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Microstructural diffusion changes are independent of macrostructural volume loss in moderate to severe Alzheimer's disease.

ABSTRACT: Although it is established that Alzheimer's disease (AD) leads to cerebral macrostructural atrophy, microstructural diffusion changes have also been observed, but it is not yet known whether these changes offer unique information about the disease pathology. Thus, a multi-modal imaging study was conducted to determine the independent contribution of each modality in moderate to severe AD. Seventeen patients with moderate-severe AD and 13 healthy volunteers underwent diffusion-weighted and T1-weighted MR scanning. Images were processed to obtain measures of macrostructural atrophy (gray and white matter volumes) and microstructural damage (fractional anisotropy and mean diffusivity). Microstructural diffusion changes independent of macrostructural loss were investigated using an ANCOVA where macrostructural maps were used as voxel-wise covariates. The reverse ANCOVA model was also assessed, where macrostructural loss was the dependent variable and microstructural diffusion tensor imaging maps were the imaging covariates. Diffusion differences between patients and controls were observed after controlling for volumetric differences in medial temporal, retrosplenial regions, anterior commissure, corona radiata, internal capsule, thalamus, corticopontine tracts, cerebral peduncle, striatum, and precentral gyrus. Independent volumetric differences were observed in the entorhinal cortex, inferior temporal lobe, posterior cingulate cortex, splenium and cerebellum. While it is well known that AD is associated with pronounced volumetric change, this study suggests that measures of microstructure provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD and in those thought to be spared. As such this work provides great understanding of the topography of pathological changes in AD that can be captured with imaging.

SUBMITTER: Canu E

PROVIDER: S-EPMC2889147 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Microstructural diffusion changes are independent of macrostructural volume loss in moderate to severe Alzheimer's disease.

Canu Elisa E McLaren Donald G DG Fitzgerald Michele E ME Bendlin Barbara B BB Zoccatelli Giada G Alessandrini Franco F Pizzini Francesca B FB Ricciardi Giuseppe K GK Beltramello Alberto A Johnson Sterling C SC Frisoni Giovanni B GB Frisoni Giovanni B GB

Journal of Alzheimer's disease : JAD 20100101 3

Although it is established that Alzheimer's disease (AD) leads to cerebral macrostructural atrophy, microstructural diffusion changes have also been observed, but it is not yet known whether these changes offer unique information about the disease pathology. Thus, a multi-modal imaging study was conducted to determine the independent contribution of each modality in moderate to severe AD. Seventeen patients with moderate-severe AD and 13 healthy volunteers underwent diffusion-weighted and T1-wei ...[more]

PMID: 20157252

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Project description:Diffusion MRI (dMRI) studies using the tensor model have identified abnormal white matter development associated with perinatal risk factors in preterm infants studied at term equivalent age (TEA). However, this model is an oversimplification of the underlying neuroanatomy. Fixel-based analysis (FBA) is a novel quantitative framework, which identifies microstructural and macrostructural changes in individual fibre populations within voxels containing crossing fibres. The aim of this study was to apply FBA to investigate the relationship between fixel-based measures of apparent fibre density (FD), fibre bundle cross-section (FC), and fibre density and cross-section (FDC) and perinatal risk factors in preterm infants at TEA. We studied 50 infants (28 male) born at 24.0-32.9 (median 30.4) weeks gestational age (GA) and imaged at 38.6-47.1 (median 42.1) weeks postmenstrual age (PMA). dMRI data were acquired in non-collinear directions with b-value 2500 s/mm2 on a 3 Tesla system sited on the neonatal intensive care unit. FBA was performed to assess the relationship between FD, FC, FDC and PMA at scan, GA at birth, days on mechanical ventilation, days on total parenteral nutrition (TPN), birthweight z-score, and sex. FBA reveals fibre population-specific alterations in FD, FC and FDC associated with clinical risk factors. FD was positively correlated with GA at birth and was negatively correlated with number of days requiring ventilation. FC was positively correlated with GA at birth, birthweight z-scores and was higher in males. FC was negatively correlated with number of days on ventilation and days on TPN. FDC was positively correlated with GA at birth and birthweight z-scores, negatively correlated with days on ventilation and days on TPN and higher in males. We demonstrate that these relationships are fibre-specific even within regions of crossing fibres. These results show that aberrant white matter development involves both microstructural changes and macrostructural alterations.

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Dataset Information

Microstructural diffusion changes are independent of macrostructural volume loss in moderate to severe Alzheimer's disease.

Publications

Microstructural diffusion changes are independent of macrostructural volume loss in moderate to severe Alzheimer's disease.

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