Aging eyes and aging brains in studying alzheimer's disease: Modern ophthalmic data collection in the adult changes in thought (ACT) study

研究阿尔茨海默病时的眼睛老化和大脑老化：成人思想变化 (ACT) 研究中的现代眼科数据收集

• 批准号: 10237257
• 负责人: Cecilia Sungmin Lee
• 金额: $ 339.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10237257
• 关键词: Adult; Age related macular degeneration; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease risk; Amyloid beta-Protein; Angiography; Anterior; Archives; Autopsy; Bayesian Modeling; Biological Markers; Blood Vessels; Brain; California; Cerebrovascular Disorders; Characteristics; Clinic; Clinical; Clinical Data; Clinical Research; Cognition; Collaborations; Communities; Consent; Data; Data Collection; Dementia; Diabetic Retinopathy; Diagnosis; Disease; Disease model; Drusen; Elderly; Evaluation; Evolution; Eye; Eye diseases; Fundus; Fundus photography; Ganglion Cell Layer; Glaucoma; Goals; Home; Image; Impaired cognition; Investigation; Laboratories; Lead; Life; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Manuals; Measures; Microvascular Dysfunction; Modeling; Modernization; Nerve Degeneration; Nerve Fibers; Neuraxis; Occipital lobe; Ophthalmology; Optical Coherence Tomography; Participant; Pathology; Perfusion; Persons; Predisposition; Process; Prospective cohort study; Provider; Publishing; Research; Research Personnel; Resources; Retina; Risk; Role; Scanning; Selection Bias; Series; Severities; Severity of illness; Structure; Technology; Testing; Time; Universities; Vascular Diseases; Visit; aging brain; area striata; automated algorithm; base; cognitive change; cohort; data sharing; deep learning; diagnosis quality; epidemiology study; fiber cell; follow-up; high risk; imaging biomarker; imaging modality; improved; innovation; interest; neuroimaging; neuropathology; novel; paired helical filament; population based; prospective; public repository; research study; resilience; tau Proteins; tau-1; vascular contributions

PROJECT SUMMARY ABSTRACT The overarching goals of this R01 proposal are to improve scientific understanding of potential mechanisms by which ophthalmic diseases lead to the risk of Alzheimer’s disease. The investigators will leverage modern ophthalmic data with state-of-the-art imaging and extensive archived clinical data from a well-characterized cohort of older adults. The investigators propose to examine the effect of structural and functional changes in retina and longitudinal severity of ophthalmic diseases on Alzheimer’s disease and related neuropathology. The proposal builds on the resources of the Adult Changes in Thought (ACT) study, a prospective longitudinal, population-based, dementia-free cohort of over 5,500 people to date established in 1994 which has detected >1,014 research quality diagnoses of Alzheimer’s disease and >1,254 dementia to date. ACT follows consenting participants to autopsy and has performed state-of-the arts autopsy on >781 decedents to date. In this extremely well-characterized cohort, the investigators found that several ophthalmic diseases (diabetic retinopathy, glaucoma, age-related macular degeneration) are significantly associated with the risk of developing Alzheimer’s disease. The investigators will use three advanced ophthalmic imaging modalities at both home and clinical research study visits: fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA), to obtain quantitative data relevant to these ophthalmic diseases. The study team will establish the distribution (Aim 1a) and 2- and 4-year evolution of ophthalmic imaging characteristics found in older adults in the community and determine associations with change in cognition (Aim 1 b, c). Additionally, magnetic resonance imaging (MRI) and MRI angiography (MRA) will be obtained in a subset of participants to investigate the contribution of small (retinal) and large (cerebral) vascular disease towards cognitive changes (Aim 1d). The study team will continue ACT study’s strong commitment for meaningful data sharing. In collaboration with the Laboratory of Neuro Imaging at University of Southern California, the study team will promulgate these ophthalmic data in addition to neuroimaging data to the research community (Aim 1e). In Aim 2, the investigators will use extensive clinical ophthalmology data captured over many decades and incorporate them in novel longitudinal models of eye disease severity. The investigators will analyze eye disease severity along with extensive neuropathology data from the ACT study, including both standard (Aim 2a) and novel quantitative (Aim 2b) neuropathology data, to further scientific understanding of neuropathological mechanisms underlying associations between eye conditions and Alzheimer’s disease risk. The brain is not amenable to direct observations during life. In contrast, the eye is an anterior extension of the central nervous system and may provide a valuable window to illuminate neurodegenerative processes in the aging brain. Proposed investigations will substantially enhance scientific understanding of the role of modern ophthalmic evaluations in delineating risk of Alzheimer's disease and other forms of neuropathology.

项目摘要 R01提案的总体目标是通过以下方式提高对潜在机制的科学认识 哪些眼科疾病会导致阿尔茨海默病的风险。调查人员将利用现代 眼科数据与最先进的成像和广泛的存档临床数据， 一群老年人。研究人员建议检查结构和功能变化的影响， 视网膜和纵向眼科疾病的严重程度对阿尔茨海默病和相关的神经病理学。 该提案建立在成人思想变化（ACT）研究的资源基础上，这是一项前瞻性的纵向研究， 1994年建立了一个以人口为基础的无痴呆症队列，迄今已有5 500多人， 迄今为止，已有超过1，014例阿尔茨海默病和超过1，254例痴呆症的研究质量诊断。ACT遵循 迄今为止，已对超过781名死者进行了最先进的尸检。 在这个特征非常明确的队列中，研究人员发现，几种眼科疾病（糖尿病） 视网膜病变、青光眼、年龄相关性黄斑变性）与以下风险显著相关： 患上阿尔茨海默病。研究人员将使用三种先进的眼科成像模式， 家庭和临床研究访视：眼底照相、光学相干断层扫描（OCT），以及 OCT血管造影术（OCTA），以获得与这些眼科疾病相关的定量数据。研究团队 将确定发现的眼科成像特征的分布（Aim 1a）以及2年和4年的演变 在社区的老年人中，并确定与认知变化的关联（目标1 B，c）。此外，本发明还 将在一部分受试者中获得磁共振成像（MRI）和MRI血管造影（MRA）， 研究小（视网膜）和大（脑）血管疾病对认知变化的影响 (Aim 1 d）。研究团队将继续ACT研究对有意义的数据共享的坚定承诺。在 该研究小组与南加州大学神经成像实验室合作， 向研究团体公布这些眼科数据以及神经影像学数据（目标1e）。 在目标2中，研究人员将使用几十年来获得的广泛的临床眼科数据， 将其纳入眼科疾病严重程度的新纵向模型中。调查人员将分析眼睛 疾病严重程度沿着ACT研究的广泛神经病理学数据，包括标准（Aim 2a）和新的定量（目的2b）神经病理学数据，以进一步科学地了解 神经病理学机制之间的关联眼睛的条件和阿尔茨海默氏病的风险。 大脑在人的一生中是不适合直接观察的。相比之下，眼睛是眼睛的前部延伸， 中枢神经系统，并可能提供一个有价值的窗口，照亮神经退行性过程中， 老化的大脑拟议的调查将大大提高科学的理解，现代的作用， 眼科评估在描述阿尔茨海默病和其他形式的神经病理学的风险。