Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study

Robin G Morris,Thomas R Barrick,Bhavini Patel,Philip M Rich,Andrew J Lawrence,Jean-Claude Baron,Hugh S Markus,Andrew D Mackinnon

doi:10.1371/journal.pone.0061014

Abstract

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD.

Highlights

Cerebral small vessel disease (SVD) is the most common pathology underlying vascular dementia, and is a major cause of lesser degrees of vascular cognitive impairment (VCI) [1]
Post-hoc t-tests based on standardised regression coefficients and pooled variance were conducted to look for significant differences in the regression coefficients obtained for each predictor in the two cognitive models, none reached significance. In this well phenotyped cohort of patients with symptomatic small vessel disease and radiological leukoaraiosis, we found a characteristic cognitive profile with impaired performance in executive function and processing speed, relative to working memory and episodic memory
On analysis of single predictors, impaired executive function and processing speed were associated with lacunar infarct count, reduced brain volume, and white matter ultrastructural damage determined using diffusion tensor imaging (DTI)

Summary

Introduction

Cerebral small vessel disease (SVD) is the most common pathology underlying vascular dementia, and is a major cause of lesser degrees of vascular cognitive impairment (VCI) [1]. Radiological correlates are lacunar infarcts, with or without more diffuse areas of white matter hyperintensities (WMH), referred to as leukoaraiosis. Other features are brain atrophy and cerebral microbleeds. Cognitive impairment in SVD is characterised by prominent impairment of executive function and processing speed, with relative preservation of episodic memory [1,2]. There are few specific treatments for cognitive impairment in SVD. The development of evidence based treatment approaches depends upon better understanding of the mechanisms of cognitive decline

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