Title: Multimorbidity in Brain and Cognitive Ageing
Funder: The Academy of Medical Sciences

Abstract: Most dementia patients have pre-existing cardiovascular diseases. However, the mechanisms underlying this multimorbidity remain unclear and we currently lack knowledge of when, how, and for whom cardiovascular interventions may effectively delay or prevent dementia. This project will address these uncertainties with a multi-modal lifespan approach to understand multimorbidity in brain ageing. I will investigate the role of two physiological processes in the heart-brain link, viz. aortic/carotid compliance, and cerebrovascular reactivity (CVR, the brain’s ability to maintain stable oxygenation). I will perform cerebrovascular magnetic resonance imaging (MRI), vascular ultrasonography, and neuropsychological tests in 215 participants of the long-running Whitehall-II cohort. This cohort has received regular cardiovascular/cognitive assessments for 30 years, and brain MRI scans 5-7 years ago. Using this extensive lifespan data, I will test the hypothesis that poor cardiovascular health in mid-life (40-65 years) leads to low aortic and carotid compliance (Aim 1) and low CVR (Aim 2) in older ages (>65 years), which in turn accelerates brain atrophy and cognitive decline. I will examine if these relationships are moderated by the APOE4 allele, a risk gene common to both Alzheimer’s and cardiovascular disease. This project will enable direct inferences of how peripheral circulation affects cognitive decline. It will evaluate carotid stiffness and CVR as novel targets for dementia trials and inform optimal prevention strategies. The Springboard Award will allow me to generate one of the world’s most comprehensive datasets to study multimorbidity in brain ageing and employ my first Research Assistant as I launch my own group at Oxford.

Lay abstract: Having more than one disease at the same time is called “multimorbidity”. This is especially common in people with dementia, who often also have heart diseases. Improving heart health could help to prevent nearly a third of dementia cases but we still do not know when and how these treatments are most effective. This project will address these questions by using state-of-the-art brain and cardiac scans. I will perform ultrasound scans of the heart to measure the health of the large blood vessels which supply our brain. I will use brain magnetic resonance imaging (MRI) scans to study the brain’s smallest blood vessels, and also conduct a number of memory tests. Importantly, I will do this in 215 participants of the long-running Whitehall-II study, who have already received regular cardiovascular health checks to measure blood pressure and cholesterol for 30 years, and a brain MRI scan 5-7 years ago. Using this extensive lifespan data, I will test if poor cardiovascular health in mid-life (40-65 years old) can damage the blood vessels entering the brain, and if this in turn affects faster memory decline in older age (>65 years old). The longitudinal nature of this study will allow me to pinpoint the best window of time to manage heart health in order to delay or prevent memory decline. The Springboard Award will help me generate one of the world’s most comprehensive datasets to study multimorbidity in ageing and employ my first Research Assistant as I launch my own group at Oxford.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL;MENTAL HEALTH