Psychiatry & Psychotherapy Podcast - Alzheimer's Dementia

Episode Date: August 13, 2021

Alzheimer's disease is a devastating neurodegenerative condition that affects the entire family. As psychiatrists and psychologists, we often support these patients and their families throughout this entire disease process. With the recent and controversial FDA approval of aducanumab (Aduhelm™), a new pharmacotherapy for Alzheimer's disease, we can expect to be asked about this drug from our patients and their family. By listening to this episode, you can earn 1 Psychiatry CME Credits. Link to blog. Link to YouTube video.

Hello and welcome to the Psychiatry and Psychotherapy Podcast. I'm here to talk about getting rid of burnout, increasing job satisfaction, and feeling like an expert in what you do. One thing that created a lot of burnout and angst for me was trying to get continued medical education right at the last minute. So why not join the CME membership and do CMEE while listening to this podcast? Go to Psychiatrypodcast.com. Sign up, sign in, take the test, and the certification is emailed to you in seconds.

Before I begin the episode, I wanted to give a brief introduction. Alzheimer's disease is a devastating neurodegenerative condition that affects the entire family. As psychiatrists and psychologists, we often support these patients and their families throughout the entire disease process. With recent and controversial FDA approval of adukanumab, a new pharmacotherapy for Alzheimer's disease, we can expect to be asked about this drug from our patients and their family. Initially, there was a lot of excitement from the scientific community when aducan umab and other similar pharmacotherapies first entered clinical trials. However, phase three clinical trial of several drugs in this class failed to show clinical improvement in memory and

cognitive functions, despite their high efficacy in removing CNS amyloid plaques and the classic brain pathology of Alzheimer's disease. Therefore, it would have been a very important. a surprise to many scientists and clinicians when the FDA officially approved aducanumab on June 7th, 2021. When we took a deep dive into the controversy, our findings were shocking. Not only is the new therapy aducanumab not effective in providing clinical benefits in memory and cognitive function, it is also associated with adverse side effects that we need to be ready to discuss in detail when the opportunity arises. Therefore, the entire FDA review and approval process of aducan UMAB, as well as the high price stack, is now under investigation by the Office of Inspector General of the Department of Health and Human Services and Congressional Committees. Essentially, this kind of is a different episode that looks at an important topic, dementia.

We, towards the end, we'll hint at things that we do think work and that we can talk to patients about, including exercise, diet, sleep. But I was thinking about this episode and how similar this is to the Britney Spears conservator trial. Follow the money. There's corruption, guys. People are swayed consciously and unconsciously. to do things based off of money. So none of the people on this episode have any conflicts of interest to discuss.

We don't receive any money for drug companies, exercise companies, sleep companies, diet companies. And it is my great pleasure to have this interview with Dr. Shin and Dr. Osorio. Other things to announce is that on the website, Psychiatrypodcast.com, we now have shirts that you can purchase. If you're a mental health professional, you can be rocking a nice psychiatry and psychotherapy podcast shirt. And other things to announce, we still have signups for EmotionConnection.com. This is the microexpression training. If you are a student, there is a student discount.

So you can go on there and find out about that. And thank you so much for your support, guys. I really appreciate it. I appreciate all your support in being able to promote good content. trying to look at the data as closely as I can with as little biases as I can. So here we go to the episode. Welcome back to the podcast. Today I'm joined with the amazing Dr. Carolina Sorio.

She is a geriatric psychiatrist, Ella Melinda, who I used to talk with on my breaks, who I miss dearly. And she was on some prior episodes. She runs an amazing program for dementia. she does outpatient psychiatry, some inpatient psychiatry, she does it all. And then also joining me today and Dr. Sorio is medical student and PhD graduate Sam Shin, who did a PhD focusing on neuroinflammation. So he knows quite a bit about Alzheimer's disease. It was one of the topics he dug into on a deep level and a recent level, which is nice because we like to look at the most

recent data. So we are just going to jump right in to the topic. And I am going to bring up the slides. If you go to my resource library, we'll give you a copy of the slides, a copy of the paper that Sam is working on. So Dr. Soria, you want to start maybe and talk a little bit about what we're looking at here today. Right. So today we're going to talk about the main thing is we're going to talk about the new Alzheimer's drug that was recently approved on June 7th of this year. It has a complicated name, but the brand name is Adduthon, and the generic name goes by adupanumab. So the reason why I'm very passionate about educating and talking about these recently approved drug is because when it came out, it came out with a lot of high hopes to

treat, modified Alzheimer's disease, which is we know if the terminal illness is a narrow degenerative process and therefore one of the most difficult illnesses to have as a patient and also as a family member and as the caregivers or the family members and as in the community as well. So when this came out, I was kind of a little bit sort of like really, this is really true? Am I going to finally going to give some hope to my patients that maybe we could improve their symptoms? So I started looking into this medication and then immediately all of the other doctors that are part of my institution and also treat Alzheimer's. We started to chat, text and finally decided to get together in a meeting after we had review all

lot of the data, a lot of the information, and what really was going on with medication. And in between these and that, I came across Sam, who came to work with me for two weeks, and we both have like the same kind of theories behind Alzheimer's, and it was just really amazing that he came at that moment because we were able to, you know, explore more the research, the evidence, the pathophysiology, and then he put up a small presentation for the department And then now we want to just spread more of what we know to everybody out there. So we all are very well informed about this new medication. Excellent.

