Sex differences in histopathological markers of cerebral amyloid angiopathy and related hemorrhage

Background: Men with cerebral amyloid angiopathy (CAA) may have an earlier onset of intracerebral hemorrhage and a more hemorrhagic disease course compared to women. In this cohort study, we investigated sex differences in histopathological markers associated with amyloid-β burden and hemorrhage in cognitively impaired individuals and patients with CAA, using neuropathological data from two autopsy databases. Methods: First, we investigated presence of parenchymal (Thal score) and vascular amyloid-β (CAA severity score) in cognitively impaired individuals from the National Alzheimer’s Coordinating Center (NACC) neuropathology database. Next, we examined sex differences in hemorrhagic ex vivo magnetic resonance imaging (MRI) markers and local cortical iron burden and the interaction of sex on factors associated with cortical iron burden (CAA percentage area and vessel remodeling) in patients with pathologically confirmed clinical CAA from the Massachusetts General Hospital (MGH) CAA neuropathology database. Results: In 6120 individuals from the NACC database (45% women, mean age 80 years), the presence of parenchymal amyloid-β (odds ratio (OR) (95% confidence interval (CI)) =0.68 (0.53–0.88)) but not vascular amyloid-β was less in men compared to women. In 19 patients with definite CAA from the MGH CAA database (35% women, mean age 75 years), a lower microbleed count (p