Dynamic imaging markers of incident microhemorrhages and superficial siderosis in the A4 study: A longitudinal person-interval analysis.

INTRODUCTION: Incident microhemorrhages and superficial siderosis are hemorrhagic magnetic resonance imaging (MRI) abnormalities relevant to amyloid-related imaging abnormalities with hemosiderin deposition (ARIA-H) risk stratification, but evidence exploring their short-term dynamic predictors remains limited. METHODS: We analyzed longitudinal MRI data from the A4 study, constructing a discrete person-interval dataset for modeling the short-term risk of incident hemorrhagic MRI abnormalities. Models incorporated baseline covariates, alongside dynamic variables of recent microhemorrhage accumulation and current microhemorrhage burden. The outcome was defined as two or more new microhemorrhages or one or more new superficial siderosis between consecutive MRI scans. RESULTS: Among 1069 participants (3647 intervals), 171 hemorrhagic events occurred. Both current burden (time-to-event: odds ratio [OR] 1.37, 95% confidence interval [CI] 1.09-1.73; all-event: OR 1.24, 95% CI: 1.04-1.49) and recent microhemorrhage accumulation were independently associated with an increased risk of hemorrhagic events (time-to-event: OR 1.83, 95% CI 1.01-3.30; all-event: OR 1.43, 95% CI: 1.00-2.04). DISCUSSION: Temporal imaging variables may provide independent prognostic information beyond baseline risk, supporting a dynamic model of hemorrhagic risk in Alzheimer's disease. CLINICAL TRIAL REGISTRATION: Clinical trial of Solanezumab for older individuals who may be at risk for memory loss (A4) (NCT02008357).