Development of White Matter Hyperintensity Is Preceded by Reduced Cerebrovascular Reactivity

Objective White matter hyperintensities (WMH) observed on neuroimaging of elderly individuals are associated with cognitive decline and disability. However, the pathogenesis of WMH remains poorly understood. We observed that regions of reduced cerebrovascular reactivity (CVR) in the white matter of...

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Bibliographic Details
Published in:Annals of neurology 2016-08, Vol.80 (2), p.277-285
Main Authors: Sam, Kevin, Crawley, Adrian P., Conklin, John, Poublanc, Julien, Sobczyk, Olivia, Mandell, Daniel M., Venkatraghavan, Lakshmikumar, Duffin, James, Fisher, Joseph A., Black, Sandra E., Mikulis, David J.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Aging - pathology
Anisotropy
Attention Deficit Hyperactivity Disorder
Brain - blood supply
Brain - pathology
Diffusion Tensor Imaging
Female
Humans
Male
Middle Aged
Neuroimaging
Pathogenesis
White Matter - pathology
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Summary:Objective White matter hyperintensities (WMH) observed on neuroimaging of elderly individuals are associated with cognitive decline and disability. However, the pathogenesis of WMH remains poorly understood. We observed that regions of reduced cerebrovascular reactivity (CVR) in the white matter of young individuals correspond to the regions most susceptible to WMH in the elderly. This finding prompted us to consider that reduced CVR may play a role in the pathogenesis of WMH. We hypothesized that reduced CVR precedes development of WMH. Methods We examined 45 subjects (age range = 50–91 years; 25 males) with moderate–severe WMH, and measured their baseline CVR using the blood oxygen level–dependent magnetic resonance imaging signal response to a standardized step change in the end‐tidal partial pressure of carbon dioxide. Diffusion tensor imaging and transverse relaxation time (T2) relaxometry were performed at baseline and 1‐year follow‐up, with automated coregistration between time points. Baseline fractional anisotropy (FA), mean diffusivity (MD), T2, and CVR were measured in areas that progressed from normal‐appearing white matter (NAWM) to WMH over the 1‐year period. Results CVR and FA values in baseline NAWM that progressed to WMH were lower by mean (standard deviation) = 26.5% (23.2%) and 11.0% (7.2%), respectively, compared to the contralateral homologous NAWM that did not progress (p 
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.24712