The cumulative effect of small vessel disease lesions is reflected in structural brain networks of memory clinic patients

Rutger Heinen, Naomi Vlegels*, Jeroen de Bresser, Alexander Leemans, Geert Jan Biessels, Yael D. Reijmer,

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background and purpose: Mechanisms underlying cognitive impairment in patients with small vessel disease (SVD) are still unknown. We hypothesized that cognition is affected by the cumulative effect of multiple SVD-related lesions on brain connectivity. We therefore assessed the relationship between the total SVD burden on MRI, global brain network efficiency, and cognition in memory clinic patients with vascular brain injury.

Methods: 173 patients from the memory clinic of the University Medical Center Utrecht underwent a 3 T brain MRI scan (including diffusion MRI sequences) and neuropsychological testing. MRI markers for SVD were rated and compiled in a previously developed total SVD score. Structural brain networks were reconstructed using fiber tractography followed by graph theoretical analysis. The relationship between total SVD burden score, global network efficiency and cognition was assessed using multiple linear regression analyses.

Results: Each point increase on the SVD burden score was associated with 0.260 [-0.404 - -0.117] SD units decrease of global brain network efficiency ( p < .001). Global network efficiency was associated with information processing speed (standardized B = -0.210, p = .004) and attention and executive functioning (B = 0.164, p = .042), and mediated the relationship between SVD burden and information processing speed ( p = .027) but not with executive functioning ( p = .12).

Conclusion: Global network efficiency is sensitive to the cumulative effect of multiple manifestations of SVD on brain connectivity. Global network efficiency may therefore serve as a useful marker for functionally relevant SVD-related brain injury in clinical trials.

Original languageEnglish
Pages (from-to)963-969
Number of pages7
JournalNeuroImage: Clinical
Publication statusPublished - 1 Jan 2018


  • Cerebral small vessel disease
  • Cognition
  • Diffusion-weighted imaging
  • Magnetic resonance imaging
  • Vascular cognitive impairment
  • Humans
  • Middle Aged
  • Male
  • Nerve Net/diagnostic imaging
  • Cerebral Small Vessel Diseases/complications
  • Neuropsychological Tests
  • Brain/diagnostic imaging
  • Magnetic Resonance Imaging
  • Image Processing, Computer-Assisted
  • Aged, 80 and over
  • Female
  • Aged
  • Executive Function/physiology
  • Memory Disorders/complications
  • Cognition/physiology


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