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Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology.
Brain 2008; 131(Pt 12):3286-98B

Abstract

White matter hyperintensities (WMH) are frequently seen on T(2)-weighted MRI scans of elderly subjects with and without Alzheimer's disease. WMH are only weakly and inconsistently associated with cognitive decline, which may be explained by heterogeneity of the underlying neuropathological substrates. The use of quantitative MRI could increase specificity for these neuropathological changes. We assessed whether post-mortem quantitative MRI is able to reflect differences in neuropathological correlates of WMH in tissue samples obtained post-mortem from Alzheimer's disease patients and from non-demented elderly. Thirty-three formalin-fixed, coronal brain slices from 11 Alzheimer's disease patients (mean age: 83 +/- 10 years, eight females) and 15 slices from seven non-demented controls (mean age: 78 +/- 10 years, four females) with WMH were scanned at 1.5 T using qualitative (fluid-attenuated inversion recovery, FLAIR) and quantitative MRI [diffusion tensor imaging (DTI) including estimation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA), and T(1)-relaxation time mapping based on flip-angle array). A total of 104 regions of interest were defined on FLAIR images in WMH and normal appearing white matter (NAWM). Neuropathological examination included (semi-)quantitative assessment of axonal density (Bodian), myelin density (LFB), astrogliosis (GFAP) and microglial activation (HLA-DR). Patient groups (Alzheimer's disease versus controls) and tissue types (WMH versus NAWM) were compared with respect to QMRI and neuropathological measures. Overall, Alzheimer's disease patients had significantly lower FA (P < 0.01) and higher T(1)-values than controls (P = 0.04). WMH showed lower FA (P < 0.01) and higher T(1)-values (P < 0.001) than NAWM in both patient groups. A significant interaction between patient group and tissue type was found for the T(1) measurements, indicating that the difference in T(1)-relaxation time between NAWM and WMH was larger in Alzheimer's disease patients than in non-demented controls. All neuropathological measures showed differences between WMH and NAWM, although the difference in microglial activation was specific for Alzheimer's disease. Multivariate regression models revealed that in Alzheimer's disease, axonal density was an independent determinant of FA, whereas T(1) was independently determined by axonal and myelin density and microglial activation. Quantitative MRI techniques reveal differences in WMH between Alzheimer's disease and non-demented elderly, and are able to reflect the severity of the neuropathological changes involved.

Authors+Show Affiliations

Department of Neurology, Alzheimer Center and Image Analysis Center, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. aa.gouw@vumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18927145

Citation

Gouw, A A., et al. "Heterogeneity of White Matter Hyperintensities in Alzheimer's Disease: Post-mortem Quantitative MRI and Neuropathology." Brain : a Journal of Neurology, vol. 131, no. Pt 12, 2008, pp. 3286-98.
Gouw AA, Seewann A, Vrenken H, et al. Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. Brain. 2008;131(Pt 12):3286-98.
Gouw, A. A., Seewann, A., Vrenken, H., van der Flier, W. M., Rozemuller, J. M., Barkhof, F., ... Geurts, J. J. (2008). Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. Brain : a Journal of Neurology, 131(Pt 12), pp. 3286-98. doi:10.1093/brain/awn265.
Gouw AA, et al. Heterogeneity of White Matter Hyperintensities in Alzheimer's Disease: Post-mortem Quantitative MRI and Neuropathology. Brain. 2008;131(Pt 12):3286-98. PubMed PMID: 18927145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. AU - Gouw,A A, AU - Seewann,A, AU - Vrenken,H, AU - van der Flier,W M, AU - Rozemuller,J M, AU - Barkhof,F, AU - Scheltens,P, AU - Geurts,J J G, Y1 - 2008/10/16/ PY - 2008/10/18/pubmed PY - 2009/2/3/medline PY - 2008/10/18/entrez SP - 3286 EP - 98 JF - Brain : a journal of neurology JO - Brain VL - 131 IS - Pt 12 N2 - White matter hyperintensities (WMH) are frequently seen on T(2)-weighted MRI scans of elderly subjects with and without Alzheimer's disease. WMH are only weakly and inconsistently associated with cognitive decline, which may be explained by heterogeneity of the underlying neuropathological substrates. The use of quantitative MRI could increase specificity for these neuropathological changes. We assessed whether post-mortem quantitative MRI is able to reflect differences in neuropathological correlates of WMH in tissue samples obtained post-mortem from Alzheimer's disease patients and from non-demented elderly. Thirty-three formalin-fixed, coronal brain slices from 11 Alzheimer's disease patients (mean age: 83 +/- 10 years, eight females) and 15 slices from seven non-demented controls (mean age: 78 +/- 10 years, four females) with WMH were scanned at 1.5 T using qualitative (fluid-attenuated inversion recovery, FLAIR) and quantitative MRI [diffusion tensor imaging (DTI) including estimation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA), and T(1)-relaxation time mapping based on flip-angle array). A total of 104 regions of interest were defined on FLAIR images in WMH and normal appearing white matter (NAWM). Neuropathological examination included (semi-)quantitative assessment of axonal density (Bodian), myelin density (LFB), astrogliosis (GFAP) and microglial activation (HLA-DR). Patient groups (Alzheimer's disease versus controls) and tissue types (WMH versus NAWM) were compared with respect to QMRI and neuropathological measures. Overall, Alzheimer's disease patients had significantly lower FA (P < 0.01) and higher T(1)-values than controls (P = 0.04). WMH showed lower FA (P < 0.01) and higher T(1)-values (P < 0.001) than NAWM in both patient groups. A significant interaction between patient group and tissue type was found for the T(1) measurements, indicating that the difference in T(1)-relaxation time between NAWM and WMH was larger in Alzheimer's disease patients than in non-demented controls. All neuropathological measures showed differences between WMH and NAWM, although the difference in microglial activation was specific for Alzheimer's disease. Multivariate regression models revealed that in Alzheimer's disease, axonal density was an independent determinant of FA, whereas T(1) was independently determined by axonal and myelin density and microglial activation. Quantitative MRI techniques reveal differences in WMH between Alzheimer's disease and non-demented elderly, and are able to reflect the severity of the neuropathological changes involved. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/18927145/Heterogeneity_of_white_matter_hyperintensities_in_Alzheimer's_disease:_post_mortem_quantitative_MRI_and_neuropathology_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awn265 DB - PRIME DP - Unbound Medicine ER -