🎙 Is it Alzheimer's or Something Else? Ep.11

In Part 2: Is it Alzheimer's or Something Else? Drs. Toenjes and Koren begin by answering the popular question "When do you know something is wrong? Followed by explaining amyloid proteins, DNA structure, Alzheimer's therapy and the research behind all of it.

If you enjoyed this episode, you will loves these:

• Dementia vs. Alzheimer's
• Alzheimer's Disease: The Hullabaloos of Aduhelm!
• The Future of Alzheimer's Research

Dr. Steven Toenjes, MD, a board-certified neurologist, former staff neurologist in the U.S. Navy and an award-winning director of neurology residents at the Uniformed Services University of Health Sciences and decorated Navy veteran joins Dr. Michael Koren and Michelle McCormick to discuss Alzheimer's disease in a four-part series.

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Original Air Date: March 11, 2022

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Music: Storyblocks - Corporate Inspired

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Transcript

Michelle:
Welcome to MedEvidence Truth Behind the data. Today we are talking about Alzheimer's disease and I have Dr. Michael Koren and Dr. Steven Toenjes with me. I am Michele McCormick. Dr. Michael Koren is a practicing cardiologist and CEO and founder of ENCORE Research Group. He has been principal investigator of multiple trials and has been published in the most prestigious journals.

Dr. Koren:
Also joining us are some bad ones. Let's.

Michelle:
Dr. Currin. Dr. Steven Toenjes is a board certified neurologist and principal investigator on multiple trials at ECNORE Research Group. He is a decorated Navy veteran which brought him to the Jacksonville area. And he has been practicing neurology in the area for over ten years. Gentlemen, welcome back. We are talking about dementia, Alzheimer's and but what about if it's just something else like we mentioned briefly, maybe old age?

Michelle:
Okay. My kids are convinced that as I age, my memory is gone away. Like Mom, I told you that. Mom. I told you that. How do you not remember every single word I say? And I always say, Well, I have a lot of information coming into my head all the time, but I play a lot of puzzles, and I'm hoping that that really keeps my brain healthy.

Michelle:
But I do forget where I put the keys at times. And I do walk around in circles saying, Didn't I? What did I come in this room for? Dr. Toenjes Let's talk a little bit about that. And Dr. Koren, when do you know when something's really wrong?

Dr. Toenjes:
So that's those are the the general types of complaints that come into the clinic on almost every day. And it's important to understand that there are normal changes that are associated with aging. But we do not lose our memory as we age. If there's memory loss, there is something wrong. There is damage. The difficulty is trying to decipher what someone's experiencing.

Dr. Toenjes:
And is that memory related? There's multiple cognitive domains that we have and they depend upon each other. Memory is something that very heavily depends. For example, on attention. You have to attend to a task to to formulate a memory and retrieve it. You know, one that we hear all the time or people get concerned about or will literally be a reason for a phone call.

Dr. Toenjes:
Some somebody put the milk in the cabinet and, you know, and using that as an example, I just ask where where does the milk go? And the patient will say in the refrigerator. And so that just illustrates that point, that the person knows that the milk goes in the refrigerator. They didn't forget that it goes in the refrigerator.

Michelle:
They just miss not placed it.

Dr. Toenjes:
To what they're doing. And so executive functions are complex, focusing and shifting and focusing attention that so-called processing speed does slow down as we age. And that's normal. That's normal. There's nothing you can do about that.

Michelle:
Good. I'm going to tell my kids that I'm like, this is.

Dr. Koren:
What else to tell them? That you have many more years of memories than they do.

Michelle:
Exactly. Exactly.

Dr. Koren:
So there's more processing time.

Michelle:
Yeah, well, I always heard that if. If I forget something, but it comes back to me, then I'm okay. Like, if. If if I forgot where I put the keys that morning, or if I was going to tell you something and I forgot what it was. But later on that day, I was like, Oh, that's what it is.

Dr. Toenjes:
And so that's those are the sorts of things that we precisely try to decipher with testing like formal cognitive testing or neuroscience testing to try to tease out is are we capable of defining or deciphering a memory problem? Because all of these other issues, like attention issues, are going to look like short term memory problems, but they are not.

