DS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer's Disease

DS-ARC：针对唐氏综合症相关阿尔茨海默病的远程数字认知评估

• 批准号: 10638314
• 负责人: Jason J Hassenstab
• 金额: $ 196.13万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10638314
• 关键词: Address; Adoption; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease blood test; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Biological Markers; Blood; Cellular Phone; Chromosome 21; Clinic; Clinical; Clinical Trials; Cognition; Cognitive; Data; Development; Devices; Disease; Down Syndrome; Elderly; Environment; Evaluation; Exhibits; Fatigue; Focus Groups; Geography; Glial Fibrillary Acidic Protein; Goals; Guidelines; Hematological Disease; Human Resources; Impaired cognition; Individual; International; Laboratories; Language; Life; Light; London; Measurement; Measures; Methodology; Methods; Moods; Nature; Observational Study; Outcome; Paper; Participant; Performance; Persons; Phase; Phenotype; Plasma; Population; Predisposition; Prevention trial; Process; Psychometrics; Readiness; Research; Risk; Role; Series; Serum; Site; Sleep; Source; Stress; Symptoms; Techniques; Technology; Testing; Therapeutic Intervention; Time; Validation; Work; autosomal dominant Alzheimer' s disease; autosome; cognitive ability; cognitive change; cognitive testing; cohort; cost; critical period; design; digital; digital assessment; disease phenotype; effectiveness evaluation; experience; genetic variant; handheld mobile device; improved; insight; lifetime risk; neurofilament; open source; pilot test; prevent; rate of change; research study; sleep pattern; smartphone application; smartphone based assessment; stressor; synuclein; tau-1; technology development

PROJECT SUMMARY The Down Syndrome – Ambulatory Research in Cognition (DS-ARC) study will develop and validate a smartphone-based digital cognitive assessment designed specifically for participants at risk for Down syndrome-associated Alzheimer’s disease (DS-AD). We will partner with sites in London, Barcelona, Munich, and Gothenburg to develop and validate this approach in different cultures and languages. Nearly all individuals with Down syndrome have elevated levels of Alzheimer’s disease (AD) biomarkers by the time they are in their 30s or 40s, though not all show symptoms of AD. It is during the pre-symptomatic and early symptomatic stages of DS-AD that an in-depth understanding of cognitive changes is crucial, as therapeutic interventions to stop, slow, or prevent disease are focused on these critical periods. Typically, prevention trials and observational studies in AD populations assess cognition with standard “table top” paper and pencil tests. But these conventional methods have 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 cognition is relied upon to function in daily life. Finally, by design, cognition is typically assessed in “one-shot” in extended testing sessions on an annual or semiannual basis. The DS-ARC study will address these difficulties by developing a smartphone-based assessment solution adapted specifically for individuals with Down syndrome. This approach uses a measurement “burst” design in which participants complete very brief cognitive tests on their smartphones several times per day for one week while living in their natural environments. Instead of focusing on one of these measurements, tests are averaged across the week to provide a score that captures and normalizes natural variability and dramatically increases reliability. Studies of our original ARC assessments in autosomal dominant and sporadic AD demonstrate extraordinary reliability and strong relationships with AD biomarkers, while reducing costly and burdensome in-clinic evaluations. The study has two phases: a 2-year development phase and a 3-year validation phase. In the development phase, we will adapt an existing smartphone application called the Ambulatory Research in Cognition (ARC) app for use in DS-AD studies. This will include an iterative pilot testing process for psychometrics and task development, focus groups and user experience testing to address accessibility and compatibility concerns for DS-AD populations, and readiness audits to ensure that the DS- ARC app meets strict compliance guidelines for clinical trial applications. In Phase 2, participants complete DS- ARC assessments every 6 months and complete standard clinical, cognitive, and blood tests for AD biomarkers annually. We hypothesize that DS-ARC assessments are accessible, sensitive, and reliable indicators of cognitive change in DS-AD and will exhibit associations with AD biomarkers and disease stage over and above those of conventional in-clinic assessments.

项目摘要 唐氏综合症-认知研究（DS-ARC）研究将开发和验证一个 基于智能手机的数字认知评估，专为有Down风险的参与者设计 综合征相关的阿尔茨海默病（DS-AD）。我们将与伦敦、巴塞罗那、慕尼黑、 和哥德堡，在不同的文化和语言中发展和验证这种方法。几乎所有 唐氏综合症患者在接受治疗时，阿尔茨海默病（AD）生物标志物水平升高 年龄在30或40多岁，但并非所有人都表现出AD的症状。在症状前和早期， DS-AD的症状阶段，深入了解认知变化至关重要， 阻止、减缓或预防疾病的干预措施集中在这些关键时期。通常，预防试验 在AD人群中的观察性研究用标准的“桌面”纸笔测试评估认知。 但是这些传统方法有几个缺点。首先，业绩受到日常影响 压力、疲劳、睡眠模式和情绪的波动。第二，测试在以下环境中进行： 与日常生活中依赖认知发挥作用的地方有着根本的不同。最后，通过设计， 认知通常在每年或每半年的扩展测试中以“一次性”方式进行评估。 DS-ARC研究将通过开发基于智能手机的评估解决方案来解决这些困难 专门为唐氏综合症患者设计的该方法使用测量“突发”设计， 参与者每天在智能手机上完成几次非常简短的认知测试，持续一周。 而生活在自然环境中。而不是集中在这些测量之一，测试是 平均在一周内提供一个分数，捕捉和正常化的自然变化，并显着 提高了可靠性。我们在常染色体显性和散发性AD中进行的原始ARC评估研究 显示出非凡的可靠性和与AD生物标志物的密切关系，同时降低成本和 繁重的门诊评价。该研究分为两个阶段：2年的开发阶段和3年的 验证阶段。在开发阶段，我们将调整现有的智能手机应用程序， 用于DS-AD研究的动态认知研究（ARC）应用程序。这将包括一个迭代试点 心理测量和任务开发的测试过程，焦点小组和用户体验测试，以解决 DS-AD人群的可访问性和兼容性问题，以及准备审计，以确保DS- ARC应用程序符合临床试验应用的严格合规性指南。在第二阶段，参与者完成DS- 每6个月进行一次ARC评估，并完成AD的标准临床、认知和血液检查 生物标志物每年我们假设DS-ARC评估是可访问的、敏感的和可靠的 DS-AD中认知变化的指标，并将表现出与AD生物标志物和疾病分期的相关性 超过常规的临床评估。