Q&A: Proposed changes to Alzheimer’s diagnostic criteria could be ‘game changer’ for PCPs

Key takeaways:

• Recent advancements in biomarkers of Alzheimer’s disease could have major implications for diagnosis in primary care.
• Proposed updates to the diagnostic criteria are open for public comment until Aug. 31.

At the recent Alzheimer's Association International Conference in Amsterdam, an Alzheimer’s Association workgroup proposed revisions to the diagnostic criteria for Alzheimer’s disease.

Once finalized, the criteria will update guidance published by the National Institute on Aging and Alzheimer’s Association in 2011 and a research framework published in 2018.

The updates reflect advancements in researchers’ understanding of blood-based biomarkers, “which have shown tremendous promise and performance in the ability to detect Alzheimer’s disease,” according to the association’s press release. These biomarkers may help increase access to testing due to their low cost and ease of use, the release said.

Healio spoke with Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, to learn more about the proposed criteria and how these revisions would impact Alzheimer’s disease diagnosis and management in the primary care setting.

Healio: Why did the criteria need to be changed?

Carrillo: It's clear that Alzheimer's is a very complex disease. Thirty years ago, the first diagnostic criteria were introduced by one of the Institutes at the NIH and the Alzheimer's Association. Back then, they focused on the symptomatic impact of Alzheimer's at the end stage of disease, which we call dementia.

But there are several conundrums to using that sort of symptomatic end stage of disease as a definition. One of them is, of course, that symptoms of dementia can be caused by a number of diseases. They're not always caused by Alzheimer's, although Alzheimer's is the most common cause.

Second, we know that symptoms of dementia, even when caused by Alzheimer's, are at the late stage of disease and do not represent the earliest we can detect the disease. That is important because you want to detect disease as early as possible. We know that diseases are more tractable and treatable when they are caught early.

Most importantly, I would say the reason why we have to continue to update the criteria is that we know much more today about the underlying biological changes than we did 30 years ago, and more than we did in 2011 when we updated the original 1984 criteria, and in 2018 when we updated it again. We are making great strides in not only being able to detect the earliest changes, but in treating those earliest biological changes. That’s why it’s so critical at this moment.

Healio: Can you give a brief overview of the updated criteria?

Carrillo: One of the most important things to know about the updates in the biology of Alzheimer’s that led to the proposed changes to the criteria is that when we think about diseases ... they're all based on a biology. Psychiatric diseases are an exception for now, but most tend to be based on biology.

For this particular update, we understand that the biomarkers that we assumed were detecting that underlying biology in 2011 and 2018 were going to be stagnant.

For example, in 2011, we started with the basic understanding that amyloid and tau were both proteins that change with Alzheimer's, and that they change perhaps decades before a person develops the earliest symptoms. Knowing that, we called them the hallmarks, or core markers, of the disease.

We added to that neurodegeneration, meaning cell death. The outcome of protein changes, related to amyloid beta and tau tangles, really is cell death — the cell death is what then leads to dementia syndromes.

We called that at the time “A,T and N” — for amyloid, tau and neurodegeneration — and we identified biological markers that you could perhaps get in a neurology clinic that could detect A, T and N, and sometimes in combinations. In 2018, we made a very significant update to ensure that these stages of disease that could be determined by A,T and N ... were all part of one continuum, with the understanding that these changes happen slowly, so that our loved ones don’t wake up one day with one syndrome vs. the other.

Recognizing this, we now want to clarify again that that continuum can be detected by A, T and N. But now we understand that:

• amyloid plaques and amyloid beta proteins can be detected by very different types of markers — markers that could be associated with imaging as scans of different types, not including MRIs and positron emission tomography scans;
• tau tangles can be detected through scans as well, but also cerebro spinal fluid assays and blood tests; and
• these biomarkers can be representative of different aspects of amyloid beta, of tau changes and of neurodegeneration.

Today, we also can start to detect inflammation, which we did not include in the criteria in 2018. Inflammation markers are a development that will, in the near future, be used in a neurology or specialty clinic.

We also know today that other contributors to Alzheimer's symptoms from the earliest stages can be vascular contributions. Today, we have better detection tools for those. In 2018, we mentioned them, but we didn't have adequate information that we could give to clinicians to say, “You can use this biomarker to detect these vascular contributions.” Today we feel more confident about them.

These are some of the updates that I think are very critical for our clinicians to understand, because a diagnosis of Alzheimer's is so complex. Up to now, we may have been doing a disservice to many individuals who have received Alzheimer's diagnoses in their primary care office, where some clinicians do not have the tools or the training to detect this very complex disease in the way I'm describing it.

Healio: What are the implications for primary care physicians?

Carrillo: Any revised criteria, even in their inception, take time to validate. We will need clinical studies and observational studies that try to validate and identify weaknesses and strengths of what we propose.

However, the underlying cause of this update is advancements in biological markers. Those advances include blood markers and plasma markers, and plasma markers can reach our PCPs within the next year or two. It's actually a shorter time frame than we might have thought because of the rapid advancements in technology.

We did not think we would be reaching this point where even PCPs would be able to avail themselves of a blood test. We didn't even think neurology clinics or specialty clinics would be able to avail themselves of this, and we have been proven wrong. It is a very fortuitous advance.

What this really means is that blood tests today in a specialty clinic can help us to determine who should go on to get more complicated biological marker testing, similar to how blood tests in a PCP’s office today can tell a PCP that an individual might need to move on to advanced testing for other diseases. This would allow a PCP to not only respond to a patient's request for information about their memory or a patient's complaint about their memory, but it would also allow a PCP to say, “Let’s take this complaint seriously. Let’s look for ways to identify what the causes might be through an interview.”

On top of that, once a PCP can recognize that perhaps there might be other underlying causes, a blood test might allow that PCP to better identify who might benefit from advanced testing that could be done in a geriatrician's office, or perhaps even an advanced specialty like psychiatry or neurology. That’s a big game changer for PCPs and for specialty clinics, and a huge benefit for patients who have memory concerns and may not find a specialist so quickly and so begin with primary care.

The draft revision will be open to the public for commentary until Aug. 31. Comments can be submitted here.

References:

• Proposed new diagnostic criteria for Alzheimer’s Disease unveiled at AAIC 2023. https://aaic.alz.org/releases_2023/new-alzheimers-diagnostic-criteria-unveiled.asp. Published July 16, 2023. Accessed Aug. 3, 2023.
• NIA-AA revised clinical guidelines for Alzheimer’s. https://aaic.alz.org/nia-aa.asp. Accessed Aug. 3, 2023.