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Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging.

ABSTRACT: The Alzheimer's Disease Neuroimaging Initiative (ADNI) recently added diffusion tensor imaging (DTI), among several other new imaging modalities, in an effort to identify sensitive biomarkers of Alzheimer's disease (AD). While anatomical MRI is the main structural neuroimaging method used in most AD studies and clinical trials, DTI is sensitive to microscopic white matter (WM) changes not detectable with standard MRI, offering additional markers of neurodegeneration. Prior DTI studies of AD report lower fractional anisotropy (FA), and increased mean, axial, and radial diffusivity (MD, AxD, RD) throughout WM. Here we assessed which DTI measures may best identify differences among AD, mild cognitive impairment (MCI), and cognitively healthy elderly control (NC) groups, in region of interest (ROI) and voxel-based analyses of 155 ADNI participants (mean age: 73.5 ± 7.4; 90 M/65 F; 44 NC, 88 MCI, 23 AD). Both VBA and ROI analyses revealed widespread group differences in FA and all diffusivity measures. DTI maps were strongly correlated with widely-used clinical ratings (MMSE, CDR-sob, and ADAS-cog). When effect sizes were ranked, FA analyses were least sensitive for picking up group differences. Diffusivity measures could detect more subtle MCI differences, where FA could not. ROIs showing strongest group differentiation (lowest p-values) included tracts that pass through the temporal lobe, and posterior brain regions. The left hippocampal component of the cingulum showed consistently high effect sizes for distinguishing groups, across all diffusivity and anisotropy measures, and in correlations with cognitive scores.

SUBMITTER: Nir TM

PROVIDER: S-EPMC3792746 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging.

Nir Talia M TM Jahanshad Neda N Villalon-Reina Julio E JE Toga Arthur W AW Jack Clifford R CR Weiner Michael W MW Thompson Paul M PM

NeuroImage. Clinical 20130727

The Alzheimer's Disease Neuroimaging Initiative (ADNI) recently added diffusion tensor imaging (DTI), among several other new imaging modalities, in an effort to identify sensitive biomarkers of Alzheimer's disease (AD). While anatomical MRI is the main structural neuroimaging method used in most AD studies and clinical trials, DTI is sensitive to microscopic white matter (WM) changes not detectable with standard MRI, offering additional markers of neurodegeneration. Prior DTI studies of AD repo ...[more]

PMID: 24179862

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Project description:Though mild cognitive impairment is an intermediate clinical state between healthy aging and Alzheimer's disease (AD), there are very few whole-brain voxel-wise diffusion MRI studies directly comparing changes in healthy control, mild cognitive impairment (MCI) and AD subjects. Here we report whole-brain findings from a comprehensive study of diffusion tensor indices and probabilistic tractography obtained in a very large population of healthy controls, MCI and probable AD subjects. As expected from the literature, all diffusion indices converged to show that the cingulum bundle, the uncinate fasciculus, the entire corpus callosum and the superior longitudinal fasciculus are the most affected white matter tracts in AD. Significant differences between MCI and AD were essentially confined to the corpus callosum. More importantly, we introduce for the first time in a degenerative disorder an application of a recently developed tensor index, the "mode" of anisotropy, as well as probabilistic crossing-fibre tractography. The mode of anisotropy specifies the type of anisotropy as a continuous measure reflecting differences in shape of the diffusion tensor ranging from planar (e.g., in regions of crossing fibres from two fibre populations of similar density or regions of "kissing" fibres) to linear (e.g., in regions where one fibre population orientation predominates), while probabilistic crossing-fibre tractography allows to accurately trace pathways from a crossing-fibre region. Remarkably, when looking for whole-brain diffusion differences between MCI patients and healthy subjects, the only region with significant abnormalities was a region of crossing fibres in the centrum semiovale, showing an increased mode of anisotropy. The only white matter region demonstrating a significant difference in correlations between neuropsychological scores and a diffusion measure (mode of anisotropy) across the three groups was the same region of crossing fibres. Further examination using probabilistic tractography established explicitly and quantitatively that this previously unreported increase of mode and co-localised increase of fractional anisotropy was explained by a relative preservation of motor-related projection fibres (at this early stage of the disease) crossing the association fibres of the superior longitudinal fasciculus. These findings emphasise the benefit of looking at the more complex regions in which spared and affected pathways are crossing to detect very early alterations of the white matter that could not be detected in regions consisting of one fibre population only. Finally, the methods used in this study may have general applicability for other degenerative disorders and, beyond the clinical sphere, they could contribute to a better quantification and understanding of subtle effects generated by normal processes such as visuospatial attention or motor learning.

Dataset Information

Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging.

Publications

Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging.

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