Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment
Article first published online: 12 MAR 2013
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 73, Issue 5, pages 584–593, May 2013
How to Cite
Park, J.-H., Seo, S. W., Kim, C., Kim, G. H., Noh, H. J., Kim, S. T., Kwak, K.-C., Yoon, U., Lee, J. M., Lee, J. W., Shin, J. S., Kim, C. H., Noh, Y., Cho, H., Kim, H. J., Yoon, C. W., Oh, S. J., Kim, J. S., Choe, Y. S., Lee, K.-H., Lee, J.-H., Ewers, M., Weiner, M. W., Werring, D. J. and Na, D. L. (2013), Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment. Ann Neurol., 73: 584–593. doi: 10.1002/ana.23845
- Issue published online: 28 MAY 2013
- Article first published online: 12 MAR 2013
- Accepted manuscript online: 29 JAN 2013 04:51AM EST
- Manuscript Accepted: 30 NOV 2012
- Manuscript Revised: 18 NOV 2012
- Manuscript Received: 25 AUG 2012
Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment.
We included 226 patients: 89 with Alzheimer disease–related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [11C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes.
Parietal and occipital lobar CMBs counts were higher in PiB+ ADCI with moderate WMH than PiB+ ADCI with minimal WMH, whereas PiB− patients with SVCI (ie, “pure” SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001).
Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs. Ann Neurol 2013;73:584–593