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年事实和数据报告报告称，虽然认知评估是 所有Medicare年度健康访问都需要，只有16%的受访老年人报告有任何形式的 记忆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， 对与健康老龄化或早期疾病阶段相关的轻度缺陷不敏感， 不适合在受过训练的神经心理学家之外进行常规测试。因此， 为临床应用提供了一种易于管理、可靠和灵敏的海马记忆功能测量方法。我们 我设计了记忆相似性任务（MST），一个修改后的物体识别记忆任务，以提供不 不仅是物体识别记忆的传统测量，而且是“记忆辨别”的测量， 是高度敏感的海马功能，对模式分离有很高的要求。因此， 建议是完成临床MST（cMST）版本的开发和验证，作为一个完整的 封装的工具，将准备用于临床研究和评估作为常规临床工具。 首先，我们将开发一种优化版本的MST，设计用于临床，作为一种敏感的检测方法， 海马功能，快速，但稳健，估计海马记忆性能。设计目标 它是：1）易于在短时间内管理，2）有明确的评分和结果的解释，3） 对中度海马功能障碍敏感，4）证明了可靠性，5）显示了跨 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， 与原始学习项目的预定“记忆相似性”范围。我们现在开发了一个版本的 MST使用连续识别存储格式，并优化目标、箔片和 诱饵，沿着这些诱饵的记忆相似性，用于cMST。在这里，我们将确定是否 这是理想格式，或者贝叶斯自适应版本是否是更优的上级。 然后，我们将在整个生命周期和早期痴呆症中建立cMST的规范性数据。在目标2.1中，我们将 评估cMST对健康老年人记忆衰退的敏感性和有效性，并与标准进行比较 研究级MST和传统的神经心理学测试在一个大的寿命样本。重复检测 个人将被用来建立可靠性和评估实践效果。我们将利用这些数据来创建 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 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， cMST的诊断能力。通过与我们的ADRC合作测试健康和受损的个体，我们 将获得该队列中可用的其他现有海马衰退生物标志物的主机，例如， 通过结构MRI测量单词回忆、CSF tau水平和海马体积。 最后，我们将创建一个通过在线管理大规模分发cMST的模型。最终 该提案的目标是创建一个可用于临床使用的cMST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， 无论是台式机/笔记本电脑设备或触摸屏平板电脑上的一个大的和多样化的样本。UCI的大型同意书 2接触（C2C）数据库（N=3250）为大规模数据收集提供了一个出色的测试用例， 临床或基于实验室的设置，并用于测试其作为诊断筛选工具的潜在用途。

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.