Development of the mnemonic similarity task as a tool to address age and dementia-related memory decline

开发助记相似性任务作为解决年龄和痴呆相关记忆衰退的工具

• 批准号: 10361498
• 负责人: Craig E Stark
• 金额: $ 38.07万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10361498
• 关键词: Address; Adopted; Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid beta-Protein; Bayesian Analysis; Behavioral; Biological Assay; Biological Markers; Clinical; Clinical Distribution; Clinical Research; Clinical Trials; Cognitive; Consent; Data; Data Collection; Databases; Dementia; Development; Devices; Discrimination; Disease; Disease Progression; Early identification; Elderly; Encapsulated; Evaluation; Exercise; Exhibits; Functional disorder; Goals; Healthcare; Hippocampus (Brain); Impairment; Individual; Investigation; Japanese; Levetiracetam; Link; Longevity; Magnetic Resonance Imaging; Measures; Medicare; Memory; Memory Loss; Memory impairment; Methods; Modeling; Monitor; Neuropsychological Tests; Neuropsychology; Pattern; Performance; Persons; Pharmacologic Substance; Population; Publications; Reporting; Research; Sampling; Screening procedure; Standardization; Stimulus; Structure; Surveys; Tablets; Testing; Time; Training; Treatment Effectiveness; Validation; Variant; Visit; age group; age related; base; clinical development; clinically relevant; cognitive testing; cohort; design; diagnostic screening; diagnostic value; early detection biomarkers; effectiveness evaluation; healthy aging; high risk; improved; laptop; large scale data; longitudinal design; memory recognition; mild cognitive impairment; object recognition; racial and ethnic; tau Proteins; tool; touchscreen

Project Summary The Alzheimer’s Association’s 2019 Facts and Figures Report reports that while a cognitive assessment is required for all Medicare Annual Wellness Visit, only 16% of surveyed older adults reported having any form of memory assessment. While standardized neuropsychological tasks are sensitive to gross memory deficits, they are not as sensitive to milder deficits associated with healthy aging or early disease stages and they are often poorly suited for routine testing outside of trained neuropsychologist practitioners. Thus, there is a critical need for an easy-to administer, reliable, and sensitive measure of hippocampal memory function for clinical use. We have designed the Mnemonic Similarity Task (MST), a modified object recognition memory task, to provide not only a traditional measure of object recognition memory, but also a measure of “mnemonic discrimination” that is highly sensitive hippocampal function by placing strong demands on pattern separation. Thus, the goal of this proposal is to complete the development and validation of version of the clinical MST (cMST) as a fully encapsulated tool that would be ready for use in clinical research and for evaluation as a routine clinical tool. First, we will develop an optimized version of the MST designed for clinical use as a sensitive assay of hippocampal function that rapidly, but robustly, estimates hippocampal memory performance. The design goals are that it is: 1) easy to administer in a short amount of time, 2) has clear scoring and interpretation of results, 3) is sensitive to modest hippocampal dysfunction, 4) demonstrates reliability, and 5) exhibits general utility across a range of racial/ethnic/age groups. At the core of the MST is the use of highly similar lure items that have a range of pre-determined “mnemonic similarity” to the original studied item. We have now developed a version of the MST that uses a continuous recognition memory format and optimizes the distribution of targets, foils, and lures, along with the mnemonic similarity of those lures, for use in the cMST. Here, we will determine whether that is an ideal format or whether a Bayesian adaptive version is superior. Then we will establish normative data on the cMST across the lifespan and in early dementia. In Aim 2.1, we will evaluate the sensitivity and validity of the cMST to memory decline in healthy aging, comparing it to the standard research-grade MST and to traditional neuropsychological tests in a large lifespan sample. Repeat testing of individuals will be used to establish reliability and assess practice effects. We will use these data to create normative data. In Aim 2.2, we will extend these investigations to clinical populations - specifically to those with Mild Cognitive Impairment or early AD through the UCI Alzheimer’s Disease Research Center (ADRC) to determine both viability and normative performance of our measures in these impaired populations and diagnostic ability of the cMST. By working with our ADRC for testing both healthy and impaired individuals, we will gain access to a host of other existing biomarkers of hippocampal decline available in this cohort, such as word recall, CSF tau levels, and hippocampal volume measures via structural MRI. Finally, we will create a model for large-scale distribution of the cMST via online administration. The ultimate goal of this proposal is to create an encapsulated version of the cMST that can be adopted for clinical use that is independent of a research lab. In Aim 3, we will distribute this task via a downloadable link that can be used on either desktop/laptop devices or on touchscreen tablets to a large and diverse sample. UCI’s large Consent 2 Contact (C2C) database (N=3250) provides an outstanding test case for large-scale data collection outside of a clinical or lab-based setting and for testing its potential use as a diagnostic screening tool.

项目概要 阿尔茨海默病协会的 2019 年事实和数据报告报告称，虽然认知评估 所有 Medicare 年度健康就诊都需要进行，但只有 16% 的受访老年人表示患有任何形式的 记忆力评估。虽然标准化的神经心理学任务对总体记忆缺陷很敏感，但它们 对与健康老龄化或早期疾病阶段相关的轻度缺陷不那么敏感，并且它们通常 不适合在训练有素的神经心理学家之外进行常规测试。因此，迫切需要 为临床使用提供一种易于管理、可靠且灵敏的海马记忆功能测量方法。我们 设计了助记相似性任务（MST），这是一种修改后的对象识别记忆任务，以提供不 不仅是物体识别记忆的传统衡量标准，也是“记忆辨别”的衡量标准 通过对模式分离提出强烈要求，海马功能变得高度敏感。因此，本次活动的目标 建议完成临床 MST (cMST) 版本的开发和验证，作为一个完整的 封装的工具可用于临床研究并作为常规临床工具进行评估。 首先，我们将开发 MST 的优化版本，设计用于临床用途，作为 海马功能可以快速而稳健地估计海马记忆表现。设计目标 它是：1）易于在短时间内管理，2）具有清晰的评分和结果解释，3） 对适度的海马功能障碍敏感，4) 表现出可靠性，并且 5) 表现出跨领域的普遍实用性 一系列种族/族裔/年龄组。 MST 的核心是使用高度相似的诱饵物品，这些物品具有 与原始学习项目的预先确定的“助记相似度”范围。我们现在开发了一个版本 MST使用连续识别内存格式并优化目标、箔片和 诱饵，以及这些诱饵的助记符相似性，用于 cMST。在这里，我们将确定是否 这是一种理想的格式，还是贝叶斯自适应版本是否更优越。 然后我们将建立整个生命周期和早期痴呆症 cMST 的规范数据。在目标 2.1 中，我们将 评估 cMST 对健康老龄化记忆衰退的敏感性和有效性，并将其与标准进行比较 研究级 MST 和大型生命周期样本中的传统神经心理学测试。重复测试 将使用个人来建立可靠性并评估实践效果。我们将使用这些数据来创建 规范数据。在目标 2.2 中，我们将把这些研究扩展到临床人群——特别是那些患有 轻度认知障碍或早期 AD 通过 UCI 阿尔茨海默病研究中心 (ADRC) 来 确定我们的措施在这些受损人群中的可行性和规范性表现， cMST 的诊断能力。通过与我们的 ADRC 合作对健康和受损的个体进行测试，我们 将获得该队列中可用的许多其他现有海马衰退生物标志物，例如 通过结构 MRI 进行单词回忆、脑脊液 tau 蛋白水平和海马体积测量。 最后，我们将创建一个通过在线管理大规模分发 cMST 的模型。终极 该提案的目标是创建可用于临床用途的封装版本的 cMST 独立于研究实验室。在目标 3 中，我们将通过可使用的可下载链接来分发此任务 在台式机/笔记本电脑设备或触摸屏平板电脑上进行大型且多样化的示例。 UCI 的大力同意 2 联系人（C2C）数据库（N=3250）为外部大规模数据收集提供了出色的测试用例 临床或基于实验室的环境，并测试其作为诊断筛查工具的潜在用途。