I featured guests to speak on the topic of Alzheimer's because we all need to advocate for those living with dementia, through awareness and empower those family members & people who live with the disease.
Alzheimer’s disease is a progressive, degenerative neurological disorder that slowly destroys memory and cognitive abilities. An estimated 6.2 million Americans of all ages are living with Alzheimer's disease in 2021. More than 1 in 9 people (11.3%) age 65 and older have Alzheimer's disease. The number of cases is expected to triple by 2050 as the Baby Boomer generation ages.
Although there are medications available to treat symptoms such as memory loss or confusion, these do not cure the underlying condition in most patients. Furthermore, due to high costs and insurance restrictions many people cannot afford treatment for this devastating illness.
While we don't have a cure for Alzheimer's yet, there are some promising therapies that may provide relief from symptoms or even slow down its progression in certain individuals. Researchers are working on ways to prevent or delay the onset of Alzheimer's disease through lifestyle changes such as diet and exercise to lower your risk of developing it later in life.
Joining me in conversation is Dr. George Perry, Professor of Biology, University of Texas, and Dean of the College of Sciences. He will share his work in "Living with Aging: Alzheimer's, the Disease of Our Time".
[00:00] Introduction to George Perry.
[02:21] George shares a little bit about himself on a personal level.
[03:06] What is the difference between Alzheimer's disease and dementia?
[04:17] What are the main stages that a person moves through as they develop Alzheimer's?
[12:08] What are some of the top risk factors for developing Alzheimer's disease?
[14:20] What are the current treatments or therapies for Alzheimer's?
[24:34] What types of therapies do you think are currently most promising?
[27:54] Why do you think clinicians are chasing after the same amyloid theory for the past 30 years and yet not showing something that's effective?
[36:26] What is your goal with regards to Alzheimer's therapies? What are you working on right now?
[41:43] Has artificial intelligence assisted in the diagnosis of Alzheimer's, Parkinson's, or other diseases linked to dementia?
[47:44] Do you think in 10 years we will have a cure for Alzheimer's or other forms of dementia?
[55:41] Do you have anything else that you would like to share?
[59:35] How can people contact you?
George Perry is a distinguished professor of biology and chemistry at the University of Texas at San Antonio. He has been recognized in the field of Alzheimer's disease research for his work on oxidative stress. Perry received his Bachelor of Arts degree in zoology with high honors from the University of California, Santa Barbara after which he continued to Scripps Institution of Oceanography where he obtained his Ph.D. in marine biology under David Epel in 1979.
Learn more about George Perry:
Hello, I'm Hanh Brown and thanks for tuning in. This conversation is live streaming on all the various social media platforms. I feature guests to speak on the topic of Alzheimer's because we all need to advocate for those living with dementia. We do that through awareness and empower those family members and people who live with the disease. Alzheimer's disease is a progressive degenerative neurological disorder that slowly destroys memory and cognitive abilities. An estimated 6.2 million Americans of all ages are living with Alzheimer's disease in 2021. That's about one in nine people, about 11.3%, age 65 and older has Alzheimer's disease. So the number of cases is expected to triple by 2050 as the baby boomer generation ages. Although there are medications available to treat symptoms such as memory loss or confusion, these do not cure the underlying condition, in most patients. Also due to the high costs, insurance restrictions, many people cannot afford treatment for this devastating illness. While we don't have a cure for Alzheimer's yet, there are some promising therapies that may provide relief from symptoms or even slow down it's progression, in certain individuals. Researchers are working on ways to prevent or delay the onset of Alzheimer's disease through lifestyle changes such as diet and exercise to lower your risk for developing it later in life. So joining me today is Dr. George Perry, Professor of Biology, university of Texas, and the Dean of College of Sciences. He will share his work in Living with Aging Alzheimers, the Disease of Our Time. So, Dr. George Perry, welcome to the show.George:
Great pleasure. Thank you very much for this invitation and to talk about a topic that impinges on so many people these days.Hanh:
Great. Thank you for your time. So, um, aside from your professional work, can you share with us a little bit about yourself on a personal level?George:
Ahh, personal level. Most of the time I spend myself focused on work, which it consists of research and teaching. Um, But on a person personal level, I do a lot of things in the Portuguese community, Portuguese American community in Portugal. And, um, goods and things with my family. I have two wonderful daughters and my wife and I enjoy being with them traveling otherwise, especially prior to COVID.Hanh:
Yeah, well, great. Great. Well, thanks for being here. Well, let's get started. So now, what is the difference between Alzheimer's disease and dementia?George:
Dementia is the broad candidate or category of cognitive or loss of function, higher function. So that can be brought on by strokes. It could be brought on by head trauma. It could be a disease or a condition, that results when you're in youth. So it's a generalized category. Uh, Age related dementia, uh, which is where most of Alzheimer's disease is that usually strikes people either in late middle age or advanced age. During that phase, uh, about 60% of dementia has Alzheimer's disease is, as it's basis. Other reasons you can have dementia for the agent, uh, would be strokes would be a major cause and strokes overlap Alzheimer's disease. In addition to strokes, um, uh, Diffuse Lewy Body Disease, some people with. Parkinson's disease, frontal temporal dementia, there's a long list of conditions. All of which are very serious conditions.Hanh:
Mmm Hmm. So now, what are the main stages that a person moves through as they develop Alzheimer's?George:
