A blood test to rule out Alzheimer’s Disease?

It seems that soon primary care providers could rule out Alzheimer’s Disease with a blood test. The FDA recently approved the Elecsys ptau 181 test to do just that. The target population for the test is patients with mild cognitive impairment or early dementia, not those with normal cognition, and it requires a prescription.

The pre-FDA approval testing indicated the probability of a negative result in someone who doesn’t have Alzheimer pathology was 98%. This test is not as highly reliable as the ptau 217 test for finding those who DO have the disease.

As an aside I have a friend whose husband is sure she has it and for her a negative test might shut him up at dinner parties.

This test might even have an advantage for people who are not inclined to opt in for the currently available anti-amyloid drugs. Why? Because if someone has signs of cognitive decline and it’s NOT Alzheimer’s, that could expedite the primary care physician looking at other sources for that decline in the same way they rule out conditions every day in primary care.

Why would someone not want to go the antiamyloid treatment route if they have mild Alzheimer’s? The diagnosis is associated with so many other contributing factors other than amyloid plaque buildup and some percentage of patients with documented amyloid plaque will never develop the disease. I literally just read an secondary analysis article in JAMA Neurology (Vol 82, No 12) this morning that confirms lower levels of amyloid after treatment with donanemab correlated with slower cognitive and functional decline. No test can predict whether people with normal cognition are destined to develop Alzheimer disease.

At first glance, if someone knows they would not want to take those drugs, it probably doesn’t make a lot of sense to take the test since the target of those drugs is in fact what these tests are measuring.

The thing is, we just don’t know enough yet.

Donanemab has the best extended quality of life data at roughly 30% more time in the mild stage before progression—five to six months in the clinical trial that led to FDA approval. Some would say six months is not nothing—it’s travel to a bucket list place, being functional at a grandkids wedding, finishing a family history; while others are quick to wave it off as six months of frightening uncertainty and say no thanks. And the side effects of brain swelling and microbleeds are not insignificant, particularly for people with two copies of the APOE4 gene.

That could all change as we start to get findings from the extended trials of both lecanemab and donanemab that could provide a better look at outcomes.

So what happens if the test is not negative? Here’s where it gets interesting.

“[I]t is important to understand this test is designed to rule out the presence of amyloid plaques,” Joanne Pike, DrPH, Alzheimer’s Association president and chief executive officer, noted in a press release. “It is not a test that will give an Alzheimer’s disease diagnosis, nor is it a standalone tool for detection.”

Standard workup for Alzheimer’s includes neurocognitive testing, obtaining a sample of cerebrospinal fluid (a lumbar puncture) to measure amyloid, and a specilized PET scan, all things that are generally only available at major medical centers or specialized neurology practices. Access to those specialty clinics is woefully inadequate for rural americans.

The long term answer seems obvious. We must train primary care providers to diagnose and treat Alzheimer’s Disease. This is already a robust discussion in public policy circles, chiefly pointing out there are around 11,000 neurologists in a country of 342 million people, so referring everyone for specialty treatment seems impossible for the near future.

These tests will push medical education and health care systems to build strategic plans around fundamentals that can be layered into primary care. Things like the use of telehealth expansion in collaboration with the Alzheimer’s Disease Research Centers, in the same way regional cancer centers developed the Tumor Board platform that still serves patients well, and a federal commitment to roll out the Guiding an Improved Dementia Experience (GUIDE) model currently being piloted under Medicare.

Bring. It. On!

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