Computational Modelling of Ageing Brains: Virtual Populations for In Silico Clinical Trials

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The UK population is ageing, with one-fifth aged 65 or over in 2019 and projected to rise to 24% by 2043. This is accompanied by an increased risk of chronic diseases, stroke, dementia, and atrial fibrillation. This project aims to develop models of the ageing cerebrovasculature for in silico clinical trials and medical device development. Validated models of cerebrovascular ageing will be developed to generate an ageing virtual population for in silico clinical trials of age-related cerebrovascular disease and its treatment. Using readily available data, patient "digital twins" will be created from data corresponding to physiological signals (e.g., cerebral blood flow, blood pressure) from healthy and diseased participants of different ages. A personalised in silico ageing model will be created utilising a one-dimensional model of blood flow in the brain's large vessels. An inverse problem to calibrate the model for individual patient anatomies, creating digital twins of those patients. Ageing populations of virtual brains will then be created by combining the one-dimensional blood flow model with a microcirculation model to simulate cerebrovascular disease in different age ranges. This will be validated against real patient data to confirm the accuracy of the model and assess the impact of each of its parameters. The outcome will be a validated model of cerebrovascular ageing to predict disease outcomes based on physiological age, enabling realistic virtual populations for cerebrovascular research, medical device/drug development, and investigating age-related cerebral diseases like dementia and Alzheimer's.