Dr. Toenjes:
But when we do find a memory problem, we do start to be and it's purely memory related. You start to be become concerned that someone may actually be in the early stages of a pathology like Alzheimer's disease. And now that we are come into the age of where we're starting to flirt with potential or putative disease modifying therapies for that specific situation.

Dr. Toenjes:
By the way, the most common cause of of dementia as we age, that's that's that's why we're here. And we're talking about these things, such as the kinds of research that's being done and the interesting basic science that that is unfolding with the amyloid hypothesis of Alzheimer's disease.

Dr. Koren:
Amyloid hypothesis. I love.

Michelle:
That.

Dr. Koren:
So, yeah, amyloid is a key word that is critical to a lot of discussions about how we're approaching treating Alzheimer's disease, preventing Alzheimer's disease and treating other medical conditions. So I think it's probably worthwhile to spend a few minutes just explaining to people that amyloid is so amyloid is basically an abnormal protein very, very simply. But how does that become an abnormal protein?

Dr. Koren:
And what we've learned and this gets back to some things we talked about in previous sessions, which is that we now understand that that we have DNA. DNA sends a message to our cells through RNA to make proteins that are made in the ribosomes, and then the proteins are made in the ribosomes, and that reflects the genetics of each individual.

Dr. Koren:
But once the proteins are made, other magic happens. And part of that magic is the way these proteins fold so that they can provide functions and supports the body in different ways, either structural functions or or chemical changes, etc., depending on if they're enzymes or structural proteins or other things. And if they don't fold correctly, even though they're the right material, they're not useful.

00:05:58:06 - 00:06:24:00
Dr. Koren:
So maybe a simple way to think about that. And this goes back to what my mom told me when I was a kid is, you know, if you fold your clothes and you put them in your drawer, you'll be able to find them again. Your drawer won't get all messed up in terms of be able to open it again because all the crumpled clothes that expand if you put them in and then you can open your drawer anymore and you're less likely to find an old grilled cheese sandwich and folded clothes than you would in a closet because you.

Michelle:
Forgot it was there. Right.

Dr. Koren:
Right. So and it's funny, it may sound crazy, but there is actually a decent analogy to what happens with proteins. So I'm speaking a little bit from a cardiovascular perspective now, but amyloid, which is believed to be a critical component of Alzheimer's disease, is also part of other disease processes. In particularly there's amyloidosis of the heart and there's actually an FDA approved treatment for that based on a problem with a protein called Transthyretin.

Dr. Koren:
So something now called transthyretin cardiomyopathy that we just called amyloid. And basically that's a protein that's actually responsible for transmitting thyroid hormone that stops folding correctly. And when it stops folding correctly, it accumulates in the heart. And when accumulates in the heart, you're prone to having arrhythmias and poor heart function and heart failure and can die of sudden cardiac death.

Dr. Koren:
 And now we actually know what enzymes are responsible for that folding process. And there can be treatments now, FDA approved treatments that help the proteins fold correctly.

Michelle:
That's fascinating. Yeah, actually, it's. And that's unbelievable. I picture that DNA structure that you always see the drawing of in half and then kind of unfolding. That's how I picture it in my non-medical brain. Right.

Dr. Koren:
And again, just to make sure everybody's clear on it, the DNA is the blueprint. And the blueprint is turned into a protein through RNA and through ribosomes. And then there are other things that happen to these proteins even after they get outside of the cells. But we're just learning all this stuff and we're starting now to understand that certain people have a genetic reason why these proteins don't fold appropriately.

Dr. Koren:
So, Steve, maybe you can mention what we know about amyloid in the brain and this hypothesis of folding appropriately or not.

Dr. Toenjes:
Well, the reason it's sort of been the amyloid hypothesis of Alzheimer's disease is is pathologically it seems to be one of the first steps that occurs in the process of what becomes an Alzheimer's brain. This abnormally folded beta amyloid protein is precipitating. And that actually is a process that winds up starting decades before a patient with Alzheimer's ever has their very first symptom.

Dr. Toenjes:
And so the area of abnormally folded and precipitating beta amyloid proteins starts building that progresses and is thought to kick off a process that ends in the abnormal folding and then precipitation of another, a different protein called tau protein or hyper phosphorylated tau protein. And as tau protein then starts to precipitate within the actual neurons, that causes them to enter into a process of death and degeneration.

Dr. Toenjes:
But the thought has always been that, however, this occurs, it is the initial step of abnormal protein beta amyloid that kicks off the whole process. Now there's a whole there's a whole basic science world that surrounds this process, and it involves different inflammatory influences on this process. There are there are thought to be things that influence the metabolism within neurons, like glucose metabolism within neurons.

Dr. Toenjes:
And and and the basic science understanding of this hypothesis is where therapeutics have started to then.

Dr. Koren:
Yeah. And this gets into some of the interesting research elements. So because of the hypothesis about amyloid, we're doing more and more studies, looking, using imaging to look at the degree of amyloid deposits.

Michelle:
And that was exactly what I was going to.

Dr. Koren:
Ask the different organs and of course, including the brain. Yeah. And so maybe come in a little bit about that in terms of is this imaging research makes sense? What are your thoughts about it? What's the relevance for the average patient that may be listening to this program?

Dr. Toenjes:
Sure. You know, I am vid pet or really aspect imaging study radio labeling beat amyloid within brain tissue is FDA approved. It is an imaging modality that that can be obtained. It's very almost impossible to get insurance coverage for that but I you know is a pretty strong test. It's really very useful and most useful in being pretty clear that a person does not have Alzheimer's disease if their amyloid imaging is completely normal.

Dr. Toenjes:
The specificity of of embodied pet, you know, is not perfect. There are other things that can they can produce.

Dr. Koren:
Is a good research tool. Do you think.

Dr. Toenjes:
It's a very good research tool? The difficulty, the one of the difficulties through the history of clinical trials, specifically with Alzheimer's disease and and a number of of of just strikeouts, just you know, we've thought something might be useful and then we struck out demonstrating benefit. It turns out when you look back at patients that have historically been in Alzheimer's, Alzheimer's research trials, a lot of them didn't have Alzheimer's disease.

Dr. Toenjes:
And so the research world in many studies and some of the studies that we're actively doing now, you know, include things like amyloid, SPECT, imaging, Talbot, SPECT imaging and of course, MRI based imaging do leave no question whatsoever that the person in the trial has Alzheimer's disease. And so the research world has really jumped far ahead of what's what's clinically and regular use.

Dr. Toenjes:
But all of those are those all of those more sophisticated imaging modalities stand at the ready. They are FDA approved and they are they can be used. You just can't.

Michelle:
Right.

Dr. Koren:
And and Dr. Tim just made a very important point that I'd like to emphasize, which is we're getting into this realm of a patient specific medicine where we understand the individual genetics of a patient and then can apply therapies that are relevant to that particular patient. In previous studies, probably because we didn't have the specificity of diagnosis, we were treating a bunch of people that had the general problem that we thought they could be treated for.

Dr. Koren:
But we're using a therapy that would only possibly have a benefit in a small fragment of that population. So a lot of research studies may be, quote, falsely negative because we're missing the small picture. Because the big picture, Yeah.

Michelle:
So has the Alzheimer's diagnosis gone up or has it gone down for the number of people being diagnosed now with this improved technology?

Dr. Toenjes:
The technology is not necessarily responsible for what's observed and unfortunately, dramatically expanding. I actually recommend people not look into the epidemiology of of Alzheimer's disease, because if you do, you'll start to get very, very frightened.

Michelle:
It sounds frightening. Sure.

Dr. Koren:
Yeah. Well, and also, as we treat other problems successfully, more people will have problems of older age and Alzheimer's would be one of those problems.

Dr. Toenjes:
Correct. If you look at rates of mortality, for example, you know, huge advances with statins and cardiovascular risk reduction in reducing cardiovascular death rate and stroke, death rate and disability. But Alzheimer's has really lagged behind. And so it really is jumping up in terms of, you know, etiologies for disability and death.

Dr. Koren:
So basically when the cardiologist fixed them, then we sent in neurologist and let them become demented with you guys. All right.

Dr. Toenjes:
Thank you.