Symposium 08: Neuropsychological Considerations for Alzheimer's Disease Clinical Trials

Summary abstract:

The 2011 National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for the diagnosis of Alzheimer's disease (AD) focused on clinical signs and symptoms to make a diagnosis of probable or possible AD. Under these criteria, emphasis was placed on gathering objective evidence of cognitive decline, which gave neuropsychologists a central role as diagnosticians in AD clinical trials. The release of the 2018 NIA-AA research framework put greater emphasis on the use of biomarkers, especially measures of amyloid, tau, and neurodegeneration, to define AD. Once AD is defined based on these biomarkers, it is staged via clinical signs and symptoms. Thus, the role of neuropsychologists has shifted from being central to diagnosis to a possibly more ancillary role of staging the disease once it is determined to be present. The move away from clinical signs towards biomarkers only became more prominent with the recent, controversial Food and Drug Administration approval of Aducanumab as an AD treatment based on evidence of change in biomarkers without clear evidence of clinical benefit. In this landscape, the fit of neuropsychologists in AD clinical trial research has become less clear.

This symposium will address the role of neuropsychologists in modern AD clinical trial research. The presenters will highlight varied ways in which neuropsychologists can enrich and improve AD clinical trials. First, Dr. Dustin Hammers from Indiana University will discuss how neuropsychological methods can help us to understand which participants do, and perhaps more importantly, do not get enrolled in clinical trials. Second, Dr. Mirella Diaz-Santos from the University of California Los Angeles will summarize her work to enroll Hispanic individuals in the Human Connectome Project, improving inclusivity. Third, Dr. Tamar Gollan from the University of California San Diego will summarize her work on novel behavioral markers of AD risk discovered from the study of Spanish-English bilingual patients. Fourth, Dr. Andrew Kiselica from the University of Missouri will highlight psychometric considerations in interpreting clinically meaningfully change in AD clinical trials using data from the National Alzheimer's Coordinating Center. Fifth, Dr. Samantha John from the University of Nevada at Las Vegas will discuss the influence of race/ethnicity on how clinically meaningful change is defined using data from a diverse cohort.

Dr. Kevin Duff will serve as discussant for this series of studies. He will highlight the important roles that neuropsychologists can play in improving AD clinical trial screening processes, expanding inclusion of diverse patients into trials, and enhancing interpretation of the clinical meaningfulness of trial results. He will also reflect on the future of neuropsychology's role in the AD clinical trial landscape and encourage audience questions and responses to the research presented.