Optimizing Cognitive Assessment in DIAN with Smartphone-based burst testing

认知动态研究（ARC）研究将利用智能手机的日益普及， 改进标准临床认知测试，提供参与者认知的稳健表征 显性遗传阿尔茨海默病网络（DIAN）研究。其中最重要的和面子有效的 阿尔茨海默病（AD）的指标是认知的变化，但在临床上评估认知有几个 缺点.首先，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， 在日常生活中执行要求很高的任务。最后，通过设计，认知通常被评估得非常 不经常，通常每年或每两年一次（如DIAN的情况）。一个解决方案是 增加门诊检测的频率，但这不切实际且负担沉重，尤其是对于DIAN 参与者DIAN参与者来自有~50%的机会继承一种极其罕见的 AD的常染色体显性遗传致病突变。这些突变的携带者在30岁至40岁之间出现症状。 50岁，比更常见的散发性AD早几十年。大多数仍在工作，许多 是他们年幼的孩子的主要照顾者，通常是受影响的家庭成员，因此前往 更频繁地进行评估是非常繁重的。 ARC研究将通过评估iOS和Android的认知能力来解决这些困难 应用程序安装在约248名DIAN参与者的个人智能手机上。每三个月，参与者将完成 在一周的时间里，每天进行4次非常简短的（每次<3分钟）测试。测试平均 提供一个分数，捕捉和正常化的自然变化，并显着增加 可靠性初步研究表明，ARC评估表现出非凡的可靠性，范围从0.86到 0.98.另一个优点是能够测量一天内、一周内和3- 10年内的变化。 评估间隔一个月。我们假设ARC评估将比诊所内更敏感 评估疾病阶段和AD生物标志物，DIAN中的突变携带者将显示更多的变异性， 在认知能力方面比非携带者，即使在疾病的临床前阶段。如果成功， ARC评估的灵敏度和可靠性的提高将提供非凡的统计能力， 在AD的观察性研究中描述认知下降的特征。此外，ARC评估可能有助于 通过缩短试验时间和减少参与者来进行临床试验。

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.