New blood tests can help diagnose Alzheimer’s. Are doctors ready for what’s next?

A new generation of blood tests promises to change the way doctors diagnose and treat Alzheimer’s disease.

The tests offer a fast and easy way for physicians to learn whether a patient with symptoms of cognitive decline also has the brain changes associated with Alzheimer’s. Evidence of those brain changes is required before doctors can prescribe one of two recently approved drugs that can slow down the disease.

As demand for those drugs rises, blood tests could play a crucial role in identifying patients in the early stages of Alzheimer’s who would benefit from treatment.

But the blood tests have arrived so quickly that most physicians have received little guidance on which patients to test, or how to interpret the results, a host of experts said at the Alzheimer's Association International Conference in Philadelphia.

"Right now, we don't have guidelines for the use of these tests," says Dr. Eliezer Masliah, director of the division of neuroscience at the National Institute on Aging, a part of the National Institutes of Health.

"The field is moving at a pace I never imagined 10 years ago," says Dr. Heather Whitson, a professor of medicine at Duke University who co-chaired a session at the Alzheimer's conference on developing clinical practice guidelines for the tests.

"Blood tests have developed incredibly fast for Alzheimer disease and I think [doctors] aren't used to that rate of change," says Dr. Suzanne Schindler, an associate professor of neurology at Washington University School of Medicine in St. Louis.

Related: FDA advisors strongly back new Alzheimer’s drug, despite risks and limitations

The tests indicate the presence of sticky amyloid plaques and tangled fibers called tau in the brain — the hallmarks of Alzheimer's. Until recently, finding these signs of the disease has required an uncomfortable spinal tap or a costly PET scan.

For several years, commercial labs have been offering a range of blood tests meant to detect plaques and tangles in the brain. But as recently as a few months ago, the accuracy of these tests varied widely, Schindler says, largely because they were measuring different proteins.

That's changing as more and more labs are offering blood tests that focus on an abnormal protein called ptau217.

“When you are just looking at a population of cognitively impaired individuals, these ptau217 tests perform very well,” Schindler says, with an accuracy of about 90%.

A number of ptau217 tests are now commercially available, though none has received approval from the Food and Drug Administration. As a result, insurers often won’t cover the cost, which is typically several hundred dollars.

Even so, the new tests are being ordered by more and more doctors, and not just specialists. Moreover, the public is beginning to learn about the tests and request them.

Those changes suggest the beginning of a new era in Alzheimer’s diagnosis and treatment, Schindler says — one in which primary care doctors play a critical role.

“Physicians really need to educate themselves about these tests because this is coming really soon,” she says.

A shift from symptoms to biology

The rise of blood testing reflects a larger change in the Alzheimer’s field, experts say.

"The trend now is to go toward a biological diagnosis of Alzheimer's disease," Masliah says, "a diagnosis based on biomarkers rather than just on clinical symptoms."

These markers, which can be found by PET scans or in cerebrospinal fluid, are far more accurate than cognitive tests and clinical exams for determining which patients have amyloid plaques and tau tangles in their brains.

A large study found that even dementia specialists misdiagnosed about one in four patients undergoing a cognitive evaluation. A blood test only missed about one in 10.

Related: At OHSU, researchers test a promising Alzheimer’s drug — and search for a cause

Ptau217, for example, is a biomarker that detects an abnormal version of the tau protein found in neurons affected by Alzheimer’s. Tiny amounts of this protein make their way out of brain cells and into the bloodstream.

And surprisingly, levels of this abnormal tau protein are a very accurate predictor of the accumulation of amyloid plaques, which contain a different abnormal protein.

Scientists are constantly discovering new blood biomarkers for Alzheimer’s, Masliah says. So ptau217 is likely to be joined or replaced by markers that work even better, or provide different information about what’s going on in the brain.

“All this really points to this idea that we are going to use a blood test to diagnose Alzheimer’s,” Masliah says. “And I think we are very close to that.”

Yet many primary care doctors don’t yet know how to use this new diagnostic tool, Whitson says.

So she and other experts have been compiling examples of patients who should, or should not, be considered for testing.

In the “should” category are those with clear signs of cognitive impairment, she says. For example, a patient who repeats the same question several times during an office visit, or often forgets to take medications at home, or can no longer handle their own finances.

In the “should not” category are people who have no symptoms of cognitive decline but are anxious about their brain health.

“Maybe they have a family history of Alzheimer’s disease,” she says, “so every time they forget a name they’re worried that this is it.”

Patients who have no cognitive symptoms aren’t eligible for drug treatment and may be needlessly alarmed if they were to get a positive test, Whitson says.

“A percentage of the population has amyloid in their brain and they will live out a normal lifespan and never have symptoms,” she says. “We know this.”

Related: An experimental Alzheimer’s drug outperforms one just approved by the FDA

Diagnosis is just the first step

Despite the current confusion, experts at the Alzheimer’s conference think that within a few years, primary care doctors will be offering blood tests to many of their older patients with memory problems. And they’ll know what to do when a test is, say, borderline, rather than clearly positive or negative.

But getting a diagnosis is just the first step of a long journey, says Dr. Howard Fillit, chief science officer of the Alzheimer's Drug Discovery Foundation.

When a test comes back positive, “there’s a huge effect,” Fillit says — and not just on the individual patient. “What does it mean for the family? What does it mean for the spouse?”

Primary care doctors will quickly learn how to diagnose patients with the help of blood tests, Fillif says. “The question is, will they spend the hour that’s needed to do the education and counseling?”

If they do, it’s not yet clear whether Medicare and other insurance payers will cover those services.

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