Abstract

Cerebral white matter hyperintensities (WMHs) represent macrostructural brain damage associated with various etiologies. However, the relative contributions of various etiologies to WMH volume, as assessed via different neuroimaging measures, is not well-understood. Here, we explored associations between three potential early markers of white matter hyperintensity volume. Specifically, the unique variance in total and regional WMH volumes accounted for by white matter microstructure, brain iron concentration and cerebral blood flow (CBF) was assessed. Regional volumes explored were periventricular and deep regions. Eighty healthy older adults (ages 60–86) were scanned at 3 Tesla MRI using fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), multi-echo gradient-recalled echo and pseudo-continuous arterial spin labeling sequences. In a stepwise regression model, DTI-based radial diffusivity accounted for significant variance in total WMH volume (adjusted R2 change = 0.136). In contrast, iron concentration (adjusted R2 change = 0.043) and CBF (adjusted R2 change = 0.027) made more modest improvements to the variance accounted for in total WMH volume. However, there was an interaction between iron concentration and location on WMH volume such that iron concentration predicted deep (p = 0.034) but not periventricular (p = 0.414) WMH volume. Our results suggest that WM microstructure may be a better predictor of WMH volume than either brain iron or CBF but also draws attention to the possibility that some early WMH markers may be location-specific.

Document Type

Article

Publication Date

7-5-2021

Notes/Citation Information

Published in Frontiers in Aging Neuroscience, v. 13, article 617947.

© 2021 Bauer, Zachariou, Seago and Gold

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Digital Object Identifier (DOI)

https://doi.org/10.3389/fnagi.2021.617947

Funding Information

This work was supported by the National Institutes of Health (grant numbers NIA R01 AG055449, NIA P30 AG028383, and NIGMS S10 OD023573).

Related Content

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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