LONDON -- An early look at the suggests that amyloid PET scans can have a substantial impact on disease management for patients with cognitive impairment of uncertain etiology, researchers reported here -- which, if confirmed with more data, could pave the way for Medicare and private insurance payment.
Among the first 3,979 patients enrolled in the trial, 67.8% of those with mild cognitive impairment (MCI) and 65.9% of those with atypical dementia had changes in medical management after being scanned, and the majority were adjustments in Alzheimer's-specific medications, investigator Gil Rabinovici, MD, of the University of California San Francisco, and colleagues reported during a "developing topics" session at the .
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Note that this observational study suggests that the use of PET scans to stratify patients with mild cognitive impairment often results in a change in management.
- This does not necessarily imply that the management changes are beneficial, however.
"The care plan changed in a high proportion of patients following amyloid PET, and most commonly Alzheimer's medications increased in those with amyloid and decreased in those without amyloid," Rabinovici said during a press briefing. "The caveat is these are partial results reflecting one-third of the sample, so we hope to have the final results maybe by next year's meeting."
The overall study will also examine whether those changes in management led to improved health outcomes. But Rabinovici said changes in management alone are critical: "I can tell you as someone who cares for patients, they want to know what's going on in their brain. They want to understand what the cause of their cognitive impairment is. The value of receiving that diagnosis, even if it's bad news, is that at least it leads to a clear plan in terms of what drugs to use, or possibly participating in clinical trials, and it offers some certainty."
The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study is a collaboration between Medicare, pharmaceutical companies, the Alzheimer's Association, and the American College of Radiology to meet third-party payer requirements for more evidence of clinical utility of amyloid PET scans. The scans are expensive -- about $3,000 -- so insurers including Medicare have been hesitant to pay without seeing a clear clinical benefit.
It will enroll 18,500 Medicare beneficiaries age 65 and up who have MCI or atypical dementia of uncertain etiology and meet criteria to have an amyloid PET scan. Its two goals are to assess the impact on patient care 3 months after the scan (with a goal of at least a 30% change in management plan), and to assess the impact on health outcomes a year later. For that first aim, researchers are focusing on a little over 11,000 patients).
Rabinovici and colleagues presented results from a prespecified interim analysis totaling 3,979 participants, who had a median age of 75, about half were female, and 90% were white. About 65% had MCI and 35% had atypical dementia. The most common suspected etiology was Alzheimer's disease (76%) followed by non-Alzheimer neurodegenerative disease (12%).
Overall, rates of amyloid PET positivity were 54.3% in the MCI group and 70.5% in the dementia group.
Rabinovici said the fact that two-thirds of participants had management changes far surpassed the 30% goal initially set in the study.
The most common change in management came in terms of Alzheimer's-specific medications. Among those with MCI who had management changes, 47.8% had a change in Alzheimer's drugs, 36% had a change in other drugs, and 23.9% had changes in counseling. Among dementia patients, 47.7% had a change in Alzheimer's drugs, 32.2% had changes in other drugs, and 15.3% had a change in counseling.
Among patients who had a positive scan, the rate of Alzheimer's diagnosis increased from 78% to 95%, and among those with negative scans, the rate of Alzheimer's diagnosis decreased from 73% to 14.5%, Rabinovici reported. "Many patients would have otherwise been diagnosed with Alzheimer's disease and have no biological evidence of amyloid plaques in their brain."
The proportion of patients with a positive scan who were using Alzheimer's drugs increased from 50% to 84%, and the proportion of those with a negative scan who were using Alzheimer's drugs fell from 39% to 31%.
Rabinovici said the trial will continue to recruit participants, and investigators hope to hit their enrollment goals ahead of schedule, by late 2017 or early 2018.
When asked how well amyloid PET scans correlate with the less expensive and more accessible cerebrospinal fluid (CSF) screen, Rabinovici said that, when done at expert centers, there has been good correlation between PET and CSF findings, and CSF may actually be more sensitive to the earliest stages of amyloid pathology.
"It's useful if you're trying to detect the earliest stages for an intervention, but it may lead to false positives if you're trying to determine if someone's cognitive impairment is due to Alzheimer's," he said.
CSF also provides information about tau -- although it doesn't give any clues about how tau and amyloid proteins are spreading in the brain, which is becoming key to staging Alzheimer's disease; and there are problems with standardization, as some groups have not been able to replicate results.
And PET may be better for tracking the effectiveness of a therapy that purports to remove amyloid from the brain, he said.
Rabinovici also noted that "Americans prefer to get scans," pointing to IDEAS survey data in which only 10% of physicians said they would have offered a CSF test. "They were more willing to refer to PET than to do CSF," he said.
In a subsequent presentation of European data on changes in management following amyloid PET scans -- which was not selected for uncertain etiology, and which was done at an academic center with good management -- Arno de Wilde, MD, of VU Medical Center in Amsterdam, and colleagues found scanning changed clinical diagnosis in 24% of patients, and also led to a change in management in the same proportion -- with the majority of this change (16%) being in medications.
De Wilde said a majority of their memory center patients "looked back favorably on undergoing amyloid PET," didn't have increased anxiety, and said their uncertainty was diminished.
Disclosures
The IDEAS study is funded by CMS, Avid Radiopharmaceuticals/Eli Lilly, GE Healthcare, Piramal Imaging, the Alzheimer's Association, and the American College of Radiology.
The authors disclosed financial relationships with Avid/Eli Lilly, Tau Consortium, Eisai, Genentech, Lundbeck, Merck, Putnam, and Roche.
Primary Source
Alzheimer's Association International Conference
Rabinovici GD, et al "Impact of amyloid PET on patient management: Early results from the IDEAS study" AAIC Meeting 2017; Abstract DT-01-01.