Factors associated with intracerebral hemorrhage in confirmed cerebral amyloid angiopathy.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a leading cause of lobar intracerebral hemorrhage (ICH) in the elderly. The influence of apolipoprotein E (APOE) variants, CAA pathology, and concomitant Alzheimer's disease (AD) neuropathologic changes in determining hemorrhagic risk is incompletely defined. METHODS: We analyzed 205 autopsy brains with CAA from two Spanish cohorts: a hospital-based series and a cohort of institutionalized patients with dementia. CAA severity was graded using the Vonsattel system and vascular cognitive impairment neuropathology guidelines subscore for CAA. RESULTS: Multivariate analysis identified younger age at death, APOE ε2 carriage, and vascular remodeling CAA as independent predictors of ICH. APOE ε2 was associated with ICH but not with vascular remodeling. The ε2/ε4 genotype showed the highest ICH frequency. Severity of CAA was most strongly associated with ICH in the presence of concomitant AD. DISCUSSION: These findings support a complex interaction among APOE genotype, vascular amyloid pathology, and concomitant AD changes in shaping the hemorrhagic phenotype of CAA.