Reduction in cerebral blood flow in areas appearing as white matter hyperintensities on magnetic resonance imaging

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Abstract

The purpose of this study was to examine cerebral blood flow (CBF) as measured by arterial spin labeling (ASL) in tissue classified as white matter hyperintensities (WMH), normal appearing white matter, and grey matter. Seventeen healthy older adults received structural and ASL MRI. Cerebral blood flow was derived for three tissue types: WMH, normal appearing white matter, and grey matter. Cerebral blood flow was lower in WMH areas relative to normal appearing white matter, which in turn, was lower than grey matter. Regions with consistently lower CBF across individuals were more likely to appear as WMH. Results are consistent with an emerging literature linking diminished regional perfusion with the risk of developing WMH.

Introduction

White matter hyperintensities (WMH) are areas of increased signal intensity detected on T2-weighted magnetic resonance imaging (MRI) scans. These lesions are common among older adults (Brickman et al., 2008a) and are thought to reflect small vessel vascular disease or β-amyloid peptide deposition (Gurol et al., 2006). Increased WMH volume is associated with degree of cognitive impairment among neurologically healthy older adults (Gunning-Dixon and Raz, 2000) and is predictive of rate of cognitive decline among those with Alzheimer's disease (Brickman et al., 2008b). Although these associative findings have been consistently reported, the functional significance of WMH is unclear.

Increases in total or frontal WMH volume have been associated with decreases in relative glucose metabolism in frontal regions among healthy older adults (DeCarli et al., 1995). In a longitudinal analysis, individuals with increasing severity of WMH over an 8-year period had concomitant increases in relative cerebral blood flow (CBF) in temporal areas and anterior cingulate and decreases in relative CBF in more posterior areas (Kraut et al., 2008). Further, increased severity of WMH was not associated with total parenchymal CBF in a cross-sectional analysis, but decreases in CBF over time increased the risk of developing periventricular WMH (ten Dam et al., 2007). Holland and colleagues recently showed that WMH frequency among healthy older adults and those with AD or cerebral amyloid angiopathy is greater in regions with relatively lower perfusion among younger adults (Holland et al., 2008). These findings raise the possibility that lower regional perfusion increases the risk of developing WMH.

In the current study, we sought to extend these findings by examining arterial spin labeling (ASL)-derived CBF in areas appearing as WMH on T2-weighted fluid attenuated inverse recovery (FLAIR) MRI scans in comparison to CBF in normal appearing white matter (NAWM) and grey matter among neurologically healthy older adults. Two previous studies used perfusion-weighted MRI and found a decline in blood flow in areas appearing as WMH on T2-weighted images compared with NAWM (Marstrand et al., 2002, Sachdev et al., 2004). Thus, we hypothesized that CBF would be decreased in areas appearing as WMH compared with CBF in NAWM and grey matter.

Section snippets

Subjects

Seventeen older adults ranging in age from 61 to 70 (mean ± S.D. = 64.94 ± 2.95) comprised the study sample. There were 9 women (53%) and the average number of years of formal education was 16.29 (S.D. = 1.72). Men and women did not differ in age (t(15) = 0.235, P = 0.817) or number of years of education (t(15) = 0.371, P = 0.716). All participants were right-handed and spoke English. By self-report and interview, participants did not have past or current histories of medical, neurological, psychiatric

Results

Participants in the current study had a relatively mild degree of WMH burden (mean ± S.D. WMH volume = 4.631 ± 4.836 cm3, median = 2.00, range = 0.10 to 16.90). A general linear model was constructed to evaluate differences in CBF among voxels classified as WMH, NAWM, and grey matter. Cerebral blood flow in each of these regions was treated as a repeated measure (i.e., within-subjects factor). There was a significant overall difference in CBF among these regions (F(2, 32) = 185.61, P < 0.001). Pairwise

Discussion

In the current study, we compared CASL-derived mean CBF across three tissue types — areas appearing as WMH on T2-weighted FLAIR MRI, NAWM, and grey matter — in well-screened, neurologically healthy older adults. Findings indicated that CBF was significantly reduced in areas appearing as WMH compared with both NAWM and grey matter. These results are consistent with previous reports in demonstrating an association between WMH and reduced blood flow, and replicate findings suggesting that this

Acknowledgments

This work was supported by National Institutes of Health grants AG029949 (AMB), AG26158 (YS), and AG026114 (CH) and by a grant 05-14586 from the Alzheimer's Association (AMB).

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