Key Insights on Alzheimer's Disease: Diagnosis, Treatment, and Lifestyle Factors

Today, I’m joined by Dr. Ken Sharlin, a board-certified neurologist, to discuss the truth about Alzheimer's disease—what causes it, why early detection is critical, and how functional medicine is changing the game. We dive into:

✅ The real difference between Alzheimer’s and dementia
✅ Why conventional neurology often fails patients
✅ The latest diagnostic tools & treatments—including blood-based biomarkers
✅ The power of lifestyle medicine to prevent & slow cognitive decline
✅ The future of regenerative medicine & stem cell therapy for brain health

This episode is packed with cutting-edge research and practical strategies you won’t hear from your regular doctor. Tune in now! 🎧

Transcript

Today I'm joined by Ken Sharlin, MD. Welcome to the show. Thank you so much. So I want to dive into this. So we're talking about a topic that is of great interest to so much of the population. So we're going to talk about Alzheimer's. Tell us a little bit about your background because you're uniquely qualified to talk about this topic in a way that many of the people who are on podcasts they're just really not, they're not in the, you know, in the way you are. Well, thank you. I appreciate that. I am a board certified neurologist, medical doctor. I graduated from Emory University School of Medicine back in nineteen ninety two. So, you know, past the thirty year mark, I guess, of since graduation. But neurology training was another several years. And, you know, put your boots on the ground, even in neurology training, seeing patients working in the clinic, working in the hospital. I entered independent practice in nineteen ninety eight and then been doing that since since then. I still am a general neurologist, meaning that I don't necessarily specialize. I see lots and lots of Alzheimer's, Parkinson's, MS, ALS, all kinds of things, peripheral nerve disease. But we have roughly seven million Americans currently suffering from Alzheimer's disease and then lots more in the wings with what we would call preclinical, meaning that they don't necessarily know that Alzheimer's is around the bend for them. Maybe they have a little bit of memory loss, but no one has, you know, put the pieces together or they aren't yet symptomatic because it's a disease that has a ten to twenty year incubation period and you know at least a portion of those with the changes in the brain will develop the clinical syndrome that we recognize as alzheimer's not all but probably a good number of them will and uh so it's a topic of conversation it affects so many people directly or indirectly correct you know I know for me personally you know my grandma died of dementia, I had a grandpa who had a traumatic brain injury, and ultimately that set him on the path of a neurodegenerative condition, an aunt who passed with ALS, you know, and then even other people with other neurodegenerative conditions. And, you know, before we really dive into this, a lot of the stuff we're going to talk about there, people aren't going to hear when they talk to their regular neurologist about this. So what kind of caused the shift for you or like, hey, you know what, what I'm doing in regular neurology just isn't doing it? No, it's not doing it. And, you know, I fortunately it was really a combination of different things going on personally and professionally. Personally, back in the early two thousands, I got interested in endurance sports and, you know, being kind of having a science background and geeking out on things, I started to really get into, you know, how to be the best triathlete or the best long distance cyclist I could be. And that really meant learning about the role that sleep would play, learning the role of nutrition. You can't go through one hundred and forty point six miles in a day, which is, you know, the Ironman triathlon and not consume food. nutrition, right? There's no way. So studying the art, if you will, and science and nutrition helped me be a more effective triathlete and finish a few Ironman distance races. But ultimately, what I was seeing is, hey, you know, I'm doing all these things for myself. I'm changing my body. I'm changing my brain. But I'm going to the clinic and basically seeing people falling apart and Really the only tool in my toolbox is either I prescribe a drug, send you to a surgeon, maybe send you to physical or occupational therapy, that kind of thing. And it's really a Band-Aid over a problem. And even today, I say, look, and I don't treat high blood pressure as a doctor. But as an example, if we stood at the door of your local emergency room with a clipboard and a pencil and simply checked off every time somebody came in with chest pain due to coronary disease or stroke, I mean, how many of them are on the blood pressure pills? They're on the cholesterol pills. They're on the diabetes medicines. And I'm not against medication, but the sort of thought process that too often goes with it is a sense of complacency, like my doctor's putting me on this blood pressure medicine so that I won't have that heart attack or I won't have that stroke. But in reality, most people who take these medicines will still go on to have the stroke or the heart attack. And we know this statistically is absolutely a fact. And so it's a very difficult reality to face when you know that you're dedicating your life to helping people. But ultimately, are you really making that much of a difference? And so that's where I turned to lifestyle medicine, functional medicine, regenerative medicine. and preceded by people like Dave Perlmutter, who has obviously been a pioneer in the application of functional medicine principles to neurology. And I'm a big fan of Dr. Perlmutter's, but he doesn't practice anymore. He educates others through his blogs and his podcasts and his books. But there aren't many of us out there who are actually seeing patients and applying these principles in the clinic. And that's really been a game changer for me to be able to bring all the pieces of the puzzle together. The best of both. You have to use drugs sometimes. But it would be a terrible tragedy. And I see it every day in my clinic when people come in and they're not aware that their diabetes, say, is playing a role in the diseases that affect the brain. Correct. Yep. You know, there's just such a massive lack of awareness. And as we go into this, you know. Most of these conditions, right, we're focusing on a specific type of dementia, but whether it's Parkinson's or other things, a lot of the underlying processes and contributing factors are the same. So the very first thing is just briefly explain, you know, like what's the difference between dementia and Alzheimer's and then what are the other most common types of dementia that people are impacted by? But if we can just even take one incremental step back from that, I want to just introduce the term or the phrase cognitive domains. The way our brains work is we do things like see this incredible podcast today, and then we kind of remember it and tell somebody else to watch the podcast, right? That's our memory system. And there's more to memory than just using that broad term. But let's just use, say, short-term memory as one cognitive domain. Kind of like saying, what are the parts of a house? You got the roof, you got the foundation, you got the walls, you know, you have the environmental system, the heating, the air conditioning, right? So language and visual spatial skills and all these other things compose these cognitive domains. And, you know, a condition that is very common these days or commonly diagnosed, but certainly not dementia, is attention deficit disorder and attention as a cognitive domain. So you have to realize that for a variety of reasons, we as human beings may lose our capacity within a given or a group of cognitive domains. But when we're talking about the things that lead to say Alzheimer's or dementia and Parkinson's, obviously