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).

项目总结 阿尔茨海默病(AD)表型的本质是记忆力下降。早在……开始之前 明显的痴呆症，患者及其家人注意到的记忆变化会减少 那些受影响的人的生活质量。针对症状前期和早期的治疗干预 有症状的AD阶段通常选择一个认知终点来证明疗效，但传统的 记忆力评估往往无法捕捉到疾病早期发生的这些细微变化。其中一个原因是 传统的记忆评估不能反映记忆是如何在日常生活中被依赖的 参与者。例如，对于患者来说，经历健忘之类的记忆衰退是非常痛苦的 姓名，丢失个人物品，或难以记住书或电影的情节。常规存储器 测试在很短的时间内评估回忆，通常是在学习信息后30分钟或更短的时间，而在 在病人的日常生活中，关键信息必须在更长的时间内被回忆起来，如几小时、几天、 甚至是几周来维持生活质量。多项临床研究表明，延长回忆时间 新获得的信息从通常的30分钟或更短的延迟期大幅延长到更长的时间间隔 增加衰减率，这一概念被称为加速长期遗忘(ALF)。我们已经证明了 携带常染色体显性遗传性阿尔茨海默病(ADAD)突变的参与者 症状前，在常规记忆测试中的表现类似于非携带者。最重要的是，当我们测试 突变携带者在7天后的长期召回中，他们丢失的信息比非携带者多得多， 这表明延长回忆时间可能会揭示记忆巩固方面的重要差异 早在明显的痴呆症症状出现之前就表现出来了。 在临床人群中测量ALF的一个明显挑战是负担。传统的测试将会 需要研究参与者多次访问，并需要与研究人员进行多次互动，这是 在实践上和财务上都是不可行的。智能手机的日益普及为我们提供了一个评估 阿尔茨海默病高危人群的认知能力，同时允许长期随访，而不会造成过多负担或 财务影响。在这项研究中，我们将为基于智能手机的管理和 验证其对症状前常染色体显性AD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情况审计，由此产生的应用程序源代码将是 免费提供的。最终目标是开发一种高度敏感、可访问和具有临床意义的 用于国际AD临床试验的认知终点，包括将ALF措施添加到Domainly 遗传性阿尔茨海默病网络-试验单位(DIAN-TU)。