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: 10452548
• 负责人: Cecilia Sungmin Lee
• 金额: $ 329.96万
• 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/10452548
• 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; 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.

项目概要 摘要 该 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理解： 哪些眼科疾病会导致患阿尔茨海默病的风险。调查人员将利用现代技术 眼科数据具有最先进的成像和来自充分表征的广泛存档的临床数据 老年人群。研究人员建议检查结构和功能变化的影响 视网膜和眼科疾病的纵向严重程度对阿尔茨海默病和相关神经病理学的影响。 该提案以成人思想变化 (ACT) 研究的资源为基础，该研究是一项前瞻性纵向、 1994 年建立的以人口为基础的无痴呆症队列，迄今已超过 5,500 人 迄今为止，已对超过 1,014 例阿尔茨海默病和超过 1,254 例痴呆症进行研究质量诊断。行动如下 同意参与者进行尸检，迄今为止已对超过 781 名死者进行了最先进的尸检。 在这个特征极其明确的队列中，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）与以下风险显着相关 患阿尔茨海默病。研究人员将使用三种先进的眼科成像模式 家庭和临床研究访问：眼底摄影、光学相干断层扫描 (OCT) 和 OCT血管造影（OCTA），以获得与这些眼科疾病相关的定量数据。研究团队 将建立发现的眼科成像特征的分布（目标 1a）和 2 年和 4 年演变 并确定与认知变化的关联（目标 1 b、c）。此外， 将对一部分参与者进行磁共振成像 (MRI) 和 MRI 血管造影 (MRA) 研究小（视网膜）和大（大脑）血管疾病对认知变化的影响 （目标 1d）。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 研究小组与南加州大学神经影像实验室合作 除了神经影像数据之外，还向研究界公布这些眼科数据（目标 1e）。 在目标 2 中，研究人员将使用数十年来捕获的广泛临床眼科数据， 将它们纳入眼部疾病严重程度的新型纵向模型中。研究人员将分析眼睛 疾病严重程度以及来自 ACT 研究的广泛神经病理学数据，包括标准（目标 2a）和新颖的定量（目标 2b）神经病理学数据，以进一步科学理解 眼部疾病与阿尔茨海默病风险之间关联的神经病理学机制。 大脑在一生中不适合直接观察。相反，眼睛是眼睛的前部延伸。 中枢神经系统，可能为阐明神经退行性过程提供一个有价值的窗口 老化的大脑。拟议的调查将大大增强对现代科学作用的科学理解 描述阿尔茨海默病和其他形式的神经病理学风险的眼科评估。