Characterizing Retinal Tissue Oxygenation, Structure, and Function in Alzheimer's Disease

阿尔茨海默氏病视网膜组织氧合、结构和功能的表征

• 批准号: 10557293
• 负责人: Edmund Arthur
• 金额: $ 22.28万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10557293
• 关键词: Affect; Age; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease patient; Alzheimer' s disease risk; Analysis of Covariance; Angiography; Biological Markers; Blood Vessels; Blood capillaries; Blood-Retinal Barrier; Brain; Central Nervous System; Cerebrospinal Fluid; Clinical; Cognitive; Cognitive aging; Contrast Sensitivity; Control Groups; Data; Dementia; Detection; Development; Diagnostic; Diffuse; Disease; Dropout; Early Diagnosis; Early Intervention; Elderly; Ganglion Cell Layer; Goals; Human; Impaired cognition; Individual; Ischemia; Linear Regressions; Measures; Methods; Modeling; Monitor; Nature; Nerve Degeneration; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurologist; Neurons; Nutrient; Optical Coherence Tomography; Outcome; Output; Oxygen; Participant; Pathology; Patients; Pericytes; Peripheral; Persons; Phase; Positron-Emission Tomography; Process; Public Health; ROC Curve; Reporting; Retina; Retinal Ganglion Cells; Risk; Senile Plaques; Sensory; Specificity; Spinal Puncture; Structure; Symptoms; Testing; Thick; Vision; Visual; Width; Work; arteriole; cost effective; cost efficient; curative treatments; early detection biomarkers; effective therapy; health assessment; high risk; mild cognitive impairment; multimodality; novel; pre-clinical; prevent; preventive intervention; retinal nerve fiber layer; retinal neuron; screening; tissue oxygenation; venule

Alzheimer’s disease (AD) is a progressive neurodegenerative disease affecting approximately 5.3 million people in the US, and projected to reach 13.9 million by 2026. Progress in the management and treatment of AD is limited by lack of early diagnostics, which are critical to the development of effective therapies. AD is currently described in three stages; the preclinical, the mild cognitive impairment (MCI), and Alzheimer’s dementia. The difficulty lies in detecting the disease during the preclinical phase, when patients show no clinical symptoms of cognitive impairment but there is underlying pathology. Currently, we are limited to detecting the accumulation of amyloid plaques in the brain using expensive and invasive methods such as Positron Emission Tomography and cerebrospinal fluid assessment via lumbar puncture. The goal of this proposal is to develop a novel, non-invasive, and cost-effective retinal vascular biomarker for early AD risk detection and disease monitoring. There is increasing evidence that there are retinal manifestations of AD; the neurodegeneration in the brain of AD patients has been shown to be associated with reduced retinal nerve fiber layer (RNFL) and retinal ganglion cell (RGC) layer thickness. Thus, the human retina is an easy to examine part of the brain providing an opportunity to study and to possibly detect AD early. There is breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD. We have previously characterized metrics of retinal tissue oxygenation in the form of periarteriole and perivenule capillary free zones (peripheral CFZs). Building on these prior results, our central hypothesis is that the CFZ will be enlarged in older cognitively unimpaired (CU) participants at high risk for AD, MCI, and mild AD patients, and this will be associated with reduced RNFL and RGC layer thickness, reduced field of vision, and reduced sensitivity to contrast. We will test our central hypothesis by completing the following aims: AIM 1: Quantify and evaluate differences in the peripheral CFZ, structural, and functional measures between low-risk CU older adults, high-risk CU older adults, MCI, and mild AD groups. We will collect high quality optical coherence tomography angiography images, structural, and functional measures in the 4 groups with data from the low-risk CU participants serving as baseline or control data. We will compare the CFZ, structural, and functional measures in the 4 groups of participants using analysis of covariance. AIM 2: Identify associations between the peripheral CFZ, structural, and functional measures in high-risk CU, MCI, and mild AD groups. We will use multiple linear regression models to test the associations of the CFZ versus structural and functional parameters. Outputs from this proposal will identify whether CFZ measures can be used as a potential retinal biomarker of early AD risk detection and disease monitoring. Results from our studies will advance both the NIA’s goal of understanding the nature of biomedical changes associated with AD and the goal of the National Alzheimer’s Plan to prevent and effectively treat AD by 2025.

阿尔茨海默氏病（AD）是一种进行性神经退行性疾病，影响约530万 美国的人，预计到2026年将达到1390万。 AD受到缺乏早期诊断的限制，这对于有效疗法的发展至关重要。广告是 目前在三个阶段进行描述；临床前，轻度认知障碍（MCI）和阿尔茨海默氏症 失智。困难在于在临床前阶段检测疾病，当患者显示没有 认知障碍的临床症状，但存在潜在的病理。目前，我们仅限于 使用昂贵和侵入性的方法（例如 正电子发射断层扫描和脑脊液通过腰椎刺穿。目标的目标 建议是开发一种新颖，无创和具有成本效益的视网膜血管生物标志物，以实现早期AD风险 检测和疾病监测。越来越多的证据表明AD存在视网膜表现。这 AD患者大脑中的神经变性与残留神经降低有关 纤维层（RNFL）和视网膜神经节细胞（RGC）层厚度。那，人类视网膜很容易 检查一部分大脑，提供了学习的机会，可以尽早检测AD。有 AD中内部残留的血屏损失，周围的损失和毛细血管的不良或脱落的分解。我们 以前已经表征了残留组织氧合的指标，形式为周长和周期。 毛细血管不含区域（外围CFZ）。基于这些先前的结果，我们的中心假设是CFZ 在较旧的认知独立性（CU）参与者中，AD，MCI和轻度AD的较高风险将增加 患者，这将与RNFL和RGC层厚度降低有关，视野降低以及 对比度的敏感性降低。我们将通过完成以下目的来检验中心假设：目标1： 量化和评估周围CFZ，结构和功能度量的差异 低风险的CU老年人，高风险的CU老年人，MCI和轻度AD组。我们将收集高质量 光学相干断层扫描图像图像，结构和功能度量在4组中 来自低风险CU参与者的数据作为基线或控制数据。我们将比较CFZ，结构性， 使用协方差分析，四组参与者的功能度量。目标2：识别 高风险CU，MCI和 温和的广告组。我们将使用多个线性回归模型来测试CFZ的关联 结构和功能参数。该提案的输出将确定CFZ措施是否可以 用作早期AD风险检测和疾病监测的潜在视网膜生物标志物。我们的结果 研究将促进NIA了解与生物医学变化的性质的目标 AD和国家阿尔茨海默氏症计划在2025年之前有效地对待广告的计划。