Project 460806

Background: The global prevalence of dementia is rapidly increasing. There is evidence that cardiometabolic and vascular risk factors (CmVRFs) - such as diabetes, obesity, hypertension and high cholesterol - are independently associated with dementia risk. CmVRFs are known to be leading risks for global mortality, and often co-occur in individuals rather than in isolation. However, there is limited evidence on the joint effects of different CmVRF combinations and dementia risk. Furthermore, the underlying pathological mechanisms implicated in any observed associations within this context remains unclear. This paucity of information is largely due to a lack of data available to investigate these relationships. My doctoral research aims to address these knowledge gaps by making use of the UK Biobank - one of the world's largest population-based studies - which contains data on more than half a million women and men, capturing a wealth of information including sociodemographic, lifestyle, genetic, physical, imaging measures and longitudinal electronic medical records. The objectives of this work are as follows: (1) To examine the association between individual CmVRFs and dementia risk; (2) To explore how CmVRFs could interact with each other to modify the risk of developing dementia; (3) To assess the interaction between CmVRFs and other non-metabolic/non-vascular risk factors for dementia; (4) To build upon objectives 1-3 by investigating potential underlying pathological mechanisms through exploration of neuroimaging outcomes implicated in dementia development. Implications: This research will lead to a better understanding of the potential joint impact of CmVRF combinations on dementia development and the underlying pathological mechanisms. The findings will help improve strategies for prevention by potentially prompting early clinical intervention that may help mitigate the risk of developing dementia among particularly vulnerable populations.