Association of amyloid angiopathy with microbleeds in logopenic progressive aphasia: an imaging-pathology study

M. Buciuc, J. R. Duffy, M. M. Machulda, A. J. Spychalla, J. L. Gunter, C. R. Jack, C. Giannini, A. Raghunathan, D. W. Dickson, K. A. Josephs, J. L. Whitwell

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background and purpose: Cerebral microbleeds (MB) and superficial siderosis (SS) are frequent neuroimaging findings in patients with logopenic progressive aphasia (LPA), often with frontal lobe predilection. Cerebral amyloid angiopathy (CAA) is hypothesized to be the major pathologic determinant of MB/SS in these patients; however, neuroimaging-pathologic data are limited. Methods: All patients who had been prospectively recruited by the Neurodegenerative Research Group at the Mayo Clinic (Rochester, MN) between 2010 and 2015 and met the following inclusion criteria were included: (i) received an antemortem LPA diagnosis, (ii) had a gradient-recalled echo T2*-weighted magnetic resonance imaging (MRI) performed, (iii) died and completed a brain autopsy. Demographic, genetic, neuroimaging, and clinical and pathologic characteristics were compared between patients with/without MB/SS. Two-tailed Fisher exact and Wilcoxon rank sum tests were used for comparison of categorical and continuous variables, respectively. Results: Thirteen patients met inclusion criteria, six (46%) had MB/SS on MRI. Moderate/severe CAA was associated with the presence of MB/SS (p = 0.029). As expected, MB/SS most frequently involved the frontal lobes, followed by the parietal lobes. No clear associations were found between regional MB/SS distribution and regional distribution of CAA or hypometabolism on [18F]-fluorodeoxyglucose–positron emission tomography. There was some evidence for a regional association between MB/SS and uptake on Pittsburgh compound B, although not in all patients. No formal statistical analyses to assess topographic relationships were performed due to the small sample size. Conclusions: The presence of MB/SS is a strong indicator of underlying moderate/severe CAA in LPA, although the biological mechanisms underlying the topographic distribution of MB/SS remain unclear.

Original languageEnglish (US)
Pages (from-to)670-675
Number of pages6
JournalEuropean Journal of Neurology
Issue number2
StatePublished - Feb 2021


  • atypical Alzheimer’s disease
  • cerebral amyloid angiopathy
  • logopenic progressive aphasia
  • magnetic resonance imaging
  • microbleeds
  • positron emission tomography

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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