DETECT-AD: Digital Evaluations and Technologies Enabling Clinical Translation for Alzheimer's Disease

项目摘要 这项研究(检测-AD或数字评估和支持AD临床翻译的技术) 目标是从根本上 无症状 改善早期有意义的认知功能评估 阿尔茨海默病(AD)使用基于家庭的主要被动数字评估方法。 为了实现这一目标，该方法将在一项预期的36个月的临床前AD试验模拟中进行测试，使用 当前的、可共享的、技术不可知的、基于家庭的评估平台，不断产生被动 以及交互式传感器衍生的数字生物标记物(DB)和日常认知和功能的指标(数字 活动寿命状态指示器或刻度盘)。该平台还允许远程捕获传统临床 评估。具有明确淀粉样蛋白状态的参与者(基于相对淀粉样蛋白正电子发射计算机断层扫描的β-高与β-低 负担)将被录取。β高的参与者会进步，就像他们在接受安慰剂一样；那些低水平的参与者 Aβ负担会有较小的进展，模拟有效的治疗。参与者将被问及 每日服用一种复合维生素作为研究“药物”，以模拟试验条件。主要结果将是在 DB和复合拨号来自四个关键领域：移动性(步态速度)、认知(计算机使用)、 睡眠(睡眠时间)、社交(外出时间)。具体目标是：1)确定疾病的进展速度 DBS(移动性、认知力、睡眠和社交参与度)单独和作为一个综合指标(Dial) 在食品和药物管理局阶段1-3 AD(Aβ高与Aβ低)参与者，通过建立早期基本利率(前几个月 监测)进程，然后是纵向变化；2)建立这些数据库与 试验中使用的常规措施(CDR-SOB、ADCS-PACC)；以及3)调查探索性目的 检查这些数据库的几个高价值特征以便在试验和相关研究中应用，包括：3.1) 将数据库和Dial与传统的成像和基于血液的炎症生物标记物相关联， 神经变性、血管风险或损伤以及营养健康；3.2)决定随时间的变化 嵌入式“认知时钟”(完成每周定期在线报告查询和每月认知查询的时间 测试)；3.3)建立不良事件随时间的波动(情绪；疾病；疼痛；急诊室、医生、医院就诊； 伤害；非研究用药改变)通过每周远程评估；以及3.4)评估研究伙伴的 DBS相对于AD患者的变化(移动性、睡眠、社交参与度)。 学习 因此， 成功完成这项工作 将提供基本的经过验证的数据库和拨号数据，提高治疗响应读数的灵敏度； 提升AD临床试验能力和能力。其目的不仅是验证单个应用程序或设备， 但为了推进生态有效的多领域评估，以及针对环境的整个试验， 数据库促进的协议，可以被修改和共享，以供任何未来的临床试验使用。

Project Summary This study (DETECT-AD or Digital Evaluations and Technologies Enabling Clinical Translation for AD) objective is to fundamentally asymptomatic improve assessment of meaningful cognitive function in early pre- or Alzheimer's Disease (AD) using largely passive home-based digital assessment methods.To achieve this goal the approach will be tested in a prospective 36-month pre-clinical AD trial simulation using a current, sharable, technology agnostic, home-based assessment platform, continuously generating passive and interactive sensor-derived digital biomarkers (DBs) and metrics of everyday cognition and function (digital indicators of active life status or DIALS). The platform also allows for remote capture of conventional clinical assessments. Participants with defined amyloid status (Aβ-high vs. Aβ-low based on relative amyloid PET burdens) will be enrolled. Aβ-high participants will progress as if they were receiving placebo; those with lower Aβ burdens will have less progression, simulating effective treatment. Participants will be asked to take a daily multivitamin as a study `drug' to mimic trial conditions. The primary outcome will be change in the DBs and composite DIALS from four key domains: mobility (gait speeds), cognition (computer usage), sleep (sleep times), socialization (time out of home). Specific Aims are to: 1) Determine rates of progression of DBs (of mobility, cognition, sleep and social engagement) individually and as an aggregate metric (the DIALS) in FDA stage 1-3 AD (Aβ-high vs. Aβ-low) participants, by establishing early base rates (first months of monitoring) of progression, and then, longitudinal change; 2) Establish the utility of these DBs compared to conventional measures (CDR-SoB, ADCS-PACC) used in trials; and 3) Investigate Exploratory Aims examining several high-value features of these DBs for application in trials and related studies including: 3.1) Correlate DBs and DIALS with conventional imaging and blood-based biomarkers of inflammation, neurodegeneration, vascular risk or injury, and nutritional health; 3.2) Determine the change over time of embedded “cognitive clocks” (time to complete regular weekly online report queries and monthly cognitive tests); 3.3) Establish adverse event fluctuations over time (mood; illness; pain; ER, doctor, hospital visits; injury; non-study medication changes) via weekly remote assessment; and 3.4) Assess the study partner's DBs change relative to the person with AD (mobility, sleep, social engagement). study thus Successful completion of this will provide foundational validated DB and DIALS data improving treatment response readout sensitivity; advancing AD clinical trial capability and capacity.The intent is to not only validate a single app or device, but to advance ecologically valid multi-domain assessment, as well as an entire trials-environment specific, DB-facilitated protocol that could be adapted and shared for use by any clinical trial going forward.