Medical Tests for Memory Problems: What Patients and Partners Need to Know

I was recently with a group of HABIT alumni and one of them heard some news about a new blood test for Alzheimer’s disease. In May the FDA approved this new blood test, which measures tau protein and amyloid protein in blood. These are the two protein abnormalities present in Alzheimer’s disease. You can find the full FDA new release here: FDA Clears First Blood Test Used in Diagnosing Alzheimer’s Disease | FDA

That question, though, led to some discussion of how many new tests and diagnostic tools have been developed along with new medications. One of those alumni wondered if there was a good list describing all of those tests, their results, and their uses. I didn’t know of one, so I took some time to interview my Behavioral Neurologist colleague, Dr. Bryan Woodruff, to try to create one.  Here is the result of that conversation!  What did we miss? Put your questions in the comments and we can hopefully evolve this post to answer more of those questions.

Remember, MCI can be due to Alzheimer’s disease, but not always. Other diseases cause MCI as well. In addition, read here for a reminder of the difference between MCI and dementia as well as some discussion of MCI as a syndrome with many underlying disease causes.

Dr. Locke: This new blood test approved by the FDA is sometimes described as a “biomarker” test. How do you explain to patients what a “biomarker test” is?

Dr. Woodruff: When we say biomarker tests, we mean tests that look for the biological “signature” of a disease. For Alzheimer’s disease, that signature is the buildup of proteins called amyloid plaques and tau tangles in the brain. Detecting these proteins helps us make a more definite diagnosis, often with very high accuracy.

Dr. Locke: How is that different from brain scans like an MRI or PET?

Dr. Woodruff: MRI scans give a detailed picture of the brain’s structure. They can show strokes, tumors, or brain shrinkage that suggests certain diseases, but these patterns can overlap across different conditions. FDG PET scans look at how active different brain regions are. Certain patterns can be consistent with Alzheimer’s or Lewy body disease, but they aren’t specific enough to be certain. That’s where biomarker tests are different: instead of showing changes in brain shape or activity, they show whether the disease-causing proteins themselves are present.

Dr. Locke: So, what are the current options for a biomarker test that you use in your practice?

Dr. Woodruff: There are three main options, including this newest blood test. The Amyloid PET scan uses a tracer injected into the blood that binds to amyloid plaques. The scan shows whether amyloid is present in large amounts in the brain’s thinking regions. The spinal fluid test (lumbar puncture) measures amyloid and tau proteins directly in the fluid around the brain and spinal cord. This test is very accurate, but it requires an invasive procedure. The blood tests are new options to measure amyloid and tau proteins from a blood sample, with accuracy that looks very similar to PET scans and spinal fluid tests.

Dr. Locke: Tell me more about this new blood test specifically. What does it mean?

Dr. Woodruff: It’s approved for adults age 55 and older who already have memory or thinking problems (such as MCI or dementia). A positive result means Alzheimer’s disease is the likely cause of the memory issues. A negative result means Alzheimer’s disease is unlikely. Occasionally, the test comes back inconclusive, in which case doctors may recommend another test like a PET scan or spinal fluid test.

It’s important to know that this test is not a screening test for people who feel fine but are just worried because of family history. As a group, Alzheimer’s biomarker tests are very accurate—often 90% or better. But like all medical tests, they aren’t perfect. There is a greater risk of false positives (test looks abnormal, but the person doesn’t actually have Alzheimer’s disease) and false negatives (test looks normal, but disease is present) in those without symptoms. That’s why results are always interpreted alongside your symptoms, medical history, and other test findings.

Dr. Locke: What if one of my patients is worried about their memory or has a family history of dementai? Should they get the blood test then?

Dr. Woodruff: If you are worried about your memory or family history first talk with your doctor. They would ask about current symptoms to determine if an evaluation is indicated. This blood test might be one of the tests your doctor recommends, but usually that would be after seeing results of other testing, such as a mental status screening test or a comprehensive neuropsychological evaluation. Your physician would probably do other routine lab work to rule out reversable causes of memory change and may also want you to get an MRI before proceeding with a biomarker testing.

Dr. Locke: Are there biomarker tests for other types of dementia other than Alzheimer's disease?

Dr. Woodruff: Yes, though they are less developed than those for Alzheimer’s. There is the DaTScan (DAT SPECT). This test has been used for years to help diagnose Parkinson’s disease or Lewy body dementia. It looks at changes in the brain’s dopamine system. However, other diseases can sometimes cause similar scan results. Alpha-synuclein tests are newer tests that can look for the abnormal protein found in Parkinson’s and Lewy body dementia. One uses a skin biopsy, and another looks in spinal fluid. These are available but not yet as well studied as Alzheimer’s biomarker tests. Tau PET scans are mostly used in research for now, but may become more common in the future.

Dr. Locke: Please describe more about the new treatments available. This is definitely a hot topic!

Dr. Woodruff: Two new medications have been approved that target amyloid plaques directly meaning they are a treatment for Alzheimer's disease. They are approved for people with mild disease--meaning at the MCI or mild dementia stage. Leqembi (lecanemab) and Kisunla (donanemab) are the two current options. These drugs are designed to help clear amyloid from the brain. They are not cures, but they may slow down memory decline in some patients.

Dr. Locke: How do biomarker tests fit in with these treatments?

Dr. Woodruff: Because these drugs specifically target amyloid, doctors need to confirm—through a biomarker test—that amyloid plaques are present before starting treatment.

Dr. Locke: Are these biomarker tests covered by insurance?

Dr. Woodruff: The new blood test is not always covered by insurance but this may change with the FDA approval. Amyloid PET scan are covered by Medicare in appropriate situations but it can be very expensive ($15,000+) if not covered. The spinal fluid test is usually covered by insurance, though exact out-of-pocket costs vary. Coverage rules are changing quickly as these tests become more common and can vary across insurance plans anyway.

Dr. Locke: Are there risks—medical or emotional—of getting one of these biomarker tests?

Dr. Woodruff: There are relatively minor medical risks for these tests. Blood test has only the minor risks of a blood draw. The Amyloid PET has small radiation exposure, but this is similar to other routine medical scans. The spinal fluid test involves a needle in the lower back; most people do well, but about 1 in 10 get a temporary headache afterwards. The emotional emotional risks can really vary by the person. The biggest issue is whether you want to know the result. A positive test can be stressful and life-changing. If someone is not ready to hear that Alzheimer’s is the cause of their memory issues, it may not be the right time for testing.

Dr. Locke: What about genetic testing for Alzheimer’s disease?

Dr. Woodruff: The APOE gene is the most common late-life Alzheimer’s risk gene. Carrying the “4” version increases risk, especially if you inherit two copies. But it does not guarantee disease—and people without it can still develop Alzheimer’s. Rare mutations in three other genes can directly cause early-onset Alzheimer’s, but these are very uncommon.

Dr. Locke: Should my patients all get genetic testing?

Dr. Woodruff: It’s most useful for patients who already have memory symptoms and are considering amyloid-clearing treatments. For people who are healthy but have family history, testing usually doesn’t change medical care right now.

Dr. Locke: How does genetic testing it fit with biomarker testing?

Dr. Woodruff: If you’re starting a new Alzheimer’s treatment, APOE testing is often recommended. People with two copies of the APOE-4 gene have a higher risk of side effects from the new drugs, so knowing genetic status can help guide safe treatment.

Whew!  This turned into a lengthier post/interview, but there is so much new information I just couldn't help myself! I appreciate Dr. Woodruff taking the time to answer all of these questions!  What did I miss?