Which Clinical Scenarios Warrant Amyloid PET?

Consider the Clinical Context

As with any diagnostic agent, clinical context is critical for interpreting the significance of positive and negative amyloid scans, Dr. Rabinovici said.

Among patients with dementia, amyloid PET can distinguish Alzheimer’s disease from conditions that do not involve amyloid-beta deposition, such as frontotemporal dementia or pure vascular dementia. It is not useful, however, in distinguishing Alzheimer’s disease from other conditions in which amyloid is deposited in the brain, such as cerebral amyloid angiopathy or dementia with Lewy bodies.

“It is important to consider the patient’s age when you think about the meaning of a positive scan,” he said. “A negative scan is always helpful in ruling out Alzheimer’s disease,” but a positive scan is less meaningful in older patients. Approximately 25% of cognitively normal older individuals have positive amyloid PET scans. The prevalence of amyloid positivity is about 10% at age 60 and more than 50% at age 90.

Not everyone with amyloid deposition has or develops Alzheimer’s disease dementia or mild cognitive impairment, but amyloid is a risk factor, said Dr. Rabinovici. “To summarize 15 years of research in one bullet point, it is not good to have amyloid in your brain even if you are cognitively normal,” he said. “Amyloid-positive normal controls are already showing Alzheimer’s-disease-like structural and functional changes in their brains. Over time, they are likely to decline cognitively. And they have an increased risk of cognitive impairment,” compared with people who are amyloid negative.

Research indicates that the deposition of amyloid plaques begins at least 15 years before the onset of cognitive symptoms, which may represent a window for early intervention, Dr. Rabinovici said.

When to Scan and When Not To

To guide clinicians in the appropriate use of amyloid PET, the Society for Nuclear Medicine and Molecular Imaging and the Alzheimer’s Association in 2013 published appropriate use criteria for the technology. Given amyloid PET’s cost and need for nuanced interpretation, the authors determined that it should not be a first-line test in the evaluation of cognitive complaints, Dr. Rabinovici said. Rather, it should be an ancillary test ordered by subspecialists in patients who meet the following criteria:

• Have a cognitive complaint with objectively confirmed impairment.
• Have an uncertain diagnosis, with Alzheimer’s disease as a possibility, after comprehensive evaluation by a dementia expert.
• Knowledge of their amyloid-beta status is expected to increase diagnostic certainty and alter management.

The three main clinical scenarios in which amyloid imaging may be most useful include the following:

• Cases with persistent and progressive unexplained mild cognitive impairment.
• Cases with possible (rather than probable) Alzheimer’s disease who have an atypical or mixed course or significant comorbidities (eg, vascular, psychiatric, or substance abuse disorders).
• Cases with an atypically early age of onset (ie, younger than 65).

The appropriate use criteria also highlight the following scenarios in which clinical amyloid PET is considered inappropriate: