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Maria Thomas: Everyone, again, hello, and thank you for joining us. Thank you to those of you who've joined us in person, and I know that we have a number of people online with us on a livestream right now, and we will also be posting the video for later on-demand viewing, so there will be a large audience, listening to this incredible talk today. We're so fortunate to have two wonderful physicians and clinicians with us here. My name is Maria Thomas. I am not a clinician. I lead a group called Sunday Health.
We are a cognitive care organization, meaning we provide clinical care. I'm joined by my colleague, Dr. Amy Sanders, who I will introduce in a moment, who is a cognitive neurologist, and we have a wonderful partnership with Re:Cognition Health, and we want to thank them first and foremost for hosting us today, so thank you so much for allowing us to be in this amazing space.
Dr. MacSweeney is the founder and CEO of Re:Cognition Health, and she has a number of colleagues with her here in the back, and so thank you all for making this possible today.
I will be further introducing you both in a moment, but just to explain what we'd hope to do today, we're gonna talk… I'm gonna try to moderate a little bit of a conversation here, between, Dr. Sanders and Dr. MacSweeney, and we're gonna cover a little bit of ground that we think you'll all find interesting. We did also invite questions prior to the presentation, and so we'll try to take some of the questions that we've received already.
And then if any of you, either online or here in person, have additional questions, we'll try to open that up, and we'll try to leave plenty of time for that.
So without further ado, I'm going to, get us started here. To my left is Dr. Amy Sanders. She works with us as one of our cognitive neurologists at Sunday Health.
Dr. Sanders has been practicing for over 15 years, and is now… we're delighted to have her, as our lead cognitive neurologist at Sunday Health. She has a deep, deep, knowledge and specialty in matters of cognition. Dr. Sanders trained in med school at the Albert Einstein College of Medicine in New York, and she's also had professorships both at Albert Einstein, her alma mater, and at Upstate University in New York City. Immediately prior to joining us at Sunday Health, Dr. Sanders was a founder and lead clinician at the Ayer Neuroscience Institute in Hartford, Connecticut, where she still lives today, and is joining us here in person, so we're fortunate to have her.
And to my right is Dr. Emer MacSweeney, who is here from the UK, London, where she lives, and as I mentioned earlier, is the founder and CEO of Re:Cognition Health, and I'm gonna try to do you justice, but please forgive me if I get anything wrong. Dr. MacSweeney is a neuroradiologist, and is, really, I think, a visionary in this arena, because this Re:Cognition Health company started in the UK in 2011, so we're talking nearly 15 years ago. A real vision for what was coming in the field, what is happening in the field, and set up these centers, both in the UK and in the US, as centers for
People like all of us who are interested in getting ahead of these problems and participating in relevant clinical trials, and now also in receiving the latest disease-modifying therapies we call monoclonal antibodies here in this infusion center. So, we are sitting in one of four Re:Cognition Health centers in the United States. Another is in near Chicago, or in Chicago, and two in Texas, one in Fort Worth, and one in Houston, and I know we have also a representative from Houston here today.
So, Dr. MacSweeney, is really a leading voice, in… what's in the pipeline from a pharmaceutical perspective, what's happening from a neuroradiology perspective, and I think today we're just so privileged to have this pair here to talk with us, so thank you, thank you again.
And both of these amazing women were at the Alzheimer's Association International Conference that took place in Toronto just a month ago.
And so that's really where I would like to start the conversation. I'm going to turn to you, Dr. MacSweeney. Maybe you could share with us, I think you've both been attending the conference now for years. Yeah. So maybe you could just share a little bit of You know, what were some of your impressions this year at the conference, and what was different, if anything?
Current State of Alzheimer's Research - AAIC 2025 Highlights
Dr. MacSweeney: Well, I think I would preface that by saying, really, over the last probably 2 to 3 years, there's been a very significant change in the hope and delivery of expectations of many people.
So, for such a long time, there were multiple clinical trials for new disease-modifying treatments and also for biomarkers, but really without any significant success. But I think the two really big things that everyone is very enthusiastic about now, and it's really important because it also triggers funding in research and development in this area and everything, and that is the simultaneous, development, and now coming on the market, of biomarkers with respect to Alzheimer's to detect the presence of disease really, really early. And that partnered with, at least now, two new medications that have come on the market for treatment of the Alzheimer's disease pathology itself.
And like anything that is a progressive disease, you have to treat it as early as possible. But the big conundrum has been that if you can't detect the presence of the disease accurately when it's in its very mild stages. then you're unable to give the right treatments to people with the right disease at that very early stage. So the really big new era is heralded by the fact that there's new, accurate biomarkers to make an early, accurate diagnosis of the disease pathology of Alzheimer's.
And new treatments, which, when given early, have been demonstrated to be effective in slowing progression of disease and symptoms.
Maria Thomas: Thank you.
I think you're all gonna notice a couple of themes that come up here. One is gonna be that, I'm here to ask the questions that we probably all have in our heads when we hear something like that, including, well, what do we really mean by biomarkers? And we'll get to that. And the other theme that I think I'd like to pull out right away that you touched on is the importance of starting Early.
I usually start these presentations by saying, how many people in the audience, when you turned 50, knew that you were supposed to go and get a colonoscopy? And, you know, we all know, we all know we're supposed to go to the dentist twice a year, but… what's that same motivating factor for getting our brain checked? Why isn't that on our list of things to do? So, starting early is going to be a big theme.
Dr. Sanders, I know you've attended the international conference now for years. What got you most excited about… I mean, 20 years, actually, now that I stopped to think about it. You know, it just… the air felt different.
Dr. Sanders: there was just… there was a buzz and excitement in the air that I have never felt before at that meeting. I don't think I've ever almost gotten teary In one of the plenary sessions, and when the researchers for the U.S. POINTER study, which is a big, big study that I'm sure we'll touch on later today, stood up and said, we have a positive study, I really got choked up, and I don't think I was alone in that.
So, you know, and I think that I am a… not technically card-carrying, but maybe I'll have cards printed, member of the, sort of community within Alzheimer's disease research that believes we are not likely to cure these diseases, we are much more likely to be able to prevent these diseases. And one of the other exciting things that I was unaware of before attending the meeting, and just happened to be in the right place at the right time to hear the announcement, the Alzheimer's Association is embarking upon, its… its newest, they just finished one, they're starting a new one, 10-year plan, and the focus of that 10-year plan Is, at least in large part, brain health.
Which is, sort of… moving the lens a little bit from treatment, where progress has been made, to prevention, which is where I think, really, the… the big payoff is someday going to come. We're not there yet. But, you know, I was at a different meeting earlier in the year, and, I actually got to the first plenary session, I was late. I went right back to my hotel room and listened to the whole thing, because it was so exciting. A very, very famous, clinical trial researcher stood up.
And talked for nearly an hour about how the development of the first disease-modifying therapies for Alzheimer's disease, Leqembi, Kisunla, have re-vivified the clinical trials pipeline. It was, you know.
Cognitive neurology was a dusty desert town where nothing much happened at the beginning of my career. I started in practice in 2008. So we're gonna… It's nothing like that now.
Defining Dementia and Alzheimer's Disease
Maria Thomas: Sorry, thank you. We're going to pick up on all the things that both Dr. MacSweeney and Dr. Sanders have mentioned. I do want to just back up for a second, though, and make sure that we level set. And so, Dr. Sanders, I'm going to turn to you again and, just ask some basic definitional questions. Let's start with What is dementia, and what's the difference between dementia and Alzheimer's disease?
Dr. Sanders: Actually, one of my favorite questions, because for many, many people, I bet the first answer I'm going to give is not the one that you're expecting to hear.
Because dementia is not a disease.
It is what we call a syndrome. It is a collection of symptoms.
more… Precisely. Dementia is a catch-all term. It's an umbrella term that, that… encompasses the The situation in which a person has cognitive problems, cognitive decline, in at least one area of thinking, that have progressed to the point that they are now impacting, not in a good way, a person's ability to live their daily lives. So they have… that person has functional impairment.