Yeah. So this is a place where Dr. Soros in the trenches. She's seeing these patients every day. She's having long conversations with family. And so she's imagining, you know, as she's going through this, am I going to be having conversations about this new medication? I'm going to have tons of patients who are hearing about. about it. And the controversy, I think, is pretty interesting. So Sam, why don't you jump into a

little bit about what you found in the news, the high cost and so forth? Yeah. So there's actually quite a few layers to the controversy surrounding the FDA approval of African New Map. One thing, I'll start with the cost. It's going to cost about $56,000 a year. It is designed as a 14-month treatment, so a little over that, probably over the course of the treatment. And that is a lot of money. And we have to remember that this is a very vulnerable population when if you know anybody with Alzheimer's or have been taking care of them from a clinical perspective, you know that they will hold on to anything.

So even if it costs a lot of money, people are more likely to go with it if there's even a sliver of hope. And that's where the cost comes in. I just want to kind of talk about this $56,000 year because we have many interventions that are more expensive than that. But the take-home point here is that it's not very efficacious. Yeah. And that would be like, okay, if it was the cure, it might make sense for some people to pay that much or insurance to drag us through a bunch of prior authorization. to get that medication.

Yeah, so there's a lot of hype about the cost of the drug when it came out. But what's more important, I guess, from clinical perspective, is the lack of evidence. And we'll get into the details of what biogen, the company that made this drug, had presented to the FDA. We're going to go into that deeper later. But the cost is definitely something that stands out. Yeah. So, Dr. Soria, tell me a little bit about the Alzheimer's disease public health crisis. Yeah, so we know today that Alzheimer's is a public health crisis.

Right now, it is costing Medicare about $799 billion. So imagine, it's already super expensive illness, and you want to sell a medication that is $56,000. So put that in perspective. There are more than 6 million Americans living with Alzheimer's, and by the year 2050, that is projected to rise to about 13 million, which is 29 people who are above the age of 65. More than 11 million Americans provide unpaid care for people with Alzheimer's and other dementias. So this is relating to caregivers, right, who are, you know, who have their loved ones.

In my practice, most of what I see is either the husband taking care of the wife. And in my practice, because we know that Alzheimer's is more common in women. So that is what I tend to see more. But of course, I also have wives taking care of their husbands. And a lot of that times they don't really have the means to hire someone. So for in-home health care, in California, the only insurance that pays for that is Medicare. And in order to be a Medi-Cal person, you need to be very poor. And a lot of these patients don't meet, you know, that criteria of poverty levels to be able to apply for Medi-Cal, which is also known as Medicaid.

So these people are taking care of them. And so in 2020, it is estimated that about 50.3 billion hours of caregiver is given and is valued about 250,000. is having a million dollars. Yeah. Yeah, it's a huge stress for families. And I think people don't really realize that unless they're in the trenches doing it day in and day out. Right. Okay. So let's talk a little bit about Alzheimer's, maybe some definitions. What are some of the things that have historically been thought to be the cause? So Alzheimer's disease, we classically describe it as progressive and fatal neurodegenerative condition. It's a clinical diagnosis, meaning that we make the diagnosis of Alzheimer's dementia in clinic based on what we find on

history, as well as there's quite a few cognitive testing modalities that we can use. Used to be confirmed more probably on autopsies for pathologic markers. Now with so many people having this condition, it is not as much of a routine practice. And overall, Alzheimer's disease estimated to be responsible for up to 80% of all clinical dementias. And when we're talking about the pathology that I mentioned, it's classically associated with beta amyloid proteins and tau neurofibrillary tangles. Those are kind of the step one buzzwords. And they will come back to them because they have had a huge impact on how we do research in Alzheimer's and how we go about developing therapy. At this point, as we're speaking, there's really no cure. And we do have

four FDA-approved therapies, pharmacotherapies, prior to adjudicenumab. And the effects, clinical effects of those have been quite minimal, especially when we're looking at the long term. So this is, you know, a very devastating disease that affect, you know, someone's life from 65 or 70 and on for a long time until they die. So Dr. Sorio, break down a little bit about the history of Alzheimer's disease for us. Yeah. So in 1906, there was this person called Al-Ale's Alzheimer's, and he was the very, very first person to remember. reports and out plagues an intracellular narrow fibular, sorry, narrow febrily tangles in the brain. And he observed this in a patient, 51-year-old female who had died, I mean, at 51 had died from

advanced dementia. So you can only imagine this disease had been already affected this person's brain even 10, 20 years before. Because we know Alzheimer's, when it's symptomatic, it's been more than 10 years that the disease has been affected. the brain. But it wasn't until 1984, you know, with modern biochemistry and cell biology tools that the amyloid plates and neurofibrillary tangles were analyzed and they were described as the main components of Alzheimer's disease. So, you know, the amyloid plates were basically amyloid, beta amyloid proteins that were deposited. And that was the very first one. And then in 1986, they talked about the neurofibrillary tangles, which is microtubal biting protein to tau.

And then that's how, you know, they put them together and how we came with this new theory that Alzheimer's was caused by, you know, these two, the fibular tangles and the amyloid proteins. So the amyloid beta will generate, will accumulate in the brain and that will cause abnormal tau phosphorylation. and then the tau will aggregate into neurofibrillary tangles, and these combination will cause neural death. And then with time as the cells died, there was a loss of cognitive function that eventually, you know, will take completely over the brain and the person, you know, eventually will die. So the prediction was that if you reverse the amyloid,

you will reverse or delayed Alzheimer's disease. But after 30, almost 30 years, of active research, there has been not one single amyloid targeting therapy that has been shown to be clinically beneficial. You can have someone have a pet, an amyloid, pet scan, and have that brain with a lot of beta amyloid and be totally cognitive impact, or you can have a person who has very little amyloid deposit and have cognitive problems. So there's really no clinical correlation of the imaging findings with the cognitive status of the person. Yeah, so this is starting to make me question what I learned in medical school just a

couple years ago, you know, or decade ago, I guess. Okay, well, and there's also this idea that not Alzheimer's are the same. And that's, Sam, why don't you talk a little bit about that, the three subtypes? Yeah, so this idea that not Alzheimer's the same, you know, really shouldn't come as a surprise, you know, given, you know, current advances in so many diseases we're starting to find heterogeneity and complexity in just about every disease process that we learn about. And, you know, when the amyloid hypothesis first made, it was kind of the best thing we had at the time. We had just discovered what the plaques are made of. we just figured out what the aggregates are, that they were tau proteins. So, you know, based on that, this dogma was created that, you know, it's a series of events that lead to neuronal death and cognitive dysfunction and this syndrome that we see clinically.

Well, since then, we've found quite a few things about Alzheimer's disease. and combining kind of what we find from the public health side as well as the genetic side and what we see in clinical setting, it's really there's multiple subtypes. So the first one is what's commonly known as the familiar Alzheimer's disease or also known as early onset Alzheimer's. And this only affects about probably less than 5% of all Alzheimer's. And there actually has been mutations that have been described, amyloid precursor protein, Prestonel in 1 and 2.

these mutations cause abnormal amyloid biology. And when these things were coming out right after the amyloid hypothesis, it really fed the hypothesis, gave it a lot of support saying, hey, look, we are, we're finding out mutations that lead to this disease. Another support, which describes the second category, is the trisomy 21 Down syndrome. So APP gene, which is the precursor to amyloid beta, is actually on chromosome 21.

So trisomy 21 patients have an extra copy of a BP gene. And we know from the clinical side that many Down syndrome patients develop early onset Alzheimer's. And it can be as early as in their 40s. So these two things, these two subtypes, you know, really supporting the MLOA hypothesis. Now, the thing that is often forgotten, and this is a disconnect between basic science and clinical clinical science is that the majority of Alzheimer's, more than 90%, falls under what's called the sporadic Alzheimer's disease. So this is actually what we clinically see most often, usually happens after age of 65, well into their 70s. This is the slow, insidious disease process that

we see and we have to support our patients through for many years, sometimes up to two decades. Now, this portion and the largest population, the ideology in this group is really not well defined because it's not direct amyloid biology. And we are doing a lot of genetic-based research where now we're seeing, and there's a table that kind of has many, many genes involved in multiple processes. But what we can say is that the sporadic Alzheimer's, which is the most common form, is truly heterogeneous in the geology of the disease. Okay.

So that's still fairly genetic, largely heritable, but it's not associated with genetic mutations directly related to the amyloid biology, that largest group. That's interesting. You want to think about these periodic Alzheimer's as an epigenetic illness, right? where you have this sort of group of genes, but not very clear, but then you need to have like an environmental something trigger that actually, you know, targets all these pathology

and then, you know, the disease progression. Okay. And before we keep going, I just want to clarify something. When I said about the cost, it's $799 billion of total Medicare spending in 2019. and from that number, 355, only for Alzheimer's disease. So I think that's even more... Wow. Wow. Okay.

That's a huge proportion. So, okay, so we've talked about how not Alzheimer's disease are the same. There's a lot of different genes involved. So it may be hard to identify an early causative factor, especially if there's so many different causes. Well, is that? I'll just speak kind of generally on these genes because, you know, we can get very nitpicky, but Yeah, we don't want to do that.

It's really genes involved in like cholesterol metabolism, metabolic pathways, a lot of inflammatory genes. So what I guess I meant to kind of convey earlier is that it's not just this one biological process where amyloid precursor protein turns into amyloid. Everything was focused. on how that process happens. But we're seeing that, like, biggest risk factor for developing Alzheimer's, for example, APOE4, it's a cholesterol-related gene. So we need to start looking more into other biological processes that are involved in development of Alzheimer's disease.

Wow. Yeah. So tell me about, so there's cholesterol, there's inflammation. Is the inflammation localized? like if you tested a CRP or ESR, those high? Is the inflammation like, how do we know there's inflammation? I guess would be my question. Well, Dr. Rior, do you want to talk about the type 3 diabetes?

Yeah. Yeah, so, you know, there is, so we know that there are a couple of very important risk factors for Alzheimer's. and those has to do with sort of like midlife management of hypertension, obesity, and diabetes. So we do say that there's this what we call type 3 diabetes, which is basically people who have Alzheimer's. And it has to do with these midlife risk factors, you don't control well for them. and so you start having changes in your brain, mostly related with microchemic vascular changes.

So it's not like you have a stroke and then you have cognitive problems. These are people who have like no physical symptoms whatsoever. But with poorly controlled diabetes, this very tiny, it's like microtain is chemic changes that will eventually cause cognitive impairment. And so that is why it's so important that we make this difference because we know today, we have lots of evidence, lots of research that shows that there are other things that we can do in our life to actually prevent having this disease. And there are even places where you have like mild cognitive impairment and you can reverse that. If you are very, very mindful about your lifestyle and all this intervention that we can talk about any other time that can.

help you reverse those cognitive impairments. Well, I think I want to get to that because I think that's what people are probably going to be most interested in. So we're moving beyond the amyloid hypothesis. We're looking at metabolism, inflammation, and genetics and how those all sort of interact around stress. I think that one of the big pictures that I have is like people used to die of infections, right?

A hundred years ago. Now people are dying. of chronic stress. And it's like the big picture is what does chronic stress look like? It looks like hypertension, prediabetes, diabetes, obesity. And there's so many people headed towards that bad diet, low exercise, under exercised, you know. Yeah.

Yeah. Any other comments on this sort of big paradigm shift? Yeah, so the type 3 diabetes is like kind of a phrase, nickname that kind of was coined for Alzheimer's disease because all these studies were showing that if you have diabetes, insulin resistance, hyperlipidemia, metabolic syndrome, obesity, even something like how big your waist measurements are, these things were all shown to be a risk factor for Alzheimer's disease. So clearly things that we can have some control over like diet and exercise are going to have an impact in managing Alzheimer's disease. Yeah.

So and I think I just want to mention this really quickly. You know, a lot of patients say, well, you know, they be a criteria for obesity and they said, oh, but my labs are all normal. So why should I worry about my weight? And I think why you should worry about your weight is because all that visceral fat that accumulates, meaning that fat that is inside your belly around all your organs, that fat is causing a chronic state of inflammation in your body and that eventually is going to have consequences like, you know, Alzheimer's disease. Yeah. and this fits well and inside my thoughts on the importance of exercise and diet and lifestyle, you know, and so some things like we cannot improve with medications, right? So I think it's really important as doctors to direct people towards what is going to be the biggest win.

Even if that biggest win is really difficult. Losing weight is like agonizingly difficult, you know, as someone who is, probably predisposed towards being too heavy. It's like you lose some and then you gain some and then you lose some. And then it's like try to maintain a normal exercise life as a psychiatrist. Good luck. You know, there's just like, you're on call one weekend and then the next week, next day, you're just totally out of it.

And I know me and Dr. Osorio, we've been on our own journeys there. Yeah, we definitely share the same concepts. And so I also struggle with this weighting. and the stress management and all these. And on top of it, I decided to test my genes, and I happened to have a copy of Papua E4, until that just increases a bit my risk for Alzheimer's. And I am very cognizant of my lifestyle

because I know there is good evidence, everything. The lifestyle can come in. And so I'm not perfect, right? And then I fell back and forth, but I overall try to maintain a good lifestyle so that I can live long and healthy because I don't believe in lifespan. I believe in health span.

If I want to be 80 or 90s, I want to be in the best condition that I can possibly be. Okay, so I know that some people are going to be interested in the nuts and bolts, and so we'll give them that in the handout of this new medication. But just like your summary of your dive into it,

and you guys, you know, you have slide after slide on this, it seems like if you could give me the big picture, like what happened and what your conclusions are, Dr. Osorio and Dr. Shin, that would be helpful. Yeah, I've done actually some extra digging since we put this together. I think we put it together right when the drug came out. Okay. And actually there's been a little more.

So I'll kind of start here and then Dr. Osiriam film me in. So really the big picture and the controversy all started with FDA approving the drug against its own committee. There's an independent committee that oversees this process, and all 11 members have voted against the drug being approved. Nevertheless, FDA a few months later, approved her drug. And now there's congressional hearing committees. There's actual investigations going on from the Office of Inspector General. And they are looking at financial ties between biogen, the company, and the FDA Foundation. There's allegations of the FDA personnel, people high up on the list.

They're having private meetings and so forth, which are all against the process where, you know, the FDA process that's supposed to keep this process, you know, as fair as possible for public benefit. So that's kind of the main thing as far as the controversy. There's, as far as the drug itself is concerned, it's, it's not efficacious. And what I mean by that is at phase three trials, they had two phase three trials. So they usually have a parallel trials. Now, this is the phase where you're supposed to prove efficacy of the drug over thousands of patients.

They had about 1,600 patients on each arm. And what that happened is that halfway through the study, they did their internal analysis and realized, oh, the futility analysis shows that this drug actually doesn't help. One group, one of the arms showed mild improvement. The other arm showed mild worsening. So when you averaged the two, it was exactly almost at zero as far as efficacy is concerned. And it was actually pulled by the company. But what happened is because it cost the company over $16 billion in stock.

When the news was announced and, you know, that these are being pulled and the studies are stuck, There was now, and this is a part where it's being investigated called there was this secret mission project onnings is what the biogen people internally called it to basically lobby the FDA and reanalyze all this data, really do fancy statistics trying to get this drug approved. And they have slides after slides. There's 100 plus slides on how they justify this. but the bottom line is they are essentially saying out of the two parallel studies, we're going to drop one and just look at one because that one showed efficacy. The other one, we believe it had too many outliers. There were only nine outliers in the group out of 1600.

So they're using the nine patients as an excuse to drop an entire arm of the study. And of course, the review committee said this is nonsense, but it was still approved on the basis of its controversial. So that's kind of a quick summary of all the nuts and bolts and, you know, the graphs that we have in there for anybody who's interested in looking at it further. Wow. Do I miss anything? No, I didn't. Yeah. That's really the most important part is it was all this process about how a drug is approved by the FDA, what really happened, why this drug was approved, when everybody else voted no. And so, you know, and leading to the current, you know,

investigating that is happening as with space. I do want to just quickly say that it was very clear that the drug removes amyloid. And I do also want to say that many other companies had similar drugs at the same time that also showed that. And many of the 400 trials I mentioned before also did that. So it wasn't a question about whether it removes amyloid. It was, does it improve memory? Does it improve function?

And that's the part where it's been, no, it doesn't, which kind of, you know, brings the whole thing back to him. Well, are we looking at the right thing then? Yeah. So, you know, I'm looking at the FDA data here, this slide you have, on how much does it change mini mental status examination? Right. And it's, we're not looking at a huge change. at the end of the day. Like, so mini mental status is out of like 30, right, Dr. Osorio?

And, you know, 18 is considered, oh, wait, no, let me get this right. So mini mental status is out of 30 points, greater than 25 is normal, less than 10 is severe dementia. And even the data that they're presenting, it doesn't look like you're getting much more than a one or two. point change depending on the titration. I mean, compared to placebo. Right. Yeah. So in a clinical setting, it really comes down to when you ask the patient,

hey, where are you? And if they can say the city, but not the county, but then the next time they can say the county and the city, that's the one point right there. So it's really not a big difference. But you're saying, like, even after you looked at the data further, because of this, oh, was that phase two that I was looking at there? This was phase one.

Okay, so I was phase one. So I'm talking about phase one data. So when we look further at the phase three data, it's even less convincing. Yeah, so for phase one through three, they had a bunch of measurements, but what they used as a primary endpoint or kind of if this doesn't show improvement like everything else is pointless was the CDR clinical dementia rating it's on MD Calc it's used very frequently not just in psychiatry but you know other services to kind of quickly assess the severity of dementia so at best study 302 which is a study they wanted to keep it improved the CDR rating by about one when you give

high doses of this drug. When you scroll to the next slide and look at the other study that they wanted to drop or say it's invalid, it actually worsened the CDR scoring by one. So if you have 1,600 on each arm and 1 is negative 1, one's positive 1, it's really 0 when you combine them 2. And that's what dropped this all together back in 2019 until, you know, they did the gymnastics trying to prove it. And there's a slide on some of the rationale. And it kind of is important for, you know, medical students or people taking boards, this idea about confidence interval, 95% interval. You know, the take-on point is if there's a line down to zero and if all of the error bars are not on one side or the other, if any. any little bit crosses, that means no significant difference.

This is something that's drilled into us in medical school. What it means is you need more people or increase your end to really shift the error bars one or another, right? So they have, I mean, slides after slide where they break these groups down into every little possible group. And they say, look, all of these subgroups are showing a trend. Therefore, approve our drug. We don't approve drugs at the FDA level based on a trend. And there's a slide where, I mean, they just basically single out the entire 1600 patient phase three trial saying that it's insignificant because of the number of outliers. Yeah.

Which I briefly mentioned, but again, it was a very small number of outliers. And even when you take the outliers out and redo the analysis, it doesn't change the analysis. That's the funny part. That's the part where how do you then justify this approval, right? Right. And it's not only that it could, that it, you know, does it help? But what are the side effects and the cost of very, no change, right? So if it's not doing anything, when you add both studies together and then the adverse effects, they're talking about. about phasogenic edema? Yeah, so the most scary adverse effect of this, aside from headaches and things like that, is what's called ARIA.

It stands for amyloid-related imaging abnormalities. This is a very soft name because what it really should be called is phasogenic edema or microhemages related to amyloid removal therapy. If I say it that way, I think patients are going to be a lot more scared. because I'm saying if we give this drug, there's a high chance that you're going to develop significant brain swelling that results in all sorts of downstream consequences or you could even have a hemorrhage. But it's appropriately named, you know, imaging abnormalities when in reality it's much more than just imaging abnormalities. Yeah, and it's up to think it's up to 30% of patients can have this severe. side effects.

So again, if you put together the lack of improvement on symptoms, the cost of the drug, and the side effects is definitely something that the best majority of physicians are not willing to endorse. And another thing is that you actually have higher incidents of this area, edema, and hemorrhage if you are in APOE Epsilon 4 carrier. So earlier, we talked about APOEE Epsilon 4 being a significant risk factor for Alzheimer's. So it actually doubles your risk if you're a carrier from about 20% to 43% of developing area. So, you know, it really doesn't fit where you have more side effects in the population that are most affected by this disease.

So that's just something to also kind of remember when we're discussing this with our patients. Yeah. Well, essentially you're attaching a monoclonal antibody to a part of the brain, telling the brain to clean up this piece of foreign invader. And so the brain doesn't know that that isn't a virus or that isn't a bacteria in the brain. You know that this antibody is now hitting. And so you're going to have some side effects from that potentially. Is that kind of how you see it, Dr. Sorio? Yeah, in a way. And so now that you mentioned that, let me tell you a natural way of getting rid of amyloibeta proteins in your brain.

Oh, gosh. And that's called sleep. That's called sleep. Oh my gosh. Eight to eight hours. Yes. Sleep. So that, yes, sleep. Get out. That when you're sleeping, yes, when you're sleeping, your brain is getting rid of amyloa beta proteins in your brain. Wait, Dr. Soria, before you say this, are you, do you have any conflicts of interest, to report, Sam or Dr. Osorio? No, at all. Sam, do you have any conflicts of interest to report? Okay, you're not paid by some sort of sleeping company or...

No, I do not have that conflict of interest. Where's the sleep lobby when you need them, Dr. Sorio? I want to know where the sleep lobby is, you know? Like, who cares about our sleep as doctors, right? It's like... Right. From years and years of being on call, if you're listening to this, you can probably relate. You know, I mean, especially if you're in the trenches of some psychiatric hospital,

listening to this on your way to work or from work. Okay, so sleep. Sleep is important. Yeah. Okay, give me some other, like, one thing that I looked at was this study on strength training, and we're going to look, me and Sam are going to bring this back for part two, okay? but it really looks like it slowed down the cognitive decline, the normal sort of amount of brain loss that there was per year. But I want to have Sam dig into this and give us a proper PhD level analysis on this.

So there's exercise. Is there any data to support that if you exercise, like, that's going to decrease your chance of Alzheimer's? Like, is that? Exercise? Oh, absolutely. So again, it goes down to lifestyle modifications, right? So stress management, sleep, nutrition, physical activity, avoiding risky substances, all of that stuff.

It's like, I mean, like God is treatment for your brain and your overall health. Okay, so with exercise, let's say you're a mental health professional when you're listening to this. and you're like, I do no exercise. What should I do, Dr. Osorio? I'm worried now. I don't want to develop Alzheimer's. I have a family member with Alzheimer's.

What do you say to them? Yes. Okay, so I can give you this, see if you can relate to these. There was a point in my life that when I had my first job, I was overwhelmed with stress. I was so tired that I will be in the couch every day, all the time when I was at home. so I put weight and I was feeling literally sick. Anyways, bottom line, I decided at that time that I had to change. But I wasn't a hot potato.

I was not moving at all. I was totally sedentary. So what I did is I, first thing I did is I got a pedometer and I start counting my steps. And so it's not about like exercising. It's about moving your body. So if you don't move your body at all, start with small things like counting your steps. Then, you know, then I realized that I was doing like a thousand steps a day and then I start building this program, what I would increase it every week by 500. And then out of nowhere,

I started doing 7,000 steps. And then I decided, you know what, I'm going to go the extra step because I feeling better. And I downloaded an app for a 5K. And in a year and so, I became a half marathon runner from being a couch potato. Like even when I say this today, I am totally perplexed that I I was able to get so far, just starting by counting my steps. You know, when I think of Dr. Osorio, I think of someone who's very in shape, actually. I'm very health conscious. Yes, I'm very health conscious. We'd go out to eat at a really nice restaurant in town and she would get like this super healthy thing.

That's just how you roll. So I appreciate that about you, Dr. Soria. I think, you know, wherever you start is where you start. All you need to do is create some small stress on your body, allow your body to recover, and then you adapt, and then you repeat that cycle over and over and over again. So when you're just starting, just literally getting out of the house for like a 20-minute walk, it's going to be a big enough stress to cause an adaptation. And you could just do that every day, right?

Or vary it up. So sometimes I have patients who then they start getting like some sort of pain from walking a lot. It's like, okay, let's jump on a bike. Let's jump on a rower. I've been going out on the water. It's like incredibly beautiful rowing every morning. Doing some, I have like a lifting coach. I'll post some pictures to Instagram if you want to go check it out.

Support my progress. I still have, I still have a progress to make though, you know? So it's a journey. It is a journey. Yeah. What about you, Sam? You know, there was this concept that I picked up from this podcast earlier called kind of the difference from fixed mindset to kind of having an open mindset that you can change. And I think for me, I was for so many years, I mean, I've been in medical school and graduate school for almost a decade now thinking, oh, I'm so busy.

I have time to exercise. And, you know, I was never an athletic person growing up. So that was another thing like, oh, that's just not my thing. thing. But I think just a little thing is like, well, I'm not fit to I'm not fit yet. You know, it's a small change. But it kind of gives me this hope. Like, okay, I'm going to just do a little thing here and a little thing there. And it just gets me going. I actually got the cheapest drawer I can buy. Nice. Good for you, bro. And I've been just getting on it when I can for 15 minutes. And before what inhibited was, I don't have time.

I'm too tired. But now it's like, well, I'm just going to try for a little bit. And if I stop at seven minutes, so that's seven minutes more than nothing. Absolutely. Absolutely. Great. Yeah. For the rower, I would say, just get on for three minutes.

Give yourself a nice five-minute break, drink some water, walk around, get on for another three minutes. And repeat, you know, do that three sets of three. And then every other day, add five. five seconds. So you literally, the second time you do it, three sets of three minutes and five seconds. And then take a nice five minute break each, you know, and you can, you can increase that, right? But it's so important to just start somewhere, right? So that's one thing you can do. The other thing is diet. I, um, I think I'm big on like avocado. Dr. Soroy, what do you think about avocado for the brain.

It's wonderful. And I don't. Yeah, I don't, I don't want to say diet. I want to say, um, healthy choices. Okay. Right. Because when you say diet, it sounds very restrictive and we know that restriction doesn't. You need to do something that is sustainable.

So yeah, um, healthy fats, avocado, uh, not oil, you know, like I choose, um, that are very good, walnuts. Um, there's a lot of research. how good that's for your brain. And then you also have the omega-3. So, like, I consume a lot of salmon. So if you don't eat fish, if you're vegan or whatever, we have flax seeds. You know, there's a lot of sources for these very good oils.

Yeah, flaxseed, chia seed. I just prescribed it to a patient, told them they soaked their oatmeal overnight. And so I said, throw in two tablespoons of chia seed into that with the oatmeal. And just that small shift and add a little bit of almond butter in the morning, this person needs to gain weight. So they need to add some food fats to their diet. But even just these small changes can make a big difference. So I always, you know, I had a really good dietitian that worked with me for a while, actually on my own sort of patterns. And one thing that she says, and I'll have her on in the future, is she talks about what is the smallest change that works for you?

you, that would make the biggest impact. You know, so for me, it was, I was using way too much fats on food just to increase the flavors and I'm such a foodie, you know. And so it was like limiting it to a certain amount per meal, right? And that just started to make a huge difference to lose some weight. So, yeah, I'm on a journey here. If you're listening to this, I imagine you could be on a journey too to improving your margin, right? Because margin rest, improving your sleep, diet exercise, the simple things, the hard things, right?

