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

Narayanaswamy Venketasubramanian,Nick A Weaver,Geert Jan Biessels,Xin Xu,Christopher P L H Chen,Mohammad Kamran Ikram,Boon Yeow Tan,J Matthijs Biesbroek,Saima Hilal,Albert Postma,Hugo J Kuijf

doi:10.1371/journal.pone.0166261

Abstract

Background and PurposeStudies 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.MethodsA 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.ResultsRegion 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.ConclusionsOur 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.

Highlights

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment, either by itself or in combination with other pathologies in particular Alzheimer’s disease (AD) [1]
Region of interest-based analyses showed that white matter hyperintensity (WMH) located within the anterior thalamic radiation and forceps minor were inversely associated with both executive functioning and visuomotor speed, independent of total WMH volume
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

Summary

Introduction

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment, either by itself or in combination with other pathologies in particular Alzheimer’s disease (AD) [1]. Recent studies have applied these techniques to identify strategic WMH locations in patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), i.e. a rare form of hereditary SVD) [4,5], patients with manifest arterial disease [3], elderly stroke survivors (!3 months post-stroke) [9], patients with AD [10] and community-based cohorts (i.e. patients without cognitive complaints) [6,7,11].

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