Cerebral small vessel disease in aging and Alzheimer's disease: a comparative study using MRI and SPECT

Eur J Neurol. 2013 Feb;20(2):243-50. doi: 10.1111/j.1468-1331.2012.03785.x. Epub 2012 Jun 28.


Background: White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs).

Methods: Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns.

Results: WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs.

Conclusion: Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aging / pathology
  • Aging / physiology*
  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology
  • Brain / blood supply*
  • Brain / pathology
  • Cerebral Small Vessel Diseases / complications*
  • Cerebral Small Vessel Diseases / diagnosis*
  • Cerebral Small Vessel Diseases / diagnostic imaging
  • Cerebral Small Vessel Diseases / pathology
  • Cysteine / analogs & derivatives
  • Female
  • Humans
  • Leukoaraiosis / complications
  • Leukoaraiosis / diagnostic imaging
  • Leukoaraiosis / pathology
  • Magnetic Resonance Imaging
  • Male
  • Nerve Fibers, Myelinated / pathology
  • Neuroimaging
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Tomography, Emission-Computed, Single-Photon


  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium Tc 99m bicisate
  • Cysteine