Incredibly hard to change. I don't know what's more. So you choose your heart, right? Your heart is either exercising, watching for your food and all that stuff, or your heart is to be overweight and then eventually having diabetes, hypertension, dementia, et cetera. So you choose your heart. Yep. And so the, if you're listening to this and you're like, oh, I've tried this, I've tried exercise, you know, I'm a, I'm a psychiatrist, I'm listening to this, you know, think about how do you change your environment to make this happen? So the biggest environmental change that I've done is actually hiring people, you know, that can coach me and inspire me and,

you know, keep me accountable. So if you are in this, trenches and you are busy and your life is busy. I've coached a couple physicians and just decreasing the amount of time they work for a six month period. So I have one person I'm coaching currently and we've moved his day to end like three hours earlier so that he can go exercise so that it's not like he's just adding on to his life, you know? No, exactly. And then he has someone doing his meal prep once a day. So it's like that's taken care of. So it's like he's getting some structure to his life that is allowing him to make these huge

transformations. Dr. Soraya, what are you thinking? No, I mean, you know, you and I, we think the same. And so forth we have small practices on our side surrounding coaching because we believe in these and any works. So, you know, if you have the ways to gauge yourself a coach. So Dr. Soria, if I was a professional, I'm going to put, I'm going to put the link on with this research library for Dr. Sorio, because I know she could be a great advocate to you. You have some slots open for people doing the lifestyle type of stuff as well.

Correct. Yeah. Yep. And she's on Instagram. I'll link her Instagram as well. I'll share her profile on my profile. But she's a great one to reach out to. Yeah.

So what I tell people is I want you to work on your lifestyle so that you never, ever have to go to see me on my other job where I work with the very sick people. And you say that with a micro expression of anger, Dr. Sorio, because you're so passionate about this. I really am. I believe in it. Yeah. It's like, I need coaching from you. Okay. We'll get some coaching.

We trade some coaching. All right. Well, yeah, anything else on the top of your mind, Sam, that you didn't say that you wanted to say? Well, like you've mentioned, I think we'll come back to kind of discuss the diet and exercise, the science behind that and the relationship to Alzheimer's or cognitive function. Also, we'll be hoping to look at the microbiome and its relationship to Alzheimer's disease or cognition. So that would be something very interesting. and that I'm very interested in just from personal, you know. Also, I would say therapy, Sam, because there's something about chronic stress.

And the big things that I say to clients is there's like healthy diet exercise, therapy, and sometimes looking for that more meaning, more purpose, kind of that third arm, the Logo Therapy approach. I would say those are the three sort of pillars for me. So we should look at like, we should look at all three of those. No, it's for sure. And I'm just kind of laughing here because I can't believe I didn't talk about, you know, depression, anxiety, PTSD. And that, the relationship with, you know, mental psychiatric illness to cognitive function.

And think about it like this. Yeah. If someone is chronically stressed out, right, from. either PTSD depression, high anxiety, they're chronically stressed out. And then you put on top of that, nothing that cools down the fire, diet, exercise, sleep. It's just, it's just a tough situation, right? And so this is what we see. We see people at all stages of this process. And we don't have, I get excited about doing a podcast on it because it's like, I know that there's 20,000 providers now that will potentially change the world.

Right? If we all kind of like do our part and start with ourself, I think that can change the world. So thank you. Thank you Sam. Dr. Sorio, any final comments? No, I love the part of therapy. I think that we think about trauma as like a war

or sexual abuse and trauma. There's where we call the big tea in the small. T, right? And there's day-to-day things that are traumatic, especially in medicine when we are encountering death and, you know, angry patients, all of that is traumatic. And we're very good at burying that under the rug. And it will definitely have an effect down the road. I'm actually going to do a presentation in November about PTSD and aging and the correlation of PTSD and dementia, because that is another risk factor for it. Yeah. Dr. Osir and I are actually working on a screening project.

where we're doing early screening for cognitive decline. And one aspect that we are looking into is doing screening, not just for cognition, but concurrent PTSD as well as depression and anxiety. And we'll be following those patients long term to see kind of how our interventions from the mental illness, you know, psychiatric perspective changes the cognition as well. So there's definitely a lot to look into that there. Oh, absolutely. Well, you may, the listeners may not know, but Dr. Sorio is an amazing therapist. She is an amazing

coach. And so I would be very happy to refer any of my clients to her. I would refer anyone I could refer to her who was like a friend that needed, you know, a specialist or a coach. So when I was, you know, or more of the specialist geriatric psychiatrist when I was back in. that area, now more of a coach, lifestyle coach, mentor, inspirer. So she's had her own journey and she's done her own work and she can now translate that to other people. So I'm excited to have you on here, Dr. Sorio. And Sam, so nice to meet you. Your intellect and sort of academic digging is fantastic and I appreciate that. So you guys, when you see these slides and the handout, you'll know exactly what I'm talking about. So we will do

Part two, if you have any questions, thoughts, concerns, you can shoot me an email and we will try to address those in the next time we talk. So we'll leave it there.