Objective: To investigate whether magnetic resonance imaging (MRI) markers of cerebral small vessel disease predict overall mortality in cerebral amyloid angiopathy (CAA) patients.
Methods: Subjects were consecutive survivors (age≥55) of spontaneous symptomatic CAA-related-lobar ICH and CAA presenting without lobar ICH, diagnosed according to the Boston criteria drawn from an ongoing longitudinal cohort study and Memory Disorder Unit. All subjects had brain MRI at presentation. Baseline clinical, imaging, laboratory data and mortality information were collected. Neuroimaging markers including focal (≤3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), cortical subarachnoid hemorrhage (cSAH), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) were evaluated. Overall mortality risk was assessed using Cox proportional hazards models adjusting for potential confounders.
Results: A total of 335 patients with probable CAA were enrolled, 196 presenting with lobar ICH and 139 without lobar ICH. During a median follow-up time of 3.44 years (interquartile range 1.61- 5.52 years), 181 of 335 patients (54.0%) died, 37.3% were patients with lobar ICH and 16.7% were those without. In univariable analysis, disseminated cSS, moderate to severe WMH, higher age and CAA related-lobar ICH group were predictors of overall mortality (p<0.05 for all comparisons). After adjusting for moderate to severe WMH and multiple CMBs (CMBs ≥5 foci), disseminated cSS remained as an independent neuroimaging predictor of overall mortality (HR 1.66; 95% CI 1.05-2.64, p = 0.030). Other predictors of mortality were older age (HR 1.08; 95% CI 1.06-1.11, p < 0.001) and presence of lobar ICH (HR 1.87; 95% CI 1.34-2.61, p < 0.001). The mortality risk was even greater in patients with both disseminated cSS and lobar ICH (HR 2.28; 95% CI 1.41-3.69, p = 0.001) and as well as in older patients (age>75 years) with disseminated cSS (HR 1.86; 95% CI 1.08-3.23, p = 0.026).
Conclusion: Disseminated cSS is an independent neuroimaging biomarker of increased risk of overall mortality in probable CAA, particular in those patients with lobar ICH and older age. These findings may serve identify important markers of CAA severity.