Integrating Blood-Based Biomarkers for Alzheimer’s Risk Assessment

Integrating Blood-Based Biomarkers for Alzheimer’s Risk Assessment

(PODCAST TRANSCRIPT)

VO [00:00:02]:

Welcome to the Results Are in from Quest Diagnostics conversations with diagnostics industry leaders who enable optimized care pathways for patients.

Amanda Benson [00:00:14]:

Welcome to the Results Are in by Quest Diagnostics. I'm your host, Amanda Benson. Today we'll be discussing integrating blood-based biomarkers into your practice when assessing Alzheimer's disease risk. Blood-based biomarkers tests are revolutionizing the diagnostic pathway for Alzheimer's disease, making early risk assessment and ultimately earlier diagnosis more feasible and widespread, which is crucial for timely intervention and management of the disease. This shift has elevated the role of primary care in the dementia diagnostic pathway. I can't wait to talk about this in detail. Here to discuss this important topic is Dr. Michael Racke, Medical Director for Neurology at Quest Diagnostics.

Amanda Benson [00:00:58]:

Dr. Racke, welcome to the show.

Dr. Racke [00:01:01]:

Pleasure to be here.

Amanda Benson [00:01:02]:

First, Dr. Racke, can you tell us a little bit about your background and role as medical director for neurology at Quest Diagnostics?

Dr. Racke [00:01:09]:

So, I trained as a clinical neurologist. I did a residency at Emory University in Atlanta and subsequently did a fellowship in neuroimmunology at the National Institutes of Health. I had my first faculty position at Washington University in St. Louis and then subsequently was on faculty at the University of Texas Southwestern Medical center in Dallas. And finally, I ascended to the chair of neurology at Ohio State University in Columbus, Ohio. I've been with Quest Diagnostics now for about four years, and one of the major roles I've had here is working on our portfolio in terms of developing plasma-based biomarkers for Alzheimer's disease.

Amanda Benson [00:01:55]:

To start our discussion, 78% of American adults want to incorporate a blood test that detects early risk of Alzheimer's disease into their preventative health visits. And one out of three retirees fear Alzheimer's disease more than cancer, heart attack, stroke or contagious disease. Why do you think Alzheimer's invokes such strong concerns among older adults?

Dr. Racke [00:02:20]:

Well, I think there's a number of issues for some of the disorders you mentioned. As an example, I had COVID and I've had cancer and doing fine. I think all of us have knowledge of either family members or friends who've had Alzheimer's disease. And for the most part, it is a relentless, progressive disorder that eventually robs patients of their cognitive function. And I think that many elderly fear that that could possibly happen to them. And so I think that is one of the major reasons that people are so interested in trying to identify whether they're at risk for Alzheimer's disease and what are the things they can possibly do to prevent or treat it.

Amanda Benson [00:03:06]:

What do the statistics tell you about patient desire for Alzheimer's disease testing in routine primary care?

Dr. Racke [00:03:13]:

So, like as you mentioned, we performed a survey through Harris where three out of four adults basically were very interested in having such a test. I think the thing that's become very interesting is in the last couple years, we finally have had anti amyloid therapies which potentially can slow the progression of Alzheimer's disease. I'm not sure how many people are actually aware of that, but I can tell you that those that are are very interested in knowing whether they might be candidates for such a therapy. And I think that people who know of a family member that's affected with Alzheimer's disease want to know whether they might be candidates and want to know how to get evaluated so that they could potentially receive this new treatment for Alzheimer's.

Amanda Benson [00:04:08]:

Could you explain what a blood-based biomarker test is and how it works in assessing Alzheimer's disease risk?

Dr. Racke [00:04:15]:

So let me first go back and say that I've been around the block a time or two, and when I was a resident, for example, Alzheimer's disease was what we called a clinical pathologic diagnosis. What that meant is if somebody looked like they had Alzheimer's disease, it wasn't until they passed away and had an autopsy done that one could confirm that they had the plaques and tangles characteristic of Alzheimer's disease. Those would be the beta amyloid plaques and the neurofibrillary tangles. Now, about 15 to 20 years ago, they had the development where there were tracers that were able to bind to the beta amyloid plaque. And that was basically the first time when we had a test where we could actually evaluate people with cognitive dysfunction and showed that they had amyloid plaque in their brain. More recently, we've been able to look at that, the measure beta amyloid in the spinal fluid and the phosphorylated tau, or what we call P tau, in the spinal fluid. And those were then allowing us to again use biomarkers to identify people who had Alzheimer's disease. Now, to get spinal fluid, you actually have to do something called a lumbar puncture.

Dr. Racke [00:05:41]:

And while it's not terribly invasive, it's not particularly pleasant. And now with blood-based biomarkers, we're able, with a routine blood draw, able to identify those same biomarkers in a patient's blood. And so that allows us advantages in a number of ways. One, it's much more cost effective, and it's a test that you can repeat over time, so that one can see how somebody's biomarkers are changing over time and perhaps that then can inform whether they might need to be treated for Alzheimer's disease.

Amanda Benson [00:06:20]:

While Medicare guidelines require cognitive assessments to be part of annual wellness visits, research shows that many primary care physicians are not consistently using standardized cognitive health assessments like the Mini Mental State Examination or MMSE, during these visits. Often they are waiting until cognitive symptoms are noticeable enough to impact daily life. Yet we know that micro changes in the brain associated with Alzheimer's can begin up to 20 years before symptoms appear. How can blood-based biomarkers complement these assessments to provide a more proactive approach to, to Alzheimer's risk detection?

Dr. Racke [00:06:58]:

So that's a very interesting question because I would say that most of our work so far has concentrated on using the plasma-based biomarkers as a way to evaluate whether a patient has a positive or negative amyloid PET scan. But I think one of the things that's rapidly changing and we've done some work on this with the group at UCSF, the University of California, San Francisco, looking at tablet-based cognitive assessment tools. And one of the things that's very clear is that using digital cognitive assessment that can happen in less than 10 minutes, and combining that with a blood-based biomarker, can dramatically enhance the sensitivity and specificity of, of identifying people not only having cognitive impairment, but whether that cognitive impairment could be early signs of Alzheimer's disease. And I think that's highly relevant from the perspective that when you look at the clinical trials, the first 20 or so clinical trials for Alzheimer's disease all failed because essentially they tried to remove amyloid after the patient already had moderate to severe Alzheimer's disease. And even though one could remove the amyloid, it didn't have any effect on cognitive function. The more recent studies have definitely shown that the earlier you intervene, the more likely you are to be able to slow cognitive decline. And clearly that's something that we all like to see in terms of patients who are at risk for Alzheimer's disease, who are the earliest signs of Alzheimer's disease.

Amanda Benson [00:08:45]:

So how can early risk assessments through blood-based biomarkers influence long term patient outcomes?

Dr. Racke [00:08:52]:

So I can tell you that there's a number of different ways that people are approaching this. I would say right now we're still at the stage where if somebody has notes, memory problems, and they get evaluated, if the biomarkers are positive for Alzheimer's disease, then one can potentially evaluate whether they are a candidate for things like anti amyloid therapy. But I can tell you there are also larger prospective studies that are being done that are examining whether a patient has, say you mentioned earlier about the microscopic changes for Alzheimer's disease. And that would include that people who are putting amyloid into their brain and don't yet have a positive PET scan and really don't notice any cognitive dysfunction that many of those patients, if they do, for example, wellness interventions, I'm talking about exercise, losing weight, making sure that you're not deficient in B vitamins, vitamin D, making sure you're not insulin resistant, making sure you don't smoke, that all those things can slow down the deposition of amyloid in the brain. And that one of the things that's been seen in some of these studies, that one can actually improve the amyloid biomarkers. And so I think that as those become, I would say more definitive, that I think people are going to then look at that and say this is an intervention that we can do and potentially help these patients in terms of preventing the onset of Alzheimer's disease.

Amanda Benson [00:10:40]:

Thank you for that. What does research say about how early blood tests can assess the risk of Alzheimer's?

Dr. Racke [00:10:46]:

So there's a, you know, I would say the, as we mentioned earlier, it's the beta amyloid. And typically in the blood you do what's called the beta amyloid 42 to 40 ratio. And this is a way of detecting how whether somebody is putting amyloid into their brain and at risk for late onset Alzheimer's disease. Typically, if somebody then has a positive P tau, I would say the most common test that's used for that right now is probably P Tau 217. There's also P Tau 181. And then there are other tests that are available that that's then basically saying you have both of these things that are available. We are participating, for example, in something called the Altsmatch study, which is looking at people in their 50s who are asymptomatic but do have a positive 42:40 ratio. And there are studies that are going on to see whether intervening in those patients can slow down the onset of Alzheimer's disease.

Dr. Racke [00:11:57]:

One of the issues if you have a positive 42:40 ratio is you really don't know where on the Alzheimer's continuum somebody might be. And there one of the, I guess I'll say drawbacks of just looking at the amyloid is that one doesn't know whether somebody could be getting Alzheimer's disease two years from now or 20 years from now. And that certainly makes a big difference in terms of wanting to do something like a medication intervention. But I think in terms of wellness strategies, you know, those are things that really don't necessarily cost that much and not only benefit the brain, but other organ systems as well. So these are strategies that definitely benefit not only brain health, but cardiovascular health and other areas as well.

Amanda Benson [00:12:50]:

How do you envision primary care physicians integrating blood-based biomarker testing into their current practices?

Dr. Racke [00:12:57]:

So that's a really important question. I would say that if you look at, there have been recently a couple articles in Neurology Today, which is sort of the news source for the American Academy of Neurology. One of the things that has not gone very well as these anti amyloid treatments have become available is that really it's been taken up in terms of looking at all the patients who potentially could receive this treatment. And there are a number of reasons for that. These treatments aren't without risk. Not everybody necessarily is willing to accept that kind of risk. But I think the, the other thing that's important to recognize is that, you know, if one identifies these people early, one can then do things like these wellness interventions. And you know, again, that's another area where maybe not everybody is going to be willing to do that, but there are going to be people that are interested in that kind of strategy to try to prevent the onset of Alzheimer's disease.

Amanda Benson [00:14:09]:

So what challenges might PCPs face and how can they overcome these?

Dr. Racke [00:14:15]:

Well, I would say that there's, you know, there's probably lots of challenges. For many of the things that I've mentioned, these are not necessarily easy strategies to take hold. I mean, if you look at our hospitals today, I would say that some of the things that I've mentioned in terms of obesity, smoking, even though I would say smoking has definitely gone down, these are still all things that do affect a significant part of the population. And you know, it's one thing to say, oh yeah, you should stop smoking, you should exercise, you should lose weight, you should, you know, do things that are stimulating to your brain. But it's not necessarily easy for everybody to, to sort of do all these different wellness type interventions. And you know, this includes some of the things like there was a recent study by Dean Ornish's group showing that that included, you know, becoming a vegan. And I could tell you that for most people, we think that that's a very healthy strategy, but that's not an easy thing for everybody to adopt.

Amanda Benson [00:15:30]:

So 87% of primary care providers believe that blood tests for early AD detection will become standard care. What steps do you think are necessary to accelerate the adoption of these tests in routine practice?

Dr. Racke [00:15:44]:

So I can tell you that Weil, as an example with the Affordable Care act, you can't, if somebody were at risk for developing Alzheimer's disease or that they had Alzheimer's disease, you couldn't penalize that person and not allow them to obtain health insurance. But there are other types of things that, where we don't necessarily have clear guidance on things like life insurance, disability insurance. And so I think one of the issues, why people might be hesitant to get these types of evaluations is that they're worried that that could significantly affect what they're able to do in terms of protecting their family financially. The flip side to that is that I think there are people that want to know very specifically so that they know why they still have some pretty good cognitive function, that they take those steps that are necessary to be able to take care of their family financially. And you know, so there's this balance. And I think one of the things that is going to be important coming up is not just the idea that we are going to, I think we're going to be able to treat Alzheimer's disease better and better over the coming years, but the other thing is what are we going to do in terms of, you know, when we identify patients who are at risk for Alzheimer's disease, you know, how are we going to handle things like, you know, life insurance, disability insurance and things like that?

Amanda Benson [00:17:18]:

How can blood-based biomarkers help streamline specialist referrals and what impact might this have on reducing wait times for patients?

Dr. Racke [00:17:27]:

Well, I can tell you I've, I've spoken to many physician, primary care physician groups where they say that if they do identify people who have blood-based biomarkers that put them at risk for Alzheimer's disease, that that's helped accelerate them getting into see a specialist at a memory clinic. And I think that by identifying those patients earlier and getting them into the memory clinic earlier, that often allows them to either participate in clinical trials or identify whether they are a candidate for anti amyloid therapy. And I can tell you for pretty much any neurologic illness, the earlier you identify the problem and enact an intervention, then you're much more likely to get a positive outcome.

Amanda Benson [00:18:21]:

Can you speak to how assessing risk earlier through blood-based biomarker tests could influence lifestyle changes that impact disease progression?

Dr. Racke [00:18:29]:

Yeah, so I think I've already mentioned that there have been studies to suggest that wellness interventions, which include things like exercise, losing weight, combating insulin resistance, making sure, you're taking vitamins, not smoking, that those all can have significant effect on the onset of Alzheimer's disease. In addition, there have been studies to show that by having these wellness interventions, you can actually reverse your biomarkers from being at risk for Alzheimer's disease to potentially having biomarkers that suggest you're not at risk. Now, I think one of the issues is that, you know, when you have a positive beta amyloid 4240 in the blood, that doesn't necessarily tell you, you know, are you going to have Alzheimer's disease onset in one year or 20 years? And I think one of the issues in terms of that is that there are people, I mean, I would say most primary care physicians know that if you do these wellness interventions, they not only benefit brain health, but they also benefit things like cardiovascular health. And so I think the idea that more Americans would take up these types of wellness interventions to prevent something like Alzheimer's disease, that's still going to be something that primary care physicians are going to have to work hard to get people to make those lifestyle changes.

Amanda Benson [00:20:10]:

So for patients who may already fear an Alzheimer's diagnosis, how should PCPs approach conversations about risk testing without creating additional anxiety?

Dr. Racke [00:20:20]:

Well, that's a very good question. And I think a lot of that also depends on, you know, the relationship the physician has with the patient and, you know, understanding is this a potentially a candidate for anti amyloid therapy and potentially other types of intervention? I think one of the things that not necessarily many people appreciate, for example, in the original aducanumab studies, about 25% of the Medicare population would have been excluded from being able to go on aducanumab because they had met exclusionary criteria. And so I think that's something that the primary care physician has to have in the back of their mind, you know, is this somebody that potentially would be able to be a candidate for anti amyloid therapy and then being able to have that conversation with somebody probably even before you do the test whether they would be interested in that kind of intervention.

Amanda Benson [00:21:24]:

Looking to the future, how do you see the landscape of Alzheimer's disease diagnostics evolving, particularly with Quest Diagnostics leading the charge in blood-based biomarker research?

Dr. Racke [00:21:35]:

So I can tell you that, you know, there we've spoken mostly about the beta amyloid 4240 and a little bit about phosphorylated Taurus 217 and 181, but there are definitely other biomarkers that can inform things like whether a biomarker like neurofilament light that can inform you about neurodegeneration. There are going to be biomarkers for other things like Lewy bodies, which are formed with alpha synuclein. I think as we are better able to understand the neurodegenerative processes that are going on in patients, we'll be better able to make informed decisions about how to manage those patients. And in many ways, we're at the infancy. We've just had the first treatments that actually show some effect in slowing cognitive decline. But I look at this in many ways as just the beginning in terms of our understanding on how and how we're going to use Blood-based biomarkers with things like imaging, with more sophisticated cognitive testing in order to be able to come up with the best strategies to help these patients.

Amanda Benson [00:22:58]:

Finally, what advice would you give to PCPs who want to stay ahead of the curve in Alzheimer's risk assessment and support their patients in a meaningful way?

Dr. Racke [00:23:07]:

So I would say one of the things is that I've spoken to many people when they talk about the wellness, the Medicare wellness visit, that they're using what's referred to as the mini cog, which is the mini cognitive assessment, which to be honest is not very sensitive, and that there would be many people who could score well on a mini cog and in fact have significant cognitive issues already. I think one of the things that is potentially going to happen is that as we use these digital cognitive assessments that we're going to be able to pick up things earlier. Because I can tell you, many patients, they don't recognize themselves when they're starting to have memory issues. And you know, often it is maybe a co worker or a family member, but sometimes they think, oh, you know, they're a little bit older, but for the most part they're still independent and doing okay. When in fact, you know, that this could represent already some significant cognitive decline from what their baseline was and that this might be a candidate for some type of therapeutic intervention. And I think that's, you know, I think the biggest thing is going to be though, whether we have ability for intervening in that 20 year period when we first are able to identify people who are at risk for Alzheimer's disease, but really before they really have significant problems. Because I can tell you, while these medications are expensive, we as a society spend a lot more money on taking care of people who are demented at the end of life, who are no longer able to be independent. And that ability to, to keep people living independently, not only does that improve their quality of life, but it also significantly reduces the costs for taking care of these people.

Amanda Benson [00:25:09]:

Thank you for that. And thank you so much for joining me in this conversation today.

Dr. Racke [00:25:13]:

Dr. Raki Amanda, thanks for having me today. I think this is the kind of discussion that can help people in terms of how they look at blood-based biomarkers for Alzheimer's disease and how they may utilize them in care of their patient.

Amanda Benson [00:25:30]:

Absolutely. Thank you. That brings us to the end of today's episode. I'd like to extend a huge thank you to Dr. Michael Rackey for sharing his insights on the critical role that blood-based biomarkers can play in early Alzheimer's risk assessment and how primary care physicians physicians can be the first line of defense against cognitive decline. We learned today how incorporating these innovative blood tests with routine cognitive health assessments could dramatically change the way we assess and manage Alzheimer's risk, possibly providing patients with the opportunity for earlier intervention. You won't want to miss our upcoming episodes where we dive into more groundbreaking research and real world stories that impact patient care. Thanks for tuning in.

Amanda Benson [00:26:15]:

I'm Amanda Benson and we'll see you next time on the Results are in by Quest Diagnostics.

VO [00:26:26]:

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