Abstract WP127: Cerebral Microbleeds, Cerebral Amyloid Angiopathy, And Their Relationships To Quantitative Markers Of Neurodegeneration

Abstract

Introduction: Age-related cognitive impairment is driven by the complex interplay of neurovascular and neurodegenerative disease. There is a strong relationship between cerebral microbleeds (CMBs), cerebral amyloid angiopathy (CAA), and the cognitive decline observed in conditions such as Alzheimer’s disease. In the early, preclinical phase of cognitive impairment, the extent to which CMBs and underlying CAA impact volumetric changed in the brain related to neurodegenerative disease remains unclear. Methods: We performed cross-sectional analyses from 3 large cohorts: The Northern Manhattan Study (NOMAS), Alzheimer’s Disease Neuroimaging Initiative (ADNI), and the Epidemiology of Dementia in Singapore study (EDIS). We conducted a confirmatory analysis of 82 autopsied cases from the Brain Arterial Remodeling Study (BARS). We implemented multivariate regression analyses to study the association between two related markers of cerebrovascular disease – MRI-based CMBs and autopsy-based CAA, as independent variables, and volumetric markers of neurodegeneration, as dependent variables. Results: We included 2657 participants with available MRI data and 82 autopsy cases from the BARS. In a meta-analysis of NOMAS, ADNI and EDIS, superficial CMBs were associated with larger gray (β=4.49 ± 1.13, P=0.04) and white (β=4.72 ± 2.1, P=0.03) matter volumes. The association between superficial CMBs and larger white matter volume was more evident in participants with one CMB (B=5.17 ± 2.47, P=0.04) than in those with ≥ 2 CMBs (β=1.97 ± 3.41, P=0.56). In the BARS, CAA was associated with increased cortical thickness (β = 6.5 ± 2.3, P=0.016) but not with increased brain weight (β=1.54 ± 1.29, P=0.26). Discussion: Superficial CMBs are associated with larger morphometric brain measures. This association is strongest in brains with fewer CMBs, suggesting that the CMBs/CAA contribution to neurodegeneration may not relate to tissue loss, at least in early stages of disease.