Delirium is increasingly recognised as a marker of altered trajectories in cognitive and physical function. This talk will draw together evidence from prospective cohorts and nested mechanistic studies to explore the relationship between delirium, baseline cognitive reserve, and long-term outcomes. Emerging insights from CSF and plasma biomarkers, alongside serial neurophysiology, will be discussed. Ultimately, considering how acute illness may interact with vulnerability, resilience, and neurodegeneration across the life course.