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Dr. Doug Elwood: Hi! Everyone! Welcome! Welcome! Welcome to Sunday health's webinar. Brain health breakthroughs. We're gonna get started in a few minutes here.
Great to see so many people joining as you're settling in. You can take a minute to familiarize yourself with the options here at the bottom of the zoom the QA. Captions. We'll go through some of these as we go along.
All of you are gonna be muted and hidden today, and we'll come back. We'll say this again, as everybody keeps joining. But you will be able to ask questions as we go, and we'll talk about that a few minutes. But welcome to all those who are still joining.
If you'd like to say hello in the chat, tell us where you're calling from today, please feel free to do that. Just keep in mind that it does show your name as you enter that in the chat.
Welcome to those who are still joining. So the Sunday health webinar on brain health breakthroughs. Excited to have you here today. We're gonna get started in a few minutes, just letting more people join
again as you're waiting. If you want to take a minute to familiarize yourself, you can see the QA. And the show captions there at the bottom of the screen. Talk about that more. But you will be muted and hidden from view today. But you will be able to ask questions in the Q. And a
and again, we're just letting everybody join here. Get started in just a couple minutes, excited to have everybody, though.
See more people joining again. Welcome Sunday health webinar, brain health breakthroughs excited to talk to everyone today.
If you want to let us know where you're calling from, you can see there in the chat some messages popping up. Please feel free to do that. Just keep in mind that it does. Show your name as you as you enter that in
all of you will be muted and hidden from view today. But there are a couple of ways you can still connect, such as the chat. We'll explain more as we get started here.
Glad everybody's joining us today for the webinar. Excited to talk about brain health breakthroughs. I'm going to get started here in just a couple of minutes.
Fantastic turnout today. I'm glad everybody's joining us
again for those who are new. You're in the right place. If you're looking for the Sunday health webinar. We'll be talking about brain health breakthroughs today as you're settling in. Take a look down at the bottom of the screen. You can see the Q. And a. And the captions which we'll talk about in a minute, you will be muted and hidden. But there are ways to connect. such as through the Q. And A.
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Alright. I think we're just about ready to start here again. Welcome to everyone. This is the right place. If you're looking for the Sunday health, webinar. We're going to be talking about brain health breakthroughs. I think we're ready to go ahead and get started here.
Introduction to Sunday Health
Dr. Doug Elwood: thank you for everybody who joins. We're very excited to start this webinar and excited that you're able to join us today
quickly about Sunday health. Sunday health is a medical practice, as you can see here we are very much dedicated to preventive diagnostic and ongoing cognitive care. We are live seeing patients in DC. Maryland and Virginia, and if you haven't learned more about us hopefully, you can learn some today and feel free to reach out to us with any questions after this webinar or an ongoing
Agenda and Logistics
Dr. Doug Elwood: just as a quick agenda. For today we are talking about brain health breakthroughs. We're going to look at the latest research on prevention. We're going to go into some of the new innovations that are facilitating early detection as well as talk about the 1st disease modifying treatments, and we will have a Q. And A at the end. We're going to leave time for that. Feel free to put your questions again. At the bottom of the zoom screen. There's a Q&A there, and there is a box that you can press
that makes that anonymous if you'd like to keep it anonymous we will try to get to as many as we can at the end. But please realize we're not going to have time to get to all of them. But we'll do our best to address as many as we can. And again, after the webinar. If you have any questions, please feel free to reach out. There is a caption button at the bottom of the zoom. You can turn that on as well.
and this will be recorded. So if you want to watch it again later, or if somebody who's here today, and you want to tell them about it, then that would be great to for them as well.
Speaker Introductions
Dr. Doug Elwood: So for quick introductions I'll start with myself. I'm here with 2 fantastic physicians, Dr. Amy Sanders and Dr. Clay Ackerly. I'll have them introduce themselves right after me. But by quick way of self introduction, I'm Dr. Doug Elwood. I'm the chief medical officer here at Sunday health. I oversee all the clinical activities and the care model. I'm not one of the actual physicians. So if you do go through the Sunday health
model, which I hope you will, then you won't be seeing me, but I am absolutely open to feedback on the process, and any ways that we can improve and learn from your your journey with us
just quickly about Sunday health. As I just mentioned, we are a cognitive care practice. We're live in DC. Maryland, Virginia, and we are actively seeing patients with no wait time. But this is not about Sunday health. This is about what gets us excited every day, and that's the breakthroughs that we really feel are coalescing to form a watershed moment in this field, and you have different
items coming together in a convergence of diagnostics, therapeutics, and interventions that are really reshaping the field, and how many are looking at it? And we're really excited to talk about that. That's really the purpose of today. We're about to get started before we do, just to go over some quick, logistical items again. Thanks to everyone who submitted questions. We're going to try to get to a lot of those you do have a chance to enter questions down at the Q. And a. As we go.
This session is being recorded as I mentioned, so you could watch it later, or let others know that they can. And you can also turn on captions. As I mentioned.
So with all that said, we're going to go ahead and introduce our speakers again, both of whom I'm excited to have here today. Why don't we start with you, Dr. Clay Ackerly.
Dr. Clay Ackerly Introduction
Dr. Clay Ackerly: Wonderful. Thank you, Dr. Elwood. It's great to be here, and I know a number of my patients are here today and have had the chance to meet with the Sunday health team. So thank you to Sunday health for your care of my patients, and certainly excited to be a senior clinical advisor to the Sunday health team. My day job is as a practicing primary care physician. I've had a longstanding interest in the care of older adults, and one of the
biggest, meatiest, most challenging topics that we handle together is, how do we, you know, tackle and optimize our brain span, as the term of art is coming. So how do we not only extend lifespan, but also brain span. As we age so excited to be here and dive into this important topic.
