Development and validation of novel tests in the DCT drawing analysis platform for the detection of Alzheimer’s Disease-related early cognitive

在 DCT 绘图分析平台中开发和验证新测试，用于检测与阿尔茨海默病相关的早期认知

• 批准号: 10221367
• 负责人: Sean Michael Tobyne
• 金额: $ 23.78万
• 依托单位: LINUS HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-02 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221367
• 关键词: Development; validation; novel; tests; DCT

Project Summary/Abstract Early detection of AD and AD-related dementias is critical for the development of novel therapeutic agents and for effective patient treatment and care. Linus Health has acquired a platform able to detect subtle changes in behavior indicative of early cognitive impairment by using a digital pen to record drawing motions and automatically analyzing that data using a combination of artificial intelligence and neuropsychological analysis. DCTclockTM, the first test on this platform, has been successfully launched and is able to detect subtle cognitive change in early Alzheimer’s Disease (AD) and AD-related dementias earlier than standard cognitive tests, correlate with known AD biomarkers such as amyloid and tau in preclinical-AD subjects, and detect known APOE genetic risk in cognitively healthy participants. The test is FDA-cleared to market for general cognitive assessment and is currently used in multinational clinical trials, research initiatives, and by practicing clinicians for patient care. Linus Health is now conducting a study involving ~200 participants ranging from cognitively healthy to demented to validate a tablet as input device for the drawing data, and to collect data on a set of novel tablet-based drawing tasks including: a symbol task, a visual retention task, a trail making task, a path-finding task, and a visuoconstructional task. We aim to analyze task data collected in the study to produce a set of easily-deployable, rapid, cost-effective, and sensitive tests to be used as cognitive digital biomarkers in clinical trials for AD and AD-related dementias. The first aim is to develop novel cognitive measures from these additional tests and obtain preliminary validation. Existing data will be split into training and testing sets. The training set will be analyzed to develop metrics, following an interpretable hierarchical analysis structure with low-level drawing measurements combined in a set of composite scales tied to a cognitive concept (i.e., information processing), and then further combined to obtain a simple 0-100 score for performance on the test. The testing set will be used to conduct preliminary validation consisting of a Receiver Operating Characteristic curve analysis, correlation measures to existing neuropsychological tests, and test-retest reliability measurements to ensure repeat testing stability. The second aim is to implement the developed metrics in the commercial Linus platform. Robust software will be created for the measurement, storage, and display of the novel metrics, setting a foundation to enable usage of the metrics by research and commercial partners.

项目摘要/摘要 早期发现AD和与AD相关的痴呆症对于新型治疗剂的发展至关重要 有效的患者治疗和护理。 Linus Health已经获得了一个平台，能够检测到微妙的变化 通过使用数字笔记录绘图动作和 使用人工智能和神经心理学分析的组合自动分析数据。 DCTClockTM是该平台上的第一个测试，已成功启动，能够检测到微妙的 早期阿尔茨海默氏病（AD）和与广告相关的痴呆症的认知变化早于标准认知 测试，与临床前AD受试者中的已知AD生物标志物（例如淀粉样蛋白和TAU）相关，并检测 认知健康参与者中已知的APOE通用风险。该测试已通过FDA清算到一般的市场 认知评估，目前用于跨国临床试验，研究计划以及实践中 患者护理的临床医生。 Linus Health现在正在进行一项研究，涉及约200名参与者 认知健康的痴呆症以验证平板电脑作为图形数据的输入设备，并收集有关 一组基于平板电脑的新型绘图任务，包括：符号任务，视觉保留任务，跟踪任务，一个 路径找到任务和视觉构造任务。 我们旨在分析研究中收集的任务数据，以生成一组易于删除，快速，成本效益， 在AD和AD相关痴呆症的临床试验中，敏感的测试被用作认知数字生物标志物。 第一个目的是从这些其他测试中制定新的认知措施并获得初步 验证。现有数据将分为培训和测试集。将分析培训集以开发 指标，遵循可解释的分层分析结构，具有低级图测量 结合一组与认知概念（即信息处理）相关的复合量表，然后 进一步合并以获得简单的0-100分数以进行测试的性能。测试集将用于 进行由接收器操作特征曲线分析，相关性组成的初步验证 现有神经心理学测试和测试可靠性测量的措施以确保重复 测试稳定性。第二个目的是在商业Linus平台中实施开发的指标。 将创建可靠的软件，用于用于新颖指标的测量，存储和显示，设置一个 基础，可以通过研究和商业合作伙伴来使用指标。