Using the eye to unlock changes in the health of the aging brain: a state of the art data analysis approach

随着年龄的增长，人们的大脑和身体退化的程度差别很大。随着年龄的增长，认知能力会下降，范围从正常的认知老化到不同的痴呆症。个人之间的差异下降的决定因素没有得到充分的了解，在我们的社会寻求应对人口老龄化带来的挑战时，这是一个重大的知识差距[1]。磁共振成像已被用来研究大脑中与年龄相关的变化的患病率和机制，如血管完整性。尤其重要的是小血管的健康--这些血管的内层受损会导致这种屏障的破坏和物质渗入脑组织，从而导致进一步的损伤和认知能力的下降。由于分辨率的限制，常规磁共振成像不可能直接评估大脑的微血管，但视网膜微血管可以直接成像，而且由于它与大脑的微血管具有相似的胚胎起源和解剖和生理特性，眼睛提供了一个独特的“窗口”来研究体内反映大脑中发生的类似变化的微血管变化[2]。这个项目将通过利用我们团队和现有数据库LBC1936的背景工作来研究年龄相关认知下降背景下的视网膜，LBC1936具有目前~82岁的老年人的特别好的特征纵向队列[3]。在过去的12年里，对认知、体力活动和健康的评估一直在定期收集，同时还收集了详细的大脑磁共振图像和视网膜眼底图像。通过分析这些关联数据，包括结构方程建模和卷积神经网络等技术，学生将调查在个人晚年的重要时期发生的与年龄相关的视网膜、大脑和认知变化之间的关系。该项目将研究从视网膜测量的参数，帮助预测或模拟老年人认知变化的轨迹，区分正常认知老化和明显恶化。学生将参与成像的多个方面，从采集到图像测量和数据分析。他们将为吸血鬼项目提供资金，这是爱丁堡大学和邓迪大学联合发起的一项为期15年的倡议，由倡导者麦吉利夫雷和特鲁科指导，该项目正在建设一个世界级的视网膜分析专业虚拟中心。在吸血鬼和LBC团队成员的支持下，这名学生将学习最先进的数据分析技术，并将这些技术作为研究大脑健康的视网膜生物标记物的尖端手段。学生将通过参加各自大学合作伙伴提供的课程获得关键技能，包括爱丁堡成像学院的在线材料，并与我们研究小组的专家成员互动。到项目结束时，学生本身将成为视网膜成像和分析方面的专家，并将研究传统的生物标记物(即临床、认知和磁共振成像)和新的视网膜终点1。Deary，I.J.等人，与年龄相关的认知衰退。BR Med Bull，2009年。92：135-52.2页。视网膜血管图像分析作为脑血管疾病的潜在筛查工具：基于大脑和视网膜微血管之间同源性的理论基础。J·阿纳特。2005年。第206(4)：第319-348.3页。等人，《队列概况：1921年和1936年洛锡安出生的队列》。INJ Epidinool，2012年。41(6)：第1576-84页。

People differ greatly in the degree to which their brains and bodies deteriorate with age. With ageing comes a decline in cognitive ability, a spectrum ranging from normal cognitive ageing through to different dementias. The determinants of the differences in decline between individuals are not fully understood and represent a significant knowledge gap as our society looks to meet the challenges presented by an ageing population [1]. MR imaging has been used to investigate the prevalence of and mechanisms for age-related changes in the brain such as vascular integrity. Of particular importance is the health of small blood vessels - damage to the lining of these can see failure of this barrier and leakage of material into brain tissue, which cause further injury and leads to cognitive decline. Direct assessment of the brain's microvasculature is not possible with routine MR imaging due to the limitations of its resolution but the retinal microvascular be can imaged directly and as it shares similar embryological origins and anatomical and physiological properties with the brain's microvasculature, the eye provides a unique "window" to study microvascular changes in vivo that reflect similar changes occurring in the brain [2]. This project will investigate the retina in the context of age-related cognitive decline by leveraging background work by our group and an existing data repository, LBC1936, that features an exceptionally well-characterised longitudinal cohort of elderly individuals currently ~82 years old [3]. Assessments of cognition, physical activity and health have been collected at regular intervals over the past 12 years along with detailed MR images of the brain and retinal fundus images. Through analysis of this linked data, including techniques such as structural equation modelling and convolutional neural networks, the student will investigate the relationships between age-related changes in the retina, brain and cognition that have occurred in individuals over an important period of later life. The project will look at parameters measured from the retina helping to predict or model the trajectory of cognitive change in the elderly, separating out normal cognitive ageing from pronounced deterioration. The student will engage with multiple aspects of imaging from acquisition to image measurement and data analysis. They will feed into the VAMPIRE project, a 15-year joint initiative between the Universities of Edinburgh and Dundee, directed by proposers MacGillivray and Trucco, which is building a world-class virtual centre of expertise in retinal analysis. The student, with support from members of the VAMPIRE and LBC teams, will learn about state-of-the-art data analysis techniques and apply these as a cutting-edge means of investigating retinal biomarkers of brain health. The student will gain key skills by attending courses offered by the respective university partners including on-line materials in the Edinburgh Imaging Academy and interact with the expert members of our research group. By the end of the project, the student will themselves be expert in retinal imaging and analysis and will have investigated conventional biomarkers (i.e. clinical, cognitive and MR imaging) and novel retinal endpoints.1. Deary, I.J., et al., Age-associated cognitive decline. Br Med Bull, 2009. 92: p. 135-52.2. Patton, N., et al., Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat. 2005. 206(4): p. 319-348.3. Deary, I.J., et al., Cohort profile: the Lothian Birth Cohorts of 1921 and 1936. Int J Epidemiol, 2012. 41(6): p. 1576-84.