University of California, San Francisco (UCSF)

Optimizing Clinical Trial Enrichment and Endpoints in Alzheimer’s Disease

Research Area

Grant Type



Clinical trials that target Alzheimer’s disease (AD) are complicated because the disease can present very differently from one person to the next. Not everyone at risk for AD goes on to develop dementia. Some people can live for decades with AD pathophysiologyin their brains, whereas the illness progresses rapidly in others. There are also differences in the clinical symptoms caused by AD. In the classic presentation, memory deficits are the initial and most prominent cognitive difficulties. However, a substantial portion of patients with AD exhibit primary deficits in language, visuospatial, executive or behavioral abilities. It is likely that a trial for patients with AD could include patients with vastly different symptoms and disease course. This makes it very difficult to determine who should be included in a study and which outcome measure would make it most likely for us to detect a drug effect if it occurs. The overarching goal of this proposal is to prepare us to conduct the most cost-effective and powerful clinical trials possible in AD. This project will address these concerns by finding ways to predict disease course and determine which outcome measure should be used to track each individual. We will accomplish this by integrating several types of biomarkers that measure different aspects of the complex pathophysiology of AD. The proposed research will help establish guidelines for trial enrichment and inform a discussion about alternative clinical trial methods for AD and other neurodegenerative conditions.