INTRODUCTION: We quantified the association of mild (ie, involving one or two body systems) and complex (ie, involving ≥3 systems) multimorbidity with structural brain changes in older adults.

METHODS: We included 390 dementia-free participants aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen who underwent brain magnetic resonance imaging at baseline and after 3 and/or 6 years. Using linear mixed models, we estimated the association between multimorbidity and changes in total brain tissue, ventricular, hippocampal, and white matter hyperintensities volumes.

RESULTS: Compared to non-multimorbid participants, those with complex multimorbidity showed the steepest reduction in total brain (β*time −0.03, 95% CI −0.05, −0.01) and hippocampal (β*time −0.05, 95% CI −0.08, −0.03) volumes, the greatest ventricular enlargement (β*time 0.03, 95% CI 0.01, 0.05), and the fastest white matter hyperintensities accumulation (β*time 0.04, 95% CI 0.01, 0.07).

DISCUSSION: Multimorbidity, particularly when involving multiple body systems, is associated with accelerated structural brain changes, involving both neurodegeneration and vascular pathology.