Abstract
BackgroundWhite matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH). Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT) Val158Met polymorphism in healthy populations remains unclear.MethodsWe recruited 315 ethnic Chinese adults with a mean age of 54.9±21.8 years (range: 21–89 y) to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant.ResultsNegative correlations between the Digit Span Forward (DSF) score and frontal WMH volumes (r = −.123, P = .032, uncorrected) were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (P = .016, uncorrected), whole brain (P = .047, uncorrected), and a trend over the frontal region (P = .050, uncorrected) were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen’s f) revealed a small effect.ConclusionsThe results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.
Highlights
Cerebral white matter hyperintensities (WMH) are highintensity areas observed on T2-weighted MR images and indicate white matter damage
To test the hypothesis that cognitive performance is related to regional WMH volumes and that this relationship can be modulated by COMT polymorphisms in a healthy Chinese population, we examined the correlations between regional WMHs and neurocognitive performances, evaluated the effect of the COMT genotype on regional WMHs, and determined whether the COMT genotype can modulate the relationship between regional WMHs and cognitive ability
The results of WMH regression analysis of 315 participants showed a negative correlation between regional WMH volumes and Digit Span Forward (DSF) scores in the frontal lobe (r = 2.123; P = .032, uncorrected)
Summary
Cerebral white matter hyperintensities (WMH) are highintensity areas observed on T2-weighted MR images and indicate white matter damage. Several studies have shown that Met homozygous people have increased frontal cortex signal-to-noise ratios [9,10] and improved performance in prefrontal-dependent cognitive tasks, such as working memory, whereas those with highactivity Val alleles have relatively inferior performance and inefficient dorsolateral prefrontal function [9,10]. White matter lesions can be observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH). Their presence may be correlated with cognitive impairment; the relationship between regional WMH volume and catechol-O-methyltransferase (COMT) Val158Met polymorphism in healthy populations remains unclear
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