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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease patient Alzheimer&apos 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

项目摘要

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.

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，影响约 530 万人在美国，预计到 2026 年将达到 1390 万人。管理和治疗方面的进展 AD 因缺乏早期诊断而受到限制，而早期诊断对于开发有效的 AD 疗法至关重要。目前分为三个阶段：临床前、轻度认知障碍（MCI）和阿尔茨海默病困难在于在临床前阶段发现这种疾病，此时患者没有表现出任何症状。认知障碍的临床症状但存在潜在的病理学目前，我们仅限于。使用昂贵的侵入性方法检测大脑中淀粉样斑块的积累，例如通过腰椎穿刺进行正电子发射断层扫描和脑脊液评估。提案旨在开发一种新型、非侵入性且具有成本效益的视网膜血管生物标志物，用于检测早期 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； AD 患者大脑中的神经退行性变已被证明与视网膜神经减少有关纤维层（RNFL）和视网膜神经节细胞（RGC）层的厚度由此可见，人类视网膜是一个易于测量的层。检查大脑的一部分，提供了研究并可能及早发现 AD 的机会。 AD We 中视网膜内血屏障的破坏、周细胞丢失和毛细血管无灌注或脱落。之前已经以小动脉周围和小静脉周围的形式表征了视网膜组织氧合的指标基于这些先前的结果，我们的中心假设是 CFZ。在 AD、MCI 和轻度 AD 高风险的老年认知未受损 (CU) 参与者中，该值会增大患者，这将与 RNFL 和 RGC 层厚度减少、视野缩小以及我们将通过完成以下目标来检验我们的中心假设：目标 1：量化和评估外围 CFZ、结构和功能测量之间的差异我们将收集高质量的低危CU老年人、高危CU老年人、MCI和轻度AD人群。 4 组的光学相干断层扫描血管造影图像、结构和功能测量来自低风险 CU 参与者的数据作为基线或控制数据，我们将比较 CFZ、结构、使用协方差分析对 4 组参与者进行功能测量 AIM 2：识别。高危 CU、MCI 和中枢神经系统周围 CFZ、结构和功能测量之间的关联我们将使用多重线性回归模型来测试 CFZ 与轻度 AD 组的关联。该提案的结构和功能参数将确定 CFZ 措施是否可以实施。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。研究将推进 NIA 的目标，即了解与 AD 以及国家阿尔茨海默病计划到 2025 年预防和有效治疗 AD 的目标。