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

项目总结摘要 R01提案的首要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阿尔茨海默病的风险。调查人员将利用现代 眼科数据，具有最先进的成像和广泛的归档临床数据，来自具有良好特征的 一群年长的成年人。研究人员建议检查结构和功能变化对 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。 该提案建立在成人思维变化(ACT)研究的资源基础上，这是一项前瞻性的纵向研究， 到目前为止，1994年建立的基于人口的、无痴呆症的队列超过5500人，已经检测到 到目前为止，有1,014例阿尔茨海默病和1,254例痴呆症的研究质量诊断。接下来是行动 同意参与者进行尸检，到目前为止已经对781名死者进行了最先进的尸检。 在这一极具特征的队列中，研究人员发现，几种眼科疾病(糖尿病 视网膜病变、青光眼、老年性黄斑变性)与 患上阿尔茨海默氏症。研究人员将使用三种先进的眼科成像方式 家庭和临床研究访问：眼底摄影、光学相干断层扫描(OCT)和 OCT血管造影术(OCTA)，以获得与这些眼科疾病相关的定量数据。学习团队 将确定所发现的眼科成像特征的分布(目标1a)和2年和4年的演变 并确定与认知变化的联系(目标1，b，c)。另外， 将对一部分参与者进行磁共振成像(MRI)和磁共振血管成像(MRA)检查，以 研究小血管(视网膜)和大血管(脑血管)疾病对认知改变的贡献 (目标1D)。研究团队将继续ACT Study对有意义的数据共享的坚定承诺。在……里面 与南加州大学神经成像实验室合作，研究小组将 将这些眼科数据和神经成像数据发布给研究界(目标1e)。 在目标2中，研究人员将使用几十年来收集的大量临床眼科数据和 将它们纳入眼病严重程度的新型纵向模型中。调查人员将分析眼睛 疾病严重程度以及来自ACT研究的广泛神经病理数据，包括标准(AIM 和新的定量(目标2b)神经病理学数据，以进一步科学地理解 眼睛状况和阿尔茨海默病风险之间潜在的神经病理机制。 在生活中，大脑不能直接观察。相反，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，以阐明神经退行性变的过程 大脑老化。拟议的调查将大大加强对现代生物多样性的作用的科学理解 眼科评估在描述阿尔茨海默病和其他形式的神经病理学风险方面的作用。

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.