Which Clinical Scenarios Warrant Amyloid PET?

• For the initial evaluation of cognitive complaints.
• To screen cognitively normal individuals outside the context of research or clinical trials.
• When requested solely based on a family history of dementia or the presence of other Alzheimer’s disease risk factors, such as the ApoE4 gene.
• As a substitute for genetic testing for mutations that cause Alzheimer’s disease.
• For nonmedical reasons, such as insurance, legal, or employment decisions.

Finally, the criteria identify scenarios where amyloid imaging is unlikely to be useful, including as a means of determining the severity of dementia, straightforward clinical cases, and to differentiate Alzheimer’s disease from other diseases that involve the deposition of amyloid-beta.

Effects on Management and Outcomes

Relatively few studies have assessed amyloid PET’s impact on clinical decision making and patient outcomes, Dr. Rabinovici said. In 2013, the US Centers for Medicare and Medicaid Services (CMS) determined that there was insufficient evidence to justify reimbursement of amyloid PET and said that it would reimburse the scans for patients who enroll in studies to assess amyloid PET’s clinical utility, under a mechanism called coverage with evidence development. For CMS to reconsider its coverage decision, studies must demonstrate that amyloid PET changes patient management in the short term and improves dementia outcomes long term. The Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) study, which Dr. Rabinovici chairs, is a multisite study to assess the utility of amyloid PET in Medicare beneficiaries age 65 and older who meet appropriate use criteria for amyloid imaging.

The IDEAS study enrolled more than 18,000 participants and finished recruiting patients this year. It aims to examine how the scans affect patient management plans at three months and medical outcomes at 12 months. “The primary hypothesis is that, in these diagnostically uncertain cases, knowing the amyloid result will change management, and that will translate into better outcomes,” Dr. Rabinovici said.

Results regarding amyloid PET’s influence on patient management at three months will be presented soon, and 12-month outcome data are expected to be presented in 2019.

An interim analysis of the first 3,979 patients found that, three months after the amyloid PET scans, patients’ management plans had changed from the pre-PET management plan in about 67% of cases. Changes included starting or stopping Alzheimer’s-disease-specific medications and other neurologic therapies and changes in patient counseling.

Matched With Controls

To assess 12-month outcomes, investigators plan to use Medicare claims data to compare medical outcomes for patients enrolled in the study with those for matched controls who did not undergo amyloid PET. The primary objective is to determine whether amyloid PET is associated with a 10% or greater reduction in hospitalizations and emergency room visits. The researchers plan to use an algorithm to match each IDEAS study participant with a control with a similar dementia diagnosis, pre-scan dementia-related resource utilization, age, race, gender, ethnicity, geographic location, and comorbid chronic conditions.

Further imaging advances, such as tau PET tracers, are in development but have not yet received regulatory approval from the FDA, Dr. Rabinovici said. Tau PET has the potential to detect pathology in tauopathies such as progressive supranuclear palsy, corticobasal degeneration, chronic traumatic encephalopathy, and subtypes of frontotemporal dementia, as well as Alzheimer’s disease, he said.

—Jake Remaly

Suggested Reading

Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535-562.

Johnson KA, Minoshima S, Bohnen NI, et al. 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. Alzheimers Dement. 2013;9(1):e1-e16.