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 newsJan 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


  1. These are very encouraging preliminary results from the IDEAS trial showing that amyloid imaging has a major impact on clinical diagnosis and treatment. These data provide further evidence that many patients with memory loss probably do not have Alzheimer's disease. The foundation of medical care rests on an accurate diagnosis. Amyloid PET is a powerful tool for making the correct diagnosis leading to better education and planning and treatment and referral for appropriate clinical trials to slow the progression of AD. It is important to extend the IDEAS trial so we can more carefully study the impact of this diagnostic advance in clinical practice.

  2. I think excellent work is emerging from the IDEAS study. The findings will likely have a significant impact on clinical practice for amyloid imaging and perhaps set the stage for similar studies involving other upcoming AD biomarkers. It will be important to see how the treatment decisions made through amyloid PET will impact clinical outcomes.

    For example, patients with dementia with Lewy bodies (DLB), in whom clinical diagnosis and differentiation from AD may be difficult, may benefit from acetylcholinesterase inhibitors (ChEIs). Patients with DLB who fulfill the clinical criteria may have a negative amyloid PET scan but still they would be ideal candidates for ChEI therapy. These factors will be critical for making treatment decisions based on amyloid PET scans.

  3. The AAIC presentation showed convincing evidence, even in the interim analysis, that amyloid PET is valuable in clinical care. The data show that amyloid PET alters diagnosis, diagnostic confidence, and patient management. The observed frequency of changes were significantly greater than had been hypothesized in formulating sample size during the design of the study. The findings are consistent with our single site experience reported at AAIC; the availability of clinical amyloid PET is transformative for cognitive care practice, but often also for patients and families.

    The IDEAS study does not sufficiently capture all the ways amyloid PET scanning affects patient and family experiences and outcomes. Our center’s studies—IMPACT and IMPACT2, also reported at the AAIC—are trying to document some of these patient-reported outcomes.

    IDEAS is not a typical study—it is a coverage with evidence development trial in which Medicare ultimately decides what result is sufficient. In most clinical trials, the results of the interim analysis would lead to early termination and implementation of the positive findings. The fact that the sponsor has judged the trial should continue raises the question about what criterion Medicare (or the general medical community) will use to judge sufficient benefit.

    There are limitations in the design of any clinical trial. There needs to be a broader discussion of these limitations and how we should deal with them. For example, it is likely that the enrolled dementia experts are more likely to benefit rather than misuse the technology. Should access be limited as defined by appropriate-use criteria? What would happen if primary care providers also had access to amyloid PET? Would this improve or worsen care? What is the effect of not having access to this technology in large regions of the country? If it becomes reimbursed and accepted in practice, wouldn’t access improve?

    The magnitude of the effect on medication decisions was a pleasant surprise. There were no details about the nature of the medication changes provided, but to have such an effect on management, it appeared that the dementia experts altered drug treatment based upon diagnosis—in my view an informed choice that reflects positively on the participating experts. In general community practice very often treatment is based upon the presence of a syndrome—dementia, delirium, mild cognitive impairment—rather than the cause of the syndrome. It is reassuring that the dementia experts aren’t simply using drugs approved for Alzheimer’s disease off-label.

    I was surprised that the study has been so successful in identifying patients over a relatively short time who meet published appropriate-use criteria for amyloid PET (I was a co-author of those guidelines). We haven’t had any idea about how often expert providers had a significant uncertainty about diagnosis (cause). The findings indicate that there are a very large number of patients in whom the cause of cognitive impairment is still uncertain, despite an otherwise complete evaluation. It is likely that only a fraction of those who might benefit have participated in the IDEAS study because many such individuals never see a qualified dementia expert or have an amyloid PET scan. Further research is needed to understand the frequency and characteristics of atypical or complex patients who qualify under appropriate-use criteria for amyloid PET.

    I am surprised at how successful the study has been in finding physicians qualified and enrolling in the IDEAS study. This was much easier to accomplish than I predicted. I am particularly surprised since I know from informal conversations that several or perhaps many NIH-funded AD centers are not participating. It is the NIH-funded AD centers that generally would have been expected to have a large proportion of dementia experts. There was no previous effort to identify dementia experts in the United States (as defined in the appropriate-use criteria), and this is an important outcome of the study. I hope we will learn more about them in due time (type of practice, age, specialty, location, etc.). Patients and families have a great deal of difficulty identifying dementia experts and dementia care teams and this could be the start of an important resource for them. It is likely that many other dementia experts are not part of the IDEAS study because of logistics (no nearby participating PET center or administrative issues).

    The study has been remarkably successful in identifying willing PET sites that are now trained in reading amyloid PET. This is surprising because in the past it was argued that facilities prepared to perform PET for patients with dementia were not widely available, making using advanced imaging technology on a clinical basis impossible. This can no longer be claimed.

    I have called amyloid PET a disruptive technology. It will no longer be acceptable to make a casual or intuitive clinical diagnosis of Alzheimer’s disease dementia when a diagnostic test can be definitive. This will be threatening to current practice patterns and standard of care. Despite the enthusiasm among dementia specialists, like any disruptive innovation, tremendous opposition can be expected. Rationalizations for the current standard of care will be voiced (“there is no effective treatment”; “it is too expensive”; “patients can’t tolerate it or become upset”; etc.). Changes in reimbursement will be important, but will not alter this opposition. If reimbursement no longer supports these now outdated practices, medical practice will be revolutionized.

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News Citations

  1. $100M IDEAS: CMS Blesses Study to Evaluate Amyloid Scans in Clinical Practice
  2. HAI—Amyloid Imaging in the Clinic: New Guidelines and Data
  3. Miami: Diagnosis and Amyloid Scan Can Be at Odds
  4. Phase 3 Trial Data for Solanezumab and Bapineuzumab Released
  5. Brain Imaging in Trials—How to Make It Work?
  6. Amyloid Scans in the Clinic: Seeing Is Believing?
  7. With Amyloid Scan in Hand, Physicians Manage AD Differently

Therapeutics Citations

  1. Memantine

Paper Citations

  1. . Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design. Alzheimers Dement (Amst). 2017;6:143-151. Epub 2017 Jan 23 PubMed.
  2. . The Diagnostic Value of Amyloid Pet in an Unselected Cohort of Memory Clinic Patients. Alzheimer's & Dementia, July 2016, Volume 12, Issue 7, Supplement
  3. . Deciding About Diagnostic Testing for Alzheimer’s Disease: Patients’ Views and Experiences. Alzheimer's & Dementia, July 2016, Volume 12, Issue 7, Supplement, Page P1122
  4. . Diagnostic dilemmas in Alzheimer's disease: Room for shared decision making. September 2017, Volume 3, Issue 3

External Citations

  1. Imaging Dementia—Evidence for Amyloid Scanning
  2. European AMYPAD

Further Reading