Research Paper Volume 11, Issue 22 pp 10581—10596

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

Bibek Gyanwali1,2, *, , Muhammad Amin Shaik3, *, , Chuen Seng Tan4, , Henri Vrooman5, , Narayanaswamy Venketasubramanian6, , Christopher Chen1,2, , Saima Hilal1,2,4,7, ,

  • 1 Memory Aging and Cognition Centre, National University Health System, Singapore
  • 2 Department of Pharmacology, National University of Singapore, Singapore
  • 3 Ageing Research Institute for Society and Education, Nanyang Technological University, Singapore
  • 4 Saw Swee Hock School of Public Health, National University of Singapore, Singapore
  • 5 Departments of Radiology and Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 6 Raffles Neuroscience Centre, Raffles Hospital, Singapore
  • 7 Departments of Epidemiology and Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
* Joint first authors

Received: August 14, 2019       Accepted: November 8, 2019       Published: November 25, 2019
How to Cite

Copyright © 2019 Gyanwali et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


CAA: Cerebral amyloid angiopathy; MRI: Magnetic resonance imaging; CMBs: Cerebral microbleeds; CIND: Cognitive impairment no dementia; AD: Alzheimer’s disease; FLAIR: Fluid-attenuated inversion recovery; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition; SWI: Susceptibility weighted image; STRIVE: Standards for Reporting Vascular Changes on Neuroimaging; CI: Confidence interval; OR: Odds ratios; CA: Cornu Amonis; HATA: Hippocampus amygdala transition area; GCMLDG: Molecular and granule cell layer of dentate gyrus.