Skip to main content

Should My Patient Get an Amyloid PET Scan for the Diagnosis of Alzheimers?



In April, the Food and Drug Administration (FDA) approved florbetapir F-18 (Amyvid) PET scans to identify areas of accumulation of amyloid plaques.  Centers for Medicare and Medicaid Services (CMS) though has yet to allow reimbursement for amyloid PET scans for the evaluation of dementia outside of clinical studies, citing insufficient evidence that it improves health outcomes for Medicare beneficiaries.

The CMS decision is strongly opposed by Eli Lilly and its subsidiary Avid Radiopharmaceuticals, the makers of Amyvid. The Alzheimer's Association also was "disappointed" by the CMS decision, stating that there was “clear, scientific consensus recommendations by the Association and the Society for Nuclear Medicine and Molecular Imaging (SNMMI) regarding appropriate, limited coverage, only in specific populations."

So who is right? CMS? The Alzheimers Association? The Association and the Society for Nuclear Medicine and Molecular Imaging (SNMMI)?  Eli Lilly? What about Ezekiel Emanuel? He just wrote a wonderful piece in the NY Times this weekend recommending that we should not “waste a lot of money on a test that really doesn’t help” due to the poor test characteristics of the scan and the anxiety that it can create.  Given all these voices saying different things I'd like to throw my own take on the subject:

Eric's 5 Point Summary of the Evidence for Amyloid PET Scans

1. Evidence Base for its clinical utility: poor.
  • JAMA Internal Medicine just published an exellent review on the subject, which highlights the "extremely limited data with which to evaluate the clinical utility of amyloid PET."   

2. Ability to detect amyloid in the brain: great! 
  • There are some good studies demonstrating amyloid PET is accurate in detecting amyloid in the brain if the scan is read by well-trained interpreters. Unfortunately, there isn’t really evidence of what this training should consist of as the studies showing accuracy are using 3-5 very well trained physicians in academic centers per scan.  Also of note, detection of amyloid is very different than diagnosing Alzheimer's disease (more on that below)

3. The clinical usefulness of a positive test: unclear except in the elderly where it probably isn't so good
  • The FDA-approved label for Amyvid states that a positive scan does not confirm the diagnosis of AD or other disease. Why? Amyloid plaques can be found in about a third of cognitively normal older adults as well as in other diseases.   Furthermore, the older you are, the more likely you are to have amyloid in the brain even if you don't have any cognitive impairment, significantly decreasing the positive predictive value of a amyloid PET scan.  And with every diagnostic test, its the positive predictive value that really matters. 
  • So what does a positive test really add?  There is somewhat soft evidence from a study by Doraiswamy that in the MCI population a positive amyloid PET may increase the risk for progression to clinically diagnosed Alzheimer's disease in individuals with mild cognitive impairment. However, based on this study, 29% of those with positive scans progressed to clinically diagnosed AD compared to 10% of those with negative scans. In real life terms, what does a 19% difference really mean to a patient?  Are they really going to do something different based on a 10% versus a 29% chance of developing Alzheimer's disease?

4. The clinical usefulness of a negative scan: better given given the high sensitivity to amyloid pathology of the scan (still uncertain though)
  • A negative scan means that you likely don't have many amyloid plaques in your brain, which also means you probably don’t have Alzheimer's (at least for now). However, based on the last study I mentioned on MCI, there was still a 10% conversion to clinically diagnosed Alzheimer's disease in those with negative scans. Also, a negative scan doesn't really help in figuring out what is causing the impairment other than it’s not likely Alzheimer's.  Finally, there are no good studies to suggest that a negative test changes in subsequent clinical management or whether any changes in management would produce net health benefits to those that really matter: patients and families.

5. The usefulness in prognosticating: unknown
  • Again, based on the JAMA Internal Medicine article discussed above, there is no evidence to suggest that the test can be used to accurately predict the risk or the timing of progression of mild cognitive impairment.  

