ABSTRACT
Despite the best scientific efforts, no new treatment for Alzheimer’s Disease (AD) has been approved by the
FDA since 2003. However, this may not be due to the treatment under investigation but rather clinical
heterogeneity within the study sample, as a subset of participants may not have AD or experience little to no
decline in AD symptoms. Thus, to improve the likelihood of success, AD clinical trials must homogenize or
enrich their study sample with individuals who will experience more rapid decline and are biologically-
confirmed with AD. One enrichment solution is related to the degree of performance change a person
experiences due to repeated exposure of a screening assessment, known as a practice effect. Practice effects
can be used to inform prognosis, diagnosis and treatment response in AD. We have recently designed an
online video game, called SuperG, that uses finger coordination to assess individual practice effects without
supervision in less than 7 minutes. We intend to deploy our online video game into MindCrowd, an electronic
cohort of >100,000 participants worldwide designed with the infrastructure for remote, large-scale, and widely-
distributed research to discover and study early biomarkers of AD. The long-term goal of this project is to
merge the PI’s experience in learning and video game development with his interest in AD-focused research to
enhance his career in creating next-generation, ‘crowd-sourced’ screening procedures to enrich the AD clinical
trial enterprise. The overall objective of this application is to utilize the MindCrowd electronic cohort to
determine how learning capacity, assayed with SuperG, relates to changes in cognition and daily function over
time, while providing valuable mentorship for the PI in motor-cognitive interactions, electronic cohorts and
practice effects in the context of aging. Based on extensive published and pilot work from the mentorship team,
the central hypothesis is that practice effects on SuperG will predict one-year changes in cognition and daily
function among MindCrowd older adults. Since SuperG game play is easily collected online, the rationale for
this proposed research in a distributed electronic cohort offers an affordable and efficient means to enrich
clinical trials in AD. There are two independent aims within this proposal. First, we will determine the extent
that SuperG practice effects predict one-year cognitive change in older adults. Second, we will
determine the extent that SuperG practice effects predict one-year functional change in older adults. If
successful, this project will provide cognitive aging research with a novel online screening tool that has the
potential to enrich future Alzheimer’s Disease and Related Dementia clinical trials. This project also
incorporates the PI’s career goals and training activities concerning: motor-cognitive interactions, electronic
cohorts, and practice effects, together providing for independence in the establishment of a “virtual” lab with
modern capabilities. Further, the ‘socially-distanced’ nature of this project is particularly relevant in the context
of COVID-19 and will allow for the safe inclusion of participants remotely.