people actually will write on an Instagram post saying this girl needs help. We all know that we need high cholesterol for the brain.
- [38:33]
Dr. Kellyanne Niotis
I know.
- [38:33]
Louise Nicola
I'm like, what does that mean?
- [38:35]
Dr. Kellyanne Niotis
I know. It's really a lot of misinformation and there's so much fear around statin use. It is mind blowing. Really mind blowing.
- [38:48]
Louise Nicola
I mean there's fear I just about all medications really isn't it around 5% or maybe lower of perimenopausal? Menopausal women are actually on hrt.
- [38:57]
Dr. Kellyanne Niotis
Yeah.
- [38:58]
Louise Nicola
So it's still a very. We've still got fear. That's whi. Which we don't need to bring into this right now. But there's fear around this and if you push it or advocate for it, you are supporting Big Pharma.
- [39:09]
Dr. Kellyanne Niotis
It has for me. I joke about this and said it before, but I'm an equal opportunist. I'm down for anything that's gonna work. Medications, supplements, lifestyle changes, anything. You have to be if you wanna prevent the disease. You have to be open to all of those.
- [39:22]
Louise Nicola
Especially if you're at risk.
- [39:23]
Dr. Kellyanne Niotis
Especially if you're at risk. And you know, without a doubt, we know that elevated LDL C, elevated apob is a risk factor and we know we have to treat it. There are the studies on statin use are. Unfortunately, we don't have the perfect study for it. I use statins in my patients at the appropriate dose in the right person. And I don't believe that they're associated with an increased risk of dementia. Do some people have side effects from statins? Absolutely. There are side effects and risks with every single medication. And that's why we just have to be thoughtful on what we use in a given person.
- [40:03]
Louise Nicola
Well, a good physician will be monitoring progress even over a four week period. How do you feel? Do we increase, do we decrease? Do we eliminate completely?
- [40:12]
Dr. Kellyanne Niotis
Absolutely. And I think you're right that there's a lot of confusion about LDL C. Our brain needs LDL C. It's not crossing through the blood brain barrier. It's really not it's impacting risk of dementia because it's impacting blood flow to the brain by getting caught in our blood vessels that feed our brain and depriving our brain of oxygen and nutrients and blood and all those things that we need. So it. It has nothing to do. Our brain is not using LDL cholesterol for its important neuronal processes. It's just not. And unfortunately, we don't have great ways to measure brain cholesterol, like, without doing a spinal tap. There are some great surrogate market markers that we can talk about to kind of get a sense of it, but. But LDL C is not one of them.
- [40:59]
Louise Nicola
Yeah. So I sent my mom to get a carotid ultrasound and a CAC scan five days ago because I noticed that she had a high Lp. So what are you seeing with high LPs? Because that's a genetic risk factor for CVD and one that you can't bring down with medication.
- [41:19]
Dr. Kellyanne Niotis
Not yet, but soon. So, again, the studies here are mixed. And I gave a talk to an LPA LP support group and a lot of questions about whether LP increases risk for Alzheimer's disease and other forms of dementia. And the studies are really not clear on this. Some studies say it does. There are plenty of studies that say it don't. That it doesn't. Sorry, let's repeat that. Some studies say that it does. There are plenty of studies that say that it doesn't. Some studies say that it's the combination of APOE 4 with LP that are. That makes LP problematic. We don't really know, and that's the truth.
- [42:02]
Louise Nicola
But the best course of action would be to aggressively monitor APOB if you have a high lp, because that just makes sense. Right?
- [42:10]
Dr. Kellyanne Niotis
And there's some evidence that may suggest that aspirin may have a beneficial effect in these people. And there'll be new drugs on the.
- [42:19]
Louise Nicola
Market because of vasodilator.
- [42:22]
Dr. Kellyanne Niotis
Mild blood thinning effect. And again, there'll be more drugs in the future to address lp. And I'm really looking forward to that because I truly believe what's good for the heart is good for the brain.
- [42:35]
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Louise Nicola
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Louise Nicola
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- [44:40]
Louise Nicola
So the brain is the most vascular, rich organ in the entire body, comprising of, we've got capillaries, we've got arteries, we've got veins, and those little capillaries are one cell thick. They're tiny. But they do their work in supplying the brain with blood, which is nutrients and oxygen. Now, they are the first things to go during high blood pressure and hypertension, which is why hypertension is a risk factor.
- [45:05]
Dr. Kellyanne Niotis
Absolutely.
- [45:06]
Louise Nicola
Are you aggressively monitoring that? Because the Sprint trial really changed my life.
- [45:11]
Dr. Kellyanne Niotis
Yes, absolutely. So optimal blood pressure control is of the utmost importance. But we talk a lot about high blood pressure. So I just want to mention low blood pressure.
- [45:22]
Louise Nicola
Talk to me. Because I'm low. I don't know whether it's, I don't know if I'm fit enough to have this much of a low blood pressure.
- [45:28]
Dr. Kellyanne Niotis
You know, there's a lot of people are like, there's no such thing as having too low blood pressure. Well, actually we do know that at least in older adults, adults over the age of 65, having too low of a blood pressure is actually a risk for dementia. So we have to just be really careful at about personalizing our blood pressure targets for the right person at the right time in their life. We don't want to be dropping someone who's 70 years old, blood pressure down, because they may have evidence of small vessel disease where that perfusion pressure is really needed to allow adequate blood flow to the brain. So, you know, what is the ideal blood pressure for most healthy young to middle aged adults? It's probably less than 120 over 80. I also have relatively low blood pressure.
- [46:16]
Louise Nicola
What is relatively low?
- [46:18]
Dr. Kellyanne Niotis
90S over 70s.
- [46:20]
Louise Nicola
Oh, okay. I'm better. Better than that.
- [46:22]
Dr. Kellyanne Niotis
There you go.
- [46:23]
Louise Nicola
I'm, I'm like, I'm. Sometimes I'm like one of 102, 103.
- [46:27]
Dr. Kellyanne Niotis
Yeah. So you know, that's my whole life. And that's probably been a whole life thing for you. And women tend to, you know, have lower blood pressure in early, in midlife. I don't think that that's a risk per se.
- [46:43]
Louise Nicola
You're talking much lower.
- [46:44]
Dr. Kellyanne Niotis
I'm talking about aggressively reducing people's blood pressure where they hypoperfused.
- [46:50]
Louise Nicola
Yeah. My father in 2019 had a stroke. It was a right parietal lobe, in fact. And you know, my mum measures his blood pressure every day. So I was just home in Australia, like, can you show me how you're doing it? God love him. It's the automatic one and just whack it on. However, my dad's like walking around, he's crossing his legs, he's like, you know, I said we have to have a masterclass because I think that's another. Like, this is a very sensitive.
- [47:18]
Dr. Kellyanne Niotis
Oh, yeah, yeah.
- [47:19]
Louise Nicola
And I'm used to doing it manual fashion, way manually. Yeah.
- [47:22]
Dr. Kellyanne Niotis
You know, you have to be sitting down, you have to have no exercise right before. Relax, like wake up, sit down, sit quietly for two, three, five minutes, put it on your left hand, roll up your sleeve, rest your arm at about breast level and make sure it's matched up to the middle of your arm. So there's a little, they should, there should be a little marking where you're matching it up and you want to do it very consistently. Legs uncrossed, back against the back of the chair. Go to the bathroom beforehand. Like, don't. You know, my dad does this too. He goes, and he's out there and he's mowing the lawn. And then he comes back, he's like, my blood pressure is 145. I'm like, well, you just. We're all flustered outside in the backyard. Like, you gotta chill out a little bit before you check it. So it's a really common thing.
- [48:15]
Louise Nicola
I'm mad right now, and I don't know if you share this. And it comes down to the medicalization of this disease. We have FDA approved IV therapies for Alzheimer's disease patients. The New England Journal of Medicine showed the results of. Was it lecanemab?
- [48:35]
Dr. Kellyanne Niotis
Yep.
- [48:35]
Louise Nicola
Showing that it causes microhemorrhages and brain bleeds and some brain tissue atrophy and some death in some patients when taking the iv, that upsets me. And it's also an expensive IV that I think needs to be administered. How many times a year if you were to.
- [48:51]
Dr. Kellyanne Niotis
It depends on what protocol you're using. Monthly, twice a month.
- [48:55]
Louise Nicola
The reason I bring this up is because I want to have a detailed conversation about what's happening right now in medicine and this disease. And we can go into ICD10 codes and why preventative neurology is not really recognized as a specialty.
- [49:11]
Dr. Kellyanne Niotis
I'll just put one thought out there about anti amyloid drugs, because I think there's a lot of fears about them and people who, you know, understandably feel like they don't do a whole lot for the disease. I think the truth is that we haven't studied them in the best way possible, meaning the timing of administration and the right person to administer them in. Is this going to be a holy grail? No. Like I said, we're going to need multiple drugs with multiple different targets to really, really get at this disease. But it is progress and it is an option for people who are affected by these diseases. And I hope that it'll be an option for people who are in the much, much earlier stages of disease if we can identify them early enough. But that goes into your second question, which is what's going on with preventive neurology? Why doesn't this exist? Why can't I see a neurologist at a hospital that's going to take any of these complaints seriously?
- [50:25]
Louise Nicola
Complaints such as what? Loss of memory?
- [50:28]
Dr. Kellyanne Niotis
No. Complaints such as I'm worried that I might get Alzheimer's disease. That that's a legitimate complaint. I have risk factors, and I want a doctor to think about me and my risk profile.
- [50:40]
Louise Nicola
But how many people are actually doing that?
- [50:42]
Dr. Kellyanne Niotis
How many people are practicing?
- [50:44]
Louise Nicola
No, how many people? How many people. Patients are actually going to the doctors going to their. Whether it's their primary or a neurologist saying, I'm concerned a lot.
- [50:53]
Dr. Kellyanne Niotis
I get messages from doctors asking me like I'm seeing. We're getting waves of patients who are interested in this. When I was at while Cornell managing the Alzheimer's prevention clinic there, our waiting list was five years long. I have a waiting list now.