Because of thinking impairment.
That is all that dementia means.
Most people think that dementia is a disease, so many times I will hear patients say to me, well, grandma had dementia, but thank God it wasn't Alzheimer's disease.
Dementia? Catch-all term. So whenever I tell somebody, look, I think that you have thinking problems that are causing you other problems.
I think you have dementia, then the next thing I have to tell that person is what disease I think, is causing the dementia. I've never actually counted, but I would imagine that somewhere between 75 and 100 different conditions can lead to the dementia state.
There are 4 big ones. Alzheimer's disease.
the granddaddy of them all, or the grandmommy of them all. I don't want to be gender-specific here.
And probably accounts for 60-70% of cases of dementia around the world.
Dementia with Lewy bodies, that's what Robin Williams had.
Common, much less common. Vascular dementia, which is where, in essence, the kind of disease that you think of in your heart is happening to your brain.
also a common cause of dementia. And then finally, frontotemporal dementia, which is actually a whole collection of different, conditions. That's what Bruce Willis has. And that is the, the most common and, Really, the one that's not like the others, because it tends to affect people starting usually in their late 50s, rather than, say, their late 70s. Those are the big four. Dementia, a syndrome, not a disease.
Big four, dementing diseases, Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.
Understanding Mild Cognitive Impairment (MCI)
Maria Thomas: Thank you. And I see some of you writing… in the handout that you have, there is, I forgot which page it's on, but this is covered, so, you should have that, those four, types of dementia that Dr. Sanders just mentioned.
And Dr. MacSweeney, maybe I could ask you to just elaborate, further on… we often hear mild cognitive impairment, or MCI. What is that, and is that a clinical diagnosis, and how does that differ from saying someone has received a dementia diagnosis of some sort?
Dr. MacSweeney: Yeah.
So, mild cognitive impairment is actually, again, a bit of a catch-all term in the same way as dementia is. So, I always find it quite confusing when somebody goes to see their doctor and they say, I think I've got some mild impairment of my cognition.
And after, I don't know, an hour of consultation, they come out and say, yes, you got mild cognitive impairment. It's like, yeah, I know, that's why I came to see you. So, mild cognitive impairment is just a descriptive term.
And it really describes when somebody is aware that there is something wrong with their cognition, but it is mild.
So…
The thing about most, I think, all dementias, pretty much, but particularly these progressive neurodegenerative diseases that cause dementia, is that, in fact, there is a whole phase of time, which often is probably the longest period of time, when you actually have the disease pathology in your brain.
And you are completely asymptomatic. You don't have any symptoms. Then there is a phase when the disease has progressed further, and at that point, you have mild cognitive symptoms.
Then it progresses to the next stage, which is called mild, and if it's due to Alzheimer's disease, it'll be called mild AD, mild Alzheimer's disease dementia. So this just means you've now lost independence in certain activities of daily living, which is exactly what you've just heard.
then it goes from mild AD dementia to moderate AD dementia to severe AD dementia. So it's just a continuum. And the thing about this continuum is, basically, we're all on this continuum.
And what is different today from in the past?
is that Alzheimer's disease is a biomarker diagnosis. So, you could be completely normal and have Alzheimer's disease if you have the abnormal pathology in your brain, which is this elevated toxic levels of amyloid protein, and later then the tau protein.
So, everyone on the spectrum is either normal.
With no amyloid, let's call it just amyloid for now, toxic amyloid protein in the brain. Or you can have mild cognitive impairment, have a bit more of this amyloid protein and this other protein down the brain, or you can move further down the spectrum.
And the reason why it's so exciting about studies like the POINTER study and other studies which have demonstrated that there are lots of modifiable risk factors is because as Alzheimer's disease develops over about 20 years before you develop the first symptom.
It's a perfect disease to treat. You've got 20 years to figure out how to treat this, to prevent people getting across that sort of midline divider on the continuum, where they start to develop symptoms.
So, the ideal thing, and this is where the future is so exciting, that through modifiable risk factors, like diet and exercise and things like that, we can slow down the rate of progression of developing these symptoms, but also we can all intervene as people are getting to the point where they could be getting close to developing symptoms. In the relatively near future, I think we'll actually be treating the medications. For example, these medications remove amyloid protein.
to bring that amyloid protein back into the normal range before you start to develop symptoms. So that's why Alzheimer's disease is a completely, you know, I think in the near future will be preventable.
Because it's like diabetes or hypertension. There's, like, nothing special about Alzheimer's. It's the same as any other disease, really. You, you can detect the presence of the disease with these biomarkers before symptoms develop.
And in the future, we'll be able to prevent those symptoms developing by correcting the pathology.
before the symptoms start to develop. So, same as the PSA for prostate, I mean, nearly anything… A1C. HbA1C for diabetes.
We don't wait till your legs drop off before you decide to treat your diabetes. Now, you treat your diabetes as soon as you realize that you are pre-diabetic, and your blood biomarkers are telling you that you have the disease.
Also, people for a long time had the misconception Well, I don't want to find out if I have a problem with my thinking, or any kind of cognitive problem, because there's nothing that can be done.
Dr. Sanders: Oh, my goodness, if you leave here today with only one take-home message, let it be. There is always something that can be done. I do not care what stage of disease you are at.
Oh, I ended a sentence with a preposition, shame on me. What stage of disease applies? Something can always be done.
Modifiable Risk Factors
Maria Thomas: So, thank you for that, Dr. Sanders. I want to pick up on… you were… you repeated the phrase, modifiable risk factors. Yeah. Can you talk about, the difference between modifiable and not modifiable risk factors, and give examples of each?
Dr. MacSweeney: Okay.
Modifiable risk factors is really the key thing.
And it's now well known, and actually this is part of the, the thing about this POINTER study, that Dr. Sanders referenced, is that, that was a study looking at modifiable interventions that individuals can make to decrease their risk of Alzheimer's. And one of the things that's quite important is it probably is relevant for an actual individual person, but it is one of those things, if the whole world Sort of adhered to these modifiable risk factors and corrected them.
then the risk of Alzheimer's would be reduced by, I think it's up to now, about 39-40%.
Dr. Sanders: 40%, yeah. Yeah.
Dr. MacSweeney: And those risk factors… 40%, I mean… 40%. That's a lot. Yeah. And so…
I'll give you another statistic in a sec, but those… those risk factors, number one, seems to be exercise. So, exercise, I believe, is one of the single most important factors for reducing risk of Alzheimer's disease.
Then the other ones are diet, and I think we all know the right… I'm just going to say Mediterranean-style diet. Sleep, increasingly recognized as being important.
And then the other ones are keeping cognitively active, attending to hearing problems. Hydration, actually, is a very important one as well.
But if, as I said, if everybody in the world adhered to those things, it would reduce the global instance of Alzheimer's by now 40%.
And the array of modifiable risk factors is growing.
Dr. Sanders: Yeah. Right, we're finding more and more…
Dr. MacSweeney: Microplastics. Yeah, exactly. It goes on and on. But you'd be scared to get out of bed in the morning.
Dr. Sanders: Yeah. Well, actually, that's a bad one as well. In fact, I think the latest one is if you sleep, you go to sleep…
No less than 7, but no more than 8 hours. Right, right, right. Like, too much sleep is bad for you as well, so… but I think the key thing is, you know, like, it's like the ancient Greeks, you know, the middle course is best, and moderation in all things. But adhering to those key risk factors…
I think there's… you know, it's beyond dispute that those risk factors are important. And I'll give you one statistic I saw recently, is that, like, after… I don't know if this is everywhere, but I know in the UK, after the Second World War, the instance of diabetes was 2%.
And that was because of the, sort of, like, diet and everything, you know. Right.
let's say, Calorie restriction. Significant moderation in eating. But that's an example of how… Modifiable risk factors are real.
I mean, I don't know what the incidence of diabetes, like, is now, but it's not 2%, I can tell you that.
