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 基于智能手机的数字认知评估专为有危险的参与者设计 综合征相关的阿尔茨海默氏病（DS-AD）。我们将与伦敦，巴塞罗那，慕尼黑的网站合作 和哥德堡以不同的文化和语言开发和验证这种方法。几乎全部 唐氏综合症的个体在阿尔茨海默氏病（AD）生物标志物的水平升高时 尽管并非全部显示出AD的症状，但处于30多岁或40多岁。是在症状和早期的期间 DS-AD的有症状阶段，即对认知变化的深入了解至关重要，因为治疗 停止，缓慢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 以及通过标准的“桌面”纸和铅笔测试评估AD人群评估认知的观察性研究。 但是这些常规的方法有几个缺点。首先，性能受到日常的影响 压力，疲劳，睡眠方式和情绪的波动。其次，测试发生在环境中 与认知在日常生活中起作用的根本不同。最后，根据设计， 通常，每年或半年度在扩展测试课程中以“单次”评估认知。 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 专门针对唐氏综合症的个体。这种方法在 哪些参与者每天几次对其智能手机进行非常简短的认知测试一周 生活在自然环境中。测试不是专注于这些测量之一，而是 在一周中平均以提供捕获自然变异性并急剧范围的分数 提高可靠性。对常染色体显性和零星AD的原始弧评估的研究 表现出与广告生物标志物的非凡可靠性和牢固的关系，同时降低了昂贵的和 繁重的临界评估。该研究有两个阶段：一个2年的发展阶段和3年 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 DS-AD研究中使用的认知应用程序（ARC）应用程序。这将包括一个迭代飞行员 测试精神计量学和任务开发，焦点小组和用户经验测试以解决的测试过程 DS-AD人群的可及性和兼容性问题，以及准备审核，以确保DS- ARC应用程序符合严格的临床试验申请准则。在第2阶段，参与者完成了DS- 每6个月进行一次弧度评估，并完成AD的标准临床，认知和血液测试 每年生物标志物。我们假设DS-ARC评估是可访问，敏感和可靠的 DSAD认知变化的指标，并将与AD生物标志物和疾病阶段展示 超过常规临界评估的评估。