Optimizing Cognitive Assessment in DIAN with Smartphone-based burst testing

动态认知研究(ARC)研究将利用智能手机日益普及的优势 改进标准的临床认知测试，为参与者的认知提供可靠的表征 参加了多米尼利遗传性阿尔茨海默病网络(DIAN)的研究。最重要和最有说服力的 阿尔茨海默病(AD)的指标是一种认知变化，但在临床上评估认知有几种 缺点。首先，工作表现受到压力、疲劳、睡眠模式和 心情。其次，测试发生在与认知环境根本不同的环境中 繁重的任务是在日常生活中完成的。最后，通过设计，认知能力通常被评估为 不常见，通常是每年一次或每两年一次(如DIAN的情况)。一种解决方案是 增加门诊检查的频率，但这是不切实际和繁重的，特别是对DIAN来说 参与者。Dian参与者来自有大约50%的机会继承极其罕见的 常染色体显性遗传性阿尔茨海默病。这些突变的携带者在30岁至30岁之间出现症状 50岁，比更常见的散发性阿尔茨海默病早几十年。大多数人仍在工作，还有许多人 是他们年幼子女的主要照顾者，通常也是受影响的家庭成员，因此前往 更频繁地使用网站进行评估是非常繁重的。 ARC的研究将通过评估iOS和Android的认知能力来提供这些困难的解决方案 安装在约248名DIAN参与者的个人智能手机上的应用程序。每三个月，参与者将完成 在一周的课程中，每天4次极短(每分钟3分钟)的测试。测试是平均的 提供了一个分数，该分数捕捉并正常化自然变异性，并显著增加 可靠性。试点研究表明，ARC评估显示出非凡的可靠性，范围从0.86到 0.98。另一个优势是能够测量一天内、一周内和三个月内的可变性- 评估的月度间隔。我们假设ARC评估将比门诊更敏感。 对疾病分期和AD生物标志物的评估以及DIAN的突变携带者将显示更多的变异性 在认知表现上比非携带者更好，甚至在疾病的临床前阶段也是如此。如果成功，则 ARC评估的敏感度和可靠性的提高将提供非凡的统计能力 描述阿尔茨海默病观察性研究中认知衰退的特征。此外，ARC评估可能会受益 通过缩短试验持续时间和需要更少的参与者进行临床试验。

The Ambulatory Research in Cognition (ARC) study will leverage the increasing popularity of smartphones to improve upon standard in-clinic cognitive testing, providing a robust characterization of cognition in participants enrolled in the Dominantly-Inherited Alzheimer Network (DIAN) study. One of the most important and face-valid indicators of Alzheimer’s disease (AD) is a change in cognition, but assessing cognition in-clinic has 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 cognitively demanding tasks are performed in daily life. Finally, by design, cognition is typically assessed very infrequently, usually once per year or every two years (as is the case in DIAN). One solution would be to increase the frequency of in-clinic testing, but this is impractical and burdensome, especially for DIAN participants. DIAN participants come from families that have a ~50% chance of inheriting an extremely rare autosomal dominant causal mutation for AD. Carriers of these mutations become symptomatic between 30 and 50 years of age, decades earlier than the more common sporadic form of AD. Most are still working and many are primary caretakers for their young children and often for affected family members, therefore traveling to sites more frequently for assessments is extraordinarily burdensome. The ARC study will provide a solution to these difficulties by assessing cognition with an iOS and Android app installed on ~248 DIAN participants’ personal smartphones. Every three months, participants will complete extremely brief (<3 minutes each) testing sessions 4x/day over the course of one week. Tests are averaged across the week to provide a score that captures and normalizes natural variability and dramatically increases reliability. Pilot studies show that ARC assessments demonstrate extraordinary reliability, ranging from 0.86 to 0.98. Another advantage is the ability to measure variability within a day, across a week, and across the 3- month intervals of assessments. We hypothesize that ARC assessments will be more sensitive than in-clinic assessments to disease stage and AD biomarkers and that mutation carriers in DIAN will show more variability in cognitive performance than non-carriers, even in the preclinical stages of disease. If successful, the increases in sensitivity and reliability of ARC assessments will provide extraordinary statistical power to characterize cognitive decline in observational studies of AD. In addition, ARC assessments could benefit clinical trials by shortening trial duration and requiring fewer participants.