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

项目摘要 阿尔茨海默氏症协会的2019年事实和数字报告报告称，虽然认知评估是 在所有医疗保险年度健康访问中，只有16%的受访老年人报告有任何形式的 记忆力评估。虽然标准化的神经心理任务对总记忆缺陷很敏感，但他们 对与健康衰老或早期疾病阶段相关的较轻微的缺陷不那么敏感，而且它们通常 不适合在训练有素的神经心理学家从业人员之外进行常规测试。因此，迫切需要 为临床应用提供一种易于管理、可靠和灵敏的海马区记忆功能测量方法。我们 设计了记忆相似性任务(MST)，这是一种改进的物体识别记忆任务，提供了 这不仅是物体识别记忆的传统衡量标准，也是一种“记忆识别”的衡量标准 是高度敏感的海马区功能，对模式分离提出了强烈的要求。因此，这一目标是 建议完成临床MST(CMST)版本的开发和验证 封装式工具，可用于临床研究并作为常规临床工具进行评估。 首先，我们将开发一种用于临床的MST的优化版本，作为一种敏感的 海马体的功能迅速而有力地评估了海马体的记忆表现。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) 对适度的海马体功能障碍敏感，4)表现出可靠性，5)表现出普遍的实用性 一系列的种族/民族/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 预先确定的“助记符相似度”与原始研究项目的范围。我们现在已经开发了一个版本的 MST使用连续识别存储格式并优化目标、薄片和 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 这是一个理想的格式，或者贝叶斯自适应版本是否更好。 然后，我们将建立关于整个寿命和早期痴呆症的CMST的标准数据。在Aim 2.1中，我们将 评价CMST对健康老年人记忆减退的敏感性和效度，并与标准进行比较 研究级MST和传统的神经心理学测试中的大样本寿命。重复测试 个人将被用来建立可靠性和评估实践效果。我们将使用这些数据来创建 规范性数据。在Aim 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) 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，并 CMST的诊断能力。通过与我们的ADRC合作测试健康和受损的个人，我们 将获得该队列中现有的许多其他海马区衰退的生物标志物，例如 通过结构磁共振测量单词回忆、脑脊液tau水平和海马体体积。 最后，我们将创建一个通过在线管理大规模分发CMST的模式。终极的 该提案的目标是创建可用于临床使用的CMST的封装版本 是独立于研究实验室的。在目标3中，我们将通过可下载的链接分发此任务，该链接可用于 无论是在台式机/笔记本电脑设备上，还是在触摸屏平板电脑上，都可以获得大量不同的样本。UCI的大同意 2个联系人(C2C)数据库(N=3250)为在外部进行大规模数据收集提供了出色的测试案例 临床或实验室环境，用于测试其作为诊断筛查工具的潜在用途。

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.