Impact of Strategically Located White Matter Hyperintensities on Cognition in Memory Clinic Patients with Small Vessel Disease

PLoS One. 2016 Nov 8;11(11):e0166261. doi: 10.1371/journal.pone.0166261. eCollection 2016.

Abstract

Background and purpose: Studies on the impact of small vessel disease (SVD) on cognition generally focus on white matter hyperintensity (WMH) volume. The extent to which WMH location relates to cognitive performance has received less attention, but is likely to be functionally important. We examined the relation between WMH location and cognition in a memory clinic cohort of patients with sporadic SVD.

Methods: A total of 167 patients with SVD were recruited from memory clinics. Assumption-free region of interest-based analyses based on major white matter tracts and voxel-wise analyses were used to determine the association between WMH location and executive functioning, visuomotor speed and memory.

Results: Region of interest-based analyses showed that WMHs located particularly within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume. Memory was significantly associated with WMH volume in the forceps minor, independent of total WMH volume. An independent assumption-free voxel-wise analysis identified strategic voxels in these same tracts. Region of interest-based analyses showed that WMH volume within the anterior thalamic radiation explained 6.8% of variance in executive functioning, compared to 3.9% for total WMH volume; WMH volume within the forceps minor explained 4.6% of variance in visuomotor speed and 4.2% of variance in memory, compared to 1.8% and 1.3% respectively for total WMH volume.

Conclusions: Our findings identify the anterior thalamic radiation and forceps minor as strategic white matter tracts in which WMHs are most strongly associated with cognitive impairment in memory clinic patients with SVD. WMH volumes in individual tracts explained more variance in cognition than total WMH burden, emphasizing the importance of lesion location when addressing the functional consequences of WMHs.

MeSH terms

  • Aged
  • Anterior Thalamic Nuclei / pathology
  • Cerebral Small Vessel Diseases / pathology*
  • Cognition / physiology*
  • Cognition Disorders / pathology*
  • Executive Function / physiology
  • Female
  • Humans
  • Male
  • Memory / physiology*
  • Neuropsychological Tests
  • White Matter / pathology*

Grants and funding

The Memory Aging and Cognition Centre is funded by a National Medical Council of Singapore Centre Grant (NMRC/CG/013/2013). Hugo J. Kuijf was financially supported by the project Brainbox (Quantitative analysis of MR brain images for cerebrovascular disease management), funded by the Netherlands Organisation for Health Research and Development (ZonMw) in the framework of the research programme IMDI (Innovative Medical Devices Initiative); project 104002002. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.