Caroline Wasén

Our understanding of how chronic immune activation in RA affects the brain structure is very limited, despite evidence of neurological manifestations of RA. Based on my preliminary data demonstrating atrophy in the frontoparietal cortex of RA patients, this project aims to 1) Measure the progression of brain atrophy in RA and its impact on cognition and disability, 2) Identify immune mechanisms driving RA-related brain atrophy and assess whether tumour necrosis factor (TNF) inhibition can prevent it, and 3) Test if neuroinflammation and neuronal loss in mouse models of RA can be blocked with biological disease-modifying anti-rheumatic drugs (bDMARDs).In this project, I will collect and analyse longitudinal data from two cohorts of RA patients, of which one cohort initialized TNF inhibiting treatment at baseline. This includes magnetic resonance imaging to measure brain volume changes

cognitive and functional tests to measure clinical outcome

single cell sequencing and protein measurements in serum and cerebrospinal fluid to determine immunological mechanisms

and genotyping to identify risk genes. I will also establish protocols for studying neuroinflammation and brain structure changes in RA mouse models, and investigate the effects of peripheral and central administration of bDMARDs.Identifying immune mechanisms of brain atrophy could shift RA treatment approaches to incorporate brain health, which is important to improve cognitive and functional outcomes in RA patients.