Determinants of cerebral amyloid angiopathy progression: a multicenter retrospective study

Objective: Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive decline in older adults. Imaging biomarkers as lobar cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) are characteristic of the disease, whose longitudinal evolution and clinical implications remain unclear. This study investigated predictors of radiological progression and their association with recurrent intracranial hemorrhage and mortality. Methods: We retrospectively included patients with a diagnosis of CAA, according to Boston criteria version 2.0, from three European centers. Radiological progression was defined as the appearance of new CMBs or cSS during follow-up. The primary outcome was recurrent intracranial hemorrhage; the secondary outcome was all-cause mortality. Results: Ninety-two patients were included (73 with hemorrhagic, 19 with non-hemorrhagic presentations), with a median follow-up of 34.3 months (IQR: 12.8–66.6). CMB progression occurred in 30% of patients and resulted severe cases in 15%. cSS increased in prevalence from 66% at baseline to 83% at follow-up. Baseline CMBs (OR 9.33, p < 0.001) and cSS (OR 5.94, p = 0.01) predicted their respective progression. Recurrent intracranial hemorrhage occurred in 51% and was associated with the presence of baseline cSS (OR 3.38, p = 0.046) and hemorrhagic presentation at onset (OR 4.97, p = 0.02). Overall mortality was 27%, with no significant radiological predictors identified. Radiological progression was not associated with clinical outcomes. Conclusion: CMBs and cSS are dynamic markers in CAA, with baseline presence predicting their progression. While repeat brain MRI may aid in disease monitoring, radiological progression alone does not predict clinical events.