Attempts to design a scan that could spot amyloid first began about a dozen years ago at the University of Pittsburgh. Researchers injected patients with a small, benign amount of a radioactive dye they named Pittsburgh compound B, or PIB. The dye traveled through the blood to the brain and clung exclusively to clusters of amyloid protein. Scanning the brain with a positron-emission tomography (PET) machine then produced images that highlighted any plaques by detecting radiation in the form of gamma rays emanating from the dye.
Scientists at Philadelphia-based Avid Radiopharmaceuticals built on the Pittsburgh approach by developing Amyvid, a longer-lasting dye that gave clinicians more time to scan their patients. Early results were so promising that Eli Lilly bought the company in 2010 for $300 million. Two years later the FDA approved the Amyvid test, which more than 450 imaging centers in the U.S. now offer, usually for $3,000 or more.
To Scan or Not to Scan
Together the FDA and the neurological community have approached Amyvid with a mix of enthusiasm and trepidation. Officially the test has been approved primarily to exclude Alzheimer's as a diagnosis for someone who already has cognitive impairment, which is particularly helpful when the causes are unclear. This past January an expert task force convened by the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging published guidelines that advised limiting the test's use to patients with unexplained, persisting mild cognitive impairment (MCI) and to those who either have developed dementia unusually early or have dementia with atypical symptoms, such as hallucinations or delirium. Determining whether Alzheimer's is the culprit in such cases has always been difficult, and Amyvid is exactly the kind of tool that can provide some assistance. If a scan finds few plaques, physicians can more confidently rule out Alzheimer's and explore other explanations, such as a rare and rapid degeneration of the brain's frontal lobes.
The task force also advised against amyloid scans for people with no cognitive impairment. Panelists worried not only that amyloid-positive results might send some vulnerable individuals spiraling into depression or perhaps even suicide but also that the information may make it harder for them to get long-term care insurance or renew a driver's license, says task force member Jason Karlawish, a professor of medicine and medical ethics at the University of Pennsylvania.
Despite these cautious guidelines, which Eli Lilly supports, many people in the medical community have reservations. Task force member and neurologist Norman Foster of the University of Utah worries that some doctors and patients will rely on amyloid scans as a diagnostic shortcut in lieu of a more thorough evaluation that includes a battery of memory and reasoning tests. And given the lack of effective treatment, a scan suggesting that someone with mild cognitive impairment has early Alzheimer's may yield more anxiety than practical guidance. “What do you do with that information?” asks neuroscientist William Jagust of the University of California, Berkeley.
Some experts think that if scans help patients and their families prepare for the changes in health and lifestyle that come with Alzheimer's, then they are beneficial. Others argue that the test is not meaningful if it does not alter how a patient is treated. The federal agency that oversees Medicare insurance essentially took the latter view in September, when, because of insufficient evidence that the scan improves patient health, it declined to cover Amyvid for now except in certain clinical trials. Though disappointed, Avid's CEO Daniel Skovronsky acknowledges that figuring out how best to use the scan will take considerable time and debate because it is such a new tool. “I think the discussion is actually a good thing,” he says.