Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease: The RUN DMC study

H. M. van der Holst, A. M. Tuladhar, A. G.W. van Norden, K. F. de Laat, I. W.M. van Uden, L. J.B. van Oudheusden, M. P. Zwiers, D. G. Norris, R. P.C. Kessels, F. E. de Leeuw*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)


Background: Cerebral small vessel disease (SVD) is related to verbal memory failures. It is suggested that early white matter damage, is located, among others, in the (posterior) cingulum at an early stage in neurodegeneration. Changes in the microstructural integrity of the cingulum assessed with diffusion tensor imaging (DTI), beyond detection with conventional MRI, may precede macrostructural changes and be related to verbal memory failures. Objective: To investigate the relation between cingular microstructural integrity and verbal memory performance in 503 non-demented elderly with cerebral SVD. Methods: The RUN DMC study is a prospective cohort study in elderly (50-85. years) with cerebral SVD. All participants underwent T1 MPRAGE, FLAIR and DTI scanning and the Rey Auditory Verbal Learning Test. Mean diffusivity (MD) and fractional anisotropy (FA) were assessed in six different cingular regions of interests (ROIs). Linear regression analysis was used to assess the relation between verbal memory performance and cingular DTI parameters, with appropriate adjustments. Furthermore a TBSS analysis of the whole brain was performed to investigate the specificity of our findings. Results: Both our ROI-based and TBSS analysis showed that FA was positively related to immediate memory, delayed recall, delayed recognition and overall verbal memory performance of the cingulum, independent of confounders. A similar distribution was seen for the inverse association with MD and verbal memory performance with TBSS analysis. No significant relations were found with psychomotor speed, visuospatial memory and MMSE. When stratified on hippocampal integrity, the MD and FA values of the cingular ROIs differed significantly between participants with a good and poor hippocampal integrity. Conclusion: Microstructural integrity of the cingulum, assessed by DTI, is specifically related to verbal memory performance, in elderly with SVD. Furthermore we found that when the integrity of the hippocampus is disrupted, the cingulum integrity is impaired as well.

Original languageEnglish
Pages (from-to)416-423
Number of pages8
Early online date29 Sept 2012
Publication statusPublished - 15 Jan 2013
Externally publishedYes


  • Cerebral small vessel disease
  • Cingulum
  • Diffusion tensor imaging
  • Hippocampus
  • Verbal memory
  • n/a OA procedure


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