Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging - PubMed (original) (raw)

Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging

Christopher M Holland et al. Stroke. 2008 Apr.

Abstract

Background and purpose: White-matter hyperintensities (WMHs) detected by magnetic resonance imaging are thought to represent the effects of cerebral small-vessel disease and neurodegenerative changes. We sought to determine whether the spatial distribution of WMHs discriminates between different disease groups and healthy aging individuals and whether these distributions are related to local cerebral perfusion patterns.

Methods: We examined the pattern of WMHs by T2/fluid-attenuated inversion recovery-weighted magnetic resonance imaging in 3 groups of subjects: cerebral amyloid angiopathy (n=32), Alzheimer disease or mild cognitive impairment (n=41), and healthy aging (n=29). WMH frequency maps were calculated for each group, and spatial distributions were compared by voxel-wise logistic regression. WMHs were also analyzed as a function of normal cerebral perfusion patterns by overlaying a single photon emission computed tomography atlas.

Results: Although WMH volume was greater in cerebral amyloid angiopathy and Alzheimer disease/mild cognitive impairment than in healthy aging, there was no consistent difference in the spatial distributions when controlling for total WMH volume. Hyperintensities were most frequent in the deep periventricular WM in all 3 groups. A strong inverse correlation between hyperintensity frequency and normal perfusion was demonstrated in all groups, demonstrating that WMHs were most common in regions of relatively lower normal cerebral perfusion.

Conclusions: WMHs show a common distribution pattern and predilection for cerebral WM regions with lower atlas-derived perfusion, regardless of the underlying diagnosis. These data suggest that across diverse disease processes, WM injury may occur in a pattern that reflects underlying tissue properties, such as relative perfusion.

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Figures

Figure 1

Figure 1

Atlas of normal cerebral WM perfusion. SPECT perfusion atlas generated from 47 healthy adult volunteers was masked by a coregistered WM probability atlas. (A conservative threshold of 0.75 was used for illustrative purposes only.) Perfusion values are indicated by the color bar, in which red indicates higher relative perfusion (scale, relative perfusion units).

Figure 2

Figure 2

Spatial distribution of WMHs. The WMH frequency distributions for the HA, AD/MCI, and CAA cohorts were overlaid onto the International Consortium of Brain Mapping template to which all individual subject MRI images were registered. WMH frequency corresponds to the proportion of subjects in each cohort having WMHs in that image voxel. The fourth column represents the regions of WMHs common to all subjects, with the relative frequency across the entire study population.

Figure 3

Figure 3

Statistical comparison of WMH distributions. WMH distributions were compared between the 3 groups by voxel-wise logistic regression, with and without controlling for total WMH volume in each subject. Voxels in which the prevalence of WMHs differed significantly (P<0.05) are presented according to the group with the higher WMH prevalence: HA higher (green), AD/MCI higher (red), and CAA higher (blue). Three representative slices are shown.

Figure 4

Figure 4

WMH frequency histogram with respect to normal atlas-derived perfusion for the HA (green), AD/MCI (red), and CAA (blue) cohorts. The increased prevalence of hyperintensity in regions of relatively lower normal perfusion is evident (Pearson’s _r_=−0.54, P<0.001 across all subjects).

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