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 日常生活活动的损害（ADL）是阿尔茨海默氏病（AD）痴呆的标志 以及护理人员负担的主要来源。类似于AD的认知和行为变化，微妙 复杂ADL的难度甚至可能在最轻度认知阶段之前开始 损害（MCI）。临床前广告由最少或没有症状的个体组成，但 生物标志物AD病理学的证据。作为临床前广告中的二级预防试验 启动，FDA为早期广告试验结果提供了新的指导，必须 我们开发了新的具有生态有效的工具来检测微妙但临床上有意义的 复杂ADL的改变。越来越需要老年人通过 基于电话和计算机的技术，以执行基本ADL。总体目标 建议是优化和验证一组新型的基于性能的ADL仪器， 哈佛大学自动电话任务（APT）和基于计算机的Czaja功能评估 电池（CFAB）旨在利用挑战老年人的高级任务 日常生活，并作为临床前和早期前驱AD临床试验的ADL结果。为了 第一次，我们有机会使用新的 有希望的正电子发射断层扫描（PET）Tracer，T807，又称18F-AV-1451。 1）到 日期，ADL性能与广告生物标志物之间没有一致的关联 临床正常（CN）单独或早期MCI。 2）我们现在有一个独特的机会来联系 Tau和淀粉样蛋白的新型分子成像生物标志物针对我们的新型ADL仪器。 3）没有 已建立的工具，用于检测可能在CN的CN个体的早期ADL变化 AD的临床前阶段或早期前驱AD的个体的临床前阶段。我们在这里寻找 通过进一步验证哈佛APT和CFAB来填​​补这一空白。 电话仍然是最普遍的技术通信方式，几乎是 所有人在北美拥有电话；大约三分之一的计算机；更多开始使用 智能手机；大多数需要使用交互式语音响应系统（IVR）每天完成 活动。在哈佛大学，受试者在IVR中导航以补充处方 （APT-Script），选择一个新的Buthynian（APT-PCP），然后进行银行帐户转移和付款 （APT银行）。在CFAB中，受试者补充处方（CFAB-script）并执行自动柜员 机器（ATM）交易（CFAB-ATM）。这些任务模拟了通常需要的现实生活活动 较早的。我们将评估200名受试者的哈佛大学APT和CFAB（100 CN，50个主观 认知能力下降（SCD）和50 MCI）评估其与基线时的认知功能的关系 并评估他们追踪疾病进展的能力并评估其关系 广告成像生物标志物。我们将利用其他资助的独特特征样本 招募100个CN受试者的研究，他们已经拥有成像数据，只需要 经过新颖的ADL测试。 100个SCD和MCI主题将新招募，并将接受 临床和成像评估。

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

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

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