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 日常生活能力障碍(ADL)是阿尔茨海默病(AD)痴呆的一个特征 也是照顾者负担的主要来源。类似于AD的认知和行为变化，微妙 复杂ADL的困难甚至可能在遗忘性轻度认知阶段之前就开始了 损害(MCI)。临床前AD由有轻微症状或没有症状的个体组成，但 AD病理的生物标记物证据。由于临床前AD的二级预防试验正在进行中 启动，FDA正在为AD早期试验结果提供新的指导，当务之急是 我们开发了新的生态有效的仪器来检测微妙但具有临床意义的 复杂ADL的改变。越来越多的老年人被要求通过 以电话和计算机为基础的技术，以执行基本的ADL。这个项目的总体目标是 建议是优化和验证一组新的基于性能的自动化ADL工具， 哈佛自动电话任务(APT)和基于计算机的查贾功能评估 电池(CFAB)，旨在利用挑战老年人的高级任务 并作为临床前和早期先兆AD临床试验的ADL结果。为 第一次，我们有机会在体内可视化局部tau的沉积，使用一种新的 前景看好的正电子发射断层扫描(PET)示踪剂，T807，又名。18F-AV-1451。1)至 到目前为止，在ADL表现和AD生物标志物之间还没有一致的联系 临床正常(CN)的老年人或单独的早期MCI。2)我们现在有了一个独特的机会来联系 将tau和淀粉样蛋白的新分子成像生物标志物添加到我们的新型ADL仪器中。3)没有 已建立的检测慢性阻塞性肺疾病患者早期ADL变化的工具 临床前阶段的阿尔茨海默病或早期先兆阿尔茨海默病的个体。我们在这里寻找 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交流技术方式，近 在北美，所有人都拥有手机；大约三分之一的人拥有电脑；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。在哈佛大学的APT中，受试者通过静脉注射成像仪来补充处方 (APT-SCRIPT)，选择新医生(APT-PCP)，并进行银行转账和付款 (APT-银行)。在CFAB中，受试者重新开处方(CFAB-SCRIPT)并执行自动柜员机 机器(ATM)交易(CFAB-ATM)。这些任务模拟实际生活中通常需要的活动 老年人的生活。我们将在200个科目(100个CN，50个主观科目)中评估哈佛APT和CFAB 认知功能减退(SCD)和50 MCI)，评估它们与基线认知功能的关系 在3年内，评估他们跟踪疾病进展的能力，并评估他们之间的关系 到AD成像生物标记物。我们将利用来自其他基金的独特的、具有良好特征的样本 招募100名CN受试者的研究，他们已经有了成像数据，只需要 接受新奇的ADL测试。100名SCD和MCI受试者将被新招募，并将接受 包括临床和影像评估。

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