Novel automated performance-based ADL outcomes for early AD clinical trials

用于早期 AD 临床试验的基于性能的新型自动化 ADL 结果

• 批准号: 10370360
• 负责人: GAD ASHER MARSHALL
• 金额: $ 64.18万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370360
• 关键词: Activities of Daily Living; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid; Atrophic; Behavioral; Biological Markers; Caregiver Burden; Caregivers; Cellular Phone; Clinical; Clinical Trials; Clinical dementia rating scale; Cognition; Cognitive; Communication; Companions; Complex; Computers; Data; Dementia; Deposition; Detection; Disease; Disease Progression; Early Diagnosis; Early treatment; Elderly; Funding; Goals; Health Insurance; Image; Impaired cognition; Impairment; Individual; Inferior; Internet; Knowledge; Life; Magnetic Resonance Imaging; Measures; Medical; Memory; North America; Outcome; Outcome Measure; Parietal; Patients; Performance; Physicians; Pittsburgh Compound-B; Positron-Emission Tomography; Prevention trial; Primary Care Physician; Research; Sampling; Secondary Prevention; Source; Sum; Symptoms; System; Technology; Telephone; Testing; Thick; Time; Tracer; United States Food and Drug Administration; Universities; Visualization; Voice; amnestic mild cognitive impairment; clinical outcome measures; cognitive function; design; entorhinal cortex; executive function; functional decline; imaging biomarker; improved; in vivo; instrument; instrumental activity of daily living; mild cognitive impairment; molecular imaging; novel; payment; pre-clinical; prodromal Alzheimer' s disease; recruit; regional atrophy; response; tau Proteins; β-amyloid burden

Project Summary Impairment in activities of daily living (ADL) is a hallmark of Alzheimer’s disease (AD) dementia and a major source of caregiver burden. Similar to cognitive and behavioral changes in AD, subtle difficulties in complex ADL may begin even before the stage of amnestic mild cognitive impairment (MCI). Preclinical AD consists of individuals with minimal or no symptoms but biomarker evidence of AD pathology. As secondary prevention trials in preclinical AD are being launched and the FDA is providing new guidance for early AD trial outcomes, it is imperative that we develop new ecologically valid instruments to detect subtle yet clinically meaningful alterations in complex ADL. Older individuals are increasingly required to interact via telephone and computer-based technology to perform essential ADL. The overall goal of this proposal is to optimize and validate a novel set of automated performance-based ADL instruments, the Harvard Automated Phone Task (APT) and computer- based Czaja Functional Assessment Battery (CFAB), which have been designed to tap the high level tasks that challenge seniors in daily life and to serve as ADL outcomes for preclinical and early prodromal AD clinical trials. For the first time, we have a chance to visualize regional tau deposition in vivo, using a new promising positron emission tomography (PET) tracer, T807, a.k.a. 18F-AV-1451. 1) To date, there have been no consistent associations between ADL performance and AD biomarkers in clinically normal (CN) elderly or early MCI alone. 2) We now have a unique opportunity to relate novel molecular imaging biomarkers of tau and amyloid to our novel ADL instruments. 3) There are no established instruments for detecting early ADL changes in CN individuals who may be in the preclinical stages of AD or in individuals with early prodromal AD. Here we seek to fill this gap in knowledge by further validating the Harvard APT and CFAB. The telephone is still the most prevalent technology mode of communication in the elderly, nearly all of whom in North America own a phone; about a third own a computer; more are starting to use smartphones; and most need to use an interactive voice response system (IVRS) to complete everyday activities. In the Harvard APT, subjects navigate an IVRS in order to refill a prescription (APT-Script), select a new physician (APT-PCP), and make a bank account transfer and payment (APT-Bank). In the CFAB, subjects refill a prescription (CFAB-Script) and perform automated teller machine (ATM) transactions (CFAB-ATM). These tasks simulate real-life activities commonly required of elderly. We will assess the Harvard APT and CFAB in 200 subjects (100 CN, 50 subjective cognitive decline (SCD), and 50 MCI), assess their relationship to cognitive function at baseline and over 3 years, assess their ability to track disease progression, and assess their relationship to AD imaging biomarkers. We will leverage a unique well-characterized sample from other funded studies to recruit the 100 CN subjects, who will already have imaging data and will only need to undergo the novel ADL tests. The 100 SCD and MCI subjects will be newly recruited and will undergo both clinical and imaging assessments.

项目摘要 日常生活活动能力（ADL）受损是阿尔茨海默病（AD）痴呆的一个标志 也是照顾者负担的主要来源。与AD的认知和行为变化相似， 复杂ADL的困难甚至可能在轻度认知遗忘阶段之前就开始开始 损害（MCI）。 临床前AD由具有最小症状或没有症状的个体组成， AD病理学的生物标志物证据。由于临床前AD的二级预防试验正在进行， FDA正在为早期AD试验结果提供新的指导， 我们开发了新的生态有效的仪器来检测微妙的但有临床意义的 复杂ADL的改变。 越来越多的老年人需要通过 电话和基于计算机技术来执行基本的ADL。这个项目的总体目标是 建议是优化和验证一套新的自动化的基于性能的ADL仪器， 哈佛自动电话任务（APT）和基于计算机的Czaja功能评估 电池（CFAB），旨在挖掘挑战老年人的高水平任务， 日常生活，并作为临床前和早期前驱AD临床试验的ADL结果。为 第一次，我们有机会在体内可视化区域tau沉积，使用新的 有前途的正电子发射断层扫描（PET）示踪剂，T807，又名 18F-AV-1451 1)到 迄今为止，ADL表现与AD生物标志物之间没有一致的相关性， 临床正常（CN）的老年人或单独的早期MCI。2)我们现在有一个独特的机会 tau蛋白和淀粉样蛋白的新型分子成像生物标志物与我们的新型ADL仪器。3)没有 已建立的用于检测CN个体早期ADL变化的工具， 在AD的临床前阶段或患有早期前驱AD的个体中。在这里我们寻求 通过进一步验证哈佛APT和CFAB来填补这一知识空白。 电话仍然是老年人最普遍的通信技术模式， 在北美，所有的人都拥有一部电话，大约三分之一的人拥有一台电脑，更多的人开始使用 智能手机;大多数人需要使用交互式语音应答系统（IVRS）来完成日常工作 活动在哈佛APT中，受试者导航IVRS以重新填充处方 （APT-Script），选择新医生（APT-PCP），并进行银行账户转账和付款 （APT-Bank）.在CFAB中，受试者重新填写处方（CFAB脚本）并执行自动柜员机 自动柜员机（ATM）交易（CFAB-ATM）。这些任务模拟现实生活中的活动， 老年人。我们将在200名受试者中评估哈佛APT和CFAB（100名CN，50名主观 认知功能下降（SCD）和50 MCI），评估其与基线认知功能的关系 3年以上，评估他们跟踪疾病进展的能力，并评估他们之间的关系。 AD成像生物标志物。我们将利用其他资助的独特的特征鲜明的样本， 招募100名CN受试者的研究，这些受试者已经有成像数据，只需要 进行新的ADL测试。100名SCD和MCI受试者将是新招募的， 临床和影像学评估。

项目成果

Measurement of Dimensions of Self-awareness of Memory Function and Their Association With Clinical Progression in Cognitively Normal Older Adults.

• DOI: 10.1001/jamanetworkopen.2023.9964
• 发表时间: 2023-04-03
• 期刊: JAMA network open
• 影响因子: 13.8

Associations of the Harvard Automated Phone Task and Alzheimer's Disease Pathology in Cognitively Normal Older Adults: Preliminary Findings.

• DOI: 10.3233/jad-220885
• 发表时间: 2023
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: Gonzalez C;Mimmack KJ;Amariglio RE;Becker JA;Chhatwal JP;Fitzpatrick CD;Gatchel JR;Johnson KA;Katz ZS;Kuppe MK;Locascio JJ;Udeogu OJ;Papp KV;Premnath P;Properzi MJ;Rentz DM;Schultz AP;Sperling RA;Vannini P;Wang S;Marshall GA
• 通讯作者: Marshall GA

Depressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease.

常染色体显性阿尔茨海默病的抑郁症状和海马体积。

• DOI: 10.1002/alz.13501
• 发表时间: 2024
• 期刊: Alzheimer's & dementia : the journal of the Alzheimer's Association
• 作者: Langella,Stephanie;Lopera,Francisco;Baena,Ana;Fox-Fuller,JoshuaT;Munera,Diana;Martinez,JairoE;Giudicessi,Averi;Vannini,Patrizia;Hanseeuw,BernardJ;Marshall,GadA;Quiroz,YakeelT;Gatchel,JenniferR
• 通讯作者: Gatchel,JenniferR