Timing of Cognitive Assessment
Maria Thomas: So, you both have emphasized so strongly the importance of early testing.
And you referenced this idea of the potential for preventing, or at least delaying cognitive decline. So, Dr. Sanders, I want to turn to you. What is the right time to get tested for your cognition if you're trying to be proactive? When should you do it? And what is the test anyway that we're talking about?
Dr. Sanders: Oh, so there are many testing possibilities. I always like to say that were I king of the world.
Unlikely to happen anytime soon for all sorts of different reasons, but then everybody would have a formal neuropsychological domain-specific cognitive evaluation. That means that we would evaluate their attention, their memory, their language, their reasoning ability, and their visual and spatial abilities, along with mood and that sort of thing, when they were around 35.
So, it actually takes the brain… decades to become fully, fully physically mature. So let's say that happens by the time we're 30,
Tack on another 5 years for, you know, a little life experience that by the time we're… people are my age, one hopes, become the foundation for later life wisdom.
And things after… so 35 is really when we hit the peak.
of our mental faculties' lifetime. I mean, that's a really, really crude generalization, but that's roughly when it happens.
After that is when it becomes important for us to start paying attention, and working on paying attention to our diet, our exercise, our sleep, our, that we're not taking any medications that we shouldn't be taking, that we're not drinking soda.
consuming other types of things that are not healthy for us. All kinds of things, and anybody who's ever come to see me as a patient knows that I talk about this stuff Until my poor patients get blue in the face. I can go on forever. But, so, you know,
it is never too early to start, is the basic message. It is also never too late to get examined. So, you know, even if somebody has progressed Through preclinical disease, through mild cognitive impairment, mild disease, and maybe has severe disease, there's still some evaluating that can be done, and there are always things that we can offer that will help make life better. So, there is always something that can be done, and it is never too early to start.
Genetics and Alzheimer's Disease
Maria Thomas: And, Dr. Sanders, I want to stay with you. What role does genetics play in all of this?
Dr. Sanders: multiple different roles. So, genetics is probably the best example of a non-modifiable risk factor, because you can't really change your genetics, although there are things that people call epigenetics.
I don't want to go there. That's really complicated, and it makes my head hurt. So genetics, you know, you get that, you get your genome from your parents.
And, you know, I hope that you chose wisely when you chose your parents, because those genes make a big difference for how your life is going to go. In Alzheimer's disease, and to some extent, but to probably a lesser extent, in other dementing diseases, there are genetic mutations Which confer destiny, meaning if you have the mutation, you will get the disease.
And then there are also, especially in Alzheimer's disease, other, less… Deterministic genes that confer vulnerability, or increase risk.
The mutations are really, really rare.
And, typically.
If they're going to be present in a family, they're going to affect up to 50% of family members on one side of the family, because this would be what we call an autosomal dominant genetic mutation, meaning that if it's happening, it is telling all the other genes what to do. It's a big, big boss.
The vulnerability, or risk gene, you might have heard of this one, it's called APOE, that stands for apolipoprotein E, involved in cholesterol metabolism, we all have it in our bodies and in our brains, it's totally normal.
We get, in one little address, called the epsilon, Part of the gene.
You get… Three, you have a choice of three possible variants.
So I always reason by way of Neapolitan ice cream. I think vanilla is kind of dull.
A little tasty, but dull. So that could be the E3 variant, neutral.
Doesn't protect, does not increase risk.
Then there is chocolate. Let's call that the E2 variant. This one… probably is protective. Maybe not 100% consensus around the world that it's protective, but more likely to be protective than not. And then there's strawberry. Poor, poor strawberry. That's the E4.
gene, or allele, which is what we call the bit that you get from mom, and the bit you get from dad, and those two things together kind of come together and make the gene. And the E4 is associated with increased risk.
If you have one copy, remember you get one from mom and one from dad, you have one copy, your risk goes up by 2, 3, maybe as much as 5 times. If you have two copies, your risk is probably 10 to maybe even 20 times higher than that of somebody who does not have that.
genotype. However, it's not destiny, and long-term research studies have been conducted, partly where I went to school in the Bronx, looking at people who live to be age 95,
two copies of the chocolate, I mean, sorry, of the strawberry, of the bad allele, of the one that increases risk. And these people, a lot of times.
having emigrated from Europe during World War II, a lot of times having a second or third grade education, lots of things that they kind of hadn't done right over their lifetimes, but they smoked, they drank, they didn't exercise. They lived into their mid-90s and were cognitively intact.
So clearly, those people must have some sort of protective factor.
That we haven't discovered yet. I hope we bottle it fast when somebody finally does. But, so, ApoE, a genetic risk factor, it is a risk factor. There are other mutations that confer destiny. That's a long and sort of complicated answer, but genetics is complicated. Thank you.
New Monoclonal Antibody Treatments
Maria Thomas: So, we've talked about the importance of getting, cognitively assessed early, not waiting for symptoms. We've talked about the, advent of blood-based biomarkers.
So biomarkers, meaning, you know, what they can find in your blood as a signal for whether you may be developing, this protein that we don't want to have, the amyloid protein.
I'm going to turn to you, Dr. MacSweeney, and maybe just elaborate now on the new treatments that we've referenced, and which you do indeed infuse right here in your center, the monoclonal antibodies. What are they? Why are they different? You know, and also maybe what's coming next in the pipeline?
Dr. MacSweeney: So I think probably everybody knows that there are two treatments that are on the market at the minute.
One's called Kisunla, the other name for it is Donanemab, and then the other one is, Leqembi, and it's sort of, like, proper name is Lecanemab.
And they're both the same class of medication, so I would say it's a bit like… the London analogy, but London buses, none come for ages, and then two come at once. So…
Dr. Sanders: That works for Bronxes in the Bronx as well. Alright.
Dr. MacSweeney: And so they're both the same class. They both are monoclonal antibodies, they're given by an intravenous infusion.
Kisunla takes half an hour, Leqembi takes an hour, so in other words, just a quick infusion. The medication goes up. Now, the clever bit is that it goes across the blood-brain barrier. That's the really hard part. And then, in the brain, it… I mean, it's a little bit more complex, but essentially, they…
Through a mechanism, they attach to the abnormally elevated toxic amyloid protein in the brain that is quietly killing off your brain cells, and they remove that toxic amyloid protein from the brain, and they bring your amyloid levels back down into the normal range.
And in so doing, they slow further progression of disease and symptoms.
But the most important thing is that the earlier you can access these treatments, the more effective They are, both in removing the amyloid protein, but more importantly, in slowing progression of symptoms.
And, the… way we know if you have high amyloid protein in order to be eligible for these medications.
Is we can either do something called a PET amyloid scan, which is a scanner that… you have a little tiny injection in your arm, it sort of sends a ligand up into the brain, it attaches to the amyloid protein if it's there, it reduces… it gives out a little packet of radiation, and that's what we measure.
You can do, a lumbar puncture where we analyze the CSF,
And we can see if you've got amyloid protein, abnormal levels of amyloid protein in the spinal fluid, which reflects what's going on in the brain. And then there's a new blood biomarker, which has actually been approved by FDA just very recently, and that's become something called PTAU 217. And there's actually a more complex one.
beta, an amyloid beta 42-40 ratio as well, that can be measured. And that blood test can give you an indication, particularly the PTAU 217 blood test.
If that is high, it can indicate that you're… it's a bit of a funny thing, but it indicates if your amyloid is high in the brain.
And if it is high, then in the US, you still would need to have CSF analysis a PET scan to confirm that it definitely is high amyloid protein in the brain. And if you have high amyloid protein in the brain.
And, and this is very important.
And you have mild cognitive symptoms.
And there are a few other eligibility criteria as well. But those are the key things. If you have high amyloid protein in the brain, and you have mild cognitive symptoms.
Then, you are clinically eligible.
or Kisunla or Leqembi treatment.
But what I want to emphasise is that today.
you cannot have these treatments. The treatments are not licensed.
For people who are cognitively normal.
So we're not treating people who are in that preclinical stage.
So you could have high amyloid protein in the brain, but if you're cognitively normal, you are not eligible for one of these treatments.
As it… so I was going to say, as it happens, there is a big clinical trial that's going to be reporting out soon. In fact, for Donanemab, the Kisunla medication, which is… the trial is for people who are cognitively normal.
And it will be interesting to see if the results of that demonstrate that the people who are taking the active medication, the clinical trial, versus the people who are on the placebo, all having high amyloid protein, nobody having cognitive symptoms, if the people on the active group, taking the active medication, demonstrated
So, like, a slowing in the time that they develop symptoms. So, in other words, the people on the placebo start to get cognitive symptoms, whereas the people who are on the active medication they don't develop cognitive symptoms. And that's going back to what you said, is that I do think in, I don't know, probably sooner than we think, but let's say certainly in 5 years, I do think we will be testing PTAU 217 in the blood, probably on everyone at the age of 45. And if it's high, you have a treatment to bring your amyloid back into the normal range.
Eligibility Criteria for Monoclonal Antibody Treatments
Maria Thomas: Let's just pick up on a couple things you've mentioned. You mentioned that, that people who are not… people who are cognitively normal, even if they have higher amyloid, in their… in their blood, are not eligible for the monoclonal antibody treatment on the market.
Dr. MacSweeney: I should give the little slight caveat that, there are quite a number of clinical trials going on all over, you know, all around the world at the minute. We're doing quite a few both in the UK and in our centres in the US.
And those clinical trials are for people who are cognitively normal, and they are to measure, to see if you have high amyloid or tau protein in the brain.
And if you do, then you come into those clinical trials, and obviously, as in any clinical trial, some people are on active medication, some people are on placebo, who don't know which group you're in, but those trials are actually to treat people, or they're treating the high, biomarkers, they're treating the amyloid in the tau protein to bring those back into the normal range before you develop symptoms. So that is going on in clinical trials today.
Maria Thomas: Are there any other groups that are excluded from being eligible for the monoclonal antibody therapies?
Dr. MacSweeney: So, the treatments on the market, the full set of eligibility criteria.
are, as I said, you have to have high amyloid protein, because you can't give someone a drug to reduce their amyloid protein if it's not already high. It's logical. They… they have to, as I said… now, I'm just going to elaborate further. They have to have mild cognitive impairment, the word we were using earlier.
what we call mild AD dementia, so that means they… have to have some cognitive problems, mainly short-term memory, concentration problems, thinking ability problems, but they're still able to manage independently. They might have to make lists and have all sorts of reminders and things like that, but they can still manage if they're on their own.
mild AD dementia means they've lost some independence in activities of daily living, but generally, they're functioning pretty well. I mean, they're sort of, like, fine, they're enjoying life and everything, but they can't do everything completely on their own.
So they are the only two phases of the disease.
That are eligible for treatment.
And what is very important is the progression of symptoms in Alzheimer's disease.
increases with time. So it's very, very slow, and it gets faster and faster and faster. And so, actually, what people don't always appreciate is that period of time when you've got mild cognitive impairment and mild AD dementia can actually be quite short.
And once you get into mild AD dementia, it definitely starts to move more forward.
And if you think about the fact that even though MCI might be… it could be a few years, can be a few years.
most people don't even realize they've got MCI until they're a good halfway into it, and then they don't admit they have it until they're a good three-quarters of the way into it. So, actually, for some people, and it's not a complete rule, but generally speaking, the younger you are, when you first start to develop these symptoms.
the sort of, like, more aggressive the form of disease is. Almost like everyone has their own form of the disease, virtually. So it's very hard to know, if you talk to an individual, you know, how they're going to be in the next few years. But as a very broad generalization, the younger you are when you first start to develop symptoms, the more aggressive it tends to be.
And so, there is no time to waste. Like, if you think you have problems with short-term memory, we can go through all the different symptoms, then you need to seek help as soon as you possibly can. Today, because you can get a biomarker test.
And you can get treatment. And in the US, if you're 65 or over, it's paid by Medicare and the supplementary insurances and everything. I won't go into all of that, but suffice to say, it's crazy not to, you know, not to try and access one of these treatments as soon as you possibly can.
And the other really important thing is that there are multiple other medications, as we said, you know, that, like at AAIC, it was buzzing, because there are more new disease-modifying medications in clinical trial now, or coming into later phase trials, than ever before.
And so… it's not like we're only going to have two drugs and that's it, you know, there's gonna be no more drugs. Obviously, there's gonna be lots more drugs. And so what's happening is these other drugs are all bubbling up, and not all, but some of those will come on the market as well.
But we already know that many of those treatments, they're in Phase 3 now.
They, too, we know from the Phase 2 studies, they are only active in this mild cognitive impairment, mild AD range as well. They're not active down here, and they won't be licensed down here.
And so, if you're up here, and you can get onto Kisunla or Leqembi now, if that… if your rate of progression was going to be that, but actually you can slow it down to here, you may still be in the range for hopping onto one of these drugs with a different mechanism of action, because it is a complex disease.
a different mechanism of action here, and then you get… then you get onto another one here. And what will truly change the course of an individual's disease?
Today.
Is being able to not be down there when this one comes out, but being up here when this one comes out, and then the next one, and the next one.
And so… you know, that… that is why, if you have mild cognitive symptoms now. Number one, you want to know, because if you are eligible, I'll go through the other eligible criteria, because in all, it can be… you need to get it. Number two.
If you've got reversible cause of your cognitive impairment, you could have low thyroid function, you could be low B12, low folate, you could have…
Dr. Sanders: Depressed.
Dr. MacSweeney: you know, depressed, you could have a brain tumor, you could have a whole bunch of things, and you need to know if you've got a reversible cause, because if you've got reversible cause, you need to get treated. It's not like not everything is going to be Alzheimer's. It could be any one of a number of different things.
And even if you have Alzheimer's, also, if you are also depressed, or if you also have low thyroid, or if you also have B12 problems.
then if we fix the depression and the mood and the thyroid and everything else, it's not gonna maybe cure your Alzheimer's disease, but it's probably gonna make your daily life a little bit better.
Dr. Sanders: Yeah, I mean, symptomatically.
Dr. MacSweeney: Yeah, symptomatically better. You'll be better. And, so the other criteria are, you cannot be on a blood thinner. Now, this is very, very important.
And this is related to, sort of, really the only, sort of, there's one side effect, it's really the only, sort of, like, side effect, really, of this medication, so you cannot be on the blood thinner.
And, the other one is, The side effect that… It's something called ARIA, amyloid-related imaging abnormalities.
That's the reason you can't be on a blood thinner.
But ARIA is something that can occur anyway in this condition, and so you have to, on your MRI scan, you need to check you don't already have some of the features of ARIA.
So, in other words, you need to have an MRI scan that passes the test, so to speak, to ensure you're eligible, not being on a blood thinner.
have mild cognitive impairment, which is MCI, mild cognitive impairment, or mild AD dementia, and have high amyloid protein in the brain.
Maria Thomas: So, I saw a couple puzzling looks. ARIA is A-R-I-A, and say again what the acronym is.
Dr. MacSweeney: So, it's amyloid Related Imaging Abnormality.
Dr. Sanders: amyloid-related imaging abnormalities. That was a translation from British English to American English. No, I'm joking, I'm joking.
Dr. MacSweeney: And one form that ARIA can take is in the form of brain bleeding, and that is why you cannot be on a blood-thinning medication.
Artificial Intelligence in Alzheimer's Diagnosis and Treatment
Maria Thomas: So, we have covered a lot of ground. I'm gonna ask, each of you one last question, at least for now, and then we'll turn to questions that folks online have, some of which have already been submitted, and anyone here. My last question is more forward-looking, and I'll stick with you for now, Dr. MacSweeney, which is, what is the role, if any, that you see artificial intelligence playing in the diagnosis and treatment of dementia.
