Few illnesses instill as much fear as Alzheimer's, a fatal neurodegenerative disease that destroys memory and identity. The dread is compounded by the uncertainty that often surrounds the diagnosis of the most common form of dementia.
Brain autopsies remain the only way to know for sure whether someone had the disease, which the Centers for Disease Control and Prevention estimates affects 6.5 million people in the United States. Over the past several years, sophisticated tests such as spinal taps and specialized PET scans have become available - but they are invasive and costly and not routinely used.
As a result, Alzheimer's is frequently misdiagnosed, especially in the early stages. Other illnesses, including depression, can have similar symptoms and require other treatments.
But simple blood tests designed to help doctors diagnose Alzheimer's now are on the market. More are on the way. The tests are seen as an important scientific advance, but have ignited debate about how and when they should be used.
Some experts say much more research is needed before the new tests can be widely deployed, especially in primary-care settings. Others say there already is sufficient information on the accuracy of some tests. All agree that no single test is perfect and physicians still should perform a complete clinical assessment.
Widespread use of the tests may be some time off in the future - after insurance coverage improves and even more accurate next-generation tests become available. For now, none is covered by Medicare, and private insurance coverage is patchy.
- - -
How do Alzheimer's blood tests work?
In the past few years, scientific and technological advances have made it possible to detect in the blood tiny fragments of brain proteins implicated in Alzheimer's.
That has prompted experts in academia and industry to develop blood tests for the disease. Some of the tests detect a sticky protein called amyloid beta, while others look for another protein called tau. Some search for both or other markers of disease. The abnormal accretions of amyloid plaques and tau tangles are the defining characteristics of Alzheimer's.
So far, the tests have been used mostly in clinical trials, but a few are being sold on the commercial market. They are designed to complement doctors' assessments based on symptoms and other tests, not replace them.
If you have concerns about memory or reasoning issues, you should talk to your family and doctor. Just because the tests are available does not mean people should try to get them, experts say.
- - -
Which tests are available? How much do they cost?
At least three tests - by C2N Diagnostics, Quest Diagnostics and Quanterix - are available in most states outside clinical trials.
Quest, which charges $500, said some health plans are paying for its test. C2N charges $1,250 and offers financial assistance for eligible patients. Quanterix declined to provide a price but said its test is much cheaper than amyloid PET scans, which can cost $5,000 or more. All the companies are working to secure broader insurance coverage.
Eli Lilly and Roche also have developed tests but for now are using them only in trials.
- - -
Who should get the tests?
There is a wide range of opinions on this.
Some experts say it is too early to use the tests in regular clinical care. Others say they can be used in memory centers with confirmatory tests such as PET scans or spinal taps. Some say the tests are a useful tool that can be used broadly once they are covered by insurance.
Still, many scientists agree on an important point: That the tests, which must be ordered by doctors, should be reserved for people with cognitive problems - persistent memory or logic issues, not just the occasional forgetfulness we all experience because of normal aging or stress.
Many researchers say it is too early to use the tests for people who do not have symptoms, because there isn't adequate research involving that group and the issue is rife with scientific uncertainty and ethical questions.
"The test results are intended to be used in adults presenting with cognitive impairment who are being evaluated for [Alzheimer's disease] and must be interpreted in conjunction with other diagnostic tools," Quanterix said in a statement in July when it launched its test.
C2N uses a similar description, and company officials stress that their test is not designed for the "worried well" group of people.
Quest says its test is for people with or without symptoms. Quest relies on physicians "to use their own discretion when ordering tests," said spokeswoman Kimberly Gorode, adding that the test's "clinical utility will increase once there is an FDA-approved treatment for Alzheimer's disease."
- - -
Why would I want to know if I have Alzheimer's?
Some patients with cognitive issues take a fatalistic approach toward Alzheimer's, saying an exact diagnosis is not necessary because little can be done. Currently available treatments target symptoms and often are not effective. They do not change the course of the disease.
Alzheimer's treatments may be improving. Recently reported results showed that an experimental drug called lecanemab, by Japanese drugmaker Eisai and its U.S. partner, Biogen, worked to modestly slow Alzheimer's disease. It was the first therapy to do so in a well-run trial. The Food and Drug Administration could decide whether to approve the drug as soon as January.
Recently, in a sign of the roller-coaster nature of Alzheimer's, a drug by Roche failed in clinical trials. A medication by Eli Lilly is in late-stage testing.
If a new treatment is approved by the FDA and gains Medicare coverage, blood tests could play a key role in determining who might benefit. Doctors will want to make sure patients have amyloid in their brains before prescribing the medications.
Down the road, after more research is conducted, the blood tests might be used to alert people, even those without symptoms, that they have elevated amyloid and tau in their brains, putting them at risk for Alzheimer's. Patients could start a preventive therapy early, if one exists. Or they could pursue healthier lifestyles.
"Knowing your risk can be a hugely positive motivator," said Leslie M. Shaw, a pathologist and Alzheimer's researcher at the University of Pennsylvania. "Make the changes we now know are important. Instead of being a classic couch potato, get off your duff and get going."
Even if new treatments for Alzheimer's are not cleared, many experts say, it is important for patients to know their diagnoses so they can plan for the future. Trying to hide such a diagnosis is an echo of the 1960s, when people were not told they had cancer.
"If people are having cognitive symptoms, they deserve to know their diagnosis," said Howard Fillit, co-founder and chief science officer at the Alzheimer's Drug Discovery Foundation, a nonprofit group that helps fund research into the disease. "If they test positive, they will get certainty. If they test negative, maybe they have depression or a different type of dementia that might be treated differently."
- - -
Do experts back use of the blood tests?
Many experts, even those enthusiastic about the tests, say that while they can be used carefully by specialists in memory centers, there should be more research before they are used in primary-care settings. Some specialists say they want more data on how the tests work for patients of different races, ethnic groups and genders.
"You want to know how the specific tests perform in different patients so you can really interpret them," said Matthew Schrag, a neurologist at the Vanderbilt University School of Medicine.
But other experts are eager to use the blood tests, saying they will help provide clarity to patients.
Demetrius M. Maraganore, chairman of the neurology department at Tulane University School of Medicine, who took part in a study sponsored by C2N, said he would start using that test immediately if it was covered by Medicare and insurance.
"The point is that patients seek an end to their diagnostic journey," Maraganore said. "This will help them to flip the page and start focusing on acceptance and getting the support they need."
- - -
Do the tests have FDA approval?
Not at this point. Under the FDA's current policy, agency approval is not required for laboratory-developed tests - which are developed and processed by a single laboratory. The current tests are those types of tests. They are regulated under the Clinical Laboratory Improvement Amendments program under the Centers for Medicare and Medicaid Services.
Still, some of the manufacturers are seeking the FDA's imprimatur, saying agency approval would assure health-care providers and insurers about the value of the tests.