An AI-assisted screening platform within a multivariate framework for biomarkers of mild cognitive impairment due to Alzheimer's disease

多变量框架内的人工智能辅助筛查平台，用于阿尔茨海默病引起的轻度认知障碍的生物标志物

• 批准号: 10571773
• 负责人: Delia Cabrera DeBuc
• 金额: $ 2.65万
• 依托单位: ISCREEN 2 PREVENT LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10571773
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Area Under Curve; Artificial Intelligence; Biological Markers; Biophysics; Brain; Brain Diseases; Central Nervous System Diseases; Cerebrum; Cessation of life; Cognitive; Custom; Data; Death Rate; Dementia; Development; Devices; Diagnostic tests; Discrimination; Disease; Early Diagnosis; Elderly; Electrophysiology (science); Electroretinography; Eye; Fractals; Goals; Healthcare; Heart Diseases; Impaired cognition; Impairment; Individual; Intervention; Investigation; Lead; Light; Longevity; Measurement; Measures; Methodology; Methods; Monitor; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Neurology; Nonlinear Dynamics; Ophthalmology; Organ; Outcome; Pathogenicity; Pathology; Periodicity; Physiological Processes; Population; Process; Property; ROC Curve; Regulation; Reporting; Research; Retina; Risk; Risk Factors; Sensitivity and Specificity; Signal Transduction; Stroke; Structure; Techniques; Time; United States; Visual; Visual Pathways; aged; clinical practice; cost; diagnostic technologies; diagnostic tool; disorder prevention; evidence base; healthy aging; indexing; innovation; instrument; mild cognitive impairment; mortality; multimodality; nervous system disorder; neuroregulation; new technology; non-invasive imaging; noninvasive diagnosis; novel; parent grant; potential biomarker; prospective; protective factors; retina blood vessel structure; screening; targeted treatment; tool; trend

PROJECT SUMMARY In the past decade, the rate of deaths from Alzheimer's disease (AD) and other dementias escalated more than twice the rate of deaths from heart disease. Unfortunately, there is a lack of low-cost and non-invasive diagnostic instruments to accurately identify individuals at risk of AD and ADRD. Advanced non-invasive imaging shows that retinal neurodegeneration and visual deficits occur long before the cognitive decline in AD and ADRD. This fact raises the possibility of identifying mechanisms that drive retinal pathology in AD/ADRD that could help develop effective diagnostics tools and therapies that target early disease. The well-characterized organization of the retina, with powerful non-invasive imaging and electrophysiology techniques to monitor retinal function, make it an optimal surrogate to study early CNS pathology. The brain shares many similarities with the retina. This suggests that the retina, a more accessible organ than the cortex, may provide a viable brain biomarker for testing diagnostics tools and therapies that target early disease and prevention. Notably, we happen to live in a non-linear world surrounded by objects and processes with the property of fractality and non-linearity. For example, the deficit of fractal complexity (i.e., fractality) of environmental effects can lead to fractal complexity distortion in the brain's visual pathways and abnormalities of development or aging. Particularly, non-linear dynamics of physiological processes involved in neurodegenerative disorders have a strong base of evidence, which is seen in the impaired fractal regulation of rhythmic activity in aged and diseased brains. Our multivariate biomarker methodology relies on the fractal complexity of the retinal vasculature as a potential biomarker. However, the fractality of the time-varying electroretinogram (ERG) signal that arises from different retina layers is not yet explored. Therefore, we aim to take advantage of the current electrophysiological measurements acquired in the parent grant to investigate the distortion of fractal complexity in ERG signals correlated to AD pathology as a possible means to obtain a more comprehensive assessment for the early detection of MCI due to AD. In this project, we will further innovate our multivariate biomarker methodology by investigating the fractality of ERG signals. This investigation would make our novel method a more robust tool by incorporating the combined fractality of the retinal function (ERG signals) and structure (retinal vasculature), which can shed new light on early pathogenic mechanisms that compromise retinal and brain function much before the onset of detectable dementia. To this end, we will investigate the distortion of fractality in ERG signals and explore the discrimination power of ERG's fractality measurements between groups with the receiver operating characteristic curve, sensitivity, and specificity metrics. We will use the Youden index and the area under the curve will be calculated for the ERG device calculated features. This project may enable a more comprehensive assessment of aging on ocular and cerebral function at the early stage of cognitive impairment by identifying the most initial signs of complications in the eye and brain using relevant multimodal measures of ocular abnormalities.

项目摘要 在过去的十年中，阿尔茨海默氏病（AD）和其他痴呆症的死亡率升级超过 心脏病的死亡率是死亡率的两倍。不幸的是，缺乏低成本和非侵入性诊断 准确识别有AD和ADRD风险的个人的工具。高级非侵入性成像显示 视网膜神经变性和视觉缺陷发生在AD和ADRD认知能力下降之前。这 事实提出了识别驱动AD/ADRD视网膜病理的机制的可能性 开发针对早期疾病的有效诊断工具和疗法。特色的组织 视网膜，具有强大的非侵入性成像和电生理技术来监测视网膜功能， 使研究早期CNS病理学成为最佳替代。大脑与视网膜有许多相似之处。 这表明视网膜比皮层更容易接近的器官可能为可行的脑生物标志物提供 测试针对早期疾病和预防的诊断工具和疗法。值得注意的是，我们碰巧生活在 非线性世界被物体和过程包围，具有分形和非线性的特性。为了 例如，环境效应的分形复杂性（即分形性）的不足可能导致分形复杂性 大脑的视觉途径和发育或衰老异常的变形。特别是非线性 神经退行性疾病涉及的生理过程的动力学具有强大的证据基础， 这在老年和患病大脑中节奏活性的分形调节中可以看出。我们的多变量 生物标志物方法论依赖于视网膜脉管系统的分形复杂性作为潜在的生物标志物。 然而，来自不同视网膜层产生的时变电图（ERG）信号的分形 尚未探索。因此，我们旨在利用当前的电生理测量 在父母赠款中获取，以调查与AD相关的ERG信号中分形复杂性的变形 病理是一种可能的手段，以获得更全面的评估，以便早期发现MCI 广告。在这个项目中，我们将通过研究该方法来进一步创新我们的多元生物标志物方法。 ERG信号的分形。这项调查将使我们的新颖方法通过合并而成为更强大的工具 视网膜功能（ERG信号）和结构（视网膜脉管系统）的组合分形，可以脱落 关于早期病原机制的新灯，这些机制在开始之前会损害视网膜和大脑的功能 可检测的痴呆症。为此，我们将研究ERG信号中分形的变形，并探索 ERG与接收器操作特征之间的ERG分形测量的歧视能力 曲线，灵敏度和特异性指标。我们将使用Youden索引，曲线下的区域将是 计算出ERG设备计算的功能。该项目可能可以进行更全面的评估 通过识别最初的最初，在认知障碍的早期阶段的眼部和脑功能上的衰老 使用眼异常的多模式测量，眼睛和大脑并发症的迹象。