Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment

Authors

  • Janne M. Papma,

    Corresponding author
    1. Department of Neurology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    2. Department of Radiology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    • Correspondence to: Janne M. Papma, Erasmus MC, University Medical Center Rotterdam, Department of Neurology, Room Ee2238, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail: j.papma@erasmusmc.nl

    Search for more papers by this author
  • Marius de Groot,

    1. Department of Radiology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    2. Department of Medical Informatics, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Inge de Koning,

    1. Department of Neurology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Francesco U. Mattace-Raso,

    1. Department of Geriatrics, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Aad van der Lugt,

    1. Department of Radiology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Meike W. Vernooij,

    1. Department of Radiology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    2. Department of Epidemiology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Wiro J. Niessen,

    1. Department of Radiology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    2. Department of Medical Informatics, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    3. Faculty of Applied Sciences, Delft University of Technology, The Netherlands
    Search for more papers by this author
  • John C. van Swieten,

    1. Department of Neurology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Peter J. Koudstaal,

    1. Department of Neurology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Niels D. Prins,

    1. Alzheimer Centre, VU University Medical Center, Amsterdam, The Netherlands
    Search for more papers by this author
  • Marion Smits

    1. Department of Radiology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author

Abstract

Microstructural white matter deterioration is a frequent finding in mild cognitive impairment (MCI), potentially underlying default mode network (DMN) dysfunctioning. Thus far, microstructural damage in MCI has been attributed to Alzheimer's disease pathophysiology. A cerebrovascular role, in particular the role of cerebral small vessel disease (CSVD), received less interest. Here, we used diffusion tensor imaging (DTI) to examine the role of CSVD in microstructural deterioration within the normal appearing white matter (NAWM) in MCI. MCI patients were subdivided into those with (n = 20) and without (n = 31) macrostructural CSVD evidence on MRI. Using TBSS we performed microstructural integrity comparisons within the whole brain NAWM. Secondly, we segmented white matter tracts interconnecting DMN brain regions by means of automated tractography segmentation. We used NAWM DTI measures from these tracts as dependent variables in a stepwise-linear regression analysis, with structural and demographical predictors. Our results indicated microstructural deterioration within the anterior corpus callosum, internal and external capsule and periventricular white matter in MCI patients with CSVD, while in MCI patients without CSVD, deterioration was restricted to the right perforant path, a tract along the hippocampus. Within the full cohort of MCI patients, microstructure within the NAWM of the DMN fiber tracts was affected by the presence of CSVD. Within the cingulum along the hippocampal cortex we found a relationship between microstructural integrity and ipsilateral hippocampal volume and the extent of white matter hyperintensity. In conclusion, we found evidence of CSVD-related microstructural damage in fiber tracts subserving the DMN in MCI. Hum Brain Mapp 35:2836–2851, 2014. © 2013 Wiley Periodicals, Inc.

Ancillary