Approved research

Cardiometabolic and genetic determinants of brain structure and function - a focus on obesity, type 2 diabetes and associated factors

Lay summary

This study aims to study the relative contribution of obesity, cardiometabolic factors and genetic factors to the development of brain dysfunction. The emphasis is on the role of obesity, prediabetes, type 2 diabetes, and their associated factors as exposures. Common factors predisposing to metabolic dysfunction and dementia will be of main interest. The outcomes will be structural and functional measures (cognitive and imaging. The role of sex/gender in modifying these relationships will be evaluated This body of research will shed new light on mechanisms underlying the associations between two highly prevalent disorders (diabetes and dementia), both major public health problems It relates to the major public health disorders of obesity, diabetes and dementia - hence is health-related and in the public interest. Our group has substantial expertise in the field of ageing, advanced imaging analysis, dementia and cognitive dysfunction related to diabetes. Data from the UK biobank will be collated for exposure and confounding/modifying variables. Imaging analyses will be conducted using both existing processed data and with in-house methods to generate outcome variables. Associations of interest will be examined using a combination of simple and advanced analytical methods. Data arising from these analyses will be presented at scientific conferences, and published in peer-reviewed literature. Given that we are aiming to assess the magnitude of relative contributions of the exposure factors, to explore effect modification and interaction, and to use advanced analytical techniques (including graph/network analyses) - this would require a substantial dataset given the levels of stratification required. The primary dataset includes all people with measured cognitive function, brain imaging, genomics and body composition. Available data on brain imaging in this sample will also be required. Additionally,data are required on relevant demographic, psychosocial, lifestyle,c ardiovascular, genes (SNPs), and already available blood biomarkers collected and analysed in the UK Biobank - reflecting factors relevant to linking obesity, diabetes and dementia.