R01AG081394

DS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer's Disease - Project Summary

The Down Syndrome – Ambulatory Research in Cognition (DS-ARC) study will develop and validate a smartphone-based digital cognitive assessment designed specifically for participants at risk for Down Syndrome-Associated Alzheimer's Disease (DS-AD). We will partner with sites in London, Barcelona, Munich, and Gothenburg to develop and validate this approach in different cultures and languages.

Nearly all individuals with Down Syndrome have elevated levels of Alzheimer's Disease (AD) biomarkers by the time they are in their 30s or 40s, though not all show symptoms of AD. It is during the pre-symptomatic and early symptomatic stages of DS-AD that an in-depth understanding of cognitive changes is crucial, as therapeutic interventions to stop, slow, or prevent disease are focused on these critical periods.

Typically, prevention trials and observational studies in AD populations assess cognition with standard "table top" paper and pencil tests. But these conventional methods have several drawbacks. First, performance is influenced by day-to-day fluctuations in stress, fatigue, sleep patterns, and mood. Second, the testing takes place in environments that are fundamentally different from where cognition is relied upon to function in daily life. Finally, by design, cognition is typically assessed in "one-shot" in extended testing sessions on an annual or semiannual basis.

The DS-ARC study will address these difficulties by developing a smartphone-based assessment solution adapted specifically for individuals with Down Syndrome. This approach uses a measurement "burst" design in which participants complete very brief cognitive tests on their smartphones several times per day for one week while living in their natural environments. Instead of focusing on one of these measurements, tests are averaged across the week to provide a score that captures and normalizes natural variability and dramatically increases reliability.

Studies of our original ARC assessments in autosomal dominant and sporadic AD demonstrate extraordinary reliability and strong relationships with AD biomarkers, while reducing costly and burdensome in-clinic evaluations.

The study has two phases: a 2-year development phase and a 3-year validation phase. In the development phase, we will adapt an existing smartphone application called the Ambulatory Research in Cognition (ARC) app for use in DS-AD studies. This will include an iterative pilot testing process for psychometrics and task development, focus groups and user experience testing to address accessibility and compatibility concerns for DS-AD populations, and readiness audits to ensure that the DS-ARC app meets strict compliance guidelines for clinical trial applications.

In phase 2, participants complete DS-ARC assessments every 6 months and complete standard clinical, cognitive, and blood tests for AD biomarkers annually. We hypothesize that DS-ARC assessments are accessible, sensitive, and reliable indicators of cognitive change in DS-AD and will exhibit associations with AD biomarkers and disease stage over and above those of conventional in-clinic assessments.

Washington University

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.310 - Trans-NIH Research Support

National Institute on Aging (NIA) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Saint Louis, Missouri 63130 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been extended from 03/31/28 to 03/31/29 and the total obligations have increased 99% from $1,961,277 to $3,901,583.