Abstract
Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk factors and age-related cognitive decline. WMH have primarily been associated with global white matter and gray matter (GM) changes and less is known about regional effects in GM. The purpose of this study was to test for an association between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel-based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI) study. MRI measures of GM CBF and VBM were derived from arterial spin labeling (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM data were used as dependent variables. WMH lesion burden, age and sex were used in a regression model. Visual rating of WMH with the Fazekas method was used to compare the WMH lesion volume regression approach. WMH volume was normally distributed for this group (mean volume of 22.7 mL, range: 2.2–70.6 mL). CBF analysis revealed negative associations between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed negative associations between WMH and GM volume in lingual gyrus, intracalcarine, and bilateral hippocampus (corrected p < 0.05). The visual rating scale corroborated the regression findings (corrected p < 0.05). WMH lesion volume was associated with intra-group GM CBF and structural differences in this cohort of WMH adults with mild to severe lesion burden.
Highlights
Materials and MethodsCerebral small vessel disease (SVD) is associated with cognitive and functional deterioration (Jokinen et al, 2009; Kreisel et al, 2013), stroke and death (Poggesi et al, 2011), and is reportedly the most common brain disease (Thompson and Hakim, 2009)
The distribution of White Matter Hyperintensities (WMH) volumes did not differ significantly from normal (Figure 1), WMH volumes were used as the independent variables for the cerebral blood flow (CBF) and voxel-based morphometry (VBM) voxel-wise analyses
Voxel-wise analysis of the CBF data revealed a negative relationship between WMH volume and CBF in the left anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal, anterior insula, and frontal pole (p < 0.05, corrected for age and sex)
Summary
Materials and MethodsCerebral small vessel disease (SVD) is associated with cognitive and functional deterioration (Jokinen et al, 2009; Kreisel et al, 2013), stroke and death (Poggesi et al, 2011), and is reportedly the most common brain disease (Thompson and Hakim, 2009). WMH are thought to result from chronic diffuse subclinical ischemia that primarily impacts subcortical regions (Brickman et al, 2009; Makedonov et al, 2013b; Wardlaw et al, 2013). WMH are commonly observed in cerebral white matter, SVD-associated lesions can occur in subcortical gray matter (GM) (Vermeer et al, 2007). Studies have reported negative associations between WMH lesion burden ( referred to as WMH volume) and regional GM tissue volumes, with the majority of the evidence pointing toward reduced hippocampal volume (de Leeuw et al, 2006; Godin et al, 2009; Kloppenborg et al, 2012). The use of structural MRI measures to study the impact of WMH on the brain has produced mixed results. Another study reported significant WMH and structural associations when considering only WMH adults with the most extreme (i.e., upper quartile) phenotype (Eckerstrom et al, 2011)
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