Project Summary/Abstract Alzheimer’s disease (AD) affects more than six million Americans currently and is projected to affect 14 million at a cost of $1.2 trillion in 2050. Despite its tremendous impacts and the limited influence of pharmacological therapies, attention has been brought to non-pharmacological interventions as promising therapeutic strategies for the prevention of cognitive decline. Aerobic exercise and cognitive training, particularly when in combination represent important behavioral interventions for cognition in persons at risk for AD. Both preventative medicine therapies are cost-effective strategies and aim to preserve the mental abilities, daily living performance, and cognitive well-being of individuals in the early stages of the disease. The proposed project will build on findings from the Phase II pilot where the feasibility and efficacy of Virtual Reality Cognitive Training (VRCT) combined with concurrent aerobic cycling (Exergame) was demonstrated in a clinical trial. This clinical trial was conducted utilizing a supervised intervention model, which is important for demonstrating preliminary feasibility and efficacy, but has limitations for addressing real-world feasibility and sustainability. Currently, the top two reported barriers for participation in community or facility-based, preventive medicine therapies such as exercise and cognitive training include burdens of travel or time commitment. Recently, advancements in technology have allowed for home-based (asynchronous) telerehabilitation interventions such as exercise training to be utilized as a supplement or replacement to conventional, synchronous rehabilitation programs. Although telerehabilitation is a growing form of therapy, it has yet to be studied in persons at risk for AD or with Exergame therapy. In order for Exergames to be a sustainable preventive medicine approach to AD, its feasibility and efficacy in a home-based (asynchronous) setting is needed. In order to expand our reach and marketability of the Exergame and combat these participation barriers, the sustainability and efficacy of Exergames in a home-based environment must be addressed. In support of expanding the reach and marketability of the Exergame, the purpose of this project is to: 1) develop a fully-featured version of the VRCT aspect of the Exergame that can be installed and updated remotely in order to support home-based use and, 2) assess the feasibility, efficacy, and sustainability of the Exergame in a home-based, asynchronous telerehabilitation setting via a clinical trial. Once the fully-featured Exergame with remote installation and updating capacity has been completed, the clinical trial, using a 2:2 factorial design will randomize 104 community-dwelling older adults at risk of AD to one of four arms for 3 months: home-based (asynchronous) Exergames, supervised Exergame, home-based asynchronous aerobic exercise, or supervised aerobic exercise. This project is innovative as 1) it addresses barriers for the real world use of the Exergame, which will increase the reach and marketability of the product, and 2) the clinical trial uses gold standard laboratory, real world (“field”), and novel blood biomarker efficacy and sustainability assessments of the Exergames.

Project Narrative Preventing Alzheimer’s disease (AD) is arguably the most important approach to address the dementia epidemic worldwide because 99.6% of drug trials failed and no drugs can yet prevent, cure, or even slow AD. Growing evidence suggests that aerobic exercise and cognitive training, particularly in combination, are two such promising interventions to target cognitive decline in persons at risk for AD, however compliance to such therapies in the real world setting is poor due to travel and time barriers. This proposed project will implement and test a unique Virtual Reality Cognitive Training (VRCT) combined with concurrent cycling (Exergame) that seamlessly integrates specific cognitive tasks into a virtual environment and is synchronized with cycling to promote cognitive gains, in a home-based (asynchronous) telerehabilitation model in a 2:2 factorial design clinical trial in persons at risk for AD.