ObjectiveTo investigate the prognostic relevance of cortical superficial siderosis (cSS) in patients with cerebral amyloid angiopathy (CAA).MethodsA total of 302 patients fulfilling clinical and imaging criteria for probable or possible CAA were enrolled into a prospective, multicenter cohort study and followed for 12 months. cSS was assessed on T2-/susceptibility-weighted imaging MRI. The predefined primary composite endpoint was incident stroke or death in patients with cSS compared to those without. Secondary analyses included cerebrovascular events and functional outcome measured by the modified Rankin Scale (mRS). Multiple regression analysis was performed to adjust for possible confounders.ResultscSS prevalence was 40%. The primary endpoint occurred more frequently in patients with cSS (22%, 27/121) compared to those without (8%, 15/181, p = 0.001). Rates of CAA-related incident intracranial hemorrhage were 17% (cSS) and 4% (no cSS, p = 0.0003). The proportion of patients being functionally independent (mRS 0-2) 12 months from baseline were 59% (cSS) and 82% (no cSS, p = 0.00002). Presence of cSS was associated with the primary endpoint (adjusted odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1-1.3, p = 0.0005), incident intracranial hemorrhage (adjusted OR 1.2, 95% CI 1.1-1.3, p = 0.0003), and less favorable outcome as assessed by the mRS (common OR 1.9, 95% CI 1.2-3.1, p = 0.009). Similar results were obtained in analyses restricted to patients with probable CAA and to patients with disseminated cSS (all p < 0.005).ConclusionsPatients with cSS and suspected CAA are at high risk for CAA-related incident intracranial hemorrhage and poor functional outcome. Both the presence and extent of cSS have prognostic relevance and may influence clinical decision-making.