Mixed-location cerebral microbleeds as a biomarker of neurodegeneration in a memory clinic population

Abstract

Cerebral microbleeds (CMBs) in the lobar and deep locations are associated with two distinct pathologies: cerebral amyloid angiopathy and hypertensive arteriopathy. However, the role of mixed-location CMBs in neurodegeneration remains unexplored. We investigated the associations between strictly lobar, strictly deep and mixed-location CMBs with markers of neurodegeneration. This study recruited 477 patients from a memory clinic who underwent 3T MRI scans. CMBs were categorized into strictly lobar, strictly deep and mixed-location. Cortical thickness, white matter volume and subcortical structural volumes were quantified using Free-Surfer. Linear regression models were performed to assess the association between CMBs and cerebral atrophy, and the mean difference (β) and 95% confidence intervals (CIs) were reported. In the regression analyses, mixed-location CMBs were associated with smaller cortical thickness of limbic region [β= -0.01; 95% CI= -0.02, -0.00, p=0.007) as well as with smaller accumbens volume [β= -0.01; 95% CI= -0.02, -0.00, p=0.004) and presubiculum region of hippocampus [β= -0.01; 95% CI= -0.02, -0.00, p=0.002). Strictly lobar CMBs were associated with smaller total white matter volume [β= -0.03; 95% CI= -0.04, -0.01, p<0.001] and with region specific white matter volumes. The underlying mechanism requires further research and may involve shared mechanisms of vascular dysfunction and neurodegeneration.