Metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~30% of the population and >80% of individuals with obesity. It is strongly linked with cardiovascular disease, diabetes and cancer, and is a major contributor to global multimorbidity. Prior work shows that greater liver fat, fibro-inflammation and iron are associated with smaller total and grey matter volumes, increased microvascular injury, and poorer white-matter integrity. Cognitive symptoms such as memory loss, attention deficits and confusion occur in up to 70% of MASLD cases, alongside higher rates of depression, anxiety and apathy, and reduced cerebral volume suggestive of accelerated brain ageing. MASLD is also associated with autonomic dysfunction resembling patterns seen in ageing and dementia. Such dysfunction is closely tied to impaired cerebrovascular structure and function, reduced perfusion and altered brain metabolism, all of which contribute to cognitive decline.
This PhD project will determine whether autonomic dysfunction in MASLD is associated with altered systemic and cerebral perfusion and whether this contributes to brain changes and cognitive impairment. We will examine cardiometabolic risk, structural and functional brain alterations, circadian disturbances, biological brain-age, and cognitive, psychological and functional outcomes. We will also assess whether weight loss or improved liver health relates to recovery of abnormalities. Multimodal UK Biobank data from all visits will be used, including:
1. Bulk imaging data and derived phenotypes
2. Sociodemographics
3. Lifestyle/environment
4. Early-life factors
5. Psychosocial data
6. Health/medical history
7. Externally sourced health outcomes
8. Cognitive function measures
9. Verbal interview data
10. ICD coding for liver/cognitive pathology
11. Physical measures
12. Blood biomarkers
13. ECGs (12-lead and exercise stress test) and digital phenotyping
14. Environmental exposure data
