Specific risk factors for microbleeds and white matter hyperintensities in Alzheimer's disease

Neurobiol Aging. 2013 Nov;34(11):2488-94. doi: 10.1016/j.neurobiolaging.2013.04.023. Epub 2013 May 31.


We investigated whether microbleeds and white matter hyperintensities (WMH) in Alzheimer's disease (AD) associate more with conventional vascular risk factors or with risk factors that reflect amyloid burden. A total of 371 patients with probable AD were included. WMH (Fazekas 2 or 3) were present in 107 (29%) patients and microbleeds were seen in 98 (26%). Patients with both microbleeds and WMH were older and presented more frequently with lacunes and multiple microbleeds than patients with microbleeds in isolation (all p < 0.05). Using multivariate regression models, we found that WMH presence showed independent associations with age, hypertension, current smoking, and lacune presence. Microbleeds were independently associated with male gender, higher blood pressure, lower cerebrospinal fluid Aβ42, and apolipoprotein E ε4 homozygosity. Separate analyses for microbleeds according to their location showed that these associations were driven by microbleeds in lobar locations. Our results suggest that, unlike WMH, microbleeds in AD are particularly associated with additional amyloid burden, and as such, may relate to cerebral amyloid angiopathy.

Keywords: Alzheimer's disease; ApoE; Microbleeds; Microhemorrhage; Risk factors; Small vessel disease; White matter hyperintensities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Analysis of Variance
  • Apolipoprotein E4 / genetics
  • Cerebral Hemorrhage / etiology*
  • Cerebral Hemorrhage / genetics
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Leukoencephalopathies / etiology*
  • Leukoencephalopathies / genetics
  • Magnetic Resonance Imaging
  • Male
  • Peptide Fragments / cerebrospinal fluid
  • Retrospective Studies
  • Risk Factors


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Peptide Fragments
  • amyloid beta-protein (1-42)