- [51:10]
Louise Nicola
I mean, not for at risk, just people concerned.
- [51:13]
Dr. Kellyanne Niotis
Yeah. For people who are concerned. Which is at risk. At risk. People with family histories, known genetic risk factors. But there's no perfect place for them to go in our current medical setting. And I am so passionate about talking about this because it really has to change and I really hope I can be a part of that movement leading to change. It is going to require so much of so many different people. First and foremost, we don't have formal training programs where neurologists can learn and even primary care doctors can learn how to take care of their patients, keeping their brain in mind. We don't have fellowship programs for preventive neurology. My mission and why I was brought back to Weill Cornell was really to help establish a formal training program. We established it with me and then it went, you know, and hit the floor and that was it. I was the only fellow. So we need training programs. That's the first step so doctors feel comfortable providing this level of care. But alongside that, we also need appropriate billing codes for preventive neurology. Right now, there's no way for your insurance to cover family history of Alzheimer's disease or APOE 4. That's not a diagnosis that reimburses hospitals and medical practices in any meaningful way. So until we have payers buying in and believing in the power of prevention, it's going to be a long time before this field is fully, fully formed. But by talking about it, by building training programs, we're allowing for more research dedicated specifically to this area to provide the evidence to hopefully take to these payers to show them, like, look, this stuff works. There's lots that we can be doing for our patients. Please start covering this type of care.
- [53:17]
Louise Nicola
Yeah. And it's sad and scary because it's an expensive disease that not a lot of people can really afford.
- [53:25]
Dr. Kellyanne Niotis
It's beyond expensive. And you know, as a physician, what's so frustrating to me is that whether you're on Blue Cross Blue Shield today or Aetna today or whatever it is, at some point someone is going to be paying for that cost of that patient that has Alzheimer's disease. And if we all collectively agreed to pay into prevention early on, then we would all benefit later on, and it wouldn't be like, you know, I don't want to pay for this because this person's gonna, in 30 years, not going to be on my plan. They'll be on someone else's plan. They'll be someone else's problem. But it's not someone else's problem. Like, this is our collective problem in America that we have to address together.
- [54:10]
Louise Nicola
Why do you think America isn't giving preventative neurology an opportunity and these at risk patients?
- [54:18]
Dr. Kellyanne Niotis
I think it's just been slow. Like I said, I'm grateful for the Lancet Commission. That really was one of these prime publications that show that a large majority or a large portion of dementia cases are preventable. Their first publication only came out in 2017. And to put this into perspective, preventive cardiology, the early studies were in the 1950s and 1960s, and it wasn't until the late 1980s, 1990s, that the field of preventive cardiology really started to grow. It took 30 years. You know, it's going to take a long time. And fortunately, now with social media and the Internet, I think we can get messages out there quicker. And I'm hopeful that it won't take that long. But the American Academy of Neurology says that they hope it exists and is a budding, flourishing field by 2050.
- [55:23]
Louise Nicola
Oh, wonderful. Right when there's going to be 150 million people with the disease.
- [55:28]
Dr. Kellyanne Niotis
That's. Yeah, I know. And 25 years from now, like, we can start today.
- [55:33]
Louise Nicola
Why do you think Alzheimer's disease rates are going up and why it's going to triple by the year 2050?
- [55:38]
Dr. Kellyanne Niotis
Yeah, it's a great question. I mean, right now we know we have an aging population. The baby boomers in particular are aging. And we know that 300, like you mentioned, 50 million people. There are 300 million people living with early evidence of Alzheimer's disease, meaning they have the pathological proteins in their blood, in their brain, but are walking around unknown.
- [56:05]
Louise Nicola
Well, they could be asymptomatic.
- [56:07]
Dr. Kellyanne Niotis
Exactly. That's what I'm. They're 100% unknowingly. We're about to hit a really big epidemic of neurodegenerative diseases. And we can pontificate on all of the different reasons for why that might be true. Is it because there's increased environmental toxic exposures and pollution? Like. Sure, that could be it. Like I said, the aging population, like a longstanding American diet, which was pretty poor, lack of physical Activity and a sedentary life, which is true for a lot of Americans.
- [56:47]
Louise Nicola
And we're also getting more stressed, and that's a huge risk factor. What's your take on people calling Alzheimer's type 3 diabetes?
- [56:56]
Dr. Kellyanne Niotis
I'm a little hesitant to say that, but it is true that at least in some instances of Alzheimer's disease, that there are metabolic changes that happen in the brain, the utilization of glucose, changes in the brain. I mean, it's one of the ways we can diagnose the disease by using PET scans that show us metabolism of glucose in different brain regions. So without a doubt, there is evidence to support changes in glucose utilization, energy utilization in the brain. Whether or not that's type 3 diabetes, I don't know if I would necessarily. So much more nuanced than that label it as that.
