Abstract 162: Molecular And Microstructural Alterations In Cerebral Amyloid Angiopathy-related Hemorrhagic Manifestations

Background and Purpose: We aimed to compare the amyloid load and degree of microstructural injury among Cerebral Amyloid Angiopathy (CAA) patients with either higher lobar cerebral microbleed (CMB) counts or higher cortical superficial siderosis (cSS) extent against CAA patients with lower hemorrhagic load. Methods: The study included 38 cognitively healthy probable CAA patients with lobar intracerebral hemorrhage (ICH) and 38 age, sex-matched healthy controls (HC) who underwent advanced MRI, and Pittsburgh Compound B (PiB) PET scans. Patients were categorized into CMB-Dominant (CMB-D) and cSS-Dominant (cSS-D) based on the number and extent of CMB and cSS using previously identified cutoffs (Figure). The mean global cortical amyloid load was calculated from PiB-PET scans and represented by PiB-DVR. Within the CAA cohort, the Peak Width of Skeletonized Mean Diffusivity (PSMD) was calculated from diffusion MRIs and used as a marker of microstructural integrity. Results: Patients with CAA had significantly higher PiB-DVR than HCs (1.40±0.24 vs. 1.19±0.22, p<0.001). Both CMB-D and cSS-D CAA patients had significantly higher amyloid and increased (worse) PSMD compared to CAA patients with a non-dominant low hemorrhagic load (Figure). These results did not change in separate regression models corrected for age and sex. PiB-DVR significantly correlated with increased PSMD (r=0.346, p=0.033). Conclusions: Our findings support the view that vascular amyloid load drives higher CMB counts, more extensive cSS, and microstructural injury in patients with CAA. Furthermore, the correlations among these markers suggest that these MRI-based categorizations (CMB-D and cSS-D patients) can be used for disease staging and further research.