Alzheimer’s disease testing

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Dr. Soeren Mattke: Hello, my name is Dr. Soeren Mattke. I am a physician and health services researcher on the faculty of the University of Southern California in Los Angeles. Today, I will talk about the role of blood tests for Alzheimer's pathology in the diagnosis and evaluation of that disease.

Narrator: How well are healthcare systems prepared to diagnose early-stage Alzheimer's disease today?

Dr. Soeren Mattke: In the early detection of Alzheimer's disease, we are really starting from behind. Prior research of ours has shown that only 8% of people 65 and older in the US are diagnosed at the stage of mild cognitive impairment, the stage at which we would ideally detect and diagnose and evaluate Alzheimer's disease.

Further, once they are diagnosed, they would face a peak wait time of about 23 months to see a dementia specialist for further evaluation and potential referral to treatment.

And these long wait times and gaps in detection are due to a long-standing underinvestment into memory care, even in high-income countries. For example, we estimated that NHS England would have to invest about £14 billion over the next 10 years to even reach G7 average standards of memory care infrastructure.

Narrator: What are the important considerations in scaling up memory care capacity?

Dr. Soeren Mattke: There are two important considerations when you consider scaling up memory care. The first problem is that it is a problem of prevalence of the disease, not of incidence. We have this large pool of undiagnosed patients that will strain the currently available capacity. But once we have dealt with this backlog, we can actually deal with the new cases, the incident cases, and demand will decrease.

So if we invest, we should prioritize scalable technology that does not require high-cost fixed infrastructure.

The other consideration is that this is a population-level disease. We have about 6 million people with early-stage Alzheimer's disease in the US alone. And such common conditions cannot be handled in specialty care alone. We know this from other common conditions: diabetes, heart failure, depression—they're mostly diagnosed and treated in primary care.

That is not to say that we don't need specialists. We need them to provide input to the care plan. We need them for complex and unusual cases, but we should not rely on them for the routine management of straightforward cases.

What this implies is that we need to provide primary care clinicians with workflow-compatible tools to fulfill that role. So we need to decrease complexity of the diagnostic process and make it more scalable and more compatible with what primary care docs do day-to-day.

Narrator: What are the economic benefits for healthcare systems of inserting blood tests in the Alzheimer's diagnostic pathway?

Dr. Soeren Mattke: The main difference between using blood tests and using currently available modalities to determine the Alzheimer's pathology is in the cost—lower cost per test. If you look at the recent Medicare rates, a lumbar puncture and a single assay for Alzheimer's pathology is a little shy of $500. If you do a PET scan with the amyloid tracer, we're talking about $5,000. But a blood test at the moment is about $150. And more importantly, the accuracy of these blood tests is now rivaling what we see in these legacy test modalities.

And there's another important point that relates back to my earlier argument: that blood tests do not require investment into high-cost fixed infrastructure. For example, a single PET scanner costs about £1.15 million to install in England. Moreover, it takes years for planning, budgeting, permitting, construction. So we're talking about a delay of 5 to 7 years until the device is ready for patient examinations.

In contrast, blood test samples you can collect in any clinic, and the latest generation of these tests can be processed in high-throughput analyzers that are basically found in every large lab, in every large hospital, in every large outpatient center. And there's no special handling and processing required. So you can collect blood, you can send it down to the lab just like you do with any other blood test, and you'll get your result within a day.

Narrator: How could blood-based biomarkers for Alzheimer's pathology streamline the diagnostic pathway?

Dr. Soeren Mattke: To me, the Alzheimer's blood tests fulfill the requirements of the holy triad in health services, which is faster, better, cheaper.

We estimated that we can shorten the peak wait time for a specialist appointment from about 23 months to 16 months with the introduction of a blood test compared to legacy technologies. Furthermore, this shortening of the waitlist for specialists allows us to move more patients through the funnel because we don't send so many patients without an urgent need for specialist visits to a specialist.

The blood tests improve the diagnostic accuracy in primary care, which a recent study by my Swedish colleagues has shown. We have a 30 percentage point greater diagnostic accuracy compared to clinical judgment.

And then using blood tests, based on what I showed earlier, is going to be a lot cheaper. So we compared the cost-neutral price for a blood test used in primary care that would be used for a triage indication—so basically a rule-out of the Alzheimer's pathology—and a confirmatory indication, which would be a confirmation of the Alzheimer's pathology. And you could charge up to $290 for the triage test and $1,150 for the confirmatory test, and you would still be cost-neutral relative to standard of care.

And I had said earlier, the prices of the blood tests are expected to be in the $150 range, so we're actually reducing the net cost per case diagnosed for further evaluation and treatment.

Narrator: Which roles beyond streamlining the initial diagnostic pathway could blood biomarkers play in the era of disease-modifying therapies?

Dr. Soeren Mattke: The role of blood tests in the era of disease-modifying therapies goes well beyond detection. We have talked earlier about the need to rule out or confirm the presence of pathology, but then you can also use blood tests to stage the disease. So you can understand at what level of the disease on the ATN framework a patient is.

And that helps you with prognostication: you can predict how quickly the next stage of the disease will be reached, and also what effect size the amyloid-targeting treatment might have.

And then conversely, you could use it for treatment monitoring because you can see whether targeting the biology with disease-modifying therapies changes the blood test profile in a patient, which gives you insight into whether the treatments work or not.

Narrator: What are the implications of the emergence of treatments for preclinical Alzheimer's disease for the role of blood biomarkers?

Dr. Soeren Mattke: Preclinical Alzheimer's disease treatment is the new frontier. As in any other disease in medicine, we are striving to catch it at the earliest stage possible. We do not want to wait until somebody has a heart attack to start lowering cholesterol, but we start treating at a stage where somebody might be mildly symptomatic or not symptomatic at all.

And the same is currently being trialed in Alzheimer's treatment, because the Alzheimer's pathology precedes the development of cognitive decline for years, even decades. We want to catch people at that preclinical stage, remove the Alzheimer's pathology, and potentially delay or even avoid progression to cognitive impairment.

The problem with this is twofold. First, patients will not present spontaneously in primary care because they are at best mildly symptomatic. And we will have an enormous number of patients because this is a very prevalent condition with about 20% prevalence in the 55+ population, similar to high cholesterol. So there is just no way that we can use any other modality as blood tests for detection of these cases on a large scale.

In addition, prior research has shown that we can also use the blood tests for risk stratification. Much like we decide on whether or not to lower cholesterol based on the so-called AHA equations that predict the risk of having a heart attack or stroke in the next 10 years, we can use blood tests to predict whether somebody is at meaningful risk of progressing to clinically manifest disease in the next couple of years.

So that allows us to use the blood test results for risk stratification and prioritization for treatment versus watch and wait.

Dr. Soeren Mattke: Thank you for listening. Again, my name is Soeren Mattke. I'm a physician and health services researcher. And I hope I explained to you the importance of blood-based biomarkers in the diagnosis and evaluation of Alzheimer's disease, both in the stages of early-stage clinical disease, but also in the near future in the detection, stratification, and monitoring of patients with preclinical disease.