Often referred to as the next frontier in Alzheimer disease (AD), amyloid PET imaging holds tremendous promise as a tool to aid in the early detection of AD or cognitive impairment—potentially even before the onset of dementia.
Nevertheless, the modality faces a number of barriers to widespread use. Medicare does not yet cover brain amyloid imaging with PET, and out-of-pocket fees for the test can cost several thousand dollars. Other limiting factors include patients’ access to dementia experts who can effectively use amyloid PET imaging information as a part of their diagnostic workup and radiologists who can accurately interpret the scans.
Although wider clinical use will take time, the wheels are already in motion. Used in Alzheimer’s research for more than a decade, amyloid PET imaging has been clinically available only since April 2012, when the U.S. Food and Drug Administration (FDA) approved the first radiopharmaceutical for brain amyloid PET imaging (Amyvid by Eli Lilly and Company), opening the door for approval of similar PET tracers. And patients are already beginning to ask physicians about the benefits of the new modality.
“The test is not in general use yet, but there are going to be a lot of questions about amyloid PET imaging and physicians need to be prepared,” said Dean M. Hartley, Ph.D., director of science initiatives, Medical and Scientific Relations Division, at the Alzheimer’s Association.
To offer guidance to physicians, patients affected by AD and the public, the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the Alzheimer’s Association jointly published the first criteria for the appropriate use of amyloid PET imaging to aid in the diagnosis of those with suspected AD. The criteria appeared in the January 2013 online editions of The Journal of Nuclear Medicine and Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“Our primary goal is to provide healthcare practitioners with the information and options available to provide patients with the best possible diagnosis and care in a cost effective manner,” said Maria Carrillo, Ph.D., Alzheimer’s Association vice-president of medical and scientific relations.
Drafted by SNMMI and the Alzheimer’s Association’s Amyloid Imaging Taskforce, consisting of dementia and imaging experts from across the globe, the criteria are designed to help physicians determine who is—and is not—an appropriate candidate for amyloid PET imaging.
Task force members stress that amyloid PET imaging is not the equivalent of clinical diagnosis of Alzheimer disease or dementia and is only one tool that clinicians should use to judiciously manage patients. “Currently, amyloid PET imaging can aid in the determination of someone having Alzheimer disease but cannot replace a full clinical evaluation,” Dr. Hartley said.
In amyloid PET imaging, the radiopharmaceutical is introduced into the body by injection into a vein and binds specifically to the amyloid protein, enabling visualization of areas in the brain where amyloid has clumped together into plaques—one of the defining pathologic features of AD.
However, patients with normal cognition can also have elevated levels of these plaques, as do people with conditions other than AD. Therefore, the potential clinical use of amyloid PET imaging requires careful consideration so that its proper role may be identified, according to criteria authors.
Because definitive research on health outcomes of amyloid PET imaging isn’t yet available, task force members analyzed peer-reviewed, published literature to develop a consensus of expert opinion. “Basically, the task force researched 10 indications for use of amyloid PET imaging,” Dr. Hartley said. “Three were determined as appropriate; seven were not.”
According to the task force, amyloid PET imaging should be limited to the following:
The task force determined that amyloid PET imaging is inappropriate in the following situations: Patients age 65 or older who meet standard definitions for Alzheimer disease; to determine dementia severity; based solely on family history of dementia or presence of the apolipoprotein E, type 4 (APOE 4); patients with a cognitive complaint that is unconfirmed on clinical examination; in lieu of genotyping for suspected autosomal mutation carriers; in asymptomatic individuals; non-medical use (health insurance coverage, legal decisions, or employment screening).
“One of the critical indications of PET amyloid imaging will be to aid in the diagnosis of Alzheimer’s in patients whose clinical presentations are atypical or unexplained,” said Satoshi Minoshima, M.D., Ph.D., co-chair of the task force and professor and vice-chair of radiology at the University of Washington, Seattle. “Examples include atypical symptoms, atypical age of onset and presence of comorbidities. If anti-amyloid treatments are determined effective in the future, amyloid PET imaging could be used for better therapeutic evaluations.”
Although Dr. Minoshima says the PET amyloid imaging procedure itself is relatively straightforward, the interpretation can be challenging if physicians are not familiar with the scan. For that reason, the task force recommends that the scans be read by physicians certified in nuclear medicine or nuclear radiology who have adequate specific training in amyloid PET imaging interpretation, and that imaging procedures be performed by a qualified nuclear medicine technologist with appropriate training and certification.
New training resources are available or in the works. When the FDA approved Amyvid, the agency mandated that Eli Lilly provide specific training in amyloid PET interpretation. (See sidebar.) SNMMI will soon be releasing an education program for those referring patients and reading the scans along with technical procedure guidelines for ensuring performance quality. Use of beta amyloid imaging and computer-aided analysis software for amyloid PET imaging is also in development, according to the task force.
Although insurance coverage is critical to use of amyloid PET imaging, the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) ruled in late January that adequate evidence does not exist to determine whether amyloid PET imaging changes health outcomes in suspected cases of AD. Committee members also expressed concern about possible inappropriate use of the test and the possibility of false-positive results.
SNMMI and the Alzheimer’s Association issued statements expressing disappointment in the opinion, stressing that those concerns had been addressed by the task force criteria and recommending that the Centers for Medicare & Medicaid Services (CMS) cover brain amyloid PET imaging according to those criteria. CMS, which is expected to vote on the issue this summer, generally follows committee recommendations; private payers tend to follow CMS’ lead.
Whatever the CMS decision, Dr. Hartley stressed that the task force will continue to update the criteria to reflect changes in the evolving issue. “This is a working document and it will be modified and updated to reflect any new information we receive. We are still convening and still discussing this issue.”
To access an abstract of the “Appropriate Use Criteria for Amyloid PET: A report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association,” go to jnm.snmjournals.org/content/54/3/476.abstract.
Access more information on amyloid PET imaging through the Society of Nuclear Medicine and Molecular Imaging (www.snmmi.org) and the Alzheimer’s Association (www.alz.org/Research).
For more information on the Eli Lilly and Company reader training program, go to www.amyvid.com/Pages/index.aspx.
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