It’s perfectly reasonable for an older person to briefly wonder whether they’re sliding inexorably toward dementia when they forget where they left their car keys or find themselves frantically searching the archives of their gray matter for the name of a once-familiar relative. (Been there, done that.) But, until recently, seriously investigating those suspicions involved some serious clinical procedures — MRIs, PET scans, spinal taps. That may explain the exuberance with which portions of the scientific community have suddenly embraced Alzheimer’s blood tests.
The response to this new diagnostic approach at last summer’s Alzheimer’s Association International Conference, for instance, was nothing short of celebratory: “As highly accurate blood tests for Alzheimer’s disease are moving closer to use in physician’s offices, new research suggests that they may revolutionize the accuracy of diagnoses and provide a cleaner, quicker path to research participation and treatment.”
Surveying the recent research landscape offers some evidence for their enthusiasm. Most studies suggest that identifying a particular protein (ptau217) in the blood can predict with far more accuracy than other tests the presence of damaging amyloid plaque and tau in the brain. If you identify those substances well before major cognitive dysfunction becomes apparent, the thinking goes, physicians could recommend lifestyle changes or pharmaceutical options that may delay dementia’s encroachment.
That’s the theory, anyway. The reality is a bit more complicated.
As Washington University neurologist Suzanne Schindler, MD, writes in Scientific American, the first Alzheimer’s blood test became available for clinical use in December 2020. And while many others have surfaced in the intervening years, their ability to accurately measure the key biomarkers in the blood range from stellar to subpar. (A Rutgers University study released last week suggests they may be especially inaccurate when assessing Black patients.) None of these blood tests have been approved by the Food and Drug Administration (FDA), but nothing prevents savvy marketers from pitching them to healthcare providers.
That leaves clinicians like Schindler questioning whether even a test that purports to be 90 percent accurate qualifies as an ethical diagnostic tool. “A diagnosis of Alzheimer’s disease changes the way patients see themselves and their future; the information guiding this diagnosis must be correct,” she argues. “Accuracy is especially important if patients are going to be started on an Alzheimer’s-disease-specific treatment based on this test result.”
Schindler, who attended the Alzheimer’s conference, says she was struck by the shift in thinking about dementia diagnostics, how these blood tests — imperfect though they may be — are forcing physicians to change their approach before they’re completely confident in the outcomes. “Blood tests have developed incredibly fast for Alzheimer’s disease, and I think [doctors] aren’t used to that rate of change,” she tells NPR. “Physicians really need to educate themselves about these tests because this is coming really soon.”
But the relative accuracy of the tests is only one of the issues that arise in a clinical setting. In a recent STAT News editorial, University of California, San Francisco, neurologists Naveen Reddy, MD, and Kristine Yaffe, MD, describe a post-test scenario they believe many doctors will be facing.
The hypothetical patient shows no signs of cognitive impairment, but having watched his mother suffer through Alzheimer’s, he wants to know if he’s at risk. The doctor orders the test, and the results show the presence of ptau217 protein, indicating the potential for an accumulation of amyloid plaque and tau tangles in his brain. But the subsequent MRI and neuropsychological tests tell a different story: His brain seems to be functioning normally.
“At this point, we’re stuck,” Reddy and Yaffe admit. “Should we formally diagnose him with Alzheimer’s despite showing no symptoms of the disease? And, if so, do we then initiate therapy with an antiamyloid agent? Billions of dollars and the lives of millions of individuals hinge upon the answers to these questions.”
The financial implications of mass testing — both for the individual patient and the public health infrastructure — are not insignificant, they note. Without FDA approval, insurance typically does not cover the costs, which can range as high as $1,450. Should the government eventually shoulder the expense, it could severely burden an already overburdened system.
This raises ethical questions about access and equity; at the same time, universal testing would increase the chances of overdiagnosis and overtreatment. All of which ignores the volumes of research suggesting that the amyloid plaque and tau the tests are designed to identify may have little to do with the development of the disease.
Still, Alzheimer’s blood tests are here, and it’s unreasonable to expect issues of expense and efficacy to dampen the eventual demand among a rising population of dementia-fearing Americans. As the response to Big Pharma’s mostly ineffective Alzheimer’s drugs has demonstrated, we tend to flock toward any signs of hope. This will no doubt leave clinicians struggling with this new tool while they await the strict standards required to help them decide who should be tested and when. And such guidelines will only be forthcoming after researchers can determine whether asymptomatic patients who test positive eventually develop Alzheimer’s.
Patience, in other words, is likely to be a useful companion during this new era of Alzheimer’s diagnostics and treatment. As Reddy and Yaffe note, there’s no value in promoting a new tool before we learn how to best use it.
“The real-world implementation of blood-based biomarkers will require close collaboration between manufacturers, professional organizations, patient advocacy groups, and governmental entities to ensure they are provided economically and equitably,” they write. “Only through a careful and methodical approach to their integration into the healthcare ecosystem will the full potential of these technologies be realized.”
While we all wait for that “careful and methodical” approach to bear fruit, I’m going to do my best to remember to always hang my car keys on the hook by the back door.
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