MRI Markers for Mild Cognitive Impairment: Comparisons between White Matter Integrity and Gray Matter Volume Measurements

Yu Zhang,Kristine Yaffe,Linda L Chao,Bruce L Miller,Monica Camacho,Susan C Woolley,Michael W Weiner,Catherine Madison,Norbert Schuff,Thomas P Fletcher,Howard J Rosen,Yong Fan

doi:10.1371/journal.pone.0066367

Abstract

The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer's disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy.

Highlights

Mild cognitive impairment (MCI) is a transitional stage between normal aging and early Alzheimer’s disease (AD), though not all individuals with a diagnosis of MCI convert to AD [1]
The aims of the study were: 1) to determine to what extent gray matter (GM) atrophy measured by structural MRI and white matter (WM) alterations measured by diffusion tensor imaging (DTI) in prominent brain regions affected in AD are associated with MCI; 2) to test whether WM alterations based on DTI improve the classification of MCI, in comparison to classifications based on GM volume; 3) to compare the accuracies of using GM volume and DTI measures for prediction of cognitive performance in MCI
The main findings of this study are: 1) MCI is associated with significant alterations of fractional anisotropy (FA) and DR as well as GM volume loss in specific regions, in agreement with previous findings

Summary

Introduction

Mild cognitive impairment (MCI) is a transitional stage between normal aging and early Alzheimer’s disease (AD), though not all individuals with a diagnosis of MCI convert to AD [1]. DTI studies in MCI generally rely on diffusion summary measures, such as fractional anisotropy (FA), an index of the spatial directionality of tissue water diffusion and mean diffusivity (MD), a measure of the diffusion magnitude These measures uniquely detect abnormalities in white matter (WM) regions. Aside from a previous work [19] in our laboratory, few studies [25,37,38] have compared the accuracy of DTI measurements with structural imaging measurements in characterizing brain alterations in MCI It is not clear whether the various indices of DTI are superior to, or provide complementary information to structural MRI measures of brain atrophy for accurately classifying MCI and predicting cognitive deficits

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