- [57:39]
Louise Nicola
But yes, Alzheimer's disease is such a long progression and I think to actually be diagnosed, you really like it end stage there. Because before that you've got. I don't even know what, how you classify the stages, but you've got subjective cognitive impairment, mild cognitive impairment, which is a pre dementia state. And then it's like early onset, Right. It's not exactly. If you come with these symptoms and you've got some pathology, you don't have the disease. Most likely that Progression takes around 20 or 30 years, right?
- [58:11]
Dr. Kellyanne Niotis
Yep.
- [58:12]
Louise Nicola
What are some of the changes somebody would experience along that process?
- [58:18]
Dr. Kellyanne Niotis
Yeah, and the earliest changes can be really subtle and difficult to clearly point to a brain issue. So things like loss of sense of smell, for example, you know, that, that can happen 30 years before the onset of Alzheimer's, Parkinson's, Lewy Body.
- [58:38]
Louise Nicola
That could be anything.
- [58:39]
Dr. Kellyanne Niotis
But that can be anything. It could, you know, be related to chronic sinus issues or head trauma or Covid. You know, there are so many things that can cause our sense of smell to be affected. So, you know, it's hard to point to mood changes, changes in sleep. Insomnia, for example, is a big one. Those, again, are really hard for people to point to. Like, is this a problem related to my brain or is this just hormones?
- [59:11]
Louise Nicola
That's like forgetting somebody's name or something. Like, you get a brain, you know, you like. Often when I'm on a podcast, I'm like, oh, I want to say something. What was I going to say? It's like, doesn't mean I've got early onset. It could mean stress or lack of focus.
- [59:25]
Dr. Kellyanne Niotis
Yep. And then, you know, some subtle cognitive changes can happen to people. And those subtle cognitive changes can be Difficult for even neurologists to really differentiate between. Like you mentioned, that word being at the tip of your tongue. That's really common as we get older. It's a part of normal cognitive aging. But word finding difficulty is also a problem in Alzheimer's disease.
- [59:53]
Louise Nicola
Language processing.
- [59:54]
Dr. Kellyanne Niotis
Yes, language. Language processing. Losing track of where they were in a conversation. Those are issues that also happen in Alzheimer's disease, but they can also happen to people who aren't paying attention. So it can be really, really difficult to know the difference and to really differentiate the difference between these subtle or subjective cognitive complaints and normal cognitive aging versus just a busy lifestyle in attention. Information overload.
- [60:24]
Louise Nicola
We touched on earlier amyloid. Right. But we forgot to even talk about tau.
- [60:30]
Dr. Kellyanne Niotis
Yes.
- [60:30]
Louise Nicola
Because tau is. It lives in the microtubule space of the axon, which is within the neuron itself. How is tau activated and built up, and what is it?
- [60:41]
Dr. Kellyanne Niotis
So tau is another neurotoxic protein, and feel free to jump in on any of your expertise here, but it's another neurotoxic protein that forms tangles in the brain. It becomes phosphorylated, which is a really fancy way of saying it is more predisposed to clump together into tangles and go crazy. And go crazy. And again, just like amyloid, trigger an inflammatory process, which, as you alluded to with amyloid, does the same things. Interferes with synapses, can become cytotoxic, can lead to cell death. Once these proteins are stuck inside the.
- [61:22]
Louise Nicola
Cells, well, it's the collapse there of the axon itself, which, as a neurophysiologist, I've done a lot of EMGs, and we're usually measuring something called conduction velocity, mainly in Ms. Patients. And that's what I tell people. Like conduction veloc. You know, the way that we think.
- [61:39]
Dr. Kellyanne Niotis
Yes.
- [61:40]
Louise Nicola
And. And move. And that's where it ends up collapsing.
- [61:42]
Dr. Kellyanne Niotis
Yes, exactly.
- [61:43]
Louise Nicola
To trigger amyloid, it's triggered via the innate immune system. Correct.
- [61:48]
Dr. Kellyanne Niotis
That's a really loaded question. What causes amyloid? I don't know. We don't know. The immune system's involved.
- [61:57]
Louise Nicola
The innate immune system is. Okay, let's just pencil that there. The innate immune system is involved. We can't just clear it via the glymphatic system. There's gotta be more to it than that, because that means that it'll just put you to sleep. Okay.
- [62:10]
Dr. Kellyanne Niotis
Wash your brain.
- [62:11]
Louise Nicola
You wash your brain. And I know it's so easy to say, you know, during sleep, we, you know, during N3 stage deep sleep, we go through this washing process. It's so much more nuanced than that. So what? Let's just say someone's building up this amyloid from God knows what. Now that you've just informed me and broken my heart, what clears it?
- [62:31]
Dr. Kellyanne Niotis
Our microglia, our supporting brain cells help clear amyloid plaques from the brain.
- [62:36]
Louise Nicola
Is that the only way?
- [62:38]
Dr. Kellyanne Niotis
I mean, as you said, the glymphatic system does clear it. What else then?
- [62:42]
Louise Nicola
Sleep is really important. Sleep is really important because it's only really. It's activated as well elsewhere the glymphatic system, not just during sleep.
- [62:50]
Dr. Kellyanne Niotis
You know, there was this super interesting study that came out recently from a group in Korea that was. It was done in mice, so take it with a grain of salt. But, you know, they recently discovered that that glymphatic clearance also happens through the skin and that there are certain glymphatic massages that can help clear toxic proteins and improve cognitive function in mice. And they actually really demonstrated this beautiful. What I thought was amazing about the study was that they actually demonstrated this beautiful pathway of glymph clearance from the face going out. Like you could see it on the video. It was really amazing. And I met with the researchers because they want to develop some facial stimulation device to help. But it's so simple. You can just do a simple face massage on these key areas where our lymph nodes are on our face to kind of like help support lymphatic clearance. And will that ever end up. Up helping someone's cognition? They said that you have to do it three times a day for 10 minutes. It's, you know, 30 minutes a day. Add that onto your exercise, your good eating, your good sleep, your sauna, whatever else you're doing for your brain. It's a commitment. But I do think the interesting thing about that is, you know, we're still learning. We still have so much to learn about this disease. And when we talk about, like, the glymphatic system, we had no idea that the glymphatic system was attached to our skin and there was a clearance mechanism that way.
- [64:34]
Louise Nicola
How about tau? Can you eliminate tau?
- [64:36]
Dr. Kellyanne Niotis
The thought is, yes, the same by the same pathways.
- [64:40]
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Louise Nicola
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- [65:45]
Louise Nicola
That's EcoHealth.com neuro one of the biggest controversies I face in this area is diet. Diet. We've got the mind diet and we've got this bandwagon of two players, both two neurologists. Neurologist A is saying the neuron works better with when it's fueled by ketones. So being on a ketogenic diet is much better for healthy neurons and the brain. Then we've got neurologist B who is saying no. The mind diet clearly showed that a diet rich in plants and vegetables is the best for your brain. And so it's so ideological because you've got, you know, neurologists B really going hard on only having plants and demonizing red meat. Then you've got neurologist A saying no. Get you into a ketogenic state. I'm Switzerland.
- [66:42]
Dr. Kellyanne Niotis
I'm Switzerland too. I again, there's no one size fits all. I've seen people go on the ketogenic diet and have caused pretty significant problems with inflammatory profiles, cholesterol panels. I've seen the opposite also happen that they say they feel cognitively clearer, they feel like they're processing much quicker, their attention is better, their learning is better. Again, there's no one size fits all for nutrition and diet. I think think the ketogenic diet is extremely difficult to live by. It's extremely restrictive and I'm all in the business of making this as accessible and as easy for people as possible. So my preference is always to support a more Mediterranean mind based diet because I think it's just really sustainable for most people. And you know, it's even hard to get people to commit to one thing like eating more fatty fish. That can be a lift for people.
- [67:48]
Louise Nicola
I think the plant based neurologists believe in vascular health because that's what it would come down to, right? If you want to maintain a healthy brain, you want to maintain good arterial health. And in order to do that, you have to really aggressively lower APOB and LDL C, therefore don't have any food with saturated fats in it. That's what, that's my understanding of why people push this narrative so much.
- [68:15]
Dr. Kellyanne Niotis
Well, the Mediterranean mind based diet also has things like fatty fish, extra virgin olive oil, all things that have other brain benefits that you may. Those two things you won't miss out on, but the antioxidants that are rich in berries. Like you'd miss out on that on the ketogenic diet. And there's just so much nuance when it comes to choosing the right diet for the right person. But I'm definitely not on the side of making someone's life really difficult. I want this to be as easy as possible and as sustainable as possible. Because when we're talking about prevention, this is something that you're gonna have to do for a long time, if not the rest of your life. No one's gonna be perfect on their diet. And you can't be and you shouldn't be because you should live your life.
- [69:06]
Louise Nicola
You've gotta be happy. Happiness is actually, actually a big predictor. So then what are you prescribing blueberries every day? Because I know that blueberries are great for the brain antioxidants.
- [69:18]
Dr. Kellyanne Niotis
So I mean, have I used a ketogenic diet in the right person? I have experimented with that. But in general, for most people, I do recommend a Mediterranean mind based diet. So two to three servings of a fatty fish a week. If you don't like fatty fish, supplementation might be necessary for you. Lots of berries, lots of leafy greens, limited refined carbohydrates like pastas, and you know, sugary things like corn syrup. Try to eliminate processed foods. Dairy is okay. People are always like, should I be eating dairy? That's such a complicated topic. But trying to avoid as much as you said forms of saturated fat, but also recognizing that you're a human that has to live your life. And, and this shouldn't be a thing that you feel resentment towards. It should be something that you feel happy and excited to do in your practice.
- [70:14]
Louise Nicola
Let's just say you identify a patient who is either at risk, let's just say at risk, moderately high, or whatever it might be. Do you take them through a set of cognitive tests?
- [70:26]
Dr. Kellyanne Niotis
I think there's a lot of benefit in doing baseline cognitive screenings on people, especially when with vetted tools that we have clear established norms on Are you using an EEG? I don't use EEGs, but I've explored that and, and have looked into various EEGs. I think EEGs, there's a lot of noise in EEGs. And I'll, I'll remind myself of my time reading EEGs and training and it's like watching paint dry. I think that for the purposes that I recommend, I would suggest doing some sort of cognitive screening to get a baseline. And the reason is what I mentioned before. Subtle changes to your cognition are really difficult to detect, especially in people who are extremely high functioning, who are working professionals, who have multiple degrees, for example. They can mask cognitive changes very, very easily. And they may present to a doctor and say, hey, I'm having word finding difficulty and they're going to ace the test or ace the test, score normal. And the doctor's going to be like, you're completely fine, like you're, you're scored completely normal. But it doesn't mean there wasn't a change from where they were at age 35, for example. So I think there's a lot of value in establishing a baseline that could be followed longitudinally and can serve as an important metric to look back towards.
- [72:00]
Louise Nicola
But you can also do cranial nerve testing as well. We mentioned offline, we were talking about olfactory nerve and we're talking about maybe blindfolding patients. I don't know if you would do this. And making them smell different things and seeing if they can pick up on the smell, like cinnamon.
- [72:16]
Dr. Kellyanne Niotis
We do a sniff test with these guys. A sniff test?
- [72:18]
Louise Nicola
Yes.
- [72:19]
Dr. Kellyanne Niotis
We don't blindfold them. It's already like a perfect vetted test that someone has created. Thankfully, it's a scratch and sniff test. And, and I find that really, really informative. It's not informative as a standalone test. Right. But in the picture of everything that you collect on someone, it does help inform risk.
- [72:39]
Louise Nicola
And correct me if I'm wrong, one of the latest introductions into the risk factors was hearing loss.
- [72:45]
Dr. Kellyanne Niotis
Lots of debates on why this could be. And it, again, probably is multifactorial. One thought is the brain is very use it or lose it. It needs lots of inputs, lots of sensory inputs to maintain neuroplasticity. And where hearing is processed is our temporal lobes. That happens to be the area impacted by Alzheimer's disease. So hearing is really that sensory input that part of the brain needs to stay healthy, happy, active. But also, if you lose your sense of hearing, you're more likely to be socially isolated, which is another risk factor for Alzheimer's. Disease, you're more likely to have mood derangements.
- [73:27]
Louise Nicola
I thought it was because of the temporal lobes.
- [73:30]
Dr. Kellyanne Niotis
Exactly. Like the area, the stimulation, for sure. But vision loss was recently added to this list.
- [73:37]
Louise Nicola
Okay, so that's the latest one.
- [73:38]
Dr. Kellyanne Niotis
That's the latest one. And I believed that that was a risk factor for a long time before it was added. Vision is so, so important, but that feeds back into a different region of the brain, our parietal occipital lobes. And again, there's that idea of it's use it or lose it. But again, if you are not able to see, you are also less socially engaged. And I think all of these risk factors do go hand in hand, and there are downstream or indirect consequences of all of them, and they're related.
- [74:12]
Louise Nicola
Do you think that we don't pay enough attention to the cerebellum? Oh, yes, I know. Me too.
- [74:17]
Dr. Kellyanne Niotis
The cerebellum is so cool.
- [74:19]
Louise Nicola
I know. I mean, do a, you know, one leg. You know, just stand there on one leg. See how long you can go for a minute. Why do you think we're not paying attention to the cerebellum?
- [74:28]
Dr. Kellyanne Niotis
Because, you know, we view the cerebellum as the separate part, as like the basement of the brain, like its own little brain. And the cerebellum is extremely complicated. Oh, yeah. I remember, you know, studying all the cerebellar pathways and neuroanatomy and becoming very easily overwhelmed. We don't even fully understand all that the cerebellum does, but it's involved with. With motor planning and motor learning. It's involved in our accuracy, our balance, our coordination, posture, posture. It's where when people drink alcohol, the alcohol is hitting. It's directly toxic to our cerebellum. I really think it's important, and I know we're not really focused on this for this discussion, but I think it's really important in Parkinson's disease because that tremor is your brain cerebellum not being able to find a target. We do see kinetic tremors and Parkinson's disease. A. I think more and more will be. More attention will be given to the cerebellum, but it's one of my favorite parts of the brain.
- [75:29]
Louise Nicola
I know, right? Me too. I got that in common as well. Before we move on to prevention as a whole for everybody, I'd be remiss if we didn't bring up exercise, which is where I publish most of my data, looking at really, the effects on exercise as a whole, but mainly resistance training on mild cognitive impairment. What's going on there?
- [75:50]
Dr. Kellyanne Niotis
Yeah, well, maybe you tell me because you're the expert here, but I think exercise is probably the biggest lever that we can all pull for protecting our brains and for our health collectively. The most important thing, in my opinion, for people who are sedentary is just to get up and start moving. Even like getting up and walking can be incredibly powerful for these people. But, you know, of course there are better ways to optimize exercise. I really do think a combination of resistance and aerobic training is necessary. I think they give different benefits to the brain. But the truth is the optimal dose duration, intensity isn't fully understood.
- [76:33]
Louise Nicola
Well, I did a meta analysis and really found after reading like 2000 papers and going blind from doing it, that it comes down to around two days a week, which you don't need. Need a lot of exercise to increase longevity benefits. Like people. I think, like Instagram's just taking this out of proportion. You don't need that much, Right? Yes, you do. If you want to look better and, and feel better. Yes, but that's a different story. But when it comes to the mechanism of action, what I really nail it down to is A, increased blood flow, B, we've got. If we grow muscles and we've got more mitochondria. Right. Which we haven't touched on. But then you've got the myokine pathway.
- [77:14]
Dr. Kellyanne Niotis
Yes.
- [77:14]
Louise Nicola
And the myokines are. Even if we're thinking about like IL6, Irisin, obviously, BDNF, which are fantastic for the brain, I think that's the major pathway that I see working. Cause some of them cross the blood brain barrier, some of them are anti inflammatory.
- [77:30]
Dr. Kellyanne Niotis
Yeah, absolutely. I think you nailed it. And I think different forms of exercise have different benefits for the brain. And you know the thing about resistance training and how we were talking about the interrelatedness of all of these risk factors, like a huge risk for Alzheimer's disease is falls, head injury. If you've really low muscle mass, your risk of falls is so much higher. So whether they're direct benefits, like all the ones that you just said, or indirect benefits in terms of reducing someone's fall risk, exercise is really, really important.
- [78:05]
Louise Nicola
All right, let's talk more about prevention.
- [78:07]
Dr. Kellyanne Niotis
Okay.
- [78:08]
Louise Nicola
Okay, give me everything. What does the average person. Because not everyone's going to get to see you. Not everyone is at the stage of understanding if they're risk or not. What is the. If you were to tell the world? Here are my, my top 10 things to prevent Alzheimer's disease.
- [78:26]
Dr. Kellyanne Niotis
What are they I love this. Okay, put me on the spot. Well, first, in my opinion is really understanding what your individual risk is. And that may be understanding your family history, that may be understanding your genetics, if that's right for you. But that really is a window into your risk and what areas you should really focus on. And I again am in the business of personalized and precision medicine, so that's kind of where you turn first. As you mentioned, we'll say exercise is important. It doesn't have to be super intense, you just have to be consistent with your exercise. And a combination of cardio and resistance training is what I point to. A Mediterranean mind based diet. In general, we're giving generalities here. So in general that's probably right for most people. Getting your hearing and vision checked. Super important. Easy, low hanging fruit. We just talked about how important these things are for the brain. Getting your cardiovascular risk factors in check, making sure you screen your cholesterol, and not really accepting when your physician might say that your cholesterol is, quote, normal. Even if you're, you know, 25 or 35, like high cholesterol is high cholesterol, it's only a matter of time before that will cause issues for you. So addressing that sooner rather than later is important. Making sure your blood pressure is well controlled, checking it on your own, doing a log on your own is probably best because when you're in your doctor's office office, you're flustered, you might be a little worried about seeing the physician. Checking in on your own, in your own environment, when you're most comfortable is going to give you the most accurate readings. Getting your metabolic health under control, whether that's through diet, through exercise, but also just checking your metabolic numbers to make sure that you are as honed in as you actually think you are. Super important. And then getting the right amount of sleep for you, making sure your sleep is quality, you're getting enough, you're making enough time for your sleep. And if you aren't sleeping, you're getting to the bottom of it. Is it stress, rumination, anxiety, pain, Waking up to urinate? Like, what's leading to your lack of sleep? Get to the bottom of why you can't sleep.
- [80:49]
Louise Nicola
I don't think that everyone needs to be supplementing, full stop. What are my favorite supplements across the board for everyone though, if I had to choose two, which I do, it's omega 3 fatty acids and creatine.
- [81:03]
Dr. Kellyanne Niotis
Okay.
- [81:03]
Louise Nicola
And then upon blood biomarker checking and blood work, if you are deficient in other nutrients, like if you're deficient in vitamin D then Great. Supplement with vitamin D. Yes. So these are my two. How do you. Where's your stance on that?
- [81:16]
Dr. Kellyanne Niotis
I'll even go as far to say that I 1000% agree everyone does not need to be supplementing. Some people don't even need Omega 3 supplements because they eat enough fish. They grew their own gills. So great. Good for you. If you're that person. You wouldn't know and checked until you checked your own levels. But I find that most people are deficient in omegas and it's difficult to eat enough fatty fish to get your levels appropriate. As you said, if you're deficient in certain B vitamins or D vitamins, then it's really important to get those corrected. But there's no prime supplement list that I recommend people because I don't think supplementation is like the answer and what's needed for most people. Yeah, of course there are situations when you do need supplements and we'll always address that. Creatine I think is very fascinating. It's getting a lot of attention now. You probably have stronger feelings about it than I do. It in the short term does help enhance cognition. There have been studies that showed really high doses of creatine may have help improve cognition in people with mild cognitive impairment. I've had people go on creatine and feel really bloated, a ton of gas. So again, I don't recommend all supplements to everyone because it's not right for everyone. But there are more supplements to that list that we can talk about that may have some sort of immediate cognitive enhancement.
- [82:47]
Louise Nicola
But B vitamins, alpha gpc, choline, what.