Dr. Amy Sanders Introduction
Dr. Doug Elwood: Excellent. Thank you. Dr. Ackerly and Dr. Amy Sanders.
Amy Sanders: Thank you, Doug. Yes, so my name is Amy Sanders, and I am a dementia neurologist, and I've been in practice since 2,008,
and for most of that time dementia neurology was a sleepy, quiet little backwater where people would come to see me, not really believing that there was much I could do for them. There were always things that I could do to help, but I've always believed that older adults, even if they have cognitive impairment, even if they have dementia, can still live high quality lives.
And it has been my mission. The reason I went into this field is to help people do that. As Doug mentioned, we have now reached a watershed moment. I mean.
these days. This is one of the most active, most interesting, most exhilarating areas of medicine, because now we have greater precision in our diagnostic testing, and for the 1st time, ever and just in the past, what would it be about 15 months. We have not one, but 2 on the market disease, modifying medications
for sort of a middle Pre. Alzheimer's kind of state, and the mild stages of Alzheimer's disease and the clinical trial pipeline of new medications for these dreadful diseases is.
is active and pumping out new medications, and that is also really exciting, so exceptionally exciting times. I want to welcome anybody who I have yet who I've already met at Sunday health and come see me if you haven't yet.
Prevention: The Latest Research
Dr. Doug Elwood: Perfect. Thank you, Dr. Sanders, so let's dive right in Dr. Ackley. I'd love to start with you and talking about prevention. If you can fill us in on some of the latest and greatest from a research perspective. And also just what's important to think about as we talk about prevention.
Dr. Clay Ackerly: Absolutely, I think the term for sort of preventing dementia up until recently, was seen as almost an absurd thing to say. But increasing research is showing that yes, many, many cases of dementia can be prevented. I think the seminal work is the Lancet Commission that anybody can look up online that goes through all the various modifiable risk factors for the various types of dementia. Whether that's vascular dementia, Alzheimer's type dementia, and the other related dementias
there are non modifiable risk factors, right? Those, including genetics and environmental exposures and things that have happened to us already in our past. We can't change what has happened to us if we were smokers when we were younger. If we did
play football and have a lot of concussions and traumatic brain injuries, there are lots of things that have happened to us that define where we are. But looking forward, there are a lot of modifiable risk factors, whether you're 30, 40, 50, 90 that are worth, you know, looking into some of the most recent research that has been exciting to me is how things like
vision, optimization, hearing optimization. Yes, we know that being socially engaged is important for quality of life, but improves our brain health. A lot of things that
you know. I've had patients say, well, Clay, you're telling me the things I already. No, I need to do around cardiovascular risk management. But yes, having your cholesterol under good control. Blood pressure under good control is not just about preventing heart attacks. It's about optimizing your brain. Health. Smoking is one of those things that hopefully, very few people are doing these days. But early on and say, Oh, well, you need to stop smoking.
So you don't get lung cancer. Well, turns out you need to stop smoking to help your brain as well. So I think
the recognition of these modifiable risk factors that make a real difference. The Lancet Commission saying, you know, 45%
of dementias are preventable when you look at those factors, and that doesn't even include a bucket of
of things that are reversible causes of cognitive decline. So if you are worried about your brain health, yes, there are things that you can do to prevent the progression of dementia. But there are a lot of things you can do
to improve your cognition in the near term, not just prevent dementia down the line. Sleep, optimization, mood, optimization, reduction in unnecessary substances, alcohol or otherwise. Thyroid health, vitamin health.
You know. B, 12. Deficiency is more common than we'd like to think so.
You know, as we look at those modifiable risk factors as we look at the ways that we can help optimize our cognition. That list is very, very long, and I do have to say again, this is about these changes in research, but I have to plug again the Sunday health team. This is something I care deeply about. But as an internist I feel both like standing on the shoulders of giants when there's all this just massive work that's been put into this field
over prior decades, but also a little overwhelmed in the clinic, saying, I need help thinking through what's the right combination? How do we prioritize these changes in our life, we can only do so much. There are conflicts right? Sometimes
we know that high exposures to anesthesia have a cognitive consequence. but you also need to walk in exercise which is really important for your brain. So how do you balance anesthesia for a knee replacement and the mobility and exercise that come with it. So it's not black and white. There are trade-offs that need to be made.
But I, you know. having a team to help think through these things is really really important.
In addition, one of the the realizations that the field has come up with, and I think was in retrospect somewhat common sense. But there's a long preclinical phase
to dementia where small changes are happening to our brains after our brains stop maturing. And so, whether it's in your thirties, forties, fifties, sixties, and beyond.
Now's the time. It's never too early to get involved in optimizing your brain for the long haul.
The Timeline of Brain Changes
Dr. Doug Elwood: It's such an important message. Thanks, Dr. Ackerly, and I mean you mentioned 1st of all the Lancet Commission which is in the chat there. For those who want to take a closer look. As Dr. Ackerly mentioned, it can be found on Google, and has just a great amount of detail on those modifiable risk factors. And, as you pointed out, 45% just staggering, and that long timeline. So lots of chances to improve lots of chances to be proactive and really change the way that we're thinking about it and approaching it. Really appreciate that.
Dr. Ackerly. And let's let's shift now and.
Amy Sanders: Don't jump in.
Dr. Doug Elwood: Just one second.
Amy Sanders: Both of you have mentioned the long timeline. So what they mean when they say the long timeline is decades. It's not months
for most people. It's not years. It is probably decades between the time that unhappy pathological changes that ultimately could lead to dementia start happening in the brain
decades potentially before clinical symptoms appear, and even after clinical symptoms appear, there still are ways that you can improve your situation. So I really really want to underscore and drive home. That notion of it is never too late
to make healthy changes for your brain, healthy mind, and a healthy body.
Dr. Doug Elwood: Very good point.
Dr. Doug Elwood: Thank you, Dr. Sanders. We are seeing folks raise hands. Please submit your questions, as you can see in the chat during the Q. And a. And we will or submit your questions in the Q. And a. And we will try to get back to them in the Q&A session
at the end, and we'll try to get to as many as we can. I know a lot of people have questions around that important area of prevention. We are going to shift now into detection. I'm going to come back to you, Dr. Ackerly, if you don't mind giving us a little bit of insight on what we mean by biomarkers, and then we're going to ask Dr. Sanders to go into those more deeply. But if you can just tell us what is a biomarker? Why is it important? And how should we be thinking about it?
Early Detection: Understanding Biomarkers
Dr. Clay Ackerly: Absolutely. Biomarker simply is a marker of biology, a quantitative measure of something important to our biology. For a long, long time.
you know, I was taught in medical school. The only way to diagnose Alzheimer's disease was based on autopsy. Right then there were measures of cerebral spinal fluid and specialized pet scans and getting better and better. The most common biomarker that we think of, although you can consider a blood pressure that you can do at home a biomarker or blood based biomarkers.
You get them all the time when you're checking your cholesterol, looking for diabetes and for the 1st time, and what is foundationally exciting to me is we're beginning to see these blood-based biomarkers
turn out to show real value. It's early, and there are a lot of them, and we're still trying to figure out how to apply these most appropriately to each of our patients.
but this era is here, and so I'll let Dr. Sanders, you know, dive in there. But I think a biomarker is just a measure of your biology. And now that we've got blood based biomarkers
for cognitive health. That's gonna it's gonna change a lot. But I think we're in in the 1st innings of something really really meaningful and powerful.
Detailed Overview of Biomarkers
Amy Sanders: So I'd like just 2 comments here. One I keep hearing at the big meetings that I attend about Alzheimer's disease and and other dementias that really we should not be thinking of these as an either you have it or you don't.
black and white, yes or no kind of situation. We should be thinking of this more as a continuum a la. The way that we think of atherosclerosis ultimately leading to heart disease.
And you get changes in the brain that lead to brain disease, and that brain disease often manifests itself through cognitive changes or cognitive impairment.
It is still to this day the case that to make a definitive diagnosis of a disease that causes dementia, we still need tissue. We don't, generally speaking, do brain biopsies while an individual is living. There are rare exceptions, but fortunately they're rare.
But to have a neuropathologist examine brain tissue after somebody has died under the microscope. That's still the only way to be definite about what somebody had.
what the blood-based biomarkers and the spinal fluid tests, and Mris and specialized pet scans allow us to do is in our clinical diagnosis be much, much more precise than has ever been the case before. About the likelihood that the changes
that somebody is experiencing might be due to underlying
things are most advanced in terms of Alzheimer's disease. I think the other dementias will catch up in time, but so still tissue for a definitive diagnosis, but greatly enhanced precision of diagnosis, using the biomarkers that are now available to us. Dizzyingly dizzying array of biomarkers are now.
Dr. Doug Elwood: Tell us about. Tell us about them, Dr. Sanders, if you don't mind, give us a breakdown of what they are, and why why we should be interested in them.
Imaging Biomarkers
Amy Sanders: So a few words about imaging. and really only a few words. We use Mris
structural imaging to give us sort of a picture of what the structure of the brain looks like that can be quite helpful to me, it lets me know, has blood pressure, diabetes, cholesterol caused damage to the brain. We can see that through what you'll see on a radiology report described as white matter changes.
We can also measure the size of a structure called the hippocampus. You have one on each side roughly around your ear, and the hippocampus is very important for the initial processing of incoming new memories, and we can through what is called post acquisition software processing. That's all you need to know about that happens after the pictures get taken. And they can actually measure the volume of this structure called the hippocampus.
and you generally will get from the neuroradiologist reading the MRI report that the hippocampi are x percent of what would be expected for age.
You really don't have to get too too worried unless that X percent is 5% or lower. So that's brain. MRI
pet scanning kind of a glorified X-ray. It's a quicker test than an MRI, but it works by looking at you get injected with what's called a ligand, a different kind of biomarker that circulates through your bloodstream, and and ultimately binds with certain proteins in the brain, allowing us
to see in clinical practice
abnormal Alzheimer, amyloid protein that has been deposited into the brain tissue. not yet ready for clinical prime time, but
very active in research, is the same ability to look at a different protein called Tau.
Fluid Biomarkers
Then we get to the fluid biomarkers
in order to have any of your fluid biomarkers tested. Previously, you had to have a spinal tap
nowadays. You can have a blood test instead of a spinal tap, and I don't think I know anybody who would prefer to have a spinal tap over a blood test.
So one of the reasons that we're all so excited about this is that we now have these biomarkers
through that we can test on blood
much greater access for patients, much less invasiveness for patients, and a wider array of of information for physicians like me, and
data is now coming in to show that the blood-based biomarkers are probably the equal of the cerebrospinal fluid, the spinal tap biomarkers. So that's very exciting.
Specific Blood-Based Biomarkers
All right. We've talked about them. What are these blood-based biomarkers? Let's get specific. So there's 1 called the amyloid ratio. And this is a test that is exactly what it describes. It is a ratio of abnormal Alzheimer, prone, amyloid protein and normal amyloid protein.
Everybody has amyloid protein. Some people have their amyloid protein gets processed incorrectly, and that can lead
after potentially, as much time as decades to Alzheimer's disease. So we look at the ratio, and the way that this test gets resulted is, it'll say that the ratio is lower than normal or okay. And the reason that the lower than normal ratio is considered the abnormal result is because, as abnormal amyloid protein gets deposited into amyloid plaques in the brain.
it circulates less through the bloodstream, so very logical.
There is also a protein called Tau that makes the. You may have heard of the neurofibrillary tangles.
and there are now 2 forms of Tau, both involved in Alzheimer's disease that we can check. And here, generally speaking, if you're if you're
values are elevated of either. One of these, one is called
P. Tau P. Standing for phosphorylation, phosphorylization. That's biochemistry. You don't have to worry about it anymore. Just knowing. Just know that when that Tau gets
abnormally phosphorylated, that's a problem. And we can check 2 different forms of the Tau protein that have abnormal bits of phosphorus hooked to them.
Then there are 2 tests that sort of give us a sense of
whether ongoing neurodegeneration is occurring. So neurodegeneration is a very general phenomenon. It occurs in multiple sclerosis in Parkinson's disease in Lou Gehrig's disease and in any kind of dementia, and there are 2 tests. One is called neurofilament, light chain, or nfl, for short, and the other one is called glial fibrillary acidic protein.
Happily, gfap for short, and that those 2 proteins, Nfl and Gfap both give us a sense of whether neurodegeneration is occurring, and there probably are going to be ways that we can
use those 2 markers
theorized at this point, not fully fleshed out, but to track over time. How somebody is doing? Do they appear to be prone to or vulnerable to progressing in their cognitive impairment. And that's even more exciting, because that's not just the is there a problem, or isn't there. It also kind of allows us to sort of
you know, adjust up or down our our expectations of when and how we expect that things will change.
So that's the that's the the brief overview of biomarkers.
Dr. Doug Elwood: Excellent. Thank you, Dr. Sanders. And in the chat we did drop some more information about the blood-based biomarkers and Alzheimer's, and just as a quick summary, because I know I'm sure there's a lot of questions and some big words there. But really there's this new class of biomarkers, and as Dr. Ackerly described. The biomarkers are, you know, things that we're very well acquainted with
from blood pressure to substances that are in your body like cholesterol, and as Dr. Sanders has described. Now we are able to measure some of the
things going on in the brain, and some of the deficiencies that are happening
as they represent in the blood. So some really exciting evolution in our understanding of what's happening. And as Dr. Sanders really nicely articulated, it's a continuum, so it can help us identify and potentially
monitor progression as we as we go. So things we're still learning about.
Current Use of Biomarkers in Practice
Dr. Doug Elwood: Dr. Ackerly, there's a question right now, and in general are patients asking you for these? Are you using these in your practice? How are you approaching this.
Dr. Clay Ackerly: Absolutely so, I think their early days, and
but there's enough promise that I have been asked about them, and I certainly have ordered these a number of times. I do caveat that
not exactly sure 100% how to interpret them. It is the
the strongest use cases for someone with notable. And Dr. Sanders, please correct me with with noticeable
cognitive impairment to say, Okay, could there be Alzheimer's pathology? And I know that the drug companies who are looking at the disease modifying agents there that Dr. Sanders will talk about in a minute.
The blood test can help say, Okay, you might be appropriate for these sorts of treatments, so it can help with some of the teasing out of the clinical diagnosis and saying, Are you more likely to have Alzheimer's Pathology
versus not.
There are, you know.
marrying that with genetic factors, the Apoe, you know, Gene can help us understand future risk.
and that can be frustrating
or empowering, depending on how you look at the data and what your result is. I don't want to go down a rabbit hole on that one. But
the 4 genotype is the highest risk for Alzheimer's disease in any gene. You've got 2 copies, one from Mom, one from Dad.
and if you've got 2 of the fours that does put you at, you know, meaningfully higher risk. If you've got one, not 2, a small increase in risk
so that can be helpful in my patients who also have a family history of Alzheimer's disease to understand what may have happened to mom dad. Other family members might they carry that gene? But that's just one of many, and we are looking at other genes as well. That may play a part. So the answer is we are using them. We are trying to figure out how to put this all together for each of our patients in the right way, and but it is an exciting time, for sure.
Dr. Doug Elwood: Makes sense.
Amy Sanders: I would suggest that. Yes, I absolutely agree with Dr. Ackerly, that if there is somebody who has notable, measurable, or very bothersome cognitive impairment, that then these tests can be very useful, because they give us a sense of how likely is it that the cognitive impairment is coming from an Alzheimer like process versus something else.
and we're not very good yet at describing what that something else might be, but it is very helpful to be able to say to somebody, well, this doesn't look very likely to be Alzheimer's disease. Remember, these are not.
They're described frequently, just to confuse everybody as diagnostic tests, but they are not precisely diagnostic tests. In other words, if you, if you rule in
for one of these tests, that does not
mean that you absolutely positively have Alzheimer's disease. It is a very important building block in that diagnosis, but it's not unto itself sufficient to make that diagnosis. That being said, I would say, if somebody has a very strong family history.
that would be an argument, even if they are clinically asymptomatic, potentially to have these tests done. If there is puzzlement about. Why is somebody having cognitive impairment, especially if there are other problems like problems with sleep or problems with depression or anxiety? That might be another reason to do it primarily, just to see how much attention do you need to be paying to the possibility that this is Alzheimer's disease?
So those are some areas in which it can be
advisable to have some of these tests run, even if one doesn't have notable cognitive impairment. We are also, now that we have them, we're learning about other ways in which they are useful. So Dr. Ackerly mentioned the apolipoprotein E genotype genotype just means your genetic status for a thing, and the apolipoprotein E
shortened as Apoe is a major risk factor for Alzheimer's disease. But now we're also learning that in certain forms of vascular dementia.
Whether what one's apoe genotype is may influence their their risk for further development of their vascular disease.
So
that was not something that that I knew about 2 years ago. But I know about it now, partly because we're paying much more attention to Apoe testing.
That's right.
Dr. Clay Ackerly: Maybe 2 more quick points on this.
one is.
you know.
if you, as as Dr. Sanders said.
you know, we may want to test in someone who doesn't have symptoms. And there, there are reasons to do that.
If you have a positive test.
do not fret. It's not yet entirely clear what what that might mean for your progression. But also we know that there are patients who have on autopsy
brains riddled with amyloid plaques and are cognitively normal. Right? This is this is complicated. And we're learning everything. We're learning so much
every year, every month, every week. It sounds like it seems like but I don't, you know, want these tests to be a source of anxiety. Hopefully, they can be a source of proactive engagement
and a better understanding of one's own biology. We were
in a similar position not that long ago with cardiovascular disease. By trying to understand. What does Ldl mean?
What does Hdl mean for people who had their cholesterol checked 20 years ago like, well, Hdl is protective, and there's ratios and and and we're getting more and more fine grain understanding of
of both, with cholesterol measurement on risk and tracking response to treatment. And I think we'll get there fairly quickly with this as well.
Amy Sanders: Right. So one thing that Dr. Ackerly just very helpfully did, and thank you, and shame on me for not thinking to do it. But he explained why these new blood-based biomarkers are not considered to be fully diagnostic, because we've been able to see abnormal amyloid protein on pet scans for over a decade now, and we know that people have positive amyloid pet scans, meaning that's a
that that gets you into a clinical trial that makes you potentially eligible for one of these new medications. But what if you're completely asymptomatic? We know that those people exist.
We don't yet know what they mean.
Are they eventually going to get Alzheimer's disease. They just haven't gotten old enough yet, and does old enough for that person mean 132 years, not 82 years. We don't know. And this is why we don't consider the tests yet to be diagnostic. But, boy, do they help with sort of our diagnostic, the calibration of our diagnostic theorizing.
Disease-Modifying Therapies
Dr. Doug Elwood: That's right. Thank you both. Really good, really good explanations and ways to think about that. And already addressing some of the questions in the Q. And a. As well and as a reminder. There will be a recording of this Dr. Sanders, and both of you have mentioned the link to treatments. If you don't mind Dr. Sanders, on just telling us more about the disease modifying therapies, you know. A 5 min crash course on things like what they are, how to think about them. That would be great.
Understanding Monoclonal Antibodies
Amy Sanders: So I am not a biochemist. Full disclosure, and I don't expect that anybody in the audience, boy. I sure hope, in fact, that there are no biochemists in the audience, but I'm going to reason initially by analogy, and I want you to think of your brain as a thriving, urban neighborhood.
Perhaps you're getting a little bit older.
And suddenly there's a problem with trash accumulating, and by trash I mean abnormal Alzheimery protein.
And wouldn't it be nice if
there were garbage collection that could come and get rid of this abnormal amyloid protein.
Well, garbage collectors are great, but you want to make sure that they're also not taking away your dining room table and your bedside table and your couch and your flat screen TV. You want them to be able to target the trash for removal. And that's kind of how a monoclonal antibody functions. I'm going to unpack that terminology a little bit. An antibody is basically how? How your cell, your body's
immunological systems
function. An antibody is a little bit of protein that can sort of mark another protein for removal, for clearance. And so we have these monoclonal. They're engineered in a lab to be one particular kind of cell. And this kind of cell, this bit of protein is. It's not really a cell, but it's a bit of protein that will circulate through the bloodstream.
Go into the brain.
target
abnormal, amyloid protein
flag it so that the body's regular cleanup mechanism, its normal cleanup crew can come in and see
these tagged, flagged, abnormal bits of amyloid protein and remove them from the brain.
And that is what if you read the the papers that have described
Lecanumab, the 1st monoclonal antibody that was ever FDA approved for the treatment of Alzheimer's disease. It is on the market as lechembi, a Japanese word for something along the lines of beautiful or flowery something like that. So a happy word and Denanumab, which is an Eli Lilly medication that was approved just a couple of months ago, and its brand name is Kosunla, and I have no idea what that means.
But both of those medications target
abnormal, amyloid protein by engineering these antibodies in a lab formulating them so that they can be injected into somebody's arm every 2 weeks for licanumab every 4 weeks for denanumab. And then those monoclonal antibodies circulate through the bloodstream, go to the brain where they tag and flag. Abnormal, pathological, Alzheimer amyloid for removal.
Tau monoclonal antibody treatments
are not yet FDA approved, but they are coming close. They are in mid already in mid to late stage parts of the clinical trial pipeline. So that is just exceptionally exciting stuff. These
new medications, Licanumab, Denanumab, Lekembe, Casunla, are FDA approved for people who have mild, cognitive impairment, a pre Alzheimer's disease state of cognitive impairment.
But the mild, cognitive impairment is felt to be due to abnormal amyloid or sorry, abnormal Alzheimer pathology, or for people who are in the mild stages of Alzheimer's disease. Already.
in order to determine whether somebody is eligible. To get one of these medications. You actually have to have a pretty big workup that includes
brain MRI basic labs.
Probably these days
Alzheimer, blood-based biomarkers in some cases, probably then also, perhaps an amyloid pet scan.
or people would prefer. I don't, generally speaking, meet people who prefer this way, but evidently in Europe. This is how they think, who would prefer to have a spinal tap instead of a pet scan?
The data is really so strong in support of the blood-based biomarkers as serving as that. Yes, I have abnormal amyloid pathology. So I should be eligible. We're not yet using the blood-based biomarkers in order to make that determination in a formal way, but we are getting close.
I would expect actually, I wouldn't be surprised if in the within the next year, if we are starting to do that.
Dr. Doug Elwood: Excellent thanks, Dr. Sanders, and thanks for that, and.
Amy Sanders: Did I do that all in one breath? It feels like I did.
Dr. Doug Elwood: Nicely done, nicely done. So we are. We just ran through a lot. We ran through prevention. We talked about early detection. We went through some treatment options and what's coming out on the market. Obviously, we're moving fast. There's a lot you can see we're excited about it and trying to cover all of it again. We're going to be having a recording of this.
and there's more. We're going to post a link to Dr. Sanders that she talked more about some of these treatments in a different setting if you're interested, but we'd love to open it up for some questions. So some of you have already dropped in questions as we've been going along, and others submitted beforehand. Thank you for those
as you think about, and drop some additional questions.
And if you're interested you can see here, thank you for putting that up. There's a Q&A button down at the bottom, and you can send them anonymously. Just click that button there, as you can see.
Q&A Session
Access to Neurology Care
Dr. Doug Elwood: we're going to start with a question that we got that is around access and extremely important in this topic, and a big reason why Sunday health partly exists, and the question is, why is it so hard to get a neurology appointment? Wait times of 3 months in this instance.
really frustrating, really frustrating. And we definitely understand that. And again, is a big reason why we feel Sunday health is is important in this discussion. There are areas of the country where there are no neurologists or very few. There's a term in general for a lack of practitioners called a desert. There are neurology deserts in most areas of the country.
and even where there are.
Amy Sanders: Include, including in in in a county in Virginia.
right near DC.
Dr. Doug Elwood: That's right, that's right. And even where there are neurologists because the demand can be so high.
there are wait times that are very typical reaching up to 9 to 12 months. So one of our goals here at Sunday health is to enhance access and get people seen and have this discussion much earlier on. And I'm glad we're having this webinar today because it keeps the conversation going. So thank you for that question. I know it's really frustrating.
I know there are a lot of questions that come up with this topic. It's extremely important to get the right answers and understand where you are in your own or your loved one's health journey, so we hope to help with that process as much as possible.
Amy Sanders: Also, one thing is, if you happen to live or have loved ones who live in a neurology desert, there just isn't good availability of neurology care where you live. This is one way in which telemedicine one of the few, the few good things that came out of the pandemic
telemedicine was not a thing before the pandemic and after the pandemic it was most assuredly a thing, and we hope, a permanent one, but it really allows us to expand the reach of what neurology services are available to improve access in areas where there just isn't any.
Current Practice Implementation
Dr. Doug Elwood: That's right.
So one question that's come in again is about, I understand the excitement about what is being
discussed, but how much goes in
to current practice.
Maybe, Dr. Ackerly, if you can start with that, and then we can move to Dr. Sanders.
Dr. Clay Ackerly: So I think the
we're using this in current practice today, as I mentioned earlier, we're beginning to use these blood based biomarkers.
the the treatments that have come on in just the last 18 months
are appropriate for certain patients, we know, and for those who have heard a lot of the negative press about the treatments. Yes, there's plenty of downsides. They are expensive, they have side effects. They require Iv infusions, but also the pipeline
for treatments, and there's over a hundred 50, I think clinical trials currently underway.
a lot of which you know of a lot of excitement. And so
at the quote unquote, you know, bench to bedside and research. There's a lot of the bedside that we're the excitement is we're feeling it, and also a large pipeline that's coming.
and I think
one of the things that makes me want to dive in
now
is the importance of baselines. Right? So
you may have a little bit of sleep, apnea, and a little bit of brain fog, or the elections coming. And you're anxious.
and that's leading to some brain fog and like, oh, is this
me and some early mci, or is it something else? Well, you know what? Let's get a baseline.
and we could, even
if appropriate.
get a blood based biomarker, baseline. And 10 years from now we'll actually be able to say there has been now a change. Well, so
the bottom line is, I think it's
here, and it's gonna get better. And just like.
you know, our understanding of lipid. I know I've used that example a lot, but it's true. We're getting better and better with lipids, and they've been around for a long time. We're going to continue to get better.
but this is here, and I think it's worth everybody
to be proactive as well as understanding that this is still early days of now instead of head in the sand. I don't want to know. There's nothing we could do about it. But guess what? There are things you can do about it.
Amy Sanders: Always have them.
Dr. Clay Ackerly: There always have been, and I think we now have increasing evidence that they are important, and I do feel pretty badly for a lot of my patients who have enjoyed their 2 glasses of wine a day, because that's what medicine has said is like heart healthy. And oh, by the way. Alcohol is not good for us. I am sorry, so there are things that change on us that always leads a certain frustration, and yes, there will probably be things that we are doing now that 10 years from now, even 5 years from now, we say, well, we wish we had known different.
But
this is like.
it's here.
Dr. Doug Elwood: Yeah, absolutely. The biomarkers are being used. And Dr. Sanders, I'm going to ask you about that. In a second. The treatments are being used. And Dr. Ackerly, probably most importantly to your point is that the prevention and the thinking about it in a more holistic way, and building in some of these other measures are absolutely here, and have been present with other disease states for a while, but are now really being understood for the brain, and how important they are. But, Dr. Sanders, you're ordering these
labs.
Can you tell us a little bit more about that? And and also, if you don't mind just mentioning.
go into a little bit more about the efficiency of the blood tests and the efficacy. And the if insurance is is covering them.
Insurance Coverage and Accessibility
Amy Sanders: So let me tackle the insurance question first.st and my short and sweet answer is, yes, but your mileage may vary so
insurance, as I think we all are painfully aware, is not monolithic.
So my understanding is that these tests are for the most part covered by Medicare.
I have been assured in the past
by reps from one of the lab companies that they would never balance Bill a Medicare patient, meaning that if there's a difference between, or this is how I understand balance billing, anyway, if there's a difference between what Medicare would pay and what the lab charges. The patient is not going to get a bill for that difference. The lab will just take what Medicare pays them.
But I think that
not everybody has medicare. Some people have private insurance. Some people have no insurance, I think in some cases it might be possible just to walk in off the street and say, Yes, I want these tests.
Probably not quite that simple, though, because the the menu of tests that you can order that way does not actually include any of these tests. But and I think that one of the companies did have one of these tests.
the amyloid ratio as a you can walk in off the street and order it kind of test. And they don't do that anymore. So you probably for the most part need a physician to order these tests for you.
I have not heard anything about people being told that the tests are not available when they go into. Most people go either to quest or to Labcorp, and, as far as I know, these tests are widely available in both of those settings.
They should be covered by insurance, I think occasionally insurance might deny. But if that should happen, there's a mechanism where people like me can go to bat on your behalf
with the insurance company to plead your case and say, this is why it's important that these tests be be ordered and people are. We're all just learning about them. So you know, one insurance company in one part of the country might be, you know, really, really
au coront with all of it, and the same insurance company in another part of the country. The people there just might not know as much. So
talk to your physicians, talk to your medical practices, call your insurance company, and then, sort of, you know, watch this space, not this specific space, but in general, the space of of people who who update you on. You know sort of how things are developing in terms of medical practice.
So that's the answer
as best I can give it, anyway. To the insurance question.
Are. They're they're very easy to order.
So there shouldn't be an access problem. But as Dr. Ackerly mentioned, and I think that for many primary care practices.
This is all very, very new and, boy, there is a lot of it.
So learning what it is.
how to use it.
and what it means how to interpret it is is a non-trivial process for most physicians.
and you know I'm just thrilled and excited. I mean, I bound out of bed every day, because it's just so exciting what I'm doing in my work these days, but I can see where that could be daunting and kind of overwhelming for a busy primary care practitioner who just doesn't have time to take into account all of this new, all of this new information that will come, I mean, think about 30 or 40 years ago in diabetes
we had insulin
and not much else.
And now, boy, I mean diabetes has really become an easily manageable
disease.
I mean, it's still a very serious disease. But we have glp one s. Now, and all kinds of other medications. There is a menu of medication options not just insulin.
So in Alzheimer's disease we are at the just insulin stage of things.
So again, watch this space, and 30 years from now the conversation is, I'll be long since retired, and probably dead, but the conversation will be
as different, I think, for Alzheimer's disease as
the way that conversations about diabetes are are so vastly different than they were 30 years ago.
Did I get all parts of your question.
Dr. Doug Elwood: I think you did. I think you did. Thank you.
Dr. Clay Ackerly: 30 years, is a little.
Dr. Doug Elwood: Okay.
Dr. Clay Ackerly: A little bit long.
Dr. Doug Elwood: Yeah, that's good.
Amy Sanders: That's probably true. That is probably true. We're probably much faster now. Yeah.
How Monoclonal Antibodies Work
Dr. Doug Elwood: But sticking with the treatment, and both of you have appropriately used predicates as a great example. So either atherosclerosis or other components of that. So I appreciate that. I think it helps paint a really nice picture for everyone who's listening, Dr. Sanders, just to go back to one of the points you mentioned. There's a question around
the monoclonal antibodies circulating in the brain. And, as you said, tagging and flagging, the abnormal amyloid proteins.
The question is once the proteins are tagged and flagged, then what are they removed? And if so, how.
Amy Sanders: So they they
for for Denanimab in particular.
In the clinical trials, they actually monitored people serially with pet scans.
and they would actually stop the treatment. Once
the pet scans were no longer showing
any abnormally abnormal.
We're no longer showing any deposits of abnormal Alzheimer amyloid protein.
We don't know if that's the right thing to do. There's actually a bit of swirling controversy over that question. But basically, once the this is how the bodies
immunology. It's immunological systems work.
full disclosure. Immunology might have been one of my weakest subjects in medical school, but so it's kind of ironic to me that now I'm talking about it professionally.
but the the antibody finds its target, and then it just it manages to work that into the bloodstream
and eventually out of the body. I mean, you don't exude it through your skin, but you will. You'll ultimately, you know, you'll get. You'll get rid of it in in in urine in other
It'll things will be broken down, metabolized, reused.
We don't, and we don't yet fully just one other caution here a little bit. We don't yet fully understand is complete. Abnormal is complete removal of abnormal, amyloid protein. Really, truly, the appropriate goal.
Some decade a couple of decades ago there was a vaccine that came very, very close to being. FDA approved.
and it cleared amyloid like the dickens.
The problem was that people then had really really devastating forms of meningoencephalitis, a dreadful.
potentially fatal brain disease, brain infection, basically brain inflammation. And we don't know why. That is. But that's a little cautionary tale in the back of everybody's mind about, you know. Do you really really want to get rid of all of the amyloid? We don't know, but it certainly seems to be the case that getting rid of at least some of it is the right thing to do.
Signs and Symptoms: Normal Aging vs. Concerns
Dr. Doug Elwood: Shifting back to early detection. Dr. Ackerly, how does one think about? We got some questions around signs and symptoms, and how to think about that as normal aging. And you know, memory issues, how do you approach that in the clinic? And then maybe we can jump to Dr. Sanders.
Dr. Clay Ackerly: It's a complicated
topic, and I think almost any subjective symptom of cognitive slowing, I think, is worthy of raising.
and whether it's
brain fog.
you know, cognitive slowness. The wheels aren't turning, or but also commonly around naming.
forgot this person's name.
I forgot where I was going, sort of for forgetfulness in general.
And up until now, up until recently.
we said, Okay, a lot of that is normal aging.
And a lot of that is just an aging brain. How much of that we should accept as normal or normal is an open debate, because we know a lot of the things that can reduce the risk of dementia as laid out in the Lancet Commission.
should also be able to help slow down the normal aging process of the brain.
But I think anytime you've got a cognitive concern. Raise your hand often. It can be a sign of thyroid dysfunction, sleep, dysfunction, depression, things that are not.
you know, neurodegeneration, just
neurologic slowing.
and so
seen a provider talking to your Pcp. And unfortunately.
most primary care physicians are overworked.
underpaid. Don't have the time to engage. And that's why I'm so excited that Sunday health exists, because you can also just self refer and say, you know what I want to have a deeper conversation about it. So I don't think there needs to be any threshold of concern. Also. Sometimes, in some
cases family members
don't notice these changes happening, and so it can be incumbent upon a loved one, a caregiver, to raise the hand and say, Hey, I've got a concern.
and I would just encourage anybody out there who, when I mentioned that they think of a loved one.
reach out to that individual's provider
and just raise your concerns. Know that provider can't talk to you unless you've been approved. You know that they can talk to you, but you can always talk to that provider to raise
concerns about a loved one. So I don't know if that answers the question specifically, there's no magic
number of times. You forget a person's name or where you say, Okay, let's get evaluated. That's also why I encourage a baseline cognitive assessment. I say, all the time right when patients say
I'm forgetting names. Were you ever good at names right most of the time is. No, I was never good at, I said, well, you're not going to get better at that, as you as you get older, so don't don't make that a red flag concern, but work with your providers, dive in to potential causes that can improve cognition.
Hearing Aids vision. Have you had your cataracts replaced? Yeah, are you working on sleep, optimization? Are you on medications that
can slow the brain down?
I am surprised, even though I talk to my patients all the time about antihistamines and the the challenges and the harms from Sedania antihistamines that people say, Oh, I'm not taking any sleep. Meds. I just take my unisom or advil. Pm, every night. It's like, okay, let's talk about that. So
I think there's lots of.
Amy Sanders: Taking Advil Pm. Every night. Please, please stop. Don't do that. Not good for you.
Dr. Clay Ackerly: And there's now new data. This is again a complete tangent. But, Dr. Sanders, you'll appreciate this right on the data around processed foods and its impact negative impact on the brain. And we knew potato chips and twinkies were not good for our waistlines, Brian. Not good for prediabetes. It's not good for your brain either. And so for people who are sort of
fence like on the fence, do I engage in these helpful behaviors or not because we have busy lives they're hard to do. There are plenty of barriers to acting on that. Well.
remember, your brain's at stake. Your brain span is at stake, and so engaging on all those lifestyle things, even if you don't have a major concern, you know, is brain healthy. So again, that's a little bit of a tangent, but I hope that.
Dr. Doug Elwood: Oh, not a tangent at all! That really important.
Amy Sanders: I was once working with somebody who said to me, Oh, yeah, this is going to be the part where you're going to tell me to live a healthy lifestyle. Right? I should eat better I should. I should exercise more. And Yada Yada Yada.
Well, yes, but no, I mean yes, that is the message that we're giving. But but at Sunday health, and I think.
who are brain doctors in in general.
We also now understand the why
that underlies that that messaging.
It's important to get good sleep, because if you don't, some of the body's other mechanisms that help to clear abnormal amyloid don't work
it's important to exercise, because, you know, it's a healthy mind and a healthy body. I mean, there are reasons for all of this, and there's actually medical evidence that backs it all up.
Closing
Dr. Doug Elwood: Absolutely. And I think that's a perfect place to stop. Thank you so much, Dr. Ackerly. Dr. Sanders, so important to get a variant health, baseline. We're going to put up information on how to get in contact with us. Please send us your questions. Thank you for everybody joining. Today. We had a tremendous turnout. Really appreciate everyone taking the time out of their
out of their data to join us here. If you're in DC. Maryland, Virginia, we do encourage you to schedule. It's a no cost. Introductory call with our nurse, care navigator, and to learn more about our prevention and diagnostic brain health services again. Thank you for everyone for joining. Thank you, Dr. Sanders. Thank you, Dr. Ackerly. There's more in the chat there, and feel free to reach out to us. Thanks again. Everybody.
