Beta-amyloid PET/CT scan: a new tool to diagnose Alzheimer disease

beta-amyloid plaque

I gave a talk (at Taiwanese Bible Study) last night about Alzheimer disease, focusing on the recently available tool (beta-amyloid PET/CT scan) to detect the beta-amyloid, which is the hallmark of Alzheimer disease.  If autopsy done on those who died with a clinical diagnosis of Alzheimer disease, some of them failed to show the presence of beta-amyloid plaques.  The exact incidence is unknown, but the conservative estimate is greater than 20 percent. 

Alzheimer disease is just one of the many conditions that can cause dementia, the others include frontotemporal dementia, dementia with Lewy bodies, Parkinson disease with dementia and vascular dementia.  Many Alzheimer’s disease research centers (ADRC), such as the one associated with University of Pittsburgh is conducting such study, examining the brain postmortem.  Years from now they may be able to shed further light as to how often these conditions were mistaken as Alzheimer disease during their life time.

The beta-amyloid PET/CT scan enables us to detect the beta-amyloid without doing a biopsy or autopsy.  It is done by injecting a radiotracer (Florbetapir or 18F-Pittsburgh compound B) with affinity to beta-amyloid, thus attaching to it, the emitting positron will be picked up by PET scan and the images constructed by CT scan.

A negative beta-amyloid PET/CT scan practically rules out Alzheimer disease.  The interpretation of a positive scan is more problematic; it simply indicates the presence of beta-amyloid, but not diagnostic of Alzheimer disease, as many with positive scan have no cognitive impairment at all.  It is assumed that if one with positive scan and lives long enough one will become the victim of AD.

Florbetapir F 18 (AMYViD) was approved by FDA (4/2012).  It is developed by Avid Radiopharmaceuticals of Eli Lilly.  18F-labeled Pittsburgh compound B (PIB or PiB) was approved by FDA (10/2013).  Pittsburgh compound was developed by University of Pittsburgh, the test was first conducted in 2002, published in 2004.  The one approved by FDA was the second generation, compound B, thus Pittsburgh compound B (PiB).

red = amyloid

What do we do with this expensive ($3,000) tool? The use of which will evolve as time goes by.  For the time being in the clinical practice, it should be limited to those rare occasions that finding out the presence of absence of beta-amyloid in a well-documented demented patient may alter the treatment plan or those participated in a clinical research trial.

The beta-amyloid PET/CT scan shouldn’t be done in the following conditions:

1. Classical Alzheimer dementia with typical age of onset
2. To determine the severity of dementia
3. Solely based on positive family history or presence of ApoE4 gene (3% of population have two copies of ApoE4 gene and 25% have one copy)
4. Asymptomatic individuals (a positive scan will offer one no benefit other than a worry for uncertain future)
5. Non-medical usage (legal, insurance coverage or employment screening)

This tool may affect how the clinical therapeutic trial should be conducted.  A positive scan may be a prerequisite before entering the trial in the future.  Of course, that may increase the cost of a clinical trial.  As we know the response to the currently available Alzheimer disease (AD) drugs are variable, as many of them in the trial might not have AD at all.

As yet the test is not paid by Medicare or other insurance; Medicare recently announced that it may pay for those participating in a clinical trial.  The final decision will be made later this year.

If the day will ever come (Obama has declared war on Alzheimer disease in 2012 that we’ll be able to prevent and treat AD by 2025; let’s hope he is not overly optimistic. But we have to take it what it is worth for a politician’s promise.) that the build-up of the beta-amyloid plaque can be slowed down or the progression of dementia thwarted, then this scan will be in high demand.