Abstract

Background: Vascular calcification (VC) is an independent predictor of cardiovascular and cerebrovascular events. While the clinical significance of coronary VC is well recognized, less is known about the prevalence and implications of VC in brain microcirculation. Aims: In this exploratory study, we aimed to compare calcification volume (CV) across brain regions in subjects with and without dementia documented at death. Methods: In a cohort of human donor cadavers (n=14, 57% female, all >70 y/o), brain tissue was sampled bilaterally from basal ganglia (BG), substantia nigra (SN), subventricular zone (SVZ), hippocampus (Hc), and posterior cingulate cortex (PCC), and scanned by microCT at 10 μm resolution. Reconstructed images were segmented into standardized regions of interest (ROI). CV was defined as voxel quantity ≥130 Hounsfield units within each ROI. Findings were confirmed by histologic evaluation. Results: By two-way ANOVA, CV differed significantly by region (p=0.0006) and condition (p=0.0104). Hc and PCC CVs were significantly greater in subjects with dementia compared to age-matched subjects (9.3х10e7 μm 3 vs 1.4х10e7μm 3 , p=0.007; 2.6х10e7 μm 3 vs 4.7х10e6 μm 3 , p=0.017). Conclusions: All subjects in our cohort exhibited VC in at least one brain region, indicating that the prevalence of intracranial VC exceeds published estimates. Subjects with dementia exhibited significantly higher Hc and PCC CVs than age-matched subjects without documented dementia. Although limited by small sample size, our findings support recent reports of hippocampal and BG calcification in post-mortem brain samples from humans with Alzheimer disease.

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