Digital Assessment of Long-term Forgetting in Autosomal-Dominant Alzheimer's Disease

常染色体显性阿尔茨海默病长期遗忘的数字化评估

• 批准号: 10728638
• 负责人: Jason J Hassenstab
• 金额: $ 50.5万
• 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: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728638
• 关键词: Acceleration; Alzheimer' s Disease; Alzheimer' s disease risk; Books; Cellular Phone; Clinic; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Decentralization; Dementia; Development; Digital biomarker; Disease; Distress; Effectiveness; Elderly; Episodic memory; Family member; Film; First Name; Floor; Genetic Risk; Goals; Hour; Human Resources; Impaired cognition; Inherited; International; Laboratories; Learning; Measurement; Measures; Memory; Memory Loss; Methods; Mutation; Observational Study; Participant; Patients; Pattern; Persons; Phase; Pilot Projects; Population; Populations at Risk; Prevention trial; Process; Psychometrics; Quality of life; Research; Research Design; Signal Transduction; Source Code; Symptoms; Testing; Therapeutic Intervention; Time; Visit; Visual; autosomal dominant Alzheimer' s disease; autosomal dominant mutation; clinical phenotype; clinical trial readiness; cognitive change; cognitive testing; design; digital; digital assessment; digital measure; disease phenotype; effectiveness evaluation; experience; follow-up; forgetting; improved; long term memory; memory consolidation; mild cognitive impairment; mutation carrier; novel; prevent; remote administration; remote grading; technology development; verbal

PROJECT SUMMARY The essence of the Alzheimer’s disease (AD) phenotype is a decline in memory. Well before the onset of obvious dementia, there are changes in memory that patients and family members notice which diminish quality of life for those impacted. Therapeutic interventions that target the presymptomatic and early symptomatic stages of AD often choose a cognitive endpoint to demonstrate efficacy, but conventional memory assessments often fail to capture these subtle changes that occur early in the disease. One reason is that conventional memory assessments do not reflect how memory is relied upon in the everyday lives of participants. For example, it is very distressing for patients to experience memory lapses like forgetting first names, losing personal items, or having difficulty remembering the plot of a book or film. Conventional memory testing assesses recall at short periods, typically 30-minutes or less after learning the information, whereas in the everyday lives of patients, critical information must be recalled over much longer periods like hours, days, or even weeks to maintain quality of life. Several clinical studies have demonstrated that extending recall of newly learned information past the usual 30-minute or less delay period to much longer intervals dramatically increases the rate of decay, a concept known as accelerated long-term forgetting (ALF). We have shown that participants who carry a mutation for autosomal dominant Alzheimer’s disease (ADAD) but who are presymptomatic, perform similarly to non-carriers on conventional memory testing. Critically, when we tested mutation carriers on their long-term recall at 7 days, they had lost much more information than non-carriers, suggesting that extending the recall period may reveal important differences in memory consolidation that manifest well before the onset of noticeable dementia symptoms. An obvious challenge for measuring ALF in clinical populations is burden. Conventional testing would require multiple visits from study participants and require multiple interactions with study personnel, which is practically and financially unfeasible. The increasing ubiquity of smartphones provides an opportunity to assess cognition in populations at risk for AD, while allowing for longer-term follow-up without excessive burden or financial impact. In this study, we will develop novel ALF measures for smartphone-based administration and validate their effectiveness in presymptomatic autosomal dominant AD. Our development process will include user experience studies and clinical trial readiness audits, and the resulting application source code will be made freely available. The ultimate goal is to develop a highly sensitive, accessible, and clinically meaningful cognitive endpoint for use in international AD clinical trials, including adding ALF measures to the Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU).

项目概要 阿尔茨海默病（AD）表型的本质是记忆力下降。早在发病前 明显的痴呆症，患者和家人注意到记忆力发生变化，从而减弱 受影响者的生活质量。针对症状前和早期的治疗干预措施 AD 的症状阶段通常会选择一个认知终点来证明疗效，但传统方法 记忆评估通常无法捕捉到疾病早期发生的这些微妙变化。原因之一是 传统的记忆评估并不能反映人们在日常生活中如何依赖记忆 参与者。例如，患者首先会经历遗忘等记忆衰退，这是非常痛苦的 姓名、丢失个人物品或难以记住书籍或电影的情节。常规内存 测试评估短期内的回忆，通常是学习信息后 30 分钟或更短的时间，而在 在患者的日常生活中，必须在更长的时间内回忆关键信息，例如数小时、数天、 甚至几周来维持生活质量。多项临床研究表明，延长记忆 新获知的信息经过通常的 30 分钟或更短的延迟时间，显着延长到更长的时间间隔 增加衰退速度，这个概念被称为加速长期遗忘（ALF）。我们已经证明 携带常染色体显性阿尔茨海默病 (ADAD) 突变但患有 出现症状前，在传统记忆测试中的表现与非携带者类似。关键的是，当我们测试时 突变携带者在 7 天的长期记忆中，他们比非携带者丢失了更多的信息， 表明延长回忆时间可能会揭示记忆巩固方面的重要差异 在明显的痴呆症状出现之前就表现出来。 在临床人群中测量 ALF 的一个明显挑战是负担。常规测试将 需要研究参与者的多次访问，并需要与研究人员的多次互动，这是 实际上和财务上都不可行。智能手机的日益普及提供了评估的机会 提高有 AD 风险人群的认知能力，同时允许进行长期随访，而不会造成过多的负担或 财务影响。在这项研究中，我们将开发新颖的 ALF 措施，用于基于智能手机的管理和 验证其在症状前常染色体显性 AD 中的有效性。我们的开发流程将包括 用户体验研究和临床试验准备审核，以及由此产生的应用程序源代码 免费提供。最终目标是开发一种高度敏感、易于使用且具有临床意义的方法 用于国际 AD 临床试验的认知终点，包括在显性试验中添加 ALF 测量 遗传性阿尔茨海默病网络试验单位 (DIAN-TU)。