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Updated: Jul 18, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD
M Yoshita1, E Fletcher, D Harvey
1Department of Neurology and Center for Neuroscience, University of California at Davis, 1544 Newton Ct., Davis, CA 95616, USA. myoshita@ucdavis.edu
Objective:
To analyze the extent and spatial distribution of white matter hyperintensities (WMH) in brain regions from cognitively normal older individuals (CN) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD).
Methods:
We studied 26 mild AD, 28 MCI, and 33 CN. MRI analysis included quantification of WMH volume, nonlinear mapping onto a common anatomic image, and spatial localization of each WMH voxel to create an anatomically precise frequency distribution map. Areas of greatest frequency of WMH from the WMH composite map were used to identify 10 anatomic regions involving periventricular areas and the corpus callosum (CC) for group comparisons.
Results:
Total WMH volumes were associated with age, extent of concurrent vascular risk factors, and diagnosis. After correcting for age, total WMH volumes remained significantly associated with diagnosis and extent of vascular risk. Regional WMH analyses revealed significant differences in WMH across regions that also differed significantly according to diagnosis. In post-hoc analyses, significant differences were seen between CN and AD in posterior periventricular regions and the splenium of the CC. MCI subjects had intermediate values at all regions. Repeated measures analysis including vascular risk factors in the model found a significant relationship between periventricular WMH and vascular risk that differed by region, but regional differences according to diagnosis remained significant and there was no interaction between diagnosis and vascular risk.
Conclusions:
Differences in white matter hyperintensities (WMH) associated with increasing cognitive impairment appear related to both extent and spatial location. Multiple regression analysis of regional WMH, vascular risk factors, and diagnosis suggest that these spatial differences may result from the additive effects of vascular and degenerative injury. Posterior periventricular and corpus callosum extension of WMH associated with mild cognitive impairment and Alzheimer disease indicate involvement of strategic white matter bundles that may contribute to the cognitive deficits seen with these syndromes.
Insights
White matter hyperintensities (WMH) distribution differs in Alzheimer disease (AD) and mild cognitive impairment (MCI) compared to cognitively normal individuals. Spatial location and extent of WMH are linked to cognitive decline and vascular risk.
Area of Science:
- Neuroimaging
- Neurology
- Gerontology
Background:
- White matter hyperintensities (WMH) are common in aging and associated with cognitive decline.
- Understanding the spatial distribution of WMH is crucial for comprehending their impact on cognition.
Purpose of the Study:
- To analyze the extent and spatial distribution of WMH in cognitively normal (CN) individuals, mild cognitive impairment (MCI) patients, and Alzheimer disease (AD) patients.
- To identify specific brain regions where WMH differences correlate with cognitive status and vascular risk.
Main Methods:
- MRI analysis of 26 AD, 28 MCI, and 33 CN participants.
- Quantification of WMH volume, nonlinear mapping, and spatial localization to create frequency distribution maps.
- Identification of 10 anatomic regions for group comparisons, focusing on periventricular areas and the corpus callosum (CC).
Main Results:
- Total WMH volumes correlated with age, vascular risk factors, and diagnosis.
- Significant regional differences in WMH were observed across diagnostic groups (CN, MCI, AD).
- Posterior periventricular regions and the splenium of the CC showed significant WMH differences between CN and AD groups, with MCI subjects exhibiting intermediate values.
Conclusions:
- WMH extent and spatial location are associated with cognitive impairment severity.
- Spatial WMH differences may result from additive vascular and degenerative injury.
- WMH in posterior periventricular and corpus callosum regions are linked to MCI and AD, potentially contributing to cognitive deficits.
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