Mixed-Location Cerebral Microbleeds: An Imaging Biomarker for Cerebrovascular Pathology in Cognitive Impairment and Dementia in a Memory Clinic Population

Background: Cerebral microbleeds (CMBs) in the lobar and deep locations have been associated with two distinct pathologies namely cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy. However, the role of mixed-location CMBs in cerebrovascular disease and cognitive impairment remain unexplored. Objective: The present study aims to investigate the association of strictly lobar, strictly deep and mixed-location CMBs with cognitive impairment and dementia as well as functional decline. Methods: A prospective case-control study, where 520 patients underwent 3T brain MRI to assess region and lobe-specific CMBs, and other cerebrovascular diseases (CeVD) markers such as cortical infarcts, lacunes, and white matter hyperintensities. Patients were classified as no cognitive Impairment, cognitive impairment no dementia (CIND), and dementia [Alzheimer's disease (AD) and vascular dementia (VaD)]. Severity of cognitive impairment was assessed using Clinical Dementia Rating scale. Results: Mixed-location CMBs were associated with dementia [Odds ratio (OR):1.23; 95% confidence interval (CI):1.04, 1.47]. When stratified by the presence of CeVD, mixed-location CMBs were associated with CIND [OR:1.20;95% CI:1.02, 1.42], AD [OR:1.22;95% CI:1.02, 1.46], and VaD [OR:1.33;95% CI:1.08, 1.62]. Furthermore, CMBs in frontal, parietal, and temporal regions were associated with CIND whereas those in parietal, temporal, and occipital regions were associated with AD. Mixed-location CMBs were also associated with increased severity of cognitive impairment [OR:1.02; 95% CI:1.00, 1.05]. Conclusion: Mixed-location CMBs are associated with cognitive impairment and dementia in the presence of CeVD. Furthermore mixed-location CMBs were linked with increased severity of cognitive impairment, suggesting severe parenchymal damage as well as microangiopathy to be common underlying mechanisms in the elderly.