Dynamic Imaging Markers of ARIA-H Risk in the A4 Study: A Person-Interval Analysis of Current Lesion Burden and Recent Microhaemorrhage Activity

INTRODUCTION: Amyloid-related imaging abnormalities with microhaemorrhage (ARIA-H) are an important safety consideration with anti-amyloid therapies, yet evidence exploring short-term risk prediction remains limited. METHODS: We analysed longitudinal MRI data from the A4 study, constructing a discrete person-interval dataset for modelling the short-term risk of ARIA-H. Models incorporated baseline covariates, alongside dynamic variables of recent microhaemorrhage accumulation and current microhaemorrhage burden. Incident ARIA-H was defined as 2 or more new microhaemorrhages or 1 or more new superficial siderosis between consecutive MRI scans. RESULTS: Among 1,069 participants (3,647 intervals), 171 ARIA-H events occurred. Both current burden (time-to-event: OR 1.37, 95% CI 1.09-1.73; all-event: OR 1.24, 95% CI: 1.04-1.49) and recent microhaemorrhage accumulation (time-to-event: OR 1.83, 95% CI 1.01-3.30; all-event: OR 1.43, 95% CI: 1.00-2.04) were independently associated with an increased risk of ARIA-H. DISCUSSION: Temporal imaging variables may provide independent prognostic information beyond baseline risk, supporting a dynamic model of haemorrhagic risk in Alzheimer's disease.