Conclusion Based on the 5 Points

Amyloid PET scans: not ready for prime time.  Good call CMS.

by: Eric Widera (@ewidera)

Comments

Tim Haskett said…
Succinct and to the point; 5 points that is. Another test to CHOOSE WISELY to avoid. Thanks, Eric, and, I agree, good call CMS.
Bruce Scott said…
Are you rising above the discussion of whether or not the Alzheimer's Association may have a conflict of interest regarding such imaging and some of their funding sources? :)
Eric Widera said…
I did steer clear of the issue, but now that you asked, here are my thoughts.

I have great respect for the Alzheimers association. I do take some issue with their statement that they were "disappointed" by the CMS decision, stating that there was “clear, scientific consensus recommendations by the Association and the Society for Nuclear Medicine and Molecular Imaging (SNMMI) regarding appropriate, limited coverage, only in specific populations."

This consensus statement was littered with conflicts of interests. 8 out of 14 individuals listed as either task force members or reviewers had relationships with a company that has developed radiotracers to detect beta-amyloid plaques (Avid/Lilly and GE).

Is it really that hard to find individuals that have not had a relationship with Lilly, Avid, or GE that the majority of task force members and reviewers had a conflict of interest with these companies?

Popular posts from this blog

Practical Advice for the End of Life: A Podcast with BJ Miller

This week we talk with BJ Miller, hospice and palliative care physician, public speaker, and now author with Shoshana Berger of the book "A Beginner's Guide to the End."

As we note on the podcast, BJ is about as close as we get to a celebrity in Hospice and Palliative Care.  His TED Talk "What Really Matters at the End of Life" has been viewed more than 9 million times.  As we discuss on the Podcast, this has changed BJ's life, and he spends most of his working time engaged in public speaking, being the public "face" of the hospice and palliative care movement.

The book he and Berger wrote is filled to the brim with practical advice.  I mean, nuts and bolts practical advice.  Things like:
How to clean out not only your emotional house but your physical house (turns out there are services for that!)Posting about your illness on social media (should you post to Facebook)What is the difference between a funeral home and mortuaryCan I afford to die?  …

Caring, and the Family Caregivers We Don’t See

Over lunch at a restaurant in Manhattan, my father and I talked about long-term care insurance and the emergence of senior centers and nursing homes across the U.S. that offer a variety of ethnic cuisines and cultural events, catering not only to a growing population of adults over 65, but also, to an increasingly diverse population of adults who call the U.S. their home. This conversation was different from many similar ones before it – we weren’t talking about my research; we were talking about our own lives.
My parents immigrated to the U.S. in the late ‘70s and early ‘80s, following their parents’ advice on professional opportunities that seemed unimaginable in India at the time. Although they considered moving back soon after to care for their aging parents and to raise children, they ultimately decided to stay in the U.S. As I chronicled earlier, my paternal grandparents lived with us until I completed middle school, at which point they returned to India and lived with my mater…

Top 25 Studies in Hospice and Palliative Care (#HPMtop25)

by: Kara Bishoff (@kara_bischoff )

Back in 2015 we wrote a post asking for input on what articles should belong on a list of the top 25 articles in hospice and palliative care.   We decided to focus on hospice palliative care studies and trials - as opposed to review articles, consensus statements and opinion pieces.

Here’s what we came up with. It was hard to pick just 25! We highly prioritized clinical utility and tried to achieve diversity & balance. Many others are worthy of inclusion. Take a look and let us know if you have suggested changes for next year.

Module 1: Symptom Management
Randomized, Double-Blind, Placebo-Controlled Trial of Oral Docusate in the Management of Constipation in Hospice Patients. Tarumi Y et al. JPSM, 2013.Once-Daily Opioids for Chronic Dyspnea: A Dose Increment and Pharmacovigilance Study. Currow DC et al. JPSM, 2011.Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomise…