Cortical superficial siderosis A marker of vascular amyloid in patients with cognitive impairment

Objective:To investigate the prevalence and associations of cortical superficial siderosis (cSS) utilizing MRI markers of cerebral small vessel disease and amyloid burden assessed through in vivo amyloid imaging in a cognitively impaired population.Methods:Gradient-recalled echo, T2*-weighted MRIs from 232 patients (Alzheimer disease-related cognitive impairment [ADCI], n = 90; subcortical vascular cognitive impairment [SVCI], n = 142) were reviewed for cSS. All subjects underwent in vivo amyloid imaging using [C-11] Pittsburgh compound B (PiB)-PET. A multivariate logistic regression model was constructed to evaluate the predictive factors of cSS. A follow-up MRI was performed in 154 (66.4%) of 232 patients.Results:Twelve patients (5.2%) with cSS were equally distributed in ADCI (n = 6) and SVCI (n = 6) groups, but cSS was not present in any of the patients with a negative PiB scan. cSS was associated with markers of cerebral amyloid angiopathy, including higher global PiB retention ratio, APOE epsilon 2 allele presence, and a strictly lobar distribution of cerebral microbleeds. Of those patients with baseline cSS, 33% showed progression over time; there were 2 cases of symptomatic intracranial hemorrhage.Conclusions:cSS occurred in both ADCI and SVCI groups, but not in patients with amyloid-negative SVCI, supporting the hypothesis that cSS reflects an amyloid rather than ischemic etiology. The associations with strictly lobar cerebral microbleeds and APOE epsilon 2 suggest that cerebral amyloid angiopathy, with increased vascular fragility related to APOE genotype, contributes to cSS in this population, with a high risk of progression over time and future intracranial hemorrhage.