Using an Online Video Game to Predict Functional and Cognitive Decline within the MindCrowd Electronic Cohort

摘要 尽管做出了最好的科学努力，但尚未批准治疗阿尔茨海默病(AD)的新方法 美国食品和药物管理局自2003年以来。然而，这可能不是由于正在研究的治疗，而是由于临床 研究样本中的异质性，因为参与者的子集可能没有AD或几乎没有经历 AD症状的下降。因此，为了提高成功的可能性，AD临床试验必须同质化或 丰富他们的研究样本，让他们的研究样本中有一些人会经历更快的衰退，而且是生物学上的- 已与AD确认。一个丰富的解决方案与一个人的绩效变化程度有关 由于反复暴露的经验筛查评估，称为练习效果。实践效果 可用于提示AD的预后、诊断和治疗反应。我们最近设计了一款 名为SuperG的在线视频游戏，它使用手指协调来评估个人练习效果，而不是 在不到7分钟的时间里完成监督。我们打算将我们的在线视频游戏部署到MindCrowd，一款电子产品 全球100,000名参与者，专为远程、大规模和广泛的 发现和研究AD早期生物标志物的分布式研究。这个项目的长期目标是 将PI在学习和视频游戏开发方面的经验与他对专注于AD的研究的兴趣相结合，以 促进他的事业，创造下一代，‘众包’筛查程序，以丰富AD临床 试点企业。此应用程序的总体目标是利用MindCrowd电子队列来 确定使用SuperG测试的学习能力与认知和日常功能的变化之间的关系 时间，同时在运动-认知交互方面为PI提供宝贵的指导，电子队列和 老龄化背景下的实践效应。基于导师团队的广泛出版和试点工作， 中心假设是，练习对SuperG的影响将预测一年内认知和日常生活的变化 在MindCrowd老年人中的功能。由于SuperG游戏很容易在网上收集，因此 这项在分布式电子队列中提出的研究提供了一种负担得起的有效手段来丰富 AD的临床试验。在这项提议中有两个独立的目标。首先，我们将确定程度 SuperG练习的效果预测了老年人一年的认知变化。第二，我们将 确定SuperG练习效果可以在多大程度上预测老年人一年的功能变化。如果 该项目的成功将为认知老化研究提供一种新的在线筛查工具，该工具具有 有可能丰富未来的阿尔茨海默病和相关痴呆症临床试验。这个项目还 将PI的职业目标和培训活动结合在一起：运动-认知交互，电子 队列和实践效果，共同为建立具有以下特征的“虚拟”实验室提供了独立性 现代能力。此外，这一项目的“社会距离”性质在这一背景下尤其相关 并将允许远程安全地包括参与者。

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.