title: Understanding associations between rheumatoid arthritis and associated biomarkers with brain and psychological health in the UK Biobank
Creators: name: Stanciu, Ioana
Publisher: name: University of Glasgow
Year: 2023

description: Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory condition affecting the joints, that if left untreated can result in permanent damage and reduced quality of life. The general focus of RA literature and treatment has been on pain, inflammation and maintaining joint function, with limited research on psychological factors such as mental health, sleep and cognition, and an almost complete gap for structural brain differences (vs. people without RA). Similarly, more research is needed to understand the role of rheumatoid factor (RF), an autoantibody that is used in the official classification criteria for RA. This thesis aimed to fill in these gaps in the literature, with the overall aim of investigating whether RA/RF positive (RF+) are associated with differences in mental health, sleep, cognition, and structural brain health. This thesis used data from a relatively large cohort, the UK Biobank, covering approximately 500,000 people for the baseline visit and around 40,000 participants for the imaging visit to test for associations between RA/RF and mental health, sleep, and cognition in Chapter 3; associations between RA/RF and structural brain phenotypes in Chapter 4; and associations between increased polygenic risk for RF with structural brain and cognitive differences in Chapter 5. Compared to previous studies, the current thesis had the advantage of using a very large cohort that also enabled me to control for a variety of confounders that have largely been neglected in previous literature. Chapter 3 provides evidence that self-reported RA is associated with higher neuroticism, worse sleep, and worse performance on cognitive tests for reaction time and fluid intelligence while RF+ status was associated with worse sleep. Chapter 4 suggested that self-reported RA is associated with a higher volume of white matter lesions, higher volume of the caudate, and a smaller volume for the amygdala. Chapter 5 found that a polygenic risk score (PRS) for RF was associated with markers of healthier white matter, more specifically lower volume of lesions and lower mean diffusivity, and better performance on a cognitive test for visuo-spatial processing and short-term memory. This thesis provided evidence that people with RA/RF+ status might present with differences in psychological and brain structure health that are currently unaddressed and untreated in the clinic despite being important contributors to overall health, as well as health-related quality of life. Considering that it is still unclear what exactly causes RA, as well as why some people respond well to treatments while others do not benefit from medication at all, this thesis suggests that future research should further aim for a better understanding of blood biomarkers, genetic risk factors, and psychological and brain health differences associated with RA. This could aid diagnosis, disease stratification, treatment, and health interventions, as well as a better understanding of comorbid risk factors.