memory, or we might say amnesia or amnestic cognitive decline is a qualifying feature. Like you can't have dementia of any kind unless you actually have involvement of memory. You can have cognitive impairment. You could say attention deficit disorder is a form of cognitive impairment and But it's it's not certainly a dementia. So in line with that, someone is starting to perhaps notice and occasionally they don't. Occasionally it's someone else has to tell me, you know, you're repeating yourself, whatever. And sometimes the people affected are aware. Sometimes they're not aware. Initially, there can be subjective cognitive decline or subjective cognitive impairment, meaning I know there's a problem. I'm aware of it, but I'm still fully functional. There's nothing that I can't do, but I'm struggling more than I normally would or should be struggling. No one else is necessarily aware. Then we get into mild cognitive impairment. Then at that point, other people are starting to notice. Maybe you're asking the same question over and over again. Maybe you forgot a conversation. You do that repeatedly as a as a general pattern. Folks are watching this. If you forget a conversation you had one time, that certainly doesn't mean you have cognitive impairment. Right. And we all, by the way, lose our car keys every once in a while. So if there is a consistent pattern that raises the concern, is there some sort of amnestic or memory oriented cognitive impairment? Right. The key, though, is to understand that in order to get into then dementia and particularly Alzheimer's disease, it's not just the presence of some memory loss plus minus some other cognitive domains like language or visual spatial skills or naming and things like that. It is, is there starting to be impairment in what are called instrumental activities of daily living? So can you handle your finances? Can you prepare a meal? Can you go to the store and pick up the groceries that you need? And although that is – well, I will say that these are required – There's something called the Lawton-Brody Instrumental Activities of Daily Living screening instrument, and you'd really have to have impairment in that particular instrument, these instrumental activities of daily living, to meet the clinical definition of Alzheimer's disease. When we start to differentiate, and you and I were talking before the recording of the podcast about there's dementia and then there's Alzheimer's and they overlap, but they're not exactly the same thing. Everyone who has Alzheimer's disease has dementia. Everyone who has dementia does not necessarily have Alzheimer's disease. So we can differentiate these different recognized, categorized, if you will, forms of dementia by clinical features. For example, a patient that I saw this week in clinic came in with a condition called primary progressive non-fluent aphasia. which is the Bruce Willis disease, if you will. And sometimes those individuals go on to actually have a more classic Alzheimer's presentation, but most of them end up having what is called a frontotemporal dementia. There's vascular dementia. There's Parkinson's disease-related dementia. And there's Lewy body dementia, which really may be another manifestation of Parkinson's disease dementia. And in reality, if we look at the brain under the microscope or use some of the more current biomarker-based testing where we can actually look at abnormalities in blood, spinal fluid, things like that, we can... We actually know that there's a tremendous amount of overlap and something like close to fifty percent of people who have Lewy body dementia also have the amyloid blacks and tau protein associated with Alzheimer's. So it's not as neat and clean when we start actually looking at the brain. But we do distinguish these different clinical diagnoses by their features outwardly, if you will. But again, we're now in a place in the twenty first century where we can be more precise and measure what are called biological markers and say this person has Alzheimer's, this person has Lewy body disease, this person has frontotemporal dementia. Yep. Yeah, absolutely. And we're going to dive into that a little bit more. You know, I came across a study this past year and they were saying roughly There's over eight million Americans who have mild cognitive impairment and about ninety two percent, I believe it was, were undiagnosed. And one of the things they said was that the primary care providers, they didn't want they didn't kind of know what to do. So like, well, why diagnose something if I don't know what to do? You know, so we've kind of talked a little bit about the difference between mild cognitive impairment and dementia. So with primary care providers struggling, you know, for people to even get the proper diagnosis. So what are the challenges that healthcare providers are facing in accurately diagnosing Alzheimer's disease? Initially, let's say without the biomarker confirmation, and then we'll later talk about some of the biomarkers that are coming out that people can actually get. I'll be frank. I think a lot of it is education and awareness, but neurologists and other, you know, there's a classic paper that's been published and they tend to use the term specialists, but I think they're primarily implying neurologists looking at the ability to accurately diagnose Alzheimer's disease just based on clinical presentation, meaning without these biological markers. And the accuracy historically was about sixty percent for general medical providers and about seventy percent for neurologists. So the track record, unfortunately, historically is very poor. And then it comes with sort of biases and folks not necessarily keeping up with the literature and things like that. And the old, well, you can't do anything about it myth. And there's a lot of different dimensions. But I had a patient come and see me also this past week, who went to her primary care doctor for just her general, I'm sorry, annual, like general physical, you know, preventative care, but she was in her sixties. And so the doctor thought, well, Medicare wants me to do these cognitive screening evaluations. So the doctor does a mini mental state exam, which is just a little pencil paper, five minute thing. Now, it's important to bear in mind this person had a history of traumatic brain injury. She had severe PTSD. She had fibromyalgia. She had chronic fatigue, depression. And I don't recall exactly what her score was, but let's just, you know, it wasn't great. You know, it wasn't very good. Now, this person, in reality, on a day-to-day basis outside of the doctor's office, was fully functional, fully functional. But the doctor said, after this five minute pencil and paper test, you have dementia and referred the patient to me, which of course the patient was extremely disturbed by. She came in, we did a, now I always do a pencil paper test, but I do a lot more than that. And I tend to use what's called the Montreal Cognitive Assessment. that particular test uh a quote normal score is twenty six to thirty it's a thirty point test and I think she scored twenty six so technically she was within normal range I do look at where they lost the person lost their points and if they lost all of their points on the delayed memory section then we might have a little discussion like technically this is a normal score, but hey, you lost four out of your, you know, four or five points on delayed memory. There might be a little memory problem. There's a memory problem, but not necessarily a diagnosis of dementia, right? And then it's my job to sort out What's going on? How much of this is her TBI? How much of this is her PTSD and her depression? All of these things can be risk factors for Alzheimer's, right? Or in some cases, Parkinson's. So we really have to step back. We can recognize in this case that there is some cognitive difficulty, but I certainly would never have diagnosed her with dementia. And based on the twenty twenty five criteria, It was absolutely incorrect for this doctor to have told the patient she had dementia. Yeah, because, I mean, that diagnosis hits people so hard. And like I said, lots of people, they just get the paper and pencil tests. Others, they don't get them at all. And, you know, and people are looking everywhere for help. And we'll talk about other things that can be done. But initially, you know, we'll talk about some of the new meds. But before we do that, Some of the old meds that people are getting put on, denepazil, otherwise known as Aricept, Namenda, and some of those, they really just didn't have anything. There was no good, true clinical outcomes, and they did absolutely nothing to address the underlying pathophysiological changes of dementia at all. Whereas at least some of these newer ones, which I'm going to let you tell us about some of these newer medications, they're at least meant to go after at least some of the biomarkers they're wanting. But, you know, what do we know about these medications? You know, promising or not, I know you've got a lot more experience with these than, you know, I've never personally used them, even though I do work with a lot of people with dementia. But, you know, what should we know about these medications? What are they and what should we know? Well, historically, there are really only two classes of drugs until this last year or two when the FDA formally approved two new treatments for Alzheimer's disease. But you refer to denepazil, which is called a cholinesterase inhibitor. It works by blocking an enzyme that breaks down a critical neurotransmitter involved in the memory circuitry in the brain. And it did get approved by the FDA many years ago as a result of large scale clinical trial. So it is effective, but it's minimally, I mean, you know, we can't expect a whole lot out of the drug. but it might improve, say, a score on a Montreal cognitive assessment test by a few points. The problem is that it's sort of the cough suppressant to the cold, right? You still have the cold. You might not be coughing as much, so that's not bad. it's a fairly safe and in the case of denepazil fairly well tolerated medication some of the other uh cholinesterase inhibitors have a lot more nuisance side effects they don't usually have serious serious adverse side effects in most cases uh but it's again it's it's been around a long time it only improves the symptom And because this is considered a neurodegenerative disease, people get worse over time. So there's the perception that the drug is less and less effective. But in reality, there's only so much the drug can do. um there are a couple other drugs within that class rivastigmine is one of them I sometimes use it because it's available as a transdermal patch where people can't tolerate gastrointestinal side effects of these drugs and the patch can be helpful and then there's a drug called memantine otherwise called amenda sort of in a class by itself as a different mechanism It's a partial inhibitor of the neurotransmitter glutamate. And the way it was explained to me when I first learned about the drug is if you're in, it's almost like being in a room where you have some hearing loss, but then when you wear hearing aids, it just amplifies everything. So, you know, the room is just louder, but it's really hard to just hear the person that's in front of you to turn down the noise, if you will. And you want to think of sort of turning down the noise. It's only ever been found to have some impact. And I rarely use the drug in moderate to severe disease. And most of the outcome measures are really focused on caregiver perception. So if you have a loved one affected by Alzheimer's, they can't feed themselves. They can't participate in their own bathing and toileting and things like that. They may be more able to do so, but it's not like you're going to see a dramatic impact. improvement and you know suddenly they start remembering things and that sort of thing so I often see the drug misused and given to people in early stage disease or mild cognitive impairment it really has no role there at all shouldn't be used in my opinion it's just a worthless drug fortunately it's safe but as far as its value in the toolbox very very little So we've been hurting, you know, for a long time. And you made reference to a couple new drugs. One is called Lekembe or by the generic name Lecanumab. And the other one is called Kisumla or Donanumab. And these are within the same class. One is produced by Acai Pharmaceuticals. The other is Eli Lilly Pharmaceuticals. And what each of these drugs do is target the accumulation of the end stage expression of the disease in the brain, meaning the accumulation of something called insoluble amyloid forty two protein. And they help to clear that protein in the brain. And there is some improvement as well in another protein. that probably accumulates secondarily to amyloid called tau or phosphorylated tau protein. So it has some effect indirectly on tau. And both of these drugs went through phase three clinical trials, which is the stage of the clinical trial required by the FDA. So the company can then apply for approval under the FDA. And although they use slightly different outcome measures, the bottom line with both of these is that they slow they may slow the rate of decline so they don't necessarily improve cognitive function but they may slow the rate of decline on average by about thirty percent you know so can you tell it's helping hard to say you know because you still have cognitive decline you may just you may not be getting worse as quickly as you would if you didn't take the drug It does appear that these drugs have a greater impact, a more positive impact, the earlier in the disease process that they are used. So in the folks who have just mild cognitive impairment, those instrumental activities of daily living are still intact. In the Eli Lilly study, it appears to have slowed the, as by the way, it's called Trailblazer, Eli Lilly Trailblazer to ALZ. It may slow the decline by as much as sixty percent. The big however, is that these drugs can have some pretty serious side effects. And so if you're pretty functional and say, you know, is it worth the risk of having a very serious side effect? when you're still pretty functional. Maybe it would be if you're further down the rabbit hole, but then if you're further down the rabbit hole, the drug is less effective. And there are many failed amyloid, there are many failed anti-amyloid drugs that preceded these two. Why did they fail? Why did these two succeed? I don't have the answer to that question, but it certainly raises a lot of eyebrows. If so many others failed, you know, are these drugs even all that effective as well? Yeah, and let's get into briefly, what is ARIA? So explain what that is. So it's an acronym. It stands for amyloid-related imaging abnormalities. And they fall into two broad categories. Now, bear in mind that these are findings that are identified by MRI. And these drugs have to be given intravenously. at least for now, there's been in the development pipeline a subcutaneous injection version of licanumab, but it is not commercially available as a subcutaneous injection. In the case of licanumab, you have to be infused every two weeks. In the case of dinanumab, you have to be infused once a month. With dinanumab, it is so effective at clearing the amyloid protein that after somewhere between eighteen and maybe twenty two months, the drug is generally stopped. You can do an amyloid PET scan, confirm that the amyloid is gone and then there's nothing more to treat. But during that time, and particularly within the first several months of treatment, there is an increased risk of what are called amyloid related imaging abnormalities. These are either microhemorrhages or small bleeds in the brain, which are, in my experience, fairly common, more common than the other form of ARIA, which is what is called edema. So they use the term ARIA-E, by the way, and ARIA-H, edema is E-D-E-M-A. And edema is a fancy way of saying swelling or accumulation of fluid within the tissue space that is the brain. Now, There are caveats to this in that most people who developed ARIA changes during the clinical trials were entirely asymptomatic. The vast majority, something like, oh, I think, I mean, ninety eight percent is very, very high. And that was my general experience because I was a I'm a principal investigator in clinical trials. So most of the time it is asymptomatic, but a very small percentage of the time there can be side effects or, you know, whether it's headache, nausea, It can be alteration of consciousness, seizures, in some cases, even death. And death has been reported with these drugs. So it is something to take very seriously. And as a result, the FDA has mandated and CMS has sort of rubber-stamped this, that's Medicare and Medicaid services, to say that if you're on these drugs, you must agree to have an MRI at several different time points during the infusion. I would say it's like the Monopoly game, do not pass go, do not collect two hundred dollars because if you do not get your MRI, you cannot get your next infusion. But it total a minimum requirement of about five MRIs during the first year of the infusion. The other thing is that people who carry a particular gene called APOE-IV are at about fifty percent greater risk for having these changes. But these are the folks that are at greater risk for Alzheimer's in the first place. So it's kind of a double edged sword there. again most cases of aria and it's true in my experience were asymptomatic or are asymptomatic but it's still something to take very seriously and fortunately when this does occur in most cases it resolves there are protocols in place that the doctors are supposed to follow involve holding the drug in some cases using some steroids but primarily holding the drug until a problem has resolved The other thing is that the guidelines have become a little easier because we were so afraid of RE in the very beginning that even one or two little micro hemorrhages, we'd hold the drug. Now, sometimes if it's one or two, you might just still continue to infuse. But again, it's always up to the judgment of the physician caring for the patient. Yep. And I think, you know, as you've said, and what I've read in the research is we're seeing these drugs do a better job of clearing the amyloid beta than they actually do on improving functionality. It's, you know, it seems they slow it whenever we look at, I mean, I was looking at some of the study was a year, year and a half down the road. It's like, well, you're not as bad as the others were, but there was still, you know, still quite a bit of progression. And so as we go into some of those biomarkers, you know, because as we talked about at the very beginning, this is a ultimately a diagnosis that is given ten to twenty years after certain processes are happening in the body are there certain biomarkers worth looking at you know there's new labs coming out like p tau two seventeen I think one eighty one um amyloid beta ratios that can be done through plasma or serum you know versus what it used to be was just like hey it's csf um you know What are you seeing with these? Are you finding these beneficial? And are there other labs beyond that, like neurofilament light or little fibrillary acidic protein that may be worth doing? Like I actually run all of those and I tell people like, look, this is kind of, you are your own best baseline. And then we kind of compare you years down the road. So we kind of know what you should be. Right, right. Well, to be clear, to make a diagnosis of Alzheimer's disease today, you must measure biomarkers. If you're a doctor, like this situation I mentioned earlier in the show about the person at the mini mental state test, and then doctor says, oh, based on your score, you have dementia. I mean, that's just blatantly wrong. It's almost malpractice. It's blatantly wrong. The current definition of Alzheimer's disease requires the identification of these biological markers, the levels of amyloid beta and phosphorylated tau. And I've been doing that for years. I stick a needle in someone's back and easily measure these proteins in the spinal fluid. But in the last few years, the biomarkers have been validated for in blood tests. And so it's, you know, it's much easier. And I never thought I would stop doing lumbar punctures for the diagnosis of Alzheimer's disease, but I have, and I've only even ever, I have done many tau and amyloid PET scans, but only because a clinical trial requires that, not on the clinic side of my practice, because now I can do a blood test. So I particularly like a company that is based out of St. Louis called C-to-N Diagnostics. For full transparency, I was an investigator for them. We just published another paper, but this test has been highly validated, not only being accurate, but being essentially equal to what has been considered the gold standard, which is an amyloid PET scan or a spinal fluid test. This test combines the measurement of amyloid beta-forty-two and amyloid beta-forty. It calculates what is called a forty-two to forty ratio with what is called a p-tau-two-seventeen. So we don't do the one-eighty-one anymore because this two-seventeen has been found to be more accurate. And there's a statistical calculation that goes into looking at all of these and combining them together into what is called the amyloid probability score. or the APS-II because there was an APS-I, if you will. And with that amyloid probability score, and it goes from, I think, a range of forty-eight to a hundred, if anything in that range is considered abnormal, it says in fine print under the APS-II score that it is consistent with an abnormal amyloid PET scan. And in the clinical context of the person with cognitive decline, They may have mild cognitive impairment due to the changes of Alzheimer's disease. Or of course, if instrumental activities of daily living are also impaired, it would be consistent with the clinical diagnosis of Alzheimer's disease. But you must have biomarker confirmation in twenty twenty five. You cannot tell somebody that they have Alzheimer's without biomarker confirmation. Interestingly, the opposite is not, there's a little, if you flip it around, you say, well, what if somebody is cognitively normal, but they have the biomarker changes? In that case, you cannot tell them that they have Alzheimer's disease. You can tell them that they have the pathological changes of Alzheimer's disease in their brain. blood implied in their brain right but that they are at risk for developing alzheimer's disease and I'm very pleased with that position paper that was published not very long ago because for you and I it says if you have somebody that's at risk It means there's things that they can do about it. You're at risk. Let's have a conversation about diet and lifestyle and toxins and all those other things. Right. So let's remove the risk factors, if you will. Let's improve the diabetes. Let's get rid of diabetes. You know, and the brain responds very nicely. Yeah. Cause I've been getting tons of emails, you know, from all the journals and everything with the updated guidelines. And they basically are considering that almost like stage zero. It's like, Hey, you've got no symptoms. You've got some biomarkers. It doesn't mean you've got it. You know, you've got to progress a bit more, but it's like, Hey, this is something that needs to be tracked and correlated with other things. Um, And I think one of the challenges is, like you said, a lot of people, they're not staying up with the research. But the other part, it's these are new enough, even though you've been doing this for a while, you know, and the research has been showing it. haven't yet seen that insurance is covering this you know and so a lot of people like oh man you know what's it costing you know and I know there's different labs that do