Puzzlewalk 2.0: advancing mobile health to promote brain training and physical activity for building cognitive reserve in adults with down syndrome

The National Institutes of Health Office of the Director awarded the University of Kansas Medical Center Research Institute, Inc. $439,467 on August 15, 2026, under the Trans-NIH Research Support program (CFDA 93.310) to develop and refine PUZZLEWALK 2.0, a gamified mobile health application designed to promote physical activity and cognitive training in adults with Down syndrome.

The project will enhance the existing PUZZLEWALK app through user-centered design involving adults with Down syndrome. Work includes refining the activity detection algorithm, adding cognitive training activities to supplement existing spot-the-difference puzzles, and aligning the app with usability, design, and functionality preferences of the target population. The team will assess usability of the current PUZZLEWALK version in 20 adults with Down syndrome using eye-tracking technology, system usability scales, objective app-based metrics, and interviews. A community advisory board comprising 5 people living with Down syndrome and their caregivers will participate in focus groups and beta testing to inform PUZZLEWALK 2.0 development. The underlying clinical goal is to build cognitive reserve and potentially delay Alzheimer's disease symptoms, given that individuals with Down syndrome face over 90 percent lifetime risk of Alzheimer's disease.

Performance will occur in Kansas City, Kansas. The period of performance runs through July 31, 2028.

Abstract

The lifetime risk of alzheimer's disease (ad) for individuals with down syndrome (DS) exceeds 90%, making IT their leading cause of death. The regular participation in physical and cognitive training activities across the lifespan may build cognitive reserve and delay the onset of ad clinical symptoms. However, adults with DS typically have low engagement in physical activity and limited access to cognitively stimulating activities tailored to their learning needs. The goal of this project is to develop a mobile health (mhealth) APP that promotes physical activity and cognitive training in adults with DS to build cognitive reserve and potentially delay clinical ad symptoms. The project will involve adults with DS in the design of puzzlewalk, a gamified mhealth APP that unlocks additional gameplay from time spent in physical activity. Using a user-centered design approach, the APP will be tailored to meet the specific needs and preferences of adults with DS. Improvements to the current version of puzzlewalk will focus on refining the activity detection algorithm, adding cognitive training activities to supplement the spot the difference puzzles, and aligning the APP with the usability, design, and functionality preferences of adults with DS. First, we will determine the usability of the currently available version of puzzlewalk in 20 adults with DS to inform the development of puzzlewalk 2.0. We will use eye-tracking technology, system usability scales, objective APP-based metrics (e.g., completion time, errors), and interviews to better understand the usability experience of adults with DS while engaging with the existing APP. Second, we will convene a community advisory board consisting of 5 people living with DS and their caregivers to participate in focus groups and beta testing. The advisory board will provide feedback on usability, feature relevance, visual design, layout, and gameplay preferences. Based on this feedback, we will present prototypes tailored to their preferences and test the APP once a working version is available. Third, we will evaluate the acceptability of puzzlewalk 2.0 across four weeks in a real-world setting by remotely tracking movement (i.e., steps, physical activity) via a wearable device as well as APP engagement (e.g., session frequency and duration) and user performance (e.g., levels completed, gameplay scores, error rates) in 20 adults with DS. Additionally, we will conduct interviews to collect qualitative information covering first impressions, motivators and barriers to APP usage, challenges and frustrations encountered, overall satisfaction, and feedback for the developer team. These findings will inform the final version of puzzlewalk 2.0, which will be used in a future clinical trial aimed at delivering a multifaceted intervention that targets modifiable risk factors for ad in adults with DS. Deploying a user-tested, tailored mhealth APP has the potential for broad dissemination to adults with DS, who develop ad- like pathology 20 to 30 years earlier than the general population. By engaging in physical, cognitive, and social leisure activities, users may build cognitive reserve, potentially delaying clinical symptoms of dementia and extending their quality of life.