Prognostic relevance of cortical superficial siderosis in cerebral amyloid angiopathy

Abstract

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.

Colocalization of Tau but Not β-Amyloid with Cortical Superficial Siderosis in a Case with Probable CAA

“…Previous literature has suggested that cSS represents a more severe stage of CAA [9] and is associated with amyloid positivity in patients with probable CAA [10]. However, to the best of our knowledge, there is no data available analyzing the distribution of cSS in association with local amyloid positivity and there is no data at all on cSS and tau pathology.…”

Vascular Cognitive Impairment and Dementia

“…Hemorrhagic manifestations of SVD include microbleeds, larger intracranial hemorrhages, focal subarachnoid hemorrhage, and cortical superficial siderosis. The latter is tightly linked to CAA and has prognostic relevance (98).…”

Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease

“…In CAA, Aβ40 predominantly deposits in the smooth muscle cell layers of leptomeningeal/cortical arteries and capillaries, 22‐25 which is exacerbated in males and in apolipoprotein E ( APOE ) ε4 carriers in AD 21 . CAA is responsible for ∼20% of cerebral hemorrhage cases in the elderly and increases the risk of hemorrhage as assessed by MRI 20,26 . Although BBB damage and CAA are main cerebrovascular phenotypic features frequently observed in AD, their relationship is not precisely understood.…”