Which Clinical Scenarios Warrant Amyloid PET?

LOS ANGELES—Amyloid PET scans may play an important role in neurologists’ management of patients with cognitive impairment. For the moment, clinical use should be restricted to cases that can be summarized with the mnemonic MAY—Mild, Atypical, and Young, said Gil D. Rabinovici, MD. “Those are the people who are most likely to benefit,” he said.

Although amyloid PET scans may affect diagnostic certainty and influence treatment in these scenarios, most patients do not get the scans. “They cost thousands of dollars, and most insurance will not pay for them,” Dr. Rabinovici said in a lecture at the 70th Annual Meeting of the American Academy of Neurology.

Gil D. Rabinovici, MD

Looking to the future, amyloid PET may play a larger role in clinical practice if insurance providers more readily cover the cost of the scans and if the definition of Alzheimer’s disease shifts from a clinical basis to a biologic one. Someday, neurologists may be able to offer interventions to delay or prevent the onset of dementia in patients at risk of Alzheimer’s disease, Dr. Rabinovici said.“During the coming decade, we are going to see a real paradigm shift,” he said, “from the current status quo where we are diagnosing and treating clinical dementia to a paradigm where we are doing early screening with biomarkers.” Dr. Rabinovici is the Edward Fein and Pearl Landrith Distinguished Professor in the Memory and Aging Center at the University of California, San Francisco.

Three FDA-Approved Tracers

Three amyloid-beta tracers are FDA approved for clinical use in cognitively impaired patients—18F-florbetapir (Amyvid, approved in 2012), 18F-flutemetamol (Vizamyl, approved in 2013), and 18F-florbetaben (Neuraceq, approved in 2014).

The agents were approved on the basis of studies that found that blinded visual reads of amyloid PET scans during life accurately predicted postmortem burden of amyloid pathology in the same individuals. The scans distinguish patients with moderate or frequent neuritic plaques from those with absent or sparse neuritic plaques with a sensitivity and specificity of 80% or greater. Many scans can be categorized as positive or negative, and neurologists can quickly learn to read them, Dr. Rabinovici said.

Scans have the potential to improve the accuracy of Alzheimer’s disease diagnosis. Compared with postmortem findings, the clinical diagnosis of probable Alzheimer’s disease was accurate only 70% of the time in one study. Conversely, another study found that approximately 40% of patients with a diagnosis of non-Alzheimer’s disease dementia turned out to have Alzheimer’s disease as the primary causative pathology at autopsy.

Real-Life Ramifications

To illustrate amyloid PET’s potential usefulness in clinical practice, Dr. Rabinovici described a case of a 57-year-old internist. The patient had progressive trouble finding words, but otherwise did not have major symptoms or concerns. He did poorly on repeating sentences, but the rest of his examination was normal. MRI revealed nothing remarkable.

“That is the typical standard of care that is meant for someone with a cognitive complaint,” Dr. Rabinovici said. An FDG-PET scan was suspicious but not definitive. The patient’s amyloid PET scan, however, was clearly positive and showed amyloid throughout the neocortex. “With the scans, I could diagnose him. He had mild cognitive impairment, but I thought with high likelihood due to Alzheimer’s disease.”

As a result, Dr. Rabinovici started the patient on a cholinesterase inhibitor, and the patient decided to retire early due to medical disability. In addition, the patient enrolled in a clinical trial of an investigational antiamyloid therapy.

“I was not able to cure or modify the course of his Alzheimer’s disease, but amyloid PET did have real ramifications for his life,” he said.