these but for some people to be preventative like hey you know it's worth doing even if this is a lab you do every few years now from an imaging perspective You know, it sounds like pet amyloid testing for you isn't something that's super great. You know, it's good for maybe research. What about other things? You know, neuroquants are becoming more popular. What are your thoughts on maybe correlating neuroquants with some of the labs? And for me, I think one of my dream tests would be is one of the pet scans where they do the radio tracers and they actually look at inflammation and microglial responses essentially in the brain. Because I know there's some studies that says, hey, that actually matters more than even amyloid burden. So what are things that we should consider on that side? Well, for clarity's sake, amyloid PET, spinal fluid testing for amyloid phosphorylated tau, the prescivity AD-II test from C-to-N diagnostics, they are covered by insurance, but the way that insurance works is we as providers have to provide the lab company, the insurance company, whatever, with the appropriate diagnostic codes. So if you were entirely cognitively normal, But I put in my chart that you had dementia due to Alzheimer's. I would be lying. I'm not going to do that, obviously. So today, it is impossible to order a test on a preclinical basis, right, on somebody who we might say, you know, you're diabetic and obese and, you know, have... high blood pressure and all the, you know, sleep apnea and hearing loss or what and sedentary and what have you. And you're a tremendous risk and you have a family history and you're APOE for positive. But if they're cognitively normal, the insurance is not going to cover that test, but they are very useful. They are precise and they are accurate. I have used NeuroQuant. I don't use it right now. We have access also. There are several software packages out there that compete with NeuroQuant. This is, for the audience, what is called automated three-D volumetric analysis of the brain. Basically, it's AI, we're in the age of AI, driven software that analyzes the brain and calculates the volumes of different brain regions. And, you know, I think... There are places for these tests, but in the world of Alzheimer's disease, I don't actually find them very useful anymore because it is so easy to do a blood test. And with that amyloid probability score, I get a number that I can track over time. So I have patients who have reversed their Alzheimer's disease because I've seen their passivity score go from, you know, seventy five to sixty to fifty five to forty eight to thirty eight. And it's negative changes in volume. Brain volume can be less predictable because by the time somebody. is really you know impaired yeah they probably have a lot of atrophy but early on they may or may not have as much atrophy and where and you know where you put your cut off where you say this is normal versus not being normal can be quite challenging I mean I always tell people look uh if we put ten people in the room say what's your hat size you know you're gonna get some people are small some people are medium some people are large And the size of your skull reflects the size of your brain, at least your normal cognitively, normal brain, healthy person. But the size of your brain in that sense does not reflect your cognitive capacity. You know, maybe Einstein wore a small hat, but he was a genius, right? I tend to wear a medium large, at least on the bike helmet. My wife wears a small when we go cycling. She may be smarter than me. I don't know. So, you know, where these tests may be more useful is to look at relative volume changes. So we talk a lot about a region of the brain called the hippocampus. Now, is there relative atrophy or volume loss of the hippocampus compared to the whole brain? That may be informative, but not necessarily diagnostic. Is there more of a frontotemporal pattern or what we call a parietal occipital pattern, like there would be say, in somebody who has Lewy body dementia. So they're not without their merit. I don't want to leave the audience with the impression that I believe that. I just think that my practice has evolved over time because medicine has evolved over time. And with these biomarkers being so incredibly accurate, and the ability to track disease over time with a simple blood test that is covered by insurance, I just don't do that much volumetric imaging for Alzheimer's. I think it does have a place in diseases like MS, but I found it less helpful over time with Alzheimer's. Yep. Yeah. And I'm there with you you know I did a lot of neuroquants and now I've moved somewhere else where the pricing's a bit more and with all the new biomarkers coming out with labs I'm like you know what I I'm gonna go with the labs um because of the way the research is on them because I've seen people with horrible neural quads and you're like whoa they're way more functional than you thought they'd be and then you've got people who you know they're severely you know their dementia is horrible and their volume scores look fine. So I think it can be a piece of the puzzle, but definitely not all of it. And so we've talked a lot about dementia, Alzheimer's, testing biomarkers. But one thing we talked about towards the beginning was even with the medications, they don't really do anything to change the process a ton. You're still getting worse. And so I want to kind of switch from this like, okay, look, You've got diagnosed. You're already so far down the road. The medications, they don't have a lot to do. And we've said now with the biomarkers, you now are starting to be able to pick up people at risk ten to twenty years in advance. So with the amount of research that's coming out and it's been pouring out over the past decade or so, research is showing that lifestyle factors play a significant role in both prevention and treatment of cognitive decline. How do you help patients implement sustainable lifestyle changes? And what specific interventions have you found most effective in your practice? And I really want you to kind of, as you answer this, focus on some of the sustainable part. Because I think for all of us providers out there, and then for the patients, they would agree, it's sustaining it. It's not being like, here's what I need to do. It's how do I sustain it? Of course. No doubt about it. I mean, I think the drugs that are currently available, the Leucanumab, Denanumab, I hope they go away soon. I certainly, I applaud the fact that these companies were willing to invest millions of dollars to develop these drugs. I'm glad that we have something. I'm glad that, and by the way, they're not for everyone. Of course, if you're on blood thinners, things like that, If you have a history of stroke, it's probably not a good idea to use these kinds of medications. They really have to individualize care as we do with functional medicine as well. But I think it also spurns on other research. The pipeline, as we call it, is fairly substantial. There are many drugs that are currently being investigated that are either in phase two or phase three. I'm personally most excited about things like phosphodiesterase inhibitors, which are sort of the Viagra-type medications. And there is already a body of literature that shows us that these drugs may have a profound effect on brain function and on... either preventing or reversing Alzheimer's with a much greater degree of safety. But to your question, it is very complicated. And I, first of all, want to applaud you for having a podcast show. Because in the greater context of things, we have to have our patients educated, one way or the other. And we sometimes, and I'm sure you are familiar with this term, this pre-education, this before you even came to see me in the office, You listen to or watch this podcast. You heard about Dr. Dale Bredesen. You read his book. You read my book. You read your book. You know, like people are out there. So many, you know, podcasts and blogs and Hooberman and whatever, you know, and it. While some of it's really good and some of it's okay, right? Or whatever your judgment. But the point is that it's at least stirring people's imagination. Because this really boils down to psychology in the end. And that is what is called at least the most... And I'm not a psychologist, so I'm giving you the... sort of poor man's version, but the trans-theoretical model of change, which goes like this. And this is Prochazka's theory. But it sort of guides how we understand that people move to a place of, oh my gosh, this is something that is possible and I can do this and I can sustain this. So we go from what's called pre-contemplation to, which is like, it's not even in my world, like the patient who came in to my clinic with that primary progressive non-fluent aphasia, who was a type two diabetic on insulin, which just kills me because, well, literally you and I know that every time they inject themselves with insulin as type two diabetics, they're just killing themselves a little bit more and a little bit more. And the idea that the doctor said, well, you know there's there's nothing that we have to treat primary progressive aphasia so just try to enjoy life the best you can and I said but did you know that if you improve your insulin resistance your brain will work better right I mean it was just like no and Sometimes they don't even believe you because so many doctors that have preceded me or you have told them there's nothing that can be done, right? So we have to get past these huge barriers. That's pre-contemplation. And then there's contemplation. I heard about it. I heard about that guy, Sharlin. I heard about that guy, Bredesen. I heard about that woman walls and her MS and all that. Right. Oh, but I don't, I mean, it's interesting. Right. But I'm not sure if it's for me, but I heard about it. I might even be willing to learn a little bit more about it. And then there's preparation. Like I'm on board. haven't started yet but I've totally bought into the narrative and I believe it and in fact I bought the books I subscribed to the you know whatever I'm gonna get the food delivered that's the anti-inflammatory organic whatever I'm gonna start working out I joined the gym I bought the clothes I bought you know I bought the apple watch or the aura ring I'm gonna track my sleep I'm gonna do all that but I haven't actually started it yet right preparation then there's action I'm doing it and then of course There's the fall off the wagon, the relapse or whatever you want to call it. But then sometimes that's a good thing, right? And I say to my patients, well, they'll say, well, Thanksgiving and Christmas and all those pies and cookies and cakes and all. And it was so hard to resist. And I'm like, all right. How did you feel? Oh, just terrible. You know, my brain fog came back. My joints ache. My gut was a wreck. Okay. What are you going to do about it? Well, if I'm going to do that anymore, right? So, you know, and because we as human beings, we don't respond too well to being told to do things, right? We have to kind of discover for ourselves. We make decisions emotionally, right? and so a big part of the practice as well is the dimension that is the type of communication that the best coaches have which is called neuro-linguistic programming and how do you kind of get into people's thoughts how do you get into their hearts and minds and ultimately How do they discover it so that it's sort of their idea and it's what they want to do and it's important to them and then they're ready to make that change. But it really is about change. And as you put it, sustaining that change. It's not going to come in a supplement. It's not going to come in two visits. And folks, if you're going to a doctor like one of us and they're saying, you know, You've got to work with us over an extended period of time. It's not going to be like you can't just pay for one or two visits and expect an outcome. We're telling you the truth. It's like the cliche that Rome wasn't built in a day. It is a process. It is a journey of transformation, and that's why we ask you to work with us. Work with our team. Work with us over time. Establish those new habits. Change your mindset, right? Yep. Yeah. I mean, and you know, and this is why I'm doing the podcast, you know, it's really, for me, it's about bringing stuff out of the shadows. Cause there's so many things that people just aren't even aware of. And as you talked about, right, she has no clue that her diabetes is driving her aphasia. And it's like, man, and the research is there. That's, that's kind of the sad thing is there's so much research that says, look, if you've got diabetes, you're obese, you've got hypertension. any of those stuff, the more you've got, the more likely you end up with any type of dementia, whether it's Alzheimer's, vascular, specifically vascular really goes up. And then like you said, right, if they've been told the wrong stuff, they're like, oh, but I can't do anything. So you've talked about communication and kind of the whole process. So what are some of the interventions that you have found most effective in your practice with helping these people who, are let's just kind of split into both right let's say one is they're the mild cognitive impairment right you see them they're not bombing their mocha test so that montreal cognitive assessment you know they're struggling but they're not doing horrible so let's start there first and then we will go into those who actually have alzheimer's diagnosis So I am a very grassroots, very sort of conservative, functional medicine doctor in that I firmly believe and essentially require that my patients focus on the foundations. We can't get anywhere until we've worked on sleep, on the nutrition piece, on movement, on building some stress resilience and on socialization and connection and what's waking you up in the morning and that's not your alarm clock, right? That you have a reason to wake up. And you can, again, I own a supplement company, so I'm not against supplements, but folks come in with bags and bags of supplements, but their sleep is terrible or their diets or whatever, and that's just not gonna fix them. It's not gonna fix the problem. So we have to build the foundations. We can't just focus on one, in my opinion. I have somebody that comes in and says, man, I did all the podcasts, did all the masterclasses, did all the summits, and my diet is perfect, but I'm doing terribly. And I listen and I'm like, you really have a pretty, yeah, that's a great diet. I bet you're getting lots of nutrition there. How's your sleep? Terrible, right? How's your stress? Terrible, worse, right? So I use a multidisciplinary team. You know, I kind of direct the overall ship. I'm the captain, but I also focus a lot on sleep with my patients. On the other hand, I have a dietician. We have something called neurofitness. We work on movement for the brain. We do a lot of the sort of mind-body stress resilience work with coaching, focus a lot on heart math. There are many paths to that mountaintop, but I do like heart math. But yeah, you have to have those foundations. Are there other tools? Are there other what I call gadgets and gizmos? Absolutely. There are some very interesting technologies out there. and they're well worth investigating. But you can't expect to say, shine a near infrared light on yourself, but not do the other stuff and then think your brain's going to get better, right? It's really important that we start with those foundations. Yeah, absolutely. I feel like we've had this conversation though we haven't you know because for me my five pillars are health I tell them it's the five house how do you eat sleep stress exercise and socialize And then everything else builds on top of that, right? I'll tell people supplements are meant to help to facilitate a change, medications or peptides to facilitate a change, not to be a change. And it's just like building