Amyloid PET Imaging for Alzheimer's Disease Diagnosis
By Jamie Santa Cruz
It's now possible to examine the brains of living patients to determine whether amyloid plaques, a key Alzheimer's disease pathology, are present.
In the last few years, the development of amyloid positron emission tomography (PET) imaging has made it possible to ascertain with relative certainty the presence of Alzheimer's Disease (AD) in a living human being. Theoretically, this breakthrough opens the possibility of earlier diagnosis and intervention. But given the lack of a disease-modifying agent, questions remain as to whether diagnostic certainty is worth the expense of amyloid imaging. Does an accurate diagnosis translate to better care, improved outcomes, or reduced costs?
Amyloid PET Imaging and the Transformation of AD Diagnostics
Beginning in the early 2000s, however, researchers at the University of Pittsburgh developed the first molecular imaging tracer for use in evaluating possible AD, and the FDA has since approved several different tracers that bind to beta-amyloid in the brain and can reveal amyloid plaques during a PET scan. These tracers have transformed the field, Rabinovici says, because it is now possible to examine the brain of a living patient and determine whether a key AD pathology, amyloid plaques, is present.
The new possibility of identifying amyloid plaques through PET imaging has proven significant in several ways, Rabinovici says. PET imaging has helped to demonstrate that amyloid plaques begin accumulating in the brain up to 15 years before the earliest signs of memory loss begin to manifest. The fact that plaques accumulate so early and that they can be detected through PET scans offers the potential to diagnose patients at significantly earlier stages of disease.
Additionally, the new imaging capacity has revealed the fallibility and inaccuracy of the old method of AD diagnosis. PET scans have shown that many people previously diagnosed with AD do not actually have amyloid plaques and therefore do not have AD. Indeed, Rabinovici says, false-positive diagnoses may well be as high as 20%.
Definitive Results in Expert Hands
Given these limitations, the scans are not considered a first-line test for primary care providers. However, according to Liana Apostolova, MD, MSc, a professor of neurology, radiology, and medical and molecular genetics at Indiana University, if offered to patients who meet specific criteria (ie, the patient has objective cognitive decline, but it is uncertain whether the cause is AD or another disease), and if the scan is interpreted by a dementia expert with a detailed understanding of the limitations and nuances of the test, PET imaging can provide a high degree of diagnostic certainty regarding AD.
Does Accurate Diagnosis Justify Cost?
To date, few data exist detailing whether a more accurate diagnosis would translate to differences in treatment or improved outcomes. However, Rabinovici is currently spearheading the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) Study, a large-scale clinical trial that seeks to address these questions. The research project is set to enroll more than 18,000 Medicare beneficiaries who have either mild cognitive impairment or dementia of uncertain cause and who meet specific appropriate use criteria. As part of its Coverage with Evidence Development research program, CMS has agreed to reimburse one amyloid PET scan per patient for those enrolled in the study. The main purpose of the project, according to Rabinovici, is to determine whether amyloid PET scans change management and improve outcomes for enrolled patients, but secondary questions include whether or not the scans can accelerate referrals to clinical trials, whether they can impact caregiver and family planning, and whether they reduce the cost of care.
Although firm data are forthcoming, Rabinovici says there is reason to believe the scans might have clinical utility, even given the lack of disease-modifying AD treatments. Consider, for example, cases in which it is uncertain whether a patient is suffering from AD or another condition (such as epilepsy or depression) that is more amenable to treatment. "If you can rule out AD in someone with progressive memory loss, and if there is a hint of some of these other conditions, you might pursue treating these other conditions much more aggressively," Rabinovici says.
The diagnostic certainty provided by amyloid PET imaging is valuable because it aids in connecting patients and their families with the resources and education they need to manage the disease, Apostolova says. Although there is significant support available for AD patients, many continue to doubt their conditions without a definitive diagnosis. "The patient and the family decide, 'Well, it's not certain that I have AD. Why should I go and do X, Y, and Z?' They end up with the feeling that 'My doctor couldn't tell me for sure.'"
Overcoming this lack of certainty and connecting patients with proper support is vital, Rabinovici says, not only because it helps to relieve some of the emotional burden of AD, but also because it enables more preventive care. Currently, he says, the approach to care for individuals with AD tends to be very reactive. "They might be living independently, they might be taking their own blood thinners or injecting their own insulin for diabetes. We don't really intervene until they show up in the [emergency department] because they've forgotten to take their insulin for several days.
"The idea is if you can provide patients and families with more definitive information at the earlier stage, then we might take a much more proactive approach to prevent these bad outcomes," Rabinovici says.
Ultimately, diagnostic certainty combined with education about how to care for a loved one with AD could help reduce unnecessary hospitalizations and emergency department visits. "What brings [AD patients] to the emergency department, to the hospital, is psychosis, irritability and agitation, wandering, being found on the street," Apostolova says. But the busy, loud, frightening environment of a hospital tends to only exacerbate AD patients' fear and confusion, Apostolova says, so it is far better to keep patients at home and equip families with knowledge on how to handle their care there.
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— Jamie Santa Cruz is a freelance writer based in Englewood, Colorado.