Brain amyloid imaging has become an essential tool for Alzheimer’s research, but the technology has not yet proved its value in clinical practice. Several studies are underway to investigate this. Chief among these is the massive Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) study in the United States, which examines how having an amyloid PET scan changes treatment plans and health outcomes in 18,500 Medicare beneficiaries. At the Alzheimer’s Association International Conference held July 16-20 in London, principal investigator Gil Rabinovici of the University of California in San Francisco reported interim results from the first 4,000 people scanned. The bottom line: The scans had a much greater impact than expected. After seeing scan data, physicians changed medications or recommendations for patients in two-thirds of cases, many more than previous smaller studies had reported. Secondly, and perhaps as importantly, diagnoses shifted dramatically in accordance with the scans, particularly for people without amyloid plaques who had been wrongly diagnosed with AD. The researchers are still collecting data to find out if these treatment changes made a difference in how well patients fared one year later.
Clinicians hailed the findings. “These are very encouraging preliminary results … showing that amyloid imaging has a major impact on clinical diagnosis and treatment,” Stephen Salloway of Butler Hospital at Brown University, Providence, Rhode Island, wrote to Alzforum. “The foundation of medical care rests on an accurate diagnosis,” he added, with regard to the study’s second finding (see full comment below). Kejal Kantarci of the Mayo Clinic in Rochester, Minnesota, who chaired the AAIC session, agreed. “The findings will likely have a significant impact on clinical practice, and perhaps set the stage for similar studies involving other upcoming AD biomarkers,” she wrote.
Across the pond in Europe, other ongoing studies are also strengthening the case that amyloid scanning provides clinical benefits. In the same AAIC session, Arno de Wilde of VU University Medical Center, Amsterdam, reported on Alzheimer’s Biomarkers in Daily Practice (ABIDE). This study of about 500 people took a different approach from IDEAS, enrolling a distinct population that included people with subjective cognitive complaints as well as people with clinically unambiguous AD diagnoses. In this group, amyloid scans changed physicians’ diagnoses or treatment plans about one-fourth of the time. Meanwhile, the European AMYPAD study, which will analyze about 6,000 brain scans, is still enrolling.
The IDEAS study stands out for its size, as well as its potential impact on whether insurers will cover amyloid PET. The Centers for Medicare & Medicaid Services (CMS) pays for the IDEAS scans as part of its “coverage with evidence development” process to find out if the technology helps patients. Positive findings may lead CMS to cover the scans for its beneficiaries, after which other insurers are likely to follow suit (see Apr 2015 news). The study, which was organized by the Alzheimer’s Association, now includes 674 clinical practices and 1,124 dementia experts across the United States, Rabinovici said in London. These experts enroll Medicare beneficiaries who meet appropriate-use criteria defined previously. In a nutshell, the criteria specify that patients must have either mild cognitive impairment or dementia with an uncertain cause before undergoing scanning (Jan 2013 conference news). IDEAS started enrolling in February 2016 and is on track to finish before the end of this year, with almost 12,000 people already scanned, Rabinovici noted.
For the interim analysis, the researchers included data from the first 3,979 participants. Two-thirds of them had MCI and one-third had dementia, and their average age was 75. At baseline, about three-fourths of the cohort had been diagnosed with prodromal or full-blown AD. Importantly, they were almost equally likely to have this diagnosis whether or not they turned out to actually have amyloid plaques, Rabinovici found. In other words, in a community setting, diagnosing challenging cases was only 50 percent accurate. About 40 percent of people labeled as having AD did not have amyloid plaques, while more than half of those with other diagnoses did have them. Unsurprisingly, clinicians changed many diagnoses after seeing these data, with the percentage of AD cases rising from 78 to 95 in the amyloid-positive group, and falling from 73 to 15 in the amyloid-negative group. Thus, scans seemed to have the largest effect in ruling out Alzheimer’s disease in uncertain cases.
The IDEAS study probably saw such a large effect on diagnoses because the appropriate-use criteria singled out uncertain cases, selecting for those who are most likely to benefit from amyloid scanning, Rabinovici noted. This contrasts with early trials that chose participants based on criteria for probable AD, where one-fourth to one-third turned out to be amyloid-negative (Mar 2012 conference news; Jan 2014 news; Apr 2013 conference news).
Treatment plans in IDEAS changed in synch with diagnoses. Dementia specialists wrote up an initial care plan before seeing the scan data, then revised their plan based on the results and shared their recommendations with patients. The specialists started or stopped acetylcholinesterase inhibitors or memantine for about half the cohort as a result of the scan.
Clinicians were likelier to write new prescriptions than to discontinue drugs, with about one-third of amyloid-negative cases remaining on the medications. This last point engendered discussion at AAIC, with researchers debating whether this represents inappropriate medication use. Kantarci noted that acetylcholinesterase inhibitors can be helpful for some other conditions, such as dementia with Lewy bodies, and so may still benefit some amyloid-negative patients.
Meanwhile, use of non-AD drugs, such as antidepressants, antipsychotics, and other neurologic drugs, changed in about one-third of the cohort. In one-fifth of cases, the specialists changed their recommendations for counseling about safety and long-term care. Referrals to clinical trials dropped from 20 to 12 percent, mostly due to clinicians pulling referrals for amyloid-negative people. Recommendations for follow-up MRI and FDG-PET scans changed in about 10 percent of cases. Overall, care plans shifted in some way for 67.6 percent of participants.
This number is far higher than in several previous small studies, where scans typically led to new treatment recommendations for one-fourth to one-third of patients (Aug 2015 conference news; Nov 2016 news). Rabinovici noted that many of those studies occurred in academic settings. He suggested that the current findings might more accurately represent what would happen in general medical practice.
Data from the ABIDE study complements the IDEAS findings. This three-year project analyzes how amyloid PET, MRI, and CSF measurements affect patient care (de Wilde et al., 2017). The researchers invited all patients seen at their memory clinic during 2015 and 2016 to participate, and about half agreed. The final cohort consisted of 507 people, almost 50 percent of whom had dementia, with the remainder having MCI or subjective cognitive decline. Thus, the population was much broader than that seen in IDEAS, including cases where the initial diagnosis was clear-cut and cases with no clinical diagnosis. Participants had a standard neuropsychological workup and MRI scans, but did not have lumbar punctures.
Amyloid PET scanning showed that around half the cohort had plaques. After scanning, doctors changed the diagnoses of one-quarter of the patients; they altered treatment recommendations for the same percentage, mostly the amyloid-negative patients, de Wilde said. Treatment changes included referrals for further testing or clinical trials as well as starting or stopping medications (de Wilde et al., 2016).
Wiesje van der Flier of VU University, who leads ABIDE, noted that even among people with subjective cognitive decline, amyloid imaging resulted in new treatment recommendations 10 percent of the time. “This is a very important group of patients; they constitute 25 percent of the memory clinic population, and ask for an explanation of their [cognitive] complaints,” van der Flier wrote to Alzforum. Current appropriate-use criteria in the United States exclude this group, but van der Flier believes they can benefit from scanning. She suggested that the field develop guidelines for how best to disclose scan results to this population.
Clinicians still have little information on how amyloid scanning affects a patient’s state of mind. The ABIDE study asked some participants to fill out questionnaires before and after amyloid scanning, and found that they reported more certainty about their diagnosis afterward, but no change in their anxiety regardless of the results. Studies show that patients want more information about what they can expect from diagnostic tests, and what the results mean for their own situation, van der Flier said (Kunneman et al., 2016; van der Flier et al., 2017). Rabinovici agrees that the issue of how best to disclose scan results needs more study, while noting that most patients find value in seeing the data. “People want to know, even if it’s bad news,” Rabinovici said at a AAIC press conference.—Madolyn Bowman Rogers
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- de Wilde A, van Maurik IS, Kunneman M, Bouwman F, Zwan M, Willemse EA, Biessels GJ, Minkman M, Pel R, Schoonenboom NS, Smets EM, Wattjes MP, Barkhof F, Stephens A, van Lier EJ, Batrla-Utermann R, Scheltens P, Teunissen CE, van Berckel BN, van der Flier WM. Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design. Alzheimers Dement (Amst). 2017;6:143-151. Epub 2017 Jan 23 PubMed.
- de Wilde A, van der Flier WM, Bouwman FH, Ossenkoppele R, Pelkmans W, Groot C, Zwan MD, Yaqub MM, Newman V, Lammertsma AA, van Berckel BN, Scheltens P. The Diagnostic Value of Amyloid Pet in an Unselected Cohort of Memory Clinic Patients. Alzheimer's & Dementia, July 2016, Volume 12, Issue 7, Supplement
- Kunneman M, van der Flier WM, Bouwman FH, Gillissen F, Schoonenboom NS, Zwan MD, Pel-Littel R, Smets EM. Deciding About Diagnostic Testing for Alzheimer’s Disease: Patients’ Views and Experiences. Alzheimer's & Dementia, July 2016, Volume 12, Issue 7, Supplement, Page P1122
- van der Flier WM, Kunneman M, Bouwman FH, Petersen RC, Smets EM. Diagnostic dilemmas in Alzheimer's disease: Room for shared decision making. September 2017, Volume 3, Issue 3