a house. No one wants to talk about the foundation or the framing. Everyone wants to talk about, oh, can I get granite or can I get quartz? And what about the fixtures? Because it's... ultimately the foundational stuff, it is essential, but it's not sexy. And so people want to skip it because of that. Now, you know, that part has got to be done, but now let's go on to some of the other things, you know, that can happen and can play a role as well. So how do you assess and address environmental toxin exposure? Because there's been a ton of research coming out on that with any neurodegenerative condition, as well as there's a lot more research coming out on hormonal imbalances. And, you know, and what kind of role does that play in patients with cognitive decline? Well, I think both are really critical, really critical. The toxins can be handled a few different ways. Certainly, it's important for folks. You know, we just got done talking about lifestyle. And then I said, well, how am I supposed to detoxify? Like, wait a minute. Step back a minute. When you sleep, when you eat and hydrate and poop and pee, you know, when you sweat, when you're exercising, all of that, is detoxification. So do you need to be on DMSA or do you need to be on, you know, chlorella, spirulina? Do you need to be on EDTA, whatever, all the various ways that we can sort of medically detoxify or detoxify? through nutraceuticals, maybe so. But don't forget that those foundational lifestyle factors are by themselves detoxifying. And you do need to try to identify the sources of those toxins and eliminate them as best as possible. I mean, dirty dozen, clean fifteen, get your water, your well tested. I mean, a story I tell all the time. A patient came in to see me with ALS, lived in a part, or hopefully he's still alive, lives in a part of Maryland where every house in the neighborhood has radon underneath the house, every house. And this gentleman, I said, well, that's terrible. He said, yeah, but they protect the houses. They put in a barrier so the radon doesn't come up. Oh, that's okay. Well, that's good. But he was obsessed with neti pots. So he's getting water from the ground, putting it up his nose, which is basically just a thin layer of bone from your brain every single night and introducing this toxin basically right into his brain. If you are concerned about mold, I view the whole mold mycotoxin story as a story of inflammation, as yet another driver. I don't want people to say, I don't have Alzheimer's disease, I have mold illness. There's no doubt that if you live in a toxic environment like that, it's probably going to cause some brain fog. But you know, get out of the mold. You take all of the Coley styramine or well call or charcoal or what have you, but if you're still living in that environment, you're really not going to do very much. Right. So heavy metals are, you know lead arsenic mercury cadmium we look at herpes simplex virus because the data is so interesting and the possibility of an intervention with valley cyclovir ray cyclovir is there I do check for lime I'll check mold if somebody wants me to do that those are the main things I look at from a toxin perspective and make sure that people are treated And then on your question of hormones, I would say that it's absolutely critical. You know, a hundred percent of women will go through menopause or surgical menopause one way or the other. A hundred percent of women are affected and twice as many women are affected by Alzheimer's as men. and men will develop often low will develop low testosterone not every male but many men do because metabolic syndrome and stress and all those things play a role in driving down testosterone and you know the data is really clearly emerging that when you optimize hormone levels you dramatically either reduce your risk of developing the disease or you change the trajectory of the disease with hormone optimization And there are a few exceptions, of course, where I obviously wouldn't give somebody give a woman estradiol if she was actively being treated for breast cancer. That was especially when it was estrogen receptor positive. But on the other hand, I don't want people to think that estrogen causes breast cancer. And I've had plenty of women in remission. from breast cancer that I treat with testosterone at the blessing of their oncologist go for it there is no risk of treating women with testosterone and we give them female appropriate doses and they do very well with testosterone very well so it's one of the most gratifying areas I would say because People feel well right away. And then, you know, you're doing something for their brains and the rest of their body in the long run. Yeah. You know, especially the testosterone people just forget that females have it. They're like, oh, well, that doesn't matter for them. It's like, no, actually, that's one of the most stable things. hormones females have throughout their life whereas estrogen and progesterone fluctuates based upon a cycle whereas testosterone's like no it's just kind of there and you have a lot more of it than you think they just skew the you know the metrics on it because if you really thought how much you had compared to estrogen but oh whoa that's a bit and on the detoxification side I sell people first thing you do to detox is to stop the exposure. I mean, you know, stop. And it's what we said about the pillars, right? It's stop looking for fancy supplements while you're still eating horrible food. You're not exercising, you're not moving because you're just not going to get as much out of it as you could. And then lastly, where I want to get into is, you know, with we're both, you know, always looking at the latest stuff and you've been in this arena for a while and you exclusively pretty much do neurological neurodegenerative based stuff. Whereas I'm a bit more spread. You know, I do a lot of concussions. I even do some autoimmune and stuff like that. So what are you seeing out there and what are you finding as you're, you know, through the research, through different colleagues you're talking to, and even your own experimentation, what's your perspective on the future of regenerative medicine in treating Alzheimer's disease, particularly regarding the autologous mesenchymal stem cell therapy? And what are some of the potential and limitations do you see in that? Yeah, I do think it's an exciting area. I do still think at this point that it's an adjunctive treatment. And like a lot of things, the earlier the intervention, the more robust or reliable the response is going to be. For clarity's sake, and I want to just use as an analogy, if you will, Parkinson's disease, because when people think of Parkinson's, in general, many people will know that there is a loss of dopamine-producing cells that contributes to at least the motor symptoms of the disease, what we see outwardly, the tremor, the shuffling gait, the masked facial expression, and so forth. And I have a lot of folks who are interested in... some of the stem cell research that involves putting dopamine-producing cells back into the brain to treat the disease. Now, historically, and this type of research goes back, in my world, at least into the eighties, at Emory when I was there and the neurosurgery department and Dr. Charles Watt was involved He was a member of the department, Ray Watt, sorry, different Watt, was department, in the department of neurology, went on to become president of the University of Alabama later on. But they were stereotactically introducing embryonic cells neural cells into the brain and trying to coax them into producing dopamine and replacing the cells that were lost. Now, fast forward over time, the government passed laws that says you can't harvest embryos for research anymore. There may be some immortal cell lines that are still being used. but those are older cell lines that have pre-existed that law, and no one's killing babies, to be absolutely clear, to do this type of research. But now there is a whole area of science referred to as IPSCs, or induced pluripotent stem cells, where we can basically take a cell from your body, Because every cell, whether it's a cell from your retina or muscle or bone or what have you, has the exact same DNA. It's just which genes are turned on and which genes are turned off that makes those cells specialize. So if we can program those cells, we can take a skin biopsy and we can tell it to become nerve cells and grow that out in a culture dish, if you will, in a lab. And then when you have enough cells, in theory, we could put that in the brain. But the problem, in my opinion, the reason I don't like that type of research right now, there may be some very good reasons to do it. For example, heart transplants, where we no longer have to look for a matched donor. We can just grow your heart. in the lab from your own cells and do a heart transplant and that day will come without a doubt without a doubt at all but in terms of putting cells back into the brain the problem is like the old expression the solution to the pollution right you and I know that that hasn't addressed any of the things that created the problem in the first place So mesenchymal stem cells are a particular type of pluripotent cell. They can be found, for example, in fat tissue in the body. We get them in our clinic from bone marrow, your bone marrow. The most important thing to understand about these cells is that they are cells of tissue repair. They are anti-inflammatory. They secrete signals in the form of exosomes and mRNA, microRNA rather. that basically give the instructions on how to repair injured and inflamed tissue. And they tend to respond to their environment. So if they are exposed to cerebrospinal fluid, they'll say, oh, I'm in the area where the brain and the spinal cord are located. And then they act like a homing pigeon to find the areas of injury and inflammation and start turning that down, dialing that down. Now, does that mean that it's going to cure all Alzheimer's disease and other related disorders? And the answer is probably not. But as part of an overall anti-inflammatory diet and lifestyle plan, it certainly may kick things into gear, give you the upper hand. You do have to repeat these types of procedures, which either means repeatedly harvesting bone marrow or banking your cells and having them expanded and then coming back into the clinic or procedure room and having them reintroduced into the spinal fluid, which is what we do. I don't put anything in someone's brain, put in the spinal fluid. But I think there is a future for that. We just have to make it practical. Right. Friend of mine, very good doctor does therapeutic plasma exchange therapy. Well, if you have seven million people with Alzheimer's disease, there's not enough, you know, plasma exchange machines in the world, you know, to treat all those people. Is it good science? Absolutely. It's very fascinating. Very, very fascinating. But is it practical? Right. That's another question. Yeah. And then kind of one of the last things I want to hit on, and we talked about it before we started the recording, you know, you've got people who are desperate and they're going down to Mexico or there's even people who are like, Oh yeah, we do stem cells in the U S and they're doing like injections and like the knee and everything else. Like, you know, what are people, what should they be thinking about? What should they know? Like for me, right? Like if I was to get stem cells, I would think cerebral spinal fluid or even maybe intranasal because of maybe those would be about the two best pathways of actually getting it into the brain versus some of the other stuff. So let's just touch on that really quick. Well, I certainly don't want to make any blanket statements that just because something is outside the United States, it's automatically bad. But to be clear, there are practitioners who are American citizens who have clinics outside of the United States for the very reason that they are ducking the laws of the United States. And if you go to one of these clinics and you're hurt or injured, it's going to be too bad, so sad, you know, because you have no protections at that point. So please do understand that you'll be paying your, you know, hard-earned money for these procedures and you'll be taking a risk. And when we use phrases like stem cells, people sort of get, you know, glitter or sparkles in their eyes. But please understand that there is science. This is a medical procedure. It's just like medical tourism. Can you have a good outcome if you want to have your brow lift and boob job or whatever in Thailand or Switzerland or where have you and save some money? You may have a fantastic outcome. But just being educated, being aware, being cautious, being skeptical about claims that are being made. If you think that somebody is out there curing MS and Alzheimer's by giving stem cells, my opinion is they should be given a Nobel Prize. It shouldn't be limited to that clinic. Get the word out. Get the technology out. If they're the only clinic in the world that's curing this disease, they probably are selling you a a false narrative right we want to believe these things so bad uh but I tend to be like I said more conservative that everything counts it should be measurable and trackable so it takes us right back the beginning of our discussion biomarkers tracking outcomes being as objective as possible and if you find you know there's really a good place in mexico or wherever the caribbean that's doing quality work and being honest and transparent then more power to them but some of these places are charging twenty five fifty thousand dollars too know that's a lot of money for most people and I can tell you can get those some of those procedures legally within the united states for a fraction of that cost yeah yeah that's something I just wanted to touch on because I know there's a lot you know there are some good places and then there's some that people are just going I'm like man like you've got to really vet these a lot more and I hope we've done a good job of providing people with information throughout this whole podcast on you know different thought processes, things that they could ask him, you know, so this has been really, really good. So if people like to learn more about you and what you do, cause you do have something really special. And I believe, you know, you do treat people from all over the United States who travel in for what you do. So how would people learn about you? Best place to go is my website, which is functionalmedicine.doctor. So it's not a .com website. It's functionalmedicine.doctor. Just enjoy the website. You know, we have the YouTube channel and all that good stuff, the Facebook page. I don't spend a lot of time on Twitter, but it's where X as it's now called. We have a little bit on LinkedIn. And all those are there for awareness. But the website, functionalmedicine.doctor, is definitely the place to go. You can sign up for a free consult with my coordinator. We really want to learn about you. We never, ever, ever sort of hard sell anyone because that, you know, That never works. It's not good. It's not good for anyone. It's not good for you. It's not good for us. We want people who are really interested and committed, ready to make those changes, and truly understanding what the commitments are that they are making when they come and work with our team. So it's a very open and honest conversation. Usually by the time someone is visiting us, there have been at least a few of those conversations because a lot of folks aren't ready necessarily to make the commitment the first time. But we want people to take their time. When they come, they have a fantastic experience. Awesome. Well, this has been fantastic. You know, we'll have to for sure do this again on some of the other topics in neurology. So thank you, Dr. Sharlin, so much for being here today. My pleasure. Thank you for having me.