Dataset Information

Preserved Structural Network Organization Mediates Pathology Spread in Alzheimer's Disease Spectrum Despite Loss of White Matter Tract Integrity.

ABSTRACT: Models of Alzheimer's disease (AD) hypothesize stereotyped progression via white matter (WM) fiber connections, most likely via trans-synaptic transmission of toxic proteins along neuronal pathways. An important question in the field is whether and how organization of fiber pathways is affected by disease. It remains unknown whether fibers act as conduits of degenerative pathologies, or if they also degenerate with the gray matter network. This work uses graph theoretic modeling in a longitudinal design to investigate the impact of WM network organization on AD pathology spread. We hypothesize if altered WM network organization mediates disease progression, then a previously published network diffusion model will yield higher prediction accuracy using subject-specific connectomes in place of a healthy template connectome. Neuroimaging data in 124 subjects from ADNI were assessed. Graph topology metrics show preserved network organization in patients compared to controls. Using a published diffusion model, we further probe the effect of network alterations on degeneration spread in AD. We show that choice of connectome does not significantly impact the model's predictive ability. These results suggest that, despite measurable changes in integrity of specific fiber tracts, WM network organization in AD is preserved. Further, there is no difference in the mediation of putative pathology spread between healthy and AD-impaired networks. This conclusion is somewhat at variance with previous results, which report global topological disturbances in AD. Our data indicates the combined effect of edge thresholding, binarization, and inclusion of subcortical regions to network graphs may be responsible for previously reported effects.

SUBMITTER: Powell F

PROVIDER: S-EPMC6152926 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Preserved Structural Network Organization Mediates Pathology Spread in Alzheimer's Disease Spectrum Despite Loss of White Matter Tract Integrity.

Powell Fon F Tosun Duygu D Sadeghi Roksana R Weiner Michael M Raj Ashish A

Journal of Alzheimer's disease : JAD 20180101 3

Models of Alzheimer's disease (AD) hypothesize stereotyped progression via white matter (WM) fiber connections, most likely via trans-synaptic transmission of toxic proteins along neuronal pathways. An important question in the field is whether and how organization of fiber pathways is affected by disease. It remains unknown whether fibers act as conduits of degenerative pathologies, or if they also degenerate with the gray matter network. This work uses graph theoretic modeling in a longitudina ...[more]

PMID: 29578480

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Project description:Background and purposeAlthough drowning is a leading cause of mortality and morbidity in young children, the neuropathologic consequences have not been fully determined. The purpose of this article was to quantitatively characterize white matter microstructural abnormalities in pediatric anoxic brain injury from nonfatal drowning and investigate the correlation with motor function.Materials and methodsWhole-brain T1-weighted and diffusion-weighted MR imaging datasets were acquired in 11 children with chronic anoxic brain injury and 11 age- and sex-matched neurotypical controls (4-12 years of age). A systematic evaluation form and scoring system were created to assess motor function. Tract-Based Spatial Statistics was used to quantify between-group alterations in the diffusion tensor imaging indices of fractional anisotropy and mean diffusivity and to correlate with per-subject functional motor scores.ResultsGroup-wise Tract-Based Spatial Statistics analyses demonstrated reduced fractional anisotropy in the bilateral posterior limbs of the internal capsule and the splenium of the corpus callosum (P < .001). Mean diffusivity was more diffusely increased, affecting the bilateral superior corona radiata, anterior and posterior limbs of the internal capsule, and external capsules (P < .001). Individual-subject fractional anisotropy and mean diffusivity values derived from the ROIs of the bilateral posterior limbs of the internal capsule strongly correlated with motor scores and demonstrated more potent between-group effects than with ROIs of the entire corticospinal tract.ConclusionsThese data particularly implicate the deep white matter, predominantly the posterior limbs of the internal capsule, as targets of damage in pediatric anoxic brain injury with drowning. The substantial involvement of motor-system tracts with relative sparing elsewhere is notable. These results localize white matter pathology and inform future diagnostic and prognostic markers.

Dataset Information

Preserved Structural Network Organization Mediates Pathology Spread in Alzheimer's Disease Spectrum Despite Loss of White Matter Tract Integrity.

Publications

Preserved Structural Network Organization Mediates Pathology Spread in Alzheimer's Disease Spectrum Despite Loss of White Matter Tract Integrity.

Similar Datasets

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