Metabolic Dysfunction-Associated Steatotic Liver Disease and Risk of Depressive Symptoms in Older Adults.

INTRODUCTION: There is a potential link between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and depression in later life. This study aims to examine whether MASLD is associated with elevated clinically relevant depressive symptoms in community-dwelling older adults. METHODS: This study utilised longitudinal data from a prospective cohort to quantify the association between MASLD at baseline and depressive symptom trajectories. MASLD, introduced by multinational liver societies to replace Non-Alcoholic Fatty Liver Disease (NAFLD), highlights the central role of metabolic dysfunction in the pathogenesis of steatotic liver disease. Depression trajectories were estimated across a median follow-up of 4.6 years (IQR: 0.1-7.1 years) and were identified as four distinct patterns of symptoms: 'non-depressed', 'subthreshold depression', 'persistent depression', and 'emerging depression'. Multivariable multinomial logistic regressions were performed to examine the association between baseline MASLD presence and membership of the depression trajectories, adjusting for sociodemographic and lifestyle factors, anthropometric indices, cognitive function, polypharmacy and the number of morbidities. Additional subgroup analyses were also performed. RESULTS: Of 9097 individuals (mean age 75.1 ± 4.2 years; 55.0% males), 2998 (33%) had MASLD at baseline. Participants with MASLD were significantly more likely to belong to the persistent depression trajectory (RRR = 1.13; 95% CI: 1.02-1.24) and the subthreshold depression trajectory (1.43; 1.22-1.67) than those without MASLD. CONCLUSION: This study shows that the presence of MASLD is significantly associated with an increased risk of a worse depression trajectory. In subgroup analysis, this relationship was particularly pronounced amongst females and among individuals with key cardiometabolic morbidities such as dyslipidaemia.