- [82:51]
Dr. Kellyanne Niotis
Other ones might have immediate cognitive benefits?
- [82:54]
Louise Nicola
Please don't say lion's mane.
- [82:55]
Dr. Kellyanne Niotis
Oh no, I wasn't going to say lion's mane. Certain magnesium supplements, some people feel like they give them a cognitive boost. The rage right now and what has made its rounds most recently is lithium. Low doses of lithium. And I've had patients report cognitive improvements when they started very low dose lithium. Like subjective maybe, I don't know, like that's still.
- [83:20]
Louise Nicola
Placebo effect is still real.
- [83:21]
Dr. Kellyanne Niotis
It's still real for sure. Caffeine is of course like an enhancer and you can get caffeine from lots of different things. Cocoa powder, like, you know, there are other things that can boost cognition, but there's no one size fits all.
- [83:35]
Louise Nicola
People ask me, why are you dedicating your career to this disease? I haven't personally been affected in terms of family history. As I mentioned, it's More so. Cancer. Cancer.
- [83:47]
Dr. Kellyanne Niotis
The Greeks.
- [83:48]
Louise Nicola
Yeah.
- [83:48]
Dr. Kellyanne Niotis
Yeah, I have a lot of cancer. My family do.
- [83:51]
Louise Nicola
And so you'd wonder why. It's not that I think I was. I obviously fascinated by the brain. That's what I chose to study for my career. But a woman changed my trajectory. In 2018, she came. I was responsible for doing EEGs and really picking up on early onset Alzheimer's disease. And I can't tell you how many scans I have done. And the one woman came in and. And only in her early 50s and three kids. Husband. And her husband's like, she's forgetting who we are. This is getting serious. I was younger than what I am now, and I kept asking the attending, you know, who was my boss, saying, he's like, louisa, just get them in scan, give them the results, get rid of them. And it really hurt me because when I went through her history, she's like, I did everything that my doctor told me, and I exercise and I eat well, and, you know, I'm working and we don't have. They're not really rich, but. And a real. Like, I couldn't help her a. Because I didn't have the tools, the knowledge, and it wasn't my place to help her. And she. She plays on my mind every day, but she took a real, like, steep, downhill battle. And I saw the progression, even over a year of the progression was steep, steep. And it gets to a point where there is so many people outside waiting for me, and all I could tell you was, seek help elsewhere. But that wasn't my doing. It was obviously where I was involved with. And I haven't stopped thinking about that now that I know that. Back then, I used to ask all my attendings, can't we prevent this? No.
- [85:29]
Dr. Kellyanne Niotis
I mean, that story also speaks so closely to me and my experience. I do have a family member that has been impacted by a really atypical form of dementia where, you know, she was accompanied by a lot of neuropsychiatric issues as well. And we actually have never gotten a formal full diagnosis for it. But to see her lose herself, lose her personality, lose her connections to her family, who she was once so close with with, is completely devastating. And that situation that you described played out for me countless times while I was a trainee seeing Parkinson's patients who asked, like, what else can I be doing? What else can I be doing? And for us to say, eat better and exercise more didn't feel like enough. And I was fortunate enough to cross paths with such an amazing mentor, Richard Isaacson. And he showed me a different way to thinking about neurodegenerative diseases. And it was so evident to me that the patients that were following recommendations that we spoke about today on this podcast did much better than the ones I was seeing outside of that setting. And I truly, truly, truly believe that not only is. Is not only is dementia preventable, Alzheimer's disease preventable, but also that people who are impacted early on can still do things to change the trajectory of their disease and that all hope is not lost. The disease looks so different in different people. And I do believe that what you do personally impacts how this disease looks.
- [87:28]
Louise Nicola
I'm very passionate about women as well, because she was a woman, and my grandmother, who was my best friend, was told she was. I remember. I remember her asking her doctor because I went to all her visits with her. She said, what else can I do? To the doctor? In Greek, you know, what else can I do? I. I don't want to die. And the doctor said, nothing. You can't do anything. And so this is why it touches my heart, this disease, because two out of three patients of Alzheimer's disease is female, and I'm so strong and bullish on hormone replacement therapy, because I've seen, both clinically and in the data, what it can do. It can change your life and the trajectory of your life. It can change your children's life and your spouse's life. And people don't understand that this is the only disease that robs you of who you are. And every single memory that you have, every memory that you are building, your 20s and 30s and 40s can be taken away from you just like that because of the choices that you choose to make in your 40s and in your 30s. And I'm so passionate about preventative neurology. I love what you're doing.
- [88:37]
Dr. Kellyanne Niotis
Thank you.
- [88:38]
Louise Nicola
Thank you for coming on the podcast.
- [88:39]
Dr. Kellyanne Niotis
Thank you for having me. This was such an awesome discussion. And, you know, thank you for getting the message out there that preventive neurology exists, and it's going to grow, and in our lifetime, we're going to see it be a huge, huge, huge part of medical care. And the more people that care about it today, and the more this message gets out there, the more power we have to really disseminate this message. So thank you for this opportunity.