The Future of Alzheimer's Diagnosis Is Now

The Atlantic

16 hours ago

A patient enters her general practitioner's office for a routine checkup. She is 65 years old, and—knock on wood—in good health: walking outside every morning, eating a thoughtful diet, and reading voraciously. All of this she naturally tells her doctor during the visit. However, lately she's been forgetting things here and there. Nothing major, she thinks. It's just a normal part of getting older. So this small detail she keeps to herself.
But by holding on to that detail, the patient is also putting off a conversation that could change the course of her life as well as her family's. Memory change is not always a part of normal aging, with more than 7 million adults living with Alzheimer's disease in the United States—a number that is expected to almost double in the next few decades. The fear that talking about it will lead to a road of invasive procedures, life-changing diagnoses, and painful choices is all too common.
However, new scientific developments in diagnostics have been made so medical experts can help diagnose or rule out Alzheimer's disease sooner, and more easily, than ever before with a simple blood test. In this new era, patients can rule out the disease as a diagnosis or talk to their doctors about care options and plan with their families if they receive a diagnosis.
When patients receive a timely and accurate diagnosis, this opens up the opportunity for them to make plans for the future
Brandy Matthews Vice President of Global and U.S. Medical Affairs for Eli Lilly and Company
'We have to overcome this barrier of stigma,' says Brandy Matthews, M.D., FAAN, vice president of global and U.S. medical affairs for Alzheimer's disease at Eli Lilly and Company, 'and then the reinforcement of the myths [so] that people will raise their hand when they begin to experience changes in their memory and thinking.'
In addition to the laboratory developed tests that are already available and developed under the Clinical Laboratory Improvement Amendments (CLIA) to aid in Alzheimer's disease diagnosis, the FDA recently cleared the first in vitro diagnostic (IVD) blood biomarker test. These tests can be administered to symptomatic patients as part of a cognitive workup.
'The fact that there's been a recent FDA clearance for a blood biomarker in Alzheimer's disease is really critical and really big and I think will be a sort of a monumental shift in how we diagnose Alzheimer's disease,' says Anthony 'Nino' Sireci, M.D., MSc, senior vice president of clinical biomarkers, laboratories and diagnostics at Eli Lilly and Company.
The work of developing new technology to diagnose a disease is painstaking and slow, but these breakthroughs are essential for patients. These advances not only offer hope to millions but also provide researchers like Matthews and Sireci with a profound sense of purpose.
'When patients receive a timely and accurate diagnosis, this opens up the opportunity for them to make plans for the future, to engage in lifestyle modifications, and to explore options for therapies that may target their symptoms or the underlying pathology of the disease,' says Matthews.
Way back in 1906, the German neuropathologist Alois Alzheimer identified what he called 'an unusual disease of the cerebral cortex' marked by symptoms of memory loss. Using newly available technology, he identified two key pathological proteins in the neurons of his patients' brain cells: Beta-amyloid and tau.
Beta-amyloid and tau are proteins produced naturally in the body. In patients with Alzheimer's disease, beta-amyloid starts to clump together, creating plaques between brain cells, while tau twists together into tangles inside brain cells.
'They are involved in a cascade of changes that happen in the brain, presumably initially with amyloid plaque accumulation, followed by tau tangle accumulation, leading to the dysfunction of the brain cells and then eventually neurodegeneration or shrinking of the brain. That results in the symptoms of Alzheimer's disease,' says Matthews.
To be able to have a data-driven conversation, I think, is going to be pretty big in ensuring, number one, that patients are appropriately triaged
Anthony 'Nino' Sireci, M.D. Senior Vice President of Diagnostics Development at Lilly
Beta-amyloid plaques and tau tangles are the cause of the disease, but for nearly a century following their initial discovery, they could be identified only posthumously. This changed in 2002, when scientists identified amyloid plaque in the brain of a patient with a PET scan for the first time, using an imaging agent approved by the FDA in 2012.
In 2022, the FDA cleared its first biomarker test measuring the presence of beta-amyloid in cerebrospinal fluid (CSF), drawn during a lumbar puncture (also known as a spinal tap). 'Modified fragments of those proteins are released into the cerebrospinal fluid,' says Sireci. 'And so those become some of the biomarkers that you measure in CSF.'
While effective tools and necessary parts of the diagnostic process, PET scans and spinal taps are invasive and not always readily available, depending on where patients are located. This is where blood biomarkers come in, because beta-amyloid and tau aren't released only into CSF.
'Some of them actually leak out into the blood in super small quantities,' says Sireci. 'And that's what we use as the basis for identification of blood biomarkers in patients with Alzheimer's disease.'
The traces found in these tests are smaller and harder to identify than the ones found in CSF. One challenge has been innovating over years to make blood test more closely resemble CSF – a major breakthrough developed over years of challenging work. And such tests require patients access and provider experience.
In an ideal world, a simple blood sample could be collected at any doctor's office, even in rural or underserved communities, and sent to a major reference lab where, combined with the patient's initial cognitive assessment, it could provide information to help the treating physician to diagnose Alzheimer's disease without the need for additional confirmatory testing. That would vastly expand access to timely diagnosis.
But there is still a lot of work to do between the clearance of a medical technology and its implementation. 'The obstacles now are not scientific,' says Sireci. 'Medicine is a logistical effort.'
Are the [diagnostic] assay themselves robust enough that physicians feel confident in the results and confident in how they interpret them? That's really big.
Anthony 'Nino' Sireci, M.D. Senior Vice President of Diagnostics Development at Lilly
'It's implementation,' he says. 'Are the [diagnostic] assay themselves robust enough that physicians feel confident in the results and confident in how they interpret them? That's really big.'
But with any new diagnostic tools come questions. Are physicians educated in how to understand the results? Are they confident in those results? And once they are, are they actually able to order the test at scale from high quality labs?
It's about quality and it's about access. And that's only on the medical side. What about patients? Will insurers reimburse the tests so that patients are not faced with high out-of-pocket costs? Will patients embrace them? Sireci is optimistic about both possibilities. A recent survey by the Alzheimer's Association found that 91 percent of patients would want a blood biomarker test if it were made available to them.
A readily available blood biomarker test gives doctors and patients a tool to aid in accurate and timely diagnosis. That patient who walked into her general practitioner's office? She would undergo a routine cognitive exam (a recommended standard for all patients 65 and older). She would have an honest conversation with her doctor about changes she might be perceiving in her brain function, however slight. And if the doctor thought it was necessary, a referral to a specialist for a simple blood test would be administered to help inform next steps.
Then, unlike in the decades when Alzheimer's disease could be diagnosed only symptomatically or after an invasive procedure, the doctor would lead her in an informed, fact-based discussion—right away. From that conversation, the patient could undergo a PET scan or CSF testing to confirm or rule out the diagnosis if necessary.
'To be able to have a data-driven conversation, I think, is going to be pretty big in ensuring, number one, that patients are appropriately triaged,' says Sireci, 'but also [that] they're not waiting years for a diagnosis, which unfortunately is what's happening today.'
We're moving the needle for patients and giving physicians another very powerful tool to combat this disease.
Anthony 'Nino' Sireci M.D., Senior Vice President of Diagnostics Development at Lilly
This is crucial because Alzheimer's is a progressive disease. Timing is critical. The earlier a patient is diagnosed, the more time they have for planning, which could include treatment options a patient has available to them. They can set themselves up for counseling, talk to their families, and could choose to begin medical intervention.
'We've learned over time that initiating therapy in the earlier stages of disease can have greater impact,' says Matthews. 'And even within those early symptomatic stages of disease, there's evidence, across a class of medicines, that the earliest stages of early symptomatic Alzheimer's disease may demonstrate the greatest benefit of new therapies.'
For Sireci, who has experience with Alzheimer's disease both as a doctor and as the family member of a patient, the most gratifying aspect of his research is knowing that it can help shorten what he calls the 'diagnostic odyssey.'
'Even if that just means getting the conversation to happen for the physician faster than it would've, then I'm happy,' says Sireci. 'That's a really big deal. We're moving the needle for patients and giving physicians another very powerful tool to combat this disease.'
The Future of Alzheimer's Diagnosis Is Now
Hear more from Brandy Matthews, Vice President of Global and U.S. Medical Affairs at Eli Lilly and Company, on the future of Alzheimer's diagnosis.
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