If it's classic Alzheimer's disease, um, the initial, uh, kids carefully examined by both the caregiver or a family member or, um, uh, a neurologist, some of the initial changes of the changes in mood, uh, more susceptibility for depression maybe fits of anger, et cetera, because there's an involvement of the brainstem, um, early on. Then the w but most of the time it's not detected that early. And then the next phase would be a short-term memory loss. And the distinction would be not that you can't find your car keys, but actually that you don't understand what the car keys do, things like that. So you don't understand common things. And then there's a progression from that which is mainly in the hippocampus region of the brain, that's important in incorporating short-term memories. Uh, Then it will spread throughout and there'll be other behavioral changes and loss of reasoning, and eventually ability to, you know, in the later phases, severe, there'll be loss of mobility and, uh, and probably confinement to a bed. But that is not the whole course of Alzheimer's disease, where, where someone has lost all function the more. Normal course during these parts where you can't remember your keys uh, or what they do, maybe you shouldn't be driving during some part of that, that course. And there are guidelines for that, but you can function in many different ways, uh, and live with it with a family. And it's a matter of modifying your life to fit that. And I can ask and answer more of that. But, um, some foundations like the Alzheimer's Foundation of America, just, uh, design day an apartment about how you'd have an apartment for somebody that had cognitive loss. Modifying the environment for the people to take advantage of the, uh, of what's retained is really makes a huge difference. For example, not having, uh, loose fitting rugs that people might trip on. Having bright colors because visual acuity has dropped and, uh, hearing aids, if they're not hearing to say, oh, well, they don't need to hear because they're demented. Actually, that is, uh, being able to see, well, being able to hear well and having that sensory, um, uh, input is an important part of maintaining cognition. Uh, When that's deprived, usually the patients decline much faster.Hanh:
I also think at least on a personal level, when one sense may reduce the other one increases, it gets better.George:
That's what we can hope. Yeah. By optimizing things for, uh, certain aspects, and accepting. The other part is the biggest problem for families, with people with Alzheimer's diseases is not cognitive or memory loss, it's behavioral aspects, and the behavioral aspects can be very distinct. And those are reasons that people end up the major reason people end up in nursing homes is because wandering, aggression, other things. So, I think it's also very critical, especially the average Alzheimer person is not 65 years old, although people can be 65 or 55. Those are relatively rare. The more common thing is the, it's, the people are 85 years old, or plus, because your chance of having the disease, when you were mentioning that the baby boomers are going to have more. Well, there's a paradox, actually your chance of having Alzheimer's disease at any given age is actually reduced in recent years, but more people are living to greater age and that's the greatest risk. So if you live beyond age 85, Um, your chance is about one-third to 60% with a greater penetrance of, uh, minorities for unknown reasons. It's probably very much like COVID is not something that you can easily tease apart it's diabetes, underlying education, nutrition, et cetera. Another part, well, we'll talk. Yeah, you have questions later, but we can do to reduce the risk, but dealing with the cognitive changes and those are individual differences. Some people are gonna have more visual problems. Some people may have hallucinations and seen a neurologist as well as the psychiatrist and getting the care that's personalized and not just to say, well, my mother is 85 or 95. Why, what else would you expect? Um, You should expect them to be optimized the best they can be for whatever it is.Hanh:
Yeah, we, we talked about it before the live and that is, um, there is life even when one is diagnosed with Alzheimer's and there's a lot of life, and that's what we ought to focus on, despite the decline.George:
Correct. And that is, um, you know, in our modern society, modern, extended back for at least, let's say 30 years before now and extending forward when people will be living into the eighties, many people. Uh, Alzheimer's is going to be a phase of life for a significant number of them. And, uh, it can be where they're all walled off from society and they have no value or they can be integrated into society. A colleague of mine, Peter Whitehouse, actually designed intergenerational schools and had people with Alzheimer's disease teaching in the school. Um, That doesn't make sense, does it? Well, people with Alzheimer's disease books to children, they can share life stories with them, and that can be enriching for both, but that's just replaying, you know, the, uh, nuclear family of the past, where grandparents or great-grandparents would still live with family and play a role in child care. Um, But I'm, I don't know if we can return to that, but how can we engage people? One of the key things of reducing your chance of having Alzheimer's disease is relevant for even somebody with it is to have a meaning for life. And being walled off from family and society is not a way to have meaning for life. It's when you're contributing and people do not need to have, you know, IQs of 160, to contribute to life. They can contribute in many different ways. Um, So, instead of focusing on the end stage of the disease, well, for all of us, the end stage of us is being dead, so we could focus on that, or we can say you can focus on somebody with Alzheimer's when they have no, almost no capacity. Prior to then they're going to have many capacities and many of them that could be useful, and useful to their family and useful to society. And that plays an important role in maintaining them, um, as people.Hanh:
Amen to that. Absolutely. So now, what are some of the top risk factors for developing Alzheimer's disease?George:
Um, Well, what's come out over the last few years? The risk factors and the things you can do to reduce your risk of having sort of intertwined together. So, the, um, I mean, you could say things like head trauma does increase your risk. Uh, You know, And head trauma is an extremely common event. If you've been in a car accident, I was when I was an, uh, child, um, that means you're possibly higher risk later in life. Um, Maybe playing football, but it's not so clear cut, okay. It's not like everybody plays football and has head drama will develop dementia. That's not it, but it, but it does statistically, it plays a role. Other part is nutrition. Um, Midlife obesity, um, protection, education plays a role. Uh, That doesn't mean you need to have a PhD, but it means having an educated life being mentally active, uh, stress reduction and protection from depression. And that relates back to what I was talking about, about having a meaning for life and meditation or things like meditation, all of those that lower, uh, stress levels play an important role. The other piece that's come out in the last decade is that people of minority groups are much more susceptible to having Alzheimer's disease. And we don't really know why. It's probably unlikely to be mostly genetic. It's probably more likely to be lifestyle events much as we saw for. COVID, um, people in minority groups. And probably it also extends the socioeconomic among white groups too, although the studies haven't been done to validate that.Hanh:
Very true. So now, what are the current treatments or therapies for Alzheimer's?George:
Yeah, and I should back up one other thing, is genetics, uh, depending on whether you, um, if you have a clear inheritance in the family with early onset, meaning like in your fifties and sixties, then you may have a determinant gene. Those are really rare, less than 1% of people who have Alzheimer's disease have that, but there's another gene, a risk factor, Apolipoprotein E. And if you inherit the E4 form, which is 20% of the United States population contains it, uh, you're at about threefold higher risk. So while it's 20% of the general population, it's 50% of people with Alzheimer's disease because it's that much enriched. So it isn't a factor. Does that mean that you need to do something else? Really doesn't tell you a lot. In the sense, it just means you're at higher risk. You can contain an April E4 gene and not developed disease and half the people have. Alzheimer's and that don't have it either. And you can, if somebody is interested in getting that, um, any of the, uh, DNA sequencing companies that sell genealogy or health data, uh, could determine that for you. Um, The question you asked? Um.,Hanh:
Well, okay. Back on the, on the DNA and the protein. So basically, let's say if you run the test, you come back that you are at the higher risk. Your choices are the same. You continue to do with what you're doing as far as healthy lifestyle.George:
That, that is exactly, uh, I was involved in one of the consensus reports about why there was a value to do this. I thought it wasn't of value, okay. Cause I personally do not know my genotype and I have been sequenced, unbelievable level because I do genealogy and I was trying to get as much data as I can, because I thought if I know I would just create more tension and there's really not much I can do about it except what I should be doing already. So if you knew this, yeah, you should, you know, lower fat in your diet, you should, you know, exercise, et cetera. Those are the same things that are already. Um, Could that change in the future? Of course, as we have more, have better treatments. So you asked the question about where we on treatments.Hanh:
Yeah. The current treatments or therapies.George:
Yeah. The current therapies, uh, are, um, symptomatic treatment. The ones that are broadly used and they're in two categories. Well, I'll go to a third actually. So, they're in two care categories. One of them focus on colon nergeek neural-transmission. Um, Some of the neurons involved in the disease, uh, early on are those involved in maintaining cognition in the brain. And they use a chemical called acetylcholine to transmit their information. And what, um, what companies did is they developed a drug to be able to promote the remaining activity that's there. So neurons are lost. They did a way to enhance them, much along the same logic that's done with L-DOPA for. Parkinson's disease, which has benefit at least in the early phases of the disease. For Alzheimer's this, this, uh, the best, uh, drug of this category is Aerosept. And Aerosept has some benefit for maybe a third of patients for six months to a year. So the benefits are relatively small. The cost is relatively small and the side effects are generally are not life-threatening. And the main side effect is constipation and some other issues, but you can discontinue the medication, uh, at that point. And that's very often why people don't continue it throughout the whole course of the disease. Another, uh, drug, uh, so there are three drugs like that. And then there's one drug called Namenda, which relates to the gluten energy pathway and, uh, inhibits it. And what it does is it's more in later states stages of the disease and has some benefit. If you were to look at these statistically, the benefit is very small, but then again, price and side effects are very small. A new drug was approved by the FDA, this summer, uh, I've written a lot about it because I don't think it's a drug that, uh, I would recommend. Well, I know I would'nt recommend, and that is because, um, drugs are always a blend between efficacy and side effects. All drugs have side effects. Some drugs have really strong side effects, but if they do usually it's balanced by huge amount of benefit. This particular drug did not benefit people cognitively in almost any of the trials, there've been 20 trials. This is the only one that showed a borderline effect, what's called post-talk analysis. It means you analyze things after the fact, and then it still wasn't clear, really benefited the patients. Um, usually what companies do and I'm involved in companies, uh, if you do post-talk analysis used as a basis for designing a new trial. You don't ask for approval because you've, the data's already suspect. So this drug is neither effective, nor safe. And the safety is that patients who get the drug have cerebral bleeding, they have brain swelling, and the brain shrinks the brain itself shrinks. Uh, and, um,Hanh:
Do you think?George:
40% of patients showed these side effects, also. 40% showed the side effects, and it wasn't too much of a health issue in the trial, but they were really carefully monitored. Biogen spent over $1.5 billion doing this trial. So it was executed in a, you know, extremely meticulous way. And when you're administering this to patients in hospitals that have lower capacity, you know, in terms of ability to monitor people, or patients have the issue of pain for all of these extra tests, or the discomfort of show showing up for all of these tests, that is, they required brain damaging every few months. So you have to go in for an infusion every month. You have to be monitored to see if your brain is having a problem to see if it should be discontinued every few months. And the cost is $56,000 per year for just the drug, not for the monitoring.Hanh:
Right. So, so if it's so effective and if it's the purpose is to help the masses it sounds like it's helping the 1% with that price point.George:
Yeah. If people have to pay for it, it will be for the 1% that are rich enough to pay for it. But if it was only helping the 1%, uh, of people that were economically able to pay for it, they would have a hard time recovering their money.Hanh:
So they are, Biogen is trying very hard to get it to be covered by Medicare. And this will have a, um, a big effect on the Medicare system because it cost $56,000 per year or estimated to be closer to a $100,000, by the time you do all the tests. So I think another part of this and the logic the FDA used in approving it is the logic used for cancer drugs, chemotherapy drugs. And if you think of those, my mother, uh, my family didn't have, uh, doesn't have Alzheimer's disease. We have cancer and heart disease. So my mother had cancer and had, uh, chemotherapy. Uh, You take these drugs that are extremely toxic. They do cause you to live bit longer. Uh, They're very costly. They're very painful. Um, And I would really, hate to see Alzheimer's disease go down that model because the quality of life is so jeopardized. Um, But that was the logic actually used, it, because chemotherapeutic agents are approved based on shrinking the tumor and the Biogen drug, uh, shrunk the amyloid in the brain. And I've argued for over 20 years, that the amyloid is a normal part of the biology of the brain and removing, it would be more likely to be harmful than beneficial.Hanh:
Well, I know that's a different topic, right? Because the amyloid is not the enemy.George:
Not the enemy, you know, it's like inflammation of the brain, which is, or anywhere else. Uh, Inflammation is like, you know, causes arthritis or other types of problems cause it's over accentuated. But if you don't have it, you aren't able to repair your body. You know, there's always a blend in your body between repair and, um, degeneration.Hanh:
Yeah, I had, I think a month ago I had Dr. Alberto Espay uh, speak specifically to this topic of amyloid. And I guess if anybody that's listening right now that wants to hear the in-depth live discussion, you can check out the YouTube channel. The video is over there. But now, with regard to therapies, now put the Biogen Aducanumab aside. So what types of therapies do you think that are currently most promising?George:
Well, I could say the ones that I'm, you know, working with, uh, companies, but I would, uh, I'll divorce it from that, is one of the biggest insights that's happened over the last 10 or 15 years is realizing that Alzheimer's disease is actually not so deterministic. The genetics really misled us thinking it was amyloid and it was, uh, deterministic. You have this problem and whole follows from that. Instead Alzheimer diseases becoming more like heart disease, multifactorial, and associated with lifestyle where genes play a role, but they're not the whole story. And how is this come about is understanding the lifestyle contribution. Uh, The fact minority, the minorities have two to three fold, higher risk. I mean, that's a big difference. Uh, That scene that people had to eat, um, large amounts of vegetables, lowers stress actually may reduce their risk of having the disease by 50 to 90%. Um, That's an age-related risk cause you have to always think everyone says I will do this and I will lower my chance of having disease. You actually could be increasing your chance because you're going to live longer. What you really have to look as increasing your healthspan. In other words, all of us want to live to 95 and be completely healthy. But maybe when we get to 96, if we're still alive, we'll have some other condition that would be there, but it's better that it's 96 and not, you know, 76 or 66. So, back to all of those have been really important insights. The other part in terms of companies, uh, and new therapeutics, some people are focusing on trying to restore the connections in the brain, synapse connections, trying to restore the scar tissue that develops around plaques, trying to immobilize it, um, other things. So, but if you look at one of the problems that it's been for the amyloid protein, isn't just Biogen. All of the big money in pharma has gone to the amyloid approach for 30 years. All the best and brightest people at the most prestigious institutions have tied their whole career down that approach. And therefore all of the other approaches have been tremendously underfunded. The only one that might be similar to the amyloid in a sense of funding is that in the proteins involved with forming tangles, the tau protein, and, um, but my own argument is that the tau protein has a lot of similarities to what's happening with the amyloid. Both of them tau and amyloid, uh, have, um, uh, antioxidant properties, very distinct antioxidant properties that are protecting the brain.Hanh:
So, um, I want to ask this question. So why do you think clinicians are chasing after the same amyloid theory for the past 30 years and yet not showing something that's effective? Perhaps we could be more open-minded. I mean, why what is your recommendation?George:
Uh, it's a, it's a combination of things. First thing is the, the people that develop Alzheimer's disease in early age, and then it shows clear inheritance in the family. This is not APOE, it's mutations in the amyloid precursor protein, the protein that eventually forms the amyloid or some proteins that degrade the amyloid and play a role in its formation, the presenilins one and two. So, because of that genetic link to the disease, um, several key people came up with the idea that this must be the cause of the disease. Mutations developed into Alzheimer's disease, must be the cause. They missed, they missed sort of the basic biology and to confirm that this was basic biology, what I now teach is basic biology, freshmen biology. I wanted to be certain that what the, these people were missing, they should have learned when they were a freshman in college. I can confirm that because I teach that is that, um, when you're doing genetic studies, you're just looking at association. In other words, I have this mutation. I develop the disease. It doesn't, it doesn't define the mechanism. Doesn't define the dependence. It just tells you that I have, uh, you know, I have a red finger and I develop. Alzheimer's disease, but I don't know why the red finger has anything to do with it. So, and then there's the opposite view is that the amyloid has nothing to do with the disease, okay. So there's been those two views. So I, and my colleagues, um, the thought similarly, we came up with the idea that neither were right, that the genetics told you that the amyloid was important, but it doesn't tell you how it's important. It could be that it has to be, this playing this protective role. And if it doesn't do it right, that's that allows the disease to happen or something else. So they along their study, so when that first idea came out, my colleague Mark Smith and I wrote an article called "Amyloid Junkies", and we, it was published in. Nature, very short and saying, how do you know that this is going to be the treatment. And the best way to test that is going to be to remove it from the brain and see if it benefits patients. Well, that has been done 22 times in the well done clinical studies. And in none of the studies was anybody ever saved or recovered or came back? What was done in between people did vaccines of mice and they had amyloid plaques. They removed the amyloid plaques and the mice for better problem with that is that those plaques were created. So you have something, you have a mouse that's normal, you genetically manipulate it, you put plaques in it, now you remove it, and it's back to normal, surprise. I say it's very similar to studying respiratory distress, the plastic bags over the head. It's very easy to cure. You just move the bag because it's not part of the biology. It's not a COPD or tuberculosis, or anything else. So the mice have been cured, but when people applied it to humans, it didn't. Uh, so why do people still persists when it's been tested this way? Why? Because the best and brightest and most powerful people in the field say it's still valid. They're still writing that it's valid and that we're likely to get better and better with treatment, but we've removed the amyloid. In, in the Biogen steady, there were over 3000 patients treated. There were no miraculous recoveries and the patients were treated very early. So there were still no miracles that came out. So it's persisting because the power of personality of people pushing. And then the pharmaceutical industry, Biogen invested 1.5 billion, but they're not the only one Lilly's invested huge amounts of money Roche. The list goes on. So, uh, the thought is that it might've been between 20 to $40 billion has been invested in by pharmaceutical industry as well as funders. Uh, The NIH, the Alzheimer's Association and others, um, have done so. Uh, My friend deceased friend now, Sharon Begley from STAT Magazine who I, we had many conversations over decades wrote a couple of years ago, but the "Amyloid." "Cabal" that there was a lot of collusion. The collusion does not mean that people are doing anything good or bad, but they've all decided that that's the answer. And I think they do so with a great degree of seriousness and, and, um, introspection, but science is based on evidence. Everything, that's another part I teach in biology 101. If you can't show something is false, it's not part of science. It doesn't mean it isn't true. It just isn't scientifically true. So, the amyloid idea has been tested numerous times and this particular one, the. Biogen, since it was the best documented, they, patients were imaged all the way through and show that all of them have the amyloid removed and they didn't improve. The only way you see the improvement is you analyze subgroups. Uh, I call it analyzing the Eskimos, but of course that's not politically correct, but you could say those people with APOE genotype, which is what, in fact, they did, E4 for people. So if you analyze enough small enough groups, you start to find statistical validity, but that's not considered to be, um, a valid test. It's only useful in the end. And I'm working with companies that do the same thing. We reanalyze the data, but on the basis of it, we design new trials. We don't ask for approval.Hanh:
Yeah. You know, I mentioned this already, but that, that creates a trust issue and false hope, you know? And I think, I think we talked about this a little bit before the live event is that, do you think it's more important now than ever the folks, family members, caregivers, and the ones diagnosed with dementia. We need to empower them to ask these questions, to challenge the treatment and to have a stronger voice. Do you agree with that?George:
I think so. Yes I do. But you know, all of us need to trust. I take medication for my conditions, not Alzheimer's, but other conditions. I actually never read the enclosure, okay. Because I trust that the FDA has done that analysis and the efficacy versus the side effects is a positive balance. If we don't trust that how can we do it? In patients that this is your family member and especially if you have the financial means to pay for it yourself, saying, why can't I do this? And I, I have read many patients. I want hope. I want to feel. And I, I understand that need for hope, but you know, this is what the FDA, my understanding in the early nineteen hundreds, why it was instituted because people sold so many quack, you know, snake oil drugs, and they would analyze them to make sure that the balance was, and the FDA was the world standard for this. So, in other countries only require that the drugs be safe and this particular combination, it isn't either one.Hanh:
So now, what is your goal as a professor, scientist, researcher with regards to Alzheimer's therapies? What are you working right now? What is your goal?George:
So, my primary goal is I've been working with some companies, dealing with synapse formation and changes in extracellular matrix proteins. My major focus is something that I have been studying since I was a student and that's oxidative stress. And this is what amyloid plays an important role in doing. It reduces the amount of oxidative stress. So what is oxidative stress? It's the ability of oxygen in the air to react with our body to cause damage to it. And it's why people take Vitamin E why the blueberries, all of those things are related to fighting oxidative stress and amyloid plays a role in that. And what we've been doing is trying to understand the mechanism of it. And, um, we know now that it involves, um, metals and dealing with iron and copper. Iron well, iron and copper levels don't change that much in the brain during Alzheimer's disease, how they're organized is tremendously changed. And they, um, so our current theory is that the amyloid plays a role in recycling metals from turnover of cell components. I know that's a little technical, but then if you don't turn, when your body is constantly renewing itself, for neurons, they live as long as you live, they were formed when you were a child and they will persist to the end of your days, but the internal components of them are constantly being renewed. And as they're being renewed and regenerated they're, the metals are being released from their components and they have to be repackaged. And that's what we think amyloid is doing that is playing a role in repackaging so that it doesn't cause damage. And along that line, we made a, what I think is I know it's a really important discovery a couple months ago, and that we were able to find for the first time that this re this recycling involves metallic metals, metallic iron, and metallic copper. They have never been identified in the human body before, except that people in-plant copper in their body, but naturally never. And, um, suggest that there's really novel chemistry and further in the case of iron being metallic it is not known to even be able to exist in the earth because soon as metallic iron gets exposed to air it rusts immediately. So how does the amyloid protect it? How is it all working together? So we have, and this is very common in research you, uh, I, I, and others usually think of the simplest idea and that's what the amyloid cascade idea was. It was a good idea to start with. Then you do research and usually you find your initial idea is not right. That is something much more interesting. But really interesting things are hard to imagine. So you have to do in steps. So in this case, what we had thought before is that amyloid encapsulated the metals so that they didn't cause oxidative damage. Now we, we still think that, but we think that it actually plays a role in changing them in a way that's never been described before. And we did this using a very unique instrument in England, uh, together with the collaboration, with a group in England that works at Oxford and it's a x-ray microscope hooked to a synchrotron. A synchrotron is like a huge, oval thing that produces x-rays. And, um, we were able to actually directly determine, uh, the type of metals that are there. So that's one thing I'm looking at. And then I'm looking at how neurons die during the disease and others. Uh, Will these things be important in therapeutics? Yes. Because if you could understand how, what the metals are doing, you, it isn't as simple as removing the metals. That's already been tried by someone who I collaborate with at times. Um, It didn't have benefit because it was more complicated than that, but understanding that pathway could give you different ways. And it's not a question of removing the amyloid. It may be a question for do you, maybe you want more amyloid or you want more of a certain type.Hanh:
Interesting. It's wonderful that I guess we have a forum a platform to share these findings, right? And I think it's just more and more important folks who are living with dementia, caregivers and families. I mean, have these kinds of conversations, ask these questions to their, you know, physicians, neurologists, and so forth. Uh, Empower them. So, I think it's great now with regard to artificial intelligence. So how has artificial intelligence assisted in the diagnosis of Alzheimer's, Parkinson's, or other diseases linked to dementia?George:
So far, it is just in the nascent stage in the beginning stage that people are using it, there've been some publications, um, that have come out. Um, I would say the more important piece, rather than saying a sophisticated. AI is more automated screening as that's really come, uh, come about. And there are several mechanisms for doing that. For example, the Alzheimer's Foundation of America, you can ever free screen any, anyone can do it. Um, And they even have where the nurse or practitioner even will be involved virtually, uh, with that. Uh, Does that take the place of a full neurological exam? No, but it's better than having not having. Um, So there are a lot of people who are trying to develop computer-based screening tools. So, Mentrex is one, the Alzheimer's Foundation of America, but other companies are doing it, um, either at, and I think that approach either whether it computer based approaches really are important. You have 6 million people in the United States who have this, the PET analysis and 30 million worldwide, or if not more, and you need to have something that's really inexpensive and also really non-invasive. So you have the PET analysis, Positron Emission Tomography for the amyloid. It's three to $5,000 only can be done in specialized centers, uh, exposes the patient to large amounts of radiation, which can have health consequences, uh, increased cancer risk, et cetera. So, then you can have a cerebral spinal fluid test. That's at least for the United States is not standard because it's considered to be pretty invasive. In Europe it's very standard to take cerebral spinal fluid. Is that a useful test? It could provide useful data, but again, it's not useful to do all the time. And then people have been developing blood tests at various points and saliva tests. Um, Those are still nothing AI related. Um, So the AI has been more in the cognition and more in the analyzing an MRI. And I'd say that all of that so far is not, um, not ready for prime time. And I've seen a lot of, uh, comments about, uh, the recent paper uh, saying it didn't really add that much, the one that used AI. And we have, I'm editor in chief of the Journal of Alzheimer's Disease, and we have AI papers and they're certainly in the research arena, you know, where you're developing new techniques. Definitely AI is an important element, but in terms of public health, I don't think it's ready.Hanh:
So, basically continue to put focus on more of a human centric effort.George:
I think the human centric effort is really important for multiple reasons. One is that, um, treating each person is an individual because different people will lose different capabilities. So working with each one, not just saying, oh, your mother is 85. What do you expect? I mean, I had a mother that lived to 90 and I remember a story she would tell, going to the physician about some health issue and they'd say, wow, you're, you know, 85, what do you expect? And that's why I told her would be the case. You should expect to live every day to the fullest and have physicians supporting you for that. Um, Other part is really, um, having the, having neuropsychological tests, understanding do you really have Alzheimer's disease? Another part of this piece, and I had already alluded to this is depression. So if you think about it, you know, the 85 year old is probably lost their spouse, may have financial issues, may have had to move once or twice. They have a lot of things happening in their life. Most of which are not pleasant. Are they adaptable? And think about, are you as adaptable when you're 85 as when you're 45? Not likely, okay? So, helping them with that, whether that means support or, or whatever it is, that's what I meant about working with each person and then understanding if they have behavioral issues that maybe some, um, some pharmaceutical would help them. Unfortunately until recently, and even recently it's still primitive, most, uh, drug companies have worked on trying to improve cognition. When would family suffer from are the behavior problems.Hanh:
They're, they are intertwined, but you can remember everything and if you're aggressive or you're wondering, you could becomes someone that the family can no longer take care of, because either you put yourself at risk, your children, et cetera. So really addressing all of that, whole aspects of each person, because not everybody has the same issues.Hanh:
Person Centered Care. Absolutely. The let's look 10 years from now. What do you think that in 10 years, will we have a cure for Alzheimer's or other forms of dementia? I guess, why or why not?George:
Yeah. So, I was asked what I thought about the approval. Um, Nature asked me, uh, Nature, the science magazine asked me about two months ago, what did I think? And I said, if this proceeds, it will set back the field 10 to 20 years and they put that in a quote. Why do I think so? Uh, because, uh, because the pharmaceutical industry says it'll really lead to a renaissance. It won't lead to a renaissance. It will lead to more focus on amyloid. So they will design more variations. Already, Lilly is trying to get its drug approved, which does something very similar to Biogens. Roche will get theirs and the other companies I'll make theirs because it's not that complicated to do once, you know, the path. Um, So that's one possibility. That's a really sad one that will be wrapped up. And will it be worse than it's been? No, it'll be just the same. No, the field is stagnating. The opposite is I, at the same time with limited funding, I see a lot of innovative ideas coming out of companies and others. So, you know, the basic thing is that, uh, there is an appeal to authority. I write, a friend of mine or colleague in Boston sent me some group that he wanted me to get involved with. And I won't name the group, but in particular, the new thing that I hadn't heard of, it's a European based thing. And, uh, he said, well, do you know any of the people that are already involved? I looked and the business people, I didn't know, but I did know the scientists, and I did know some of the people that were involved in foundations. And I had an, I, it was just prior to this call, so I hadn't responded. And I also should think about for before I respond, because I thought, wow, these are the same people that have held back to field all these years. The same people are involved, because they're very prestigious, they're very smart, articulate, et cetera. And I remember one of them I dealt with, I was asked to help design the X. Prize, which is something to, you know, it was one, the Space X was formed. And they wanted to have one in Alzheimer's disease. And I worked on it with a friend and it got hijacked by one of these people to eventually form something that was totally non-novel, and it's going to go nowhere. Um, When I, I was just about ready to lose it in that case, and his friend talked me out of getting angry because there was no point. Um, So the same people control um, what's happening and only say they're promoting innovation because the same people played a role in rerouting, the. Gates Foundation money and, and others. And it just ends up going down the same path. If that's the case, we will be having this same conversation 10 years from now. I, five years ago, or nearly five years ago, I debated Reisa Sperling at the American academy Of Neurology. In fact, that's where I met Alberto Espay.Hanh:
And, uh, he did a podcast with me after the debate. So, I debated her, I won the debate, um, probably just barely, but I won. And at the end, the closing of that, she said, well, I hope to be able to debate you in five years to talk about the advances, you know, I've made. Well, five years has happened and there's no advance. But I said, wouldn't it be sad if we're back here 15 years from now, and we're still having the same debate, whether I win or not, doesn't make any difference. That's, you know, that's pointless. It's whether we've really advanced. So I, I'm, I am optimistic that I will make progress in my area, but if I look at the whole picture together, I think it may just continue down the same path. And so, you've asked also, or will be asking, you know, like whether there's a lot of money for funding? And the answer is the government has put more money then the past. They've quadrupled the funding over the last several years.Hanh:
Funding towards the amyloid theory? Funding towards what?George:
They, if you ask them, they'll say that they're not spending on the amyloid theory, but if you look at the reality, the that's where it is. So there's, the ambulatory, it's kind of a contrast because we recently published in Journal of Alzheimer's Disease Reports, which is the online version of JAD. And somebody did a survey and it was a minority idea, only a minority buys into the amyloid theory, but they are the best funded, the most published. So, you know that, uh, political power is not just by number of voters, it's, you know, right voters, right? The, the influencers, and, um, so they're still influencing a lot. And the pharmaceutical industry has something that scientists and laboratories don't have. Once they get stuck down a certain path and file all our patents, it's really hard for them to move and suddenly move on a dime to something else. They usually do it by, you know, sacking all the people that are in that division and hiring a new group. So it's very different than the way scientists function.Hanh:
I think it's just more and more important for families, caregivers and folks living with dementia to empower them and give them a stronger voice and bringing these concerns. I mean, they're the user of the drugs, right? There, they're buying it, they're paying and they're using it. And I think you and I can talk about it. I mean, I have my personal journey, but I think we need to advocate with those living with dementia, more and more and normalize conversations like this. Very important.George:
Correct, but you've probably seen that many of these patients are being utilized by the pharmaceutical industry. Uh, And uh, they're saying how important it is and, etcetera. They're really appealing to their hopes. And, uh, hope is an important element. I understand. I understand that,Hanh:
It's false hope.George:
But that's not, but that is not what modern medicine is about, it's based on scientific. In other words, scientific it's demonstrable. And this and the other piece, the way in which we approve these drugs, even if the drug did work, if you look at the statistical thing, if you had to treat a hundred mothers to see an effect, would your mother be one, the one out of a hundred? When you give a drug to a person you expect that it'd be highly likely that they would respond in a positive fashion, not one out of a hundred or five out of a hundred. And that's the best that's being claimed, right now, is something like that. It's a small effect on some patients that you wouldn't even be able to detect, except if you were a trained neurologist.Hanh:
Wow. I appreciate all your wisdom and just insight and your passion in this work and serving folks with dementia. Do you have anything else that you would like to share?George:
I want to share back at the same point we started in that Alzheimer's disease is a social construct and how we view that social construct. I'm not talking about, you know, there's a biology of that. That's a, that's biology, but how we view somebody who's demented and who has diminished capacity and how we interact with that person and view them is going to make a difference in us and them, and the impact. And by just changing that view. So I have this view of amyloid in Alzheimer's disease that also relates to this. So we look at it and we say, gee, isn't it horrible. Somebody becomes demented at 85. Then you can turn around the same way. Isn't it amazing that some people live to a hundred and have complete mental capacity? I mean they're less active. What did they have? So, how does the brain maintain itself to be normal? Just changing, uh, looking at half full versus empty, you have a different view. So if you look at that hundred year old person, their brain is full of plaques and tangles. So, how are they able to be normal? You could say, well they would have became demented when, next year? Well, if everybody lives long enough, you know, if you live to 125, maybe you're, you'll be demented, also, though there are people who've lived to those ages that are not demented. So it isn't a foregone conclusion. The other part about the risk of having the disease, although you have family members that are affected, the risk, lifetime risk, of you or somebody in your family having, uh, Alzheimer's disease is actually not that high. It's about 20% or so. The fear of Alzheimer's disease is 85% of people are fearful of it. So it's very disproportionate and it's the opposite of what it is for heart disease, the opposite of what it is for cancer, you know, all debilitating conditions. So we have a fear more of it. Is it because we've lost cognition and control or is it we're just fearful of things like it? I think coming to terms with Alzheimer's disease, um, is an important element. We're all want a cure, but what if Alzheimer's disease is really hard to cure before we really, number one, we don't even barely know what it is. It's more than plaques and tangles and genes. And, uh, and maybe the cure will be 20, 30 or 40 years from now. When the companies are selling it very often, they're selling as if the people that are demented right now, or going to gain from any of this treatment. That is not true for the Biogen approach or any of these antibody approaches. They're all given to people during the early phases of the disease, so people that are already frankly, demented. So what you do? The people that are demented still have function and viewing them in a different context and having and supporting not just the person with Alzheimer's the family member. And this is what local Alzheimer's Associations and many others do really an excellent job, but even becoming better at that, um, can have changing the view of Alzheimer's disease. Not to be so fearful, not to stigmatize. To view it as this other phase of life. And how can you maximize your Perf? How can you maximize what you are then?Hanh:
I hope people that are listening or watching take all of your wisdom to heart, because it is much needed. If you are on the journey and caring for a loved one with dementia. So, I really appreciate your time. And how do people get a hold of you?George:
Uh, You could email me, well, you can do it through Linkedln as you did or Facebook. Uh, I have, and I also, ah, very good source for information is the Journal of Alzheimer's Disease Facebook page. I post articles whether I agree with them or not. Uh, I just post everything that I see in the news related to Alzheimer's disease, that Facebook page.Hanh:
I'll make sure to include that into the show notes. So I'll be visiting there.George:
So, and the other part is to email me. Um, You can include that. I'd probably prefer it be my personal email rather than my professional email.Hanh:
Sure. I will include that.George:
Well, great. Well, thank you so much for your time.George:
Thank you so much. It's been a great pleasure,Hanh: