How to Disclose Imaging Results in Alzheimer’s Trials
PET imaging can detect disease biomarkers, but its predictive power remains uncertain.
Alzheimer's disease is the most common form of dementia among older people and the sixth leading cause of death in the United States. Even worse, the number of people affected by the disease is expected to increase dramatically over the next few decades.
New molecular diagnostic techniques can detect abnormal levels of the disease biomarkers—amyloid-β peptides and tau protein—using cerebrospinal fluid analysis or an imaging technique called positron emission tomography (PET). PET imaging is one of the tools being used in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Study (A4 study), a clinical trial testing whether administration of solanezumab—an antibody targeting amyloid-β aggregation—can prevent cognitive decline among cognitively normal adults with elevated brain amyloid-β.
But according to an editorial published in October in JAMA Neurology, the A4 study illustrates a serious ethical challenge: how to responsibly disclose test results to participants, given uncertainties about the clinical meaning and predictive power of these techniques. According to editorial author Winston Chiong of the University of California, San Francisco, the A4 investigators have implemented a rigorous process that appropriately emphasizes the limitations of amyloid imaging as an individual predictor of future disease.
Still, according to a study published in the same issue, 40 percent of A4 participants expressed dissatisfaction with the categorical characterization of results as “elevated” or “not elevated,” in some cases desiring more specific information about how their levels compared to the threshold for study inclusion.
Based on this finding, Chiong suggests that investigators should pay closer attention to advising prospective participants about the present limits of these tests. He also envisions that technical and diagnostic improvements, such as the paired application of PET markers for both amyloid-β and tau, could sufficiently improve individual estimates of risk to provide prognostic information that would be useful to some cognitively normal individuals.
“What is clear is that, with the advance of molecular diagnostic tools in neurology, clinicians and investigators will increasingly be faced with the challenge of presenting patients with information of uncertain prognostic significance,” Chiong writes. “As our understanding of the mechanisms of Alzheimer’s disease and other dementias grows more complex, the task of communicating to research participants and patients the information they need to know grows more challenging and simultaneously more urgent.”