Dataset Information

Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people.

ABSTRACT:

Background

White 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.

Methods

We 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.

Results

Negative 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.

Conclusions

The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.

SUBMITTER: Liu ME

PROVIDER: S-EPMC3923794 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people.

Liu Mu-En ME Huang Chu-Chung CC Yang Albert C AC Tu Pei-Chi PC Yeh Heng-Liang HL Hong Chen-Jee CJ Liou Ying-Jay YJ Chen Jin-Fan JF Chou Kun-Hsien KH Lin Ching-Po CP Tsai Shih-Jen SJ

PloS one 20140213 2

<h4>Background</h4>White 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.<h4>Methods</h4>We 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 C ...[more]

PMID: 24551149

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Project description:BackgroundWhite matter hyperintensities (WMHs) are often measured globally, but spatial patterns of WMHs could underlie different risk factors and neuropathological and clinical correlates. We investigated the spatial heterogeneity of WMHs and their association with comorbidities, Alzheimer's disease (AD) risk factors, and cognition.MethodsIn this cross-sectional study, we studied 171 cognitively unimpