School of Medicine

Cognitive function in Down syndrome-associated Alzheimer’s focus of grant

Neurologist Beau Ances, MD, PhD, talks with his patient, Adam Kloppenberg, who has Down syndrome, at Washington University School of Medicine in St. Louis. People with Down syndrome are at very high risk of developing Alzheimer’s disease. Ances is involved in a project led by Jason Hassenstab, PhD, an associate professor of neurology, to develop tools to measure cognitive function in people with Down syndrome-associated Alzheimer’s disease. (Photo: Matt Miller/WUSM)

Nearly every person with Down syndrome eventually develops Alzheimer’s disease, yet people with the syndrome routinely are excluded from Alzheimer’s clinical trials, as the cognitive assessment tools designed for the general population often are inappropriate for people with developmental disabilities. Consequently, nobody knows whether the new Alzheimer’s therapeutics hitting the market will work for people with Down syndrome. This puts this population at risk of missing out on potentially life-changing therapies.

Jason Hassenstab, PhD, an associate professor of neurology and of psychological & brain sciences at Washington University in St. Louis, is seeking to address this exclusion, with the help of an $11 million grant from the National Institute on Aging, part of the National Institutes of Health (NIH).

The grant will fund the Down Syndrome – Ambulatory Research in Cognition study, an international collaboration that aims to build and validate novel assessment technology for clinical trials of people with Down syndrome-associated Alzheimer’s disease.

“What we’re trying to do is build an outcome measure for clinical trials that can work in a population with varying levels of intellectual ability,” said Hassenstab, the principal investigator of the international study. “This is especially important for people with Down syndrome, since most are destined to develop Alzheimer’s, but we don’t have a good way of monitoring the clinical symptoms of the disease in this population. For example, many cognitive assessment tools depend on the ability to read and write. Not all people with Down syndrome can read and write.”

The first phase of research will involve developing a smartphone app designed to measure cognitive function in people with Down syndrome.

The app will randomly ping participants with the notification, “It’s time to play a memory game!” By tapping the notification, the participants will be whisked to a gamified smartphone-based cognitive test that will take three to five minutes to complete. The notification will come multiple times a day over the span of a week.

“It’s very hard to bring in everybody to be evaluated for Alzheimer’s disease,” said Beau Ances, MD, PhD, the Daniel J. Brennan, MD, Professor of Neurology and a professor of biomedical engineering and of radiology. “Some people don’t like taking tests; some can’t take tests at all. So, we have to evaluate in a new way. If you could take the test on your phone, we could get momentary assessments, free from the confounding factors you get in a lab.”

Using a smartphone app to sample cognition so frequently will ensure that participant cognition is tested in a variety of natural environments and emotional states. It also will assess the environment, stress and distractibility of participants immediately after testing sessions, guaranteeing that these factors are accounted for. The results from these different tests will then be averaged, and the subsequent score will capture a more accurate picture of the natural variability of cognition.

Read more.