Dr. MacSweeney: dementing diseases.
That's a tricky one. Well, you can take it. What do you see? I'm also happy to jump in.
Dr. Sanders: So, okay, no, you go, but I… Alright, so, one of the most mind-blowing moments that I had on my recent trip to Toronto for AAIC was when I went to a session on artificial intelligence.
And, one of the researchers who was presenting, In the offing.
We can't do it just yet. I mean, at least I can't access it just yet. But as a clinician, I do not have access to a tau PET. So we've talked about amyloid protein and tau protein, the two proteins that really sort of go rogue in Alzheimer's disease.
took… far longer than it should have for amyloid PET to become a clinically available procedure that Medicare covers, but that is now that… that has achieved that ability. Amyloid PET is now a Medicare-covered procedure, but tau PET is not. So I, as a clinician, have zero access to tau PET.
And this woman stood up in the AI session, and she said, that AI,
In conjunction with blood-based biomarkers and clinical information, should be able In the relatively near future, to generate…
A tau PET.
An artificially generated tau PET.
That really blew my mind. I mean, I knew that they were working a lot on developing, artificial, artificial intelligence.
Inter… interventions or usefulness in neuroradiology.
And, I saw some gee whiz things in the exhibit hall about, you know, little telephones where there's gonna be an AI and not a person on the other end of the phone, and… you… Yeah, it was surprisingly realistic. I was really impressed.
So I think the short answer is we have no idea what the ultimate potential of this is.
with great potential comes potentially great risk, and so I think we have to be cautious
But I think that right now, we're all sort of in the gee whiz, isn't this exciting phase.
But, you know, it's also true that AIs can hallucinate, and they make stuff up, so you have to be careful. I mean, it's a powerful, powerful tool, but I think that we have to harness this tool.
Dr. MacSweeney: No, I mean, I would agree with that completely. I mean, the places where it's being used currently, as you referenced there, it is… one of the things that's
Sort of both time-consuming and can be… prone to errors if the readers are not sufficiently experienced, is actually, in imaging, picking up this thing called ARIA, which is seen on MRI scans.
So that is something that people are using AI now to try to, analyze the MRI scan more accurately than it's possible to do. I was quite literally reading about that just earlier today. Okay, so that's, that's one of the things that, sort of, like, is, like, being used.
Something else they're trying to use it for, and we're working with a group that are potentially doing this as well.
Where, in these PET scans that we refer to, it's possible to actually quantify the amount of amyloid protein in the brain. And so they're using, sort of like, certain AI algorithms to try to create more accurate quantification of the amount of amyloid protein in the brain on a PET scan.
Which is really helpful for the clinician, when the clinician gets that number, which happens not…
I mean, at the minute, the numbers are sort of, like, inaccurate and misleading, but one of the reasons it's quite important is because if you're on one of these treatments, for example, and you want, like, say you have a PET scan, you know, like, at .0,
And you want to know at 9 months, are you clear of your amyloid protein, or can you tell from that number whether you'll be clear at…
14 months by an extrapolation, and it's not like a straight line or anything like that, but they're using AI to try and extrapolate, you know, if you've got two points, they can extrapolate the third point, things like that.
The other thing that we're actually already using AI in is, In identifying people who have…
Cognitive impairment.
For whom it's not actually desperately obvious.
Or in whom we're trying to work out is the form of cognitive impairment that we're detecting due to, for example, Alzheimer's disease, or is it vascular disease, or is it due to Lewy body disease, or whatever? So, you know, trying to characterize the type of problem impairment that people are experiencing. And actually, in, in,
More so, actually, even in psychiatry, for people who have depression, where they're trying to determine whether medications are effective, or any other techniques are effective in relieving depression. Instead of having, you know, like, old-style psychologists ask you some questions about how you feel about yourself and all that sort of stuff, there's a sort of automated thing that's asking you questions, but it's not just measuring
How you, it's not just measuring what you answer.
It's measuring the time, the speed, the cadence, the expression in your voice, all these different things. And it's deducting way more sensitive and accurate information about you and your mood in your response to treatment.
Than, you know, someone sitting down who's just had a bad day asking you, you know, what day of the week it is.
So, I think that's gonna be a big…
Dr. Sanders: Yeah, I think that's… I agree with that fully. And we at Sunday Health are, right now working, with the local PCP practice to apply a scientifically validated algorithm that runs against a set of data, so this isn't interacting with humans.
but a set of data that would be contained, for example, in an electronic health record or in claims data. And the algorithm, and this was published in Nature last year, is capable of analyzing that data and then returning a result that would suggest, you know.
For the physician to then say, perhaps you should look at this set of patients, because there is some evidence that we've, looked at in these records that would suggest that this set of patients might be, experiencing cognitive decline. And the variables that determine that, or the subject of this paper, could be many.
And there are lots of interesting, studies out there about what those variables are. I mean, you mentioned a few, whether it's voice, but there's others in… So many of them. Yeah, many. Also, you know, if I'm testing somebody, if I'm doing cognitive testing for somebody, it's a very time and labor-consuming process for me and for the person who's being tested.
So, you know, we don't do that every week. You know, maybe it's once a year, maybe it's with some slightly less, lengthy interventions in the meantime, but not probably more than 6 months and a year.
Another way where AI, I think, is going to be helpful is in facilitating more, sort of, daily monitoring of people's cognitive fluctuations. And that will open up a whole new.
avenue of… research, really. I mean, because, we know that people are not the same from one day to the next, even from morning to afternoon. And so if we could capture some of that, what we call, intra-individual variability, that would teach us things that we probably don't know right now.
I think one of the areas where that may be… quite effective is in managing Parkinson's disease, because one of the problems there is there's so much fluctuation, related to the treatments and everything as well.
the, there's… I know in some clinical trials we're doing in Parkinson's, it's… it's using… using that sort of type of feedback and data, constant data, to determine how… how to manage the… the swipe drug into the
Q&A Session and Communication in Dementia
Maria Thomas: Well, I mean, this is clearly… this is clearly a technology that is going to impact this field and everything, but let us turn to questions now. Let's start with those of you who are present. Does anyone… would anyone like to throw out a question? Oh, we have questions, please, and then we'll come to you, sir.
[Questions section simplified to focus on key medical content, removing audience member interactions]
Maria Thomas: Let me just repeat the question, so the folks online can hear. The question is, is there ever a time to be eligible for the monoclonal antibody infusion therapies If you're beyond mild cognitive impairment, is that the question? Okay.
Dr. MacSweeney: Or do you mean moderate stage disease, as opposed to mild stage of dementia. So the mild to moderate, which is where the drug is licensed, the reason it's licensed Or… That period of the disease is because that is the stage of the disease when the drug is effective.
And so… I mean, theoretically, you would be having… you'd have to have it off-license. Now, I don't think it would be appropriate for a physician to give you a medication where potentially the benefit versus risk was not… an appropriate equation. So the reason the drug is licensed, the mild to moderate, well, mild to mild AD dementia, is because that's where the drug is most effective.
Maria Thomas: Thank you. And I actually posed the question when I was at AAIC. I went to the Lilly booth, they have Kisunla.
I went to the Eisai booth, they have Leqembi, and I asked that question, and the answer was uniformly, if somebody has progressed beyond the mild stage of the disease, unfortunately, at this stage of the… you know, as of today, the answer is regrettably no. But, remember what we've also said about, how much More is going on in the clinical trial pipeline, and it's not just
the way that we've always thought about these diseases in the past. There are all sorts of new disease mechanisms, new mechanisms of medications that are looking at different ways, it's a multifactorial disease, and drug development is now also becoming multifactorial. So, even if today.
Somebody at the moderate stage of the disease.
cannot get one of these medications. There may be medications, maybe even sooner than we know right now.
That will help people who are at later stages of disease. I mean, if I could just add to it, I mean, we have a clinical trial here, right now, in all of our centers, for people with moderate to moderately severe disease.
So the answer is, it's like everything, it's, you know, it's the right drug at the right time.
for the right stage of the disease. So, I would say if you know someone who has moderate, to write early severe disease, then they need to access the drugs on the market which are symptomatic, plus get into a clinical trial, which is for new drugs designed for that stage of the disease.
Maria Thomas: Thank you. And I'm going to turn to you, sir, and we have some questions coming online, and we'll get to your question as well.
Dr. MacSweeney: So that's quite a tricky question to answer, because,
The straight answer has to be, predicated from the data that has been generated from the clinical trials.
And there are two things to say. In the clinical trials, the people who respond best, as we said, are the people with the milder symptoms, and they're the people, actually, it's another subject, but they're the people who have the lowest… they have high amyloid, but they have the lowest amount of tau protein.
And, in both studies with the Leqembi and the Kisunla, those people in the mildest group, they do actually show, two things. A sort of, like, no decline over that first 12 months, and then slowing to just a sort of, like, 60%, rate of decline relative to people on placebo following that period. Now, there's been a recent,
something recently that came out at AAIC about Leqembi, where they've been following people in the trial, the trial's called Clarity, for a further 4 years.
sort of on treatment, and what they have found is that, a cohort of patients, again, the milder ones, did not decline, even though during that period, and some showed some improvement.
But I think it would be inappropriate at this point to say that these drugs are… providing, you know, reversing you back to normal. That is not true, and if I was to say that, that would be a false representation completely. And the key thing is that once brain cells die, unlike pretty much any other cell in the body, brain cells can't regenerate. Whereas your liver cells and your you know, your muscle cells and almost all your other cells can regenerate, but brain cells can't. And that is the reason why you have to get these drugs as fast as you can, because every day you're losing more brain cells, bazillions of more brain cells.
The only other thing I would say, and I really want to emphasize this, is anecdotal, okay? And… it's not just, like, we are treating a large number of people, both in the UK and around the air, San Kisunla.
And it can be. But, I've also swapped notes with, sort of like, you know, my opposite numbers, doing this in the US and other places.
And this is totally anecdotal, but we have noticed that our patients who are on Sundays, so many of them, and Leqembi, so many of them come back, and they look… they look better, and they feel better, and they say they're better, and their study partners say they're better, or their treatment partners, even to the extent that we have now introduced a new quality of life questionnaire.
for our patients, because we can't understand what's going on. Like, why is this? Now, one of the things we do do, is we say to people, look, this is a treatment program.
And the treatment is just one part of the program. And the other part of the program is you have got to invest diet, exercise, lifestyle, social activity, all these other things. And I literally say to my patients, I want you pitching up here for your appointments like a finely-tuned athlete, ready for a race.
And and I think they actually really, really do invest in it.
And there's a sort of, like, thing called placebo effect, but there is also these modifiable risk factors.
Dr. Sanders: Yeah, I mean, I often say this… I often say the same thing to my patients in a slightly different way, that it's all about optimizing everything that is optimizable.
And, you know, it's my job to help, sort of, you know, point you in those directions, and then, you know, tell you what to do, but then it's your job to go and do the doing. So, yes. I mean, you get one body and one brain.
And it's like, you can buy another car, you can buy another house.
You've only got one body and one brain.
And one life. And one life. One life. He just could do everything.
Communication Challenges in Dementia
Maria Thomas: Well, thank you for that. I know you have a question, but I do want to invite the online audience to submit questions. I am receiving them. I'm going to take one online question, and then we'll come to you. This is a little bit different. Dr. Sanders, maybe you can take this one. And the question is, what can be done when patients start losing words?
Dr. Sanders: Hmm. So… The first thing I would mention here is actually what not to do.
quizzing is not helpful. For the care partner. Right, the care… right, so the care partner should not start quizzing the person who is losing words.
About, you know, working on building their vocabulary, because that's… Probably going to be received as not helpful, and maybe hurtful.
So, communication in any of the dementing diseases is really important.
It is unique to the individual with the disease. There is no universal playbook for any of this.
Understanding how… The person communicates best.
Some people like to hear things, some people like to read things, some people like to have it sung.
You might not have thought to try that. Try it. Music, actually, you know, there are people who are functionally mute, because disease has progressed so far, but they can still sing Happy Birthday. So, singing and music matters. Never forget that. And
Then it is the job of the care partner to help the person communicate.
Not to communicate for them, but as much as possible to help them communicate. It's also really, really useful. This is a little tip that punches way above its weight.
You don't want to ask a person who is struggling with language as part of their disease. An open-ended question. Do not say, Grandma, what do you want for dinner?
Because Grandma just is… Grandma's gonna just choke. She's gonna freeze.
Grandma.
Would you like spaghetti or fish?
give a… An either-or, a binary choice. That, that can help.
A lot of it is going to be experimentation and exploration. No universal playbook means you guys, the person with the disease, and their helper have to be detectives. You have to figure out what works.
And what doesn't. And then remember it from one day to the next, because reinforcing things structure, sameness, always very helpful, and then reinforcing things, you know, from one day to the next can also be, very helpful. People learn things sometimes without realizing they're learning them.
Maria Thomas: And what's the difference between what you were just describing of someone who's really losing words, aphasia, I think we call it, and that, and what you often call tip-of-the-tongue.
Dr. Sanders: Yes. The tip of the tongue phenomenon. Yes, I am still actually contemplating writing myself up as a case study in the medical literature because of the tip of the… one of the tips of the tongue phenomena that I actually had, and it involves British English.
But the tip of the tongue phenomenon is one of the most well-known and usually benign Oh, so very aggravating. Features of the normal aging brain.
What's the name of that restaurant that we went to 3 weeks ago, where you had the fish, and I had the spaghetti, and it was really, really good? What was it called?
as we often say at my house, oh, between the two of us, we have a whole functioning brain. And, the tip of the tongue phenomenon is when you're reaching for a word, and in the moment that you want it, you cannot find it.
And it typically comes back to you in seconds, minutes, hours, days, or once very memorably for me.
More than 6 months.
Can't really explain that one. But,
It's typically not pathological. It typically is not the harbinger of the great slide into cognitive decline. It's annoying.
It's probably benign. It helps if you can recognize it when it happens. And then tell all your friends, because they will be happy to know also that it's typically not, pathological. Thank you. Yes.
Menopause and Cognitive Health
Maria Thomas: Sorry, she, she was, she was waiting. Valerie, we'll come to you next. Yep.
Maria Thomas: And let me just repeat the question for the online audience. What is the role of menopause in women on dementia cognitive decline? Maybe we… Dr. Sanders, you could start, perhaps?
Dr. Sanders: Oh, gosh, really? This is definitely a tricky question to answer.
probably more than 30 years ago, there was a lot of excitement about, hormone replacement therapy for women in menopause.
At the perimenopause, throughout menopause, in late menopause, and oh gee whiz, look, we can replace estrogen, and women don't lose their minds anymore.
Until… further study revealed, -oh, lots of heart attacks and strokes that we really didn't think were gonna be happening are now happening. So, probably.
It's not good to start hormone replacement therapy for a woman at menopause, at the perimenopause, and then continue it forever. I recently just had a fight with one of my patients. 82 years old, has been on hormone replacement therapy for 30 years, and does not want to come off of it, no matter how much I tried to teach her. It's dangerous for her at this point.
The current thinking, to the extent that I am competent to talk about this, it's not my primary sandbox, but… is that maybe some Medication at the perimenopause might be helpful for the future decades, but continuing it long-term is not such a good idea.
Maria Thomas: Thank you.
Dr. MacSweeney: One thing I would just sort of add to that is that, often.
cognitive symptoms due not to menopause, but due to maybe early Alzheimer's, first time prevention, these various things, can actually present a lot longer at younger
And I've certainly seen, I'm sure you have, people who were assumed to have cognitive, mild cognitive problems due to menopause.
until they suddenly start getting worse and worse, and they say, oh my goodness, maybe it's not menopause. So, yes, you know, there is some cognitive sort of, like, lapses related to menopause itself, but…
You know, if those seem to continue to, progress… I wouldn't automatically assume it's due to menopause. I think it's really good advice. Yep.
Partnership Message and Urgency of Treatment
Maria Thomas: Thank you for that. I'm gonna come to you in one second. I just want to note that we had a, a comment online that, basically, I'll try to paraphrase has to do with someone who was approved for Leqembi and then had to wait a long time for the first infusion, and so she's really appreciated hearing tonight from both of you about the importance of starting early, and that every day matters. And so, I want to take the opportunity for a little bit of a plug here, for the two groups that are here tonight, which is Re:Cognition Health and Sunday Health. The reason we're partnering together is because we have
clinical care from Sunday Health, in the form of Dr. Sanders and a whole clinical team as well.
And what we have with Re:Cognition is the opportunity to, enroll patients who might qualify into clinical trials, to get them, evaluated for whether they qualify for the new drug therapies. And so.
The reason this group is together is because we have complementary services, and we hope that for anyone listening here or online, if you haven't already been evaluated, and you want to be evaluated, either for a cognitive baseline, which is something Sunday Health can help with, or potentially for inclusion in a clinical trial.
you know, talk to one of us, afterwards, and we can give you a lot of information. Now…
Dr. MacSweeney: Do you mind if I add that? Because this is the one thing that really is so upsetting.
is, like, you know, we've been involved in all the clinical trials for Donanemab, Lecanemab, Aducanumab, you know, we've given over 10,000 of these doses of monoclonal antibodies, along with all sorts of other clinical trials. And it's just incredible that there are now drugs on the market.
What is heartbreaking is for people to be waiting to either get, sort of, like, a diagnosis, which is, to be honest, just a simple scan or, you know, like a lumbar puncture or something. It's so easy to be waiting for a biomarker diagnosis.
And to have a biomarker diagnosis and be waiting to start treatment.
All I can say is it's your life, it's your brain. And this is, you know, I'm not saying this disease is cancer, it is not, but this is the same principle of cancer.
Every day you wait for treatment with cancer, the cancer cells are multiplying. Every single hour that you wait for treatment to remove this amyloid protein, you are losing more brain cells.
So, just, like, don't wait.
It's madness.
Blood Tests and Biomarkers - Detailed Explanation
Maria Thomas: Well, thank you. Sorry about that. No, no, thank you, I much appreciate it. So, I want to turn to your question, Valerie.
Maria Thomas: So let me just repeat the question for those online. The question… I'm gonna paraphrase a little bit. The question is about the difference between the two proteins we've mentioned tonight, amyloid and tau, and also, I think, as, like, a little bit of a separate question about the types of blood tests that are available, and what they are looking for. So maybe you can take the protein question, and you can take the blood test question. I don't really care, one of you can take the… whatever question you feel comfortable with.
Dr. MacSweeney: Okay, so the first thing is I do understand why you're confused. That's the first thing. So… in the U.S
I'm just gonna say, because it is actually different in different countries. In the US, my understanding is to qualify for treatment with Kisunla or Leqembi, you have to either have a positive amyloid PET scan.
Or a positive result to confirm to confirm high amyloid via a lumbar puncture and CSF analysis, okay?
That's what you have to have. Right.
There is a blood test, which is called PTAU 217.
And the PTAU 217 blood test can give you 3 results.
One result is it's high.
And if it's high, it has an incredibly high sensitivity and specificity to indicate that you have high amyloid protein in your brain.
Okay? So that's one thing that's a little bit counterintuitive. It's a P-tau test. It's a correlated tau test. But it's telling you about the likelihood that somebody has excess amyloid. And the reason for this is because
Once you start to get symptoms with Alzheimer's disease.
Those symptoms correlate most closely with the development and progression of tau protein in the brain. So amyloid's got… not amyloid, Alzheimer's got two things. It's got amyloid in it, it's got a whole heap of things, but the key thing, it's got amyloid and it's got tau.
And… One… the amyloid protein tends to come first.
But once you start to get symptoms.
you have tau protein. So, if you have a high PTAU 217 in your blood, you have symptoms, you have a high P tau…
217 in your blood.
you have an incredibly high, it's like, I don't know, 98, 99% sensitivity and specificity, that you have high amyloid protein in your brain.
And in some countries, the drug is licensed just on the basis of the PTAU 217 test.
So, I was in Mexico recently doing a presentation, and there, you can access Because on the… just on the PTAU 217. And I think we're not far from that, even at this point. We're probably not far from that, to be honest. Then you can have a low P tau 217 result, and if you have a low P tau 217 result.
you… High level of sensitivity and specificity do not have elevated amyloid protein in your brain.
And then there's about 20% in the middle, where the PTAU 217 result comes back as intermediate. And if your PTAU 217 result comes back as intermediate…
You don't know. You might have high amyloid in the brain, you might not, and you have to have a PET scan in that situation to determine whether or not you do have high amyloid protein in the brain.
Although I actually… and I actually even heard a presenter at AAIC last month say, but don't, actually, try to confirm, a PTAU 217 with an amyloid PET, because 10% of such amyloid PETs will be false.
positives and negatives. Just a tiny bit. So, you know, and that really gave me pause, because, you know, these… the PTAU 217, especially the test that… where it's combined with the amyloid ratio, this is the famous Lumipulse test that the FDA approved in early May.
Dr. Sanders: If somebody comes in with an intermediate result, and I've had a couple of those, well, what do we do? Do we repeat the testing in 6 months? In 12 months?
nobody knows, or at least, if anybody does know, I have not yet found them. So, you know, we're learning. This is a… it's a… we're learning as we go along, because…
these exciting developments are coming quite rapidly now. And so, you know, my head is still spinning many days when I get up and go to work, in a good way, but, you know, we will be learning all along. You know, we will get better and better and more precise and more specific as time goes on.
Dr. MacSweeney: And then, I think there's another thing which you mentioned, which is a tau PET.
So there is also a thing called a tau PET scan. I don't think tau PET scans aren't really, sort of, like, in general use. They are absolutely, positively not.
Dr. Sanders: Yeah, I mean, I don't think they are. I mean, they're not in the UK, and I think they are in the US, and but in the clinical trials.
Dr. MacSweeney: We measure… we measure PTAU 217, we measure amyloid beta 42-40 ratio in the blood, we measure in the CSF, we measure… we do amyloid PET scans, and we do tau PET scans.
And that is because in the clinical trials, one, they want to be absolutely certain that people have the right pathology. But secondly, and again, this has come out of the clinical trials for, both Kisunla and Leqembi.
Is that when you stratify the people who have high amyloid, everyone's got high amyloid, but if then you stratify within that the people who have high tau, or medium and low tau.
The people who do best are the people who have medium and low tau, and they are the people who have the milder symptoms.
And they're the people who do best with the amyloid.
treatments.
So it's all a bit interconnected.
To be honest, but to keep it really simple.
like, you can do a PTAU 217 test, a amyloid beta 42-40 test in the blood, and if that's very high, your PET scan is almost definitely going to be positive. If it's very low, it's almost definitely going to be negative, and there's this range in the middle, about 20%.
Where we're not… we're not sure. And you have to back it up.
Maria Thomas: And as the non-clinician here, I'm gonna speak plainly, and you'll each correct me if this is incorrect, but I think it's important to say, because we're using a lot of language, PTAU 217, and amyloid plaque and tau, and I, you know, it's like the Greek alphabet here. But these tests that we're talking about, not the PET scan and not the lumbar puncture, but the PTAU 217, etc, these are blood tests.
And so, if you come to Sunday Health and Dr. Sanders says to you, I would like you to get a test for PTAU 217, basically how you can hear that as the patient is, oh, I need to go to LabCorp or Quest.
And I'm gonna have an order, and it says it's PTAU 217, and I'm gonna get a simple blood test. Just want to make that clear.
Dr. Sanders: Yeah, and if you have cognitive impairment, chances are pretty good, especially if you're 65 or older, that insurance will cover this. If you do not have cognitive impairment.
You… could request that somebody order this test for you. I've ordered it for one person who did not have cognitive impairment. He may well have had to pay out for it out of pocket. I let him know that that was going to be a possibility. He said he was ready to do it, and we proceeded. I don't actually know whether his insurance ultimately covered, or if he did write a check.
But just because insurance doesn't cover doesn't mean that the tests are not attainable.
They are not, however… Quest has some things at Quest where you can decide yourself that you want to get this test done, and so you, in effect, order it for yourself. The Alzheimer's disease-specific blood tests, No.
those do not qualify for that kind of testing. But we at Sunday Health have been, as I know you have, been ordering a number of these different blood tests now for, you know, over a year, and by and large, we've had good experience with getting the tests covered by Medicare and also Medicare Advantage and various commercial insurance. By and large, there's always some exceptional cases, but just to say that out loud as well.
Insurance and Access Challenges
Maria Thomas: Did you have a question? Hi.
Maria Thomas: Can I just repeat the question? So, there was a comment and a question from someone under 65 years old, talking about how in the United States, we have a sick care system, not a healthcare system, and therefore, it's not always easy, if you want to be preventative and ahead of the curve, to get that covered by insurance. So, what can one do?
Cover the question? Okay.
Dr. Sanders: So, interestingly, I actually have a collection, and it's growing every day. I saw somebody just today who's gonna be the next person in my new collection, and I think of these people as the youngsters. Thus far, they range in age from their late 30s to their early 60s.
Typically they are coming for some reason. The one guy said, I want the new blood test. That was the only reason he came. Actually, when I talked to him, he has a major family history. So there's typically something that is motivating people.
I don't see a lot of 35-year-olds coming to me saying, I've heard that it's a good idea to get a brain health exam when I'm in my mid-30s, and could I have one?
But people with concerns, because of family history, or they've had, a lot of, concussions, or who knows what causes somebody to be concerned. Remember, no universal playbook for all, any of it.
And… Without exception, literally without exception, in every single one of these patients, there is some modifiable risk factors that they could modify better and more.
And, you know, there are… people… there's a thing called subjective cognitive decline. That's when you come in and you say, I'm really worried about my memory, I'm losing focus at work, I can't remember the content of conversations, I called my next-door neighbor, you know, by my first grade teacher's name the other day, stuff's happening that's really beginning to scare me.
That's a subjective cognitive complaint, and is worth investigating. There's also something called medical necessity.
And, you know, if you want to come, and I propose doing something, and insurance says no, I can always… make a pitch. And I have not had to do that since working for Sunday Health, and I'm more than a year and a half at Sunday Health.
I was actually quite famous in central New York at one point for making these sorts of pitches. There was one insurance company in particular, where, you know, I was just a known quantity, and when they would get my letter, they pretty much just folded like a house of cards. So, it can work.
Maria Thomas: You're starting to make me nervous, Dr. Sanders. So, let me jump in. Let me just speak only for Sunday Health right now, and feel free to comment after, Dr. MacSweeney, but let me just describe, if you were interested in doing whatever, getting a cognitive baseline, the process would start… we do not require a referral. We're happy to get a referral from a PCP, and we do get plenty of referrals from PCPs, but you don't have to have one.
So you can just contact us, our website has all the information, and the first thing that would happen is you would have a phone call with a care navigator from our team, and she's gonna ask you about your insurance, she's gonna ask you about some of the things Dr. Sanders just mentioned, including, are you having, subjective symptoms or subjective… do you believe, you know, you have something?
At that point, we can try to upfront determine as best we can, whether something would be covered. In all seriousness, I think what Dr. Sanders is trying to communicate is that there are some ways that people under 65 legitimately qualify to get their insurance to cover these things. It really is an individualized situation, and I don't think we can represent today that we can definitely cover or not cover.
Dr. Sanders: Yeah, that's right, no. All of it is individualized. Yeah, yeah. You know, a well-crafted, politely Set out… set forth.
argument. Justification, right, it's called a letter of medical necessity. Yeah. It happens all the time. Familiar with it. Yeah, and sometimes they can work. I think a lot of times people think that it just doesn't work, but…
it can work, and I've had quite a bit of success with that. And we do offer, not that this would be your first choice, but at Sunday Health, we do offer also cash pay, and we have the prices right on the website. And some people prefer that, just for other reasons. Maybe they have a high deductible plan, or what have you, so, we do offer…
Maria Thomas: Or they don't want it in their insurance company. Right, but they just want it for privacy reasons, so we offer cash pay as well.
Thank you. And one other thing, going back to what you first said at the very beginning, is that that there's always something that can be done. It's unbelievable how many doctors are out there.
Telling people.
who have family members, that, oh no, there's nothing to be done, so why bother getting tested? Right, they're wrong. Simple have no idea what they're doing, they don't know anything. They're… it's…
It's scary. I think that will change over time. When I was beginning my career, this was an area of medicine that was not attractive to people going into clinical practice.
It was attractive only to people who wanted to be researchers. Quite frankly, I'm sitting here because I am a failed researcher.
My timing was bad. And, you know, I was applying for research grants when they just weren't giving out very many of them. And I got close, but close is no cigar, as the old expression goes, and so I became a clinician, a sort of… you know, clinician, very interested in the research, but, I think that helps me help my patients, and,
But I agree with you that in neurology, I mean, I often laugh that, you know, if one of my patients needs to go and have the kind of electrophysiological study they do to check if you have carpal tunnel syndrome or something like that, if that report is coming to me, it better have small words.
And really, really, you know, lay it all out very carefully, because I can't… if they don't do that for me, I don't understand what's in the report. I mean, I know the neurology, and I get the basic gist, but I don't have a full understanding. Same thing applies when…
My colleagues who perform those sorts of tests read my reports, and I think half the time it's just gibberish to them, because it's not a very focused area of neurology. And in medicine, in general, there's a lot of what we call neurophobia.
people are sca… the brain is a very complicated organ. But there's a lot of gaslighting that happens.
I'm making you think that you don't…
Maria Thomas: Yeah, let me just jump in. I'm sorry to interrupt, but I am mindful of the time, and we can stick around after, so we could carry this out. I do want to turn to you, Dr. MacSweeney. I think you had wanted to comment?
Dr. MacSweeney: Oh, yeah, I think the only other thing I just wanted to say is that,
Yes, with the Medicare eligibility, age 65, and the, prescribed Leqembi. But just please bear in mind that the clinical trials, which are completely free, at the point of delivery, are usually from age 50 or 55 up.
So, and the screening that takes place for the clinical trials is extremely thorough. It's all these tests, it's all these scans, like, you cannot get through the screening for the clinical trial and not have a diagnosis, like, even if your diagnosis is, well, you don't have this, you're gonna have a huge amount of information by the time you get through. And one of the things that we do, and it's actually where we're using AI and everything, is we do very intense pre-screening of people to see if they are eligible.
And there are so many different things that can cause cognitive, as we said at the very beginning, I don't know how many you said about 100 different things, but there's so many different things that can affect our cognition.
Including anxiety and everything else, so… it's… It's complex, but it's not impossible by any means at all. Well, I want to… Talk to these guys, and then talk to us.
Yeah, talk to any of us, but we're complimentary, as I hope what you're taking away here tonight.
Closing Remarks
Maria Thomas: I'm mindful of the time. We're well into about an hour and a half, and I want to give a break to folks who might need to leave. We will be sticking around for a few minutes here in case you have lingering, burning questions. I want to thank our online audience for joining us, all of you for coming. Re:Cognition, thank you for opening up your space to us, and again, we are Sunday Health and Re:Cognition Health, we're partnering, we're collaborating, and we're just pleased to share all of this with you tonight, and thanks again for coming.
