Groundbreaking prevention study will positively impact future Alzheimer’s research | Alzheimer's Prevention Registry

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August 24, 2022

Groundbreaking prevention study will positively impact future Alzheimer’s research

By Alzheimer's Prevention Bulletin

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A precedent-setting prevention trial in Colombia has found that the investigational medicine crenezumab did not slow or prevent decline in memory and thinking skills for cognitively healthy people with a rare genetic mutation that causes early-onset Autosomal Dominant Alzheimer’s disease (ADAD). There were small numerical differences that favored the study drug over the placebo but they were not statistically significant.

“We’re disappointed that the treatment did not demonstrate a statistically significant clinical benefit,” said Eric M. Reiman, MD, Banner Alzheimer’s Institute executive director and one of the Alzheimer’s Prevention Initiative (API) study leaders. “At the same time, we’re grateful for the impact that this pioneering study has had in shaping a new era in Alzheimer’s prevention research, and we’re extremely grateful to our research participants and their families. This trial, the data, samples, and findings that we’ll share with the research community, and the related work that we and others are doing promise to further accelerate the evaluation and approval of future prevention therapies.”

The API ADAD trial compared cognitive and biological changes over five to eight years in 252 cognitively unimpaired members of the world’s largest ADAD kindred, including carriers of the Colombian “Paisa” mutation (presenilin 1 [PSEN1] E280A). Carriers of the rare mutation are virtually certain to develop Alzheimer’s, with mild cognitive impairment (MCI) beginning around age 44. The trial included mutation carriers who were randomly assigned to receive crenezumab, carriers who were randomly assigned to receive placebo, and non-carriers from the kindred who also received placebo. Remarkably, 94% of the participants completed the trial.

“During the trial, as the field gathered more data, we increased the dose of crenezumab several times,” said Pierre N. Tariot, MD, Banner Alzheimer’s Institute director and of the API study leaders. “While the average treatment span was six years in the trial, people received the highest dose for only two years. The question remains – could we have seen a better effect with a higher dose for a longer period of time?”

While the trial did not meet its clinical endpoints, it did develop groundbreaking research strategies and methods that have helped shape Alzheimer’s prevention research. It led to a growing number of prevention trials in cognitively unimpaired persons at biological risk for Alzheimer’s and sped up the effort to find effective prevention therapies. It also established a precedent-setting commitment to the sharing of trial data and samples with the scientific field to have the greatest possible impact.

This trial was a partnership between Banner Alzheimer’s Institute’s API, the Neurosciences Group (GNA) at the University of Antioquia in Colombia, the pharmaceutical company Roche, and the National Institute on Aging (NIA) of the National Institutes of Health (NIH).

More than 15 years ago, API researchers at Banner Alzheimer’s Institute began forging a close working relationship with GNA at the University of Antioquia, which played the primary role in conducting the trial in Colombia. For three decades, long before the API trial began, GNA Director Francisco J. Lopera, MD, and his colleagues had followed and built close relationships with the affected families. With API support, GNA has now identified more than 6,000 members of the Colombia kindred in 26 extended families, including about 1,200 who carry the ADAD mutation, and it played the primary role in trial engagement, enrollment, and assessments. ADAD represents less than one percent of all cases of Alzheimer’s.

The study is already planning for new trials. This includes trials in the Colombian kindred and other at-risk populations. The study team is busy analyzing the data and samples from the API ADAD trial to inform the design of these studies.

The Alzheimer’s Prevention Initiative will continue to keep you up to date on these and other trials as scientists dig deeper into the possible causes and treatments of Alzheimer’s disease. For a list of prevention trials actively enrolling new participants, please visit our Find A Study page.