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

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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.