Almost anyone can take this quick test for Alzheimer’s without even going to the doctor. Some neurologists are saying it’s a terrible idea.
If you could get a $400 blood test that tells you within 10 days whether you’re likely to develop Alzheimer’s disease years or decades down the line, would you take it? Several biotech companies are vying to be the first to develop an Alzheimer’s blood test that doctors will use in general clinical practice to screen for the disease.
The PrecivityAD™ Alzheimer’s blood test by biotech firm C2N Diagnostics is already in use in Alzheimer’s clinical trials to screen participants for eligibility and monitor amyloid levels over the course of treatment, but these tests aren’t available to the general public — at least, not yet. Neurologists believe doctor-administered blood-based tests like these will become a normal part of clinical practice within the next few years — and that they could fill a gap in accessible, affordable Alzheimer’s diagnostics.
Meanwhile, Quest Diagnostics just released the Quest AD-Detect™ Alzheimer’s blood test that anyone 18 or older with self-described memory problems or a family history of dementia can take. Quest’s test is available at any of 2,200 lab locations across the U.S. Customers get the results on an app — no doctor involved.
How does Quest AD-Detect work? People can pay for the test online, get an appointment at a nearby Quest Diagnostics clinic, where a phlebotomist will draw their blood. The sample is then sent off for processing, the data is uploaded by the company. In as few as three days, a digital read-out of their results will be available in Quest’s mobile app.
Sounds convenient. But here’s the problem: Quest Diagnostics confirms that, in fact, the test shouldn’t be used to definitively detect Alzheimer’s disease, stating on their press release and website that the blood tests are “not a diagnostic test”— despite that the test is called “AD-Detect.”
What does that mean for the Alzheimer’s diagnostic landscape? Almost anyone — even a teenager — with $400 to spend can learn, with the click of a checkbox to confirm their eligibility, a quick blood draw and a few days’ wait time, whether they are theoretically likely to develop Alzheimer’s, an incurable neurodegenerative disease, decades into their future.
Neurologists are not excited about this development.
“This is going to be an absolute catastrophe,” said Dr. David Weisman, a neurologist at Abington Neurological Associates. And there are several very big reasons for this pessimism.
1. Quest AD-Detect’s test results have a high rate of false positives.
First of all, Weisman and other experts noted, this tool isn’t able to definitively detect Alzheimer’s disease. Weisman said that without any published evidence supporting the validity of these tests, it’s unclear whether they can be of any use as a screening tool let alone a diagnostic tool.
A spokesperson for Quest Diagnostics said that the test has a sensitivity of 89 percent, and specificity of 71 percent. Sensitivity measures whether the test can actually detect the biomarkers when they’re there, and specificity measures false positives.
“If there is no physician contact
[before ordering the test in the first place],
then there is no physician, no doctor
responsibility, no accountability, no expertise.”
What does this mean? Let’s consider that one in 10 people over the age of 65 develops Alzheimer’s. If we assume that 10,000 people take the test, all over the age of 65, and 1,000 actually have Alzheimer’s — 2,610 will receive a false positive result. And this is the best case scenario, if we assume nobody under the age of 65 who is far less likely to have Alzheimer’s takes the test.
That means there’s a 29 percent chance someone will get a false positive — a big problem when trying to detect something that is rare in the population. Even in a best case scenario, there will be more false positives than actual people with the disease that are tested.
Weisman added that this data means the test “totally sucks” for screening purposes.
2. Test results are easy to misinterpret — and that could be dangerous to patients.
Not only are the results unreliable — they may be easy to misunderstand. Even if the results are reliable and correct, the test can only tell a person if they are likely to get Alzheimer’s in the future. Legally speaking, this isn’t a diagnostic test and the company has emphasized it was developed for screening purposes.
“That’s not the way that people are going to read this,” Weisman said. “They will misunderstand [and think] that they have the disease.” (Quest Diagnostics did not respond to specific questions about the reasoning behind the name.)
That assumption, Weisman added, may pose a danger to patients. Weisman is thinking back on the initial release of at-home genetics tests. These at-home genetics tests, when they were first released, offered people the chance to look at their ancestry while also calculating their risks of developing different diseases like Alzheimer’s based on genetics.
According to Weisman, that ultimately led to serious problems for people who suddenly possessed the knowledge that they might develop a fatal disease but who weren’t prepared to process, much less, address, that potential reality. He added that, with at-home genetics tests, people sometimes tested themselves in the midst of depression, making the risk of self-harm worse.
Some patients got their test results and found out they were a carrier of the APOE4 gene, an Alzheimer’s risk factor which can make the risk of developing Alzheimer’s between one quarter more likely and 12 times more likely depending on how many copies of the gene a person carries. According to Weisman, some patients misinterpreted their test results and believed that because they carried APOE4 gene, they were certain to develop Alzheimer’s disease in their lifetime.
Accordingly, in 2013, 23andMe’s sales were shut down by the FDA and sued in California after failing to show any scientific evidence that the genetic test accurately reported the risk of developing these diseases. In 2017, the company had to get a separate approval from the FDA for marketing a test for calculating the genetic risk of Alzheimer’s. Weisman speculated the blowback from Quest’s new test could be “even worse than 23&Me, if that’s even possible.”
It’s this kind of nightmare scenario Weisman foresees for Quest AD-Detect. “It could kill people because then they will misunderstand [and think] that they have the disease, and I am very much concerned about suicide.” Statistics do show that after an Alzheimer’s diagnosis, people are more likely to engage in self-harming and suicidal behaviors.
He’s not alone. Dr. Alberto Espay, a neurologist and professor at the University of Cincinnati’s College of Medicine, is similarly skeptical about whether these tests are actually useful since the information that they provide isn’t actionable. “The direct-to-consumer tests are likely to inflict unjustified anxiety on the public,” Espay told Being Patient. “These tests have a poor predictive power for cognitive impairment.”
3. The science behind the test is untested in much of its target audience.
Blood tests for Alzheimer’s are being developed to measure the levels of these protein biomarkers in the blood as a way of understanding how much is clumping up in their brain.
Quest’s direct-to-consumer blood test measures the levels of two types of beta-amyloid proteins in the blood — Aβ42 and Aβ40 — which Quest says can help them calculate a person’s risk of developing Alzheimer’s.
According to the company’s guidelines, the levels of these proteins in the blood are used to determine whether someone is at a high, intermediate, or low risk of developing the disease. at some point later in life.
The catch: These protein biomarkers in the blood haven’t been thoroughly studied in younger people. If a person displays high levels of these biomarkers at a young age, scientists still don’t know for certain whether that makes them more likely to develop Alzheimer’s… nor are there yet clear steps someone of that age should take to seek out care and treatment.
Further, in many places, ever since the approval of disease-modifying Alzheimer’s treatment Leqembi, there is spiking demand for cognitive exams, and possibly scant availability for neurological appointments on top of that, according to Dr. Jason Karlawish at the University of Pennsylvania.
Healthcare systems are already struggling to keep up with new demands for early Alzheimer’s diagnosis and care, and with the arrival of tests like Quest’s, every perceived positive means a greater burden on care infrastructure that is unequipped to keep up.
As to whether patients and doctors can even take these test results seriously, Quest has not published any data validating their test in peer-reviewed publications. “I would really need to see the data to really understand how they’re validating this,” Weisman said. In the meantime, he said, the results mean “nothing but stress.”
Espay echoed this sentiment: “These tests are not actionable even with information about a patient (much less without [it]) and can only serve to raise unnecessary anxiety in those who are asymptomatic.”
4. There are no safety nets in place to ensure the test isn’t used by people who shouldn’t be using it, and doctors aren’t heavily involved in the administering nor the communication of test results
In addition to people showing signs of mild cognitive impairment or dementia, people who are asymptomatic but have a family history of dementia or have previously suffered a brain injury or trauma are also eligible.
Neurologists told Being Patient they feel this is casting the net too wide. As Weisman put it: “That is bonkers.”
The concept of broadly available direct-to-consumer tests like Quest’s, if applied correctly, isn’t all bad: In the hands of a trusted physician, such a test could prove to be a useful screening tool.
But making the diagnostic a “direct-to-consumer” tool, these and other experts agree, is where this idea goes off the rails.
The test is too widely available as it is, neurologists and healthcare providers agree — and as for the barriers to entry that are in place, they are not going to be easy to enforce. To ensure the test is only taken by eligible parties, Quest asks buyers to click a check-box prior to checkout — as one would see in standard “terms of service” agreements — saying they meet the criteria.
Weisman calls this low barrier to entry “clueless wrapped in stupid.” Quest, on the other hand, does not see this as risky.
The company told Being Patient that an independent physician will get in touch with people whose test tells them they’re at a high risk.
“Individuals can discuss results with a licensed physician to help them understand what their results may mean and to determine an action plan for continued care, including whether a follow-up with their physician or a specialist may be appropriate,” a Quest spokesperson told Being Patient. “A physician from the independent physician network that orders the test will proactively contact any individual who receives a result suggestive of risk for Alzheimer’s.”
Learning this, Weisman remained unconvinced: “If there is no physician contact [before ordering the test in the first place], then there is no physician, no doctor responsibility, no accountability, no expertise” of the individual patient’s condition, including lifestyle and health risk factors, family history, and true risk at large, Weisman said. Again, for a test with a high likelihood of false positives and no proof yet that the results are accurate, along with all the stress and anxiety a patient could experience when they receive their outcome, it all seems premature to Weisman, even if there is a doctor around to discuss results with a patient. “I don’t think many doctors are going to sign up to be liability sponges,” he said.