A Decade Of Digital Endpoints: Reflections From AAIC On Modernizing Alzheimer's Science

By Christine Guo, PhD

Despite a decade of progress in Alzheimer's disease research, the tools used to measure cognitive change in clinical trials have barely moved. The ADAS-Cog, MMSE, and CDR remain the dominant endpoints in most trials today, even though they were designed decades ago to detect advanced impairment, not the subtle, early-stage changes that today's disease-modifying therapies are meant to address. A review of more than a thousand phase 2 and 3 Alzheimer's trials conducted over the past twenty years found that computerized cognitive testing, once gaining modest traction as a secondary endpoint, has actually declined in use over the past decade — despite being validated across thousands of peer-reviewed studies.

As trials increasingly target early and preclinical disease, sponsors need endpoints sensitive enough to detect subtle cognitive change and reliable enough to separate a true treatment effect from measurement noise. Trial teams designing early-stage Alzheimer's studies should take a hard look at whether their chosen cognitive endpoints can actually detect the signal they're trying to measure.