How Early Can We Diagnose Alzheimer’s Disease?

New technologies are making it possible for physicians to spot the earliest signs of Alzheimer’s.

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By the time most people with Alzheimer’s seek medical care for early symptoms like short-term memory loss, the disease has been progressing without their knowledge for years.

Amyloid-beta, a toxic protein which accumulates in the brains of people with Alzheimer’s disease, “can appear 20 to even 30 years prior to there being an actual diagnosis of dementia,” said Rachel Buckley, a neuroscientist at Mass General Brigham Neuroscience Institute.

Currently, Alzheimer’s is typically diagnosed using memory tests or expensive brain imaging. But new technologies and techniques are making it possible for physicians to more quickly and easily spot the earliest signs of the disease. Even though there’s no cure for Alzheimer’s, the sooner patients get diagnosed, the sooner they can make appropriate lifestyle changes and start one of the handful of medications available to modestly slow its progression. Experts hope the latest diagnostic tools, including blood tests and improved cognitive tests, will help people stay healthier longer and may even pave the way toward making Alzheimer’s a preventable disease.

Detecting Alzheimer’s With Just a Drop of Blood

One emerging technique, called biomarker testing, takes simple and cheap route to diagnosing Alzheimer’s. Clinicians take blood or cerebrospinal fluid samples and look for traces of specific molecules linked to amyloid-beta, a toxic protein which accumulates in the brains of people with Alzheimer’s. The leading biomarker clinicians use today, called ptau-217, is a protein fragment. Several blood tests recently approved by the FDA to check for Alzheimer’s work by detecting it.

These tests are currently available for people concerned they may be experiencing Alzheimer’s-related cognitive decline. But Buckley and her Mass General colleagues wanted to know if ptau-217 could be useful before patients are aware of potential symptoms. In a recent study, they tested this biomarker’s ability to predict Alzheimer’s in cognitively healthy people. After analyzing data collected from nearly 3,000 older adults, they concluded elevated ptau-217 levels were associated with higher risks of developing dementia.

People with very high levels of the protein, they found, had a 78% chance of developing Alzheimer’s within the next 10 years. Buckley said for those individuals, the test results could be a signal to seek follow-up care from a physician.

Making Better Memory Tests

While useful, biomarker tests aren’t foolproof. Researchers don’t fully understand the role of amyloid-beta in Alzheimer’s. The protein is widely accepted as an early sign of the disease even though some people appear to be resilient to its buildup and don’t develop symptoms. Around a fifth of people in Buckley’s study never became cognitively impaired despite their elevated ptau-217 levels. Combining biomarker tests with other early indicators of cognitive decline could ensure more accurate diagnoses for patients, said Timothy Rittman, a researcher-clinician at the University of Cambridge.

In a 2022 study, Rittman and his colleagues explored whether scores on annual memory and physical function tests in healthy older adults could predict dementia onset years down the line. Sure enough, participants who were later diagnosed with Alzheimer’s performed worse on memory tests and had slower reaction times compared to healthy control volunteers. The team identified slight but significant declines in their scores beginning up to nine years prior to their diagnosis.

Amid a growing emphasis on biomarkers, Rittman said he thinks cognitive testing has become “a bit neglected” in the field of Alzheimer’s diagnostics, adding the ones used today can’t be used to screen for dementia in the wider population.

"The tests that we use in memory clinics are going to be too easy to try and pick up those subtle changes that we might see in people very few years before the diagnosis," said Rittman. Instead, they solely highlight more significant cognitive decline. He is pushing for these tests to incorporate more complex questions and challenging tasks to identify people who don’t yet have prominent symptoms.

Small Steps Toward Preventing Dementia

Biomarker tests are useful tools for clinicians. But Buckley said patients receiving Alzheimer’s therapies at her hospital ultimately want to know whether their memory is improving — biomarkers alone can’t answer those questions, underscoring the importance of cognitive testing. She pointed to an ongoing clinical trial as an example of the two approaches working together. The trial, which is testing whether the Alzheimer’s drug lecanemab can prevent the disease in people with high levels of amyloid in their brains but no symptoms, uses a p-tau217 blood test in combination with regular cognitive testing to assess efficacy.

Buckley also envisions a world in which biomarkers are key to preserving the health of older adults at risk of Alzheimer’s. If researchers successfully develop a treatment capable of stopping the disease at its earliest stages, routine biomarker testing could be used to find optimal candidates and get the therapy into their hands long before they develop symptoms, potentially preventing Alzheimer’s altogether.

“We are so close,” Buckley said. “And as soon as we have a therapy that is available and can be beneficial to unimpaired older adults, the game is going to change entirely.

About the Author

RJ Mackenzie

RJ Mackenzie is a freelance science writer based in Glasgow, Scotland. Armed with neuroscience degrees from the University of Edinburgh and the University of Cambridge, RJ writes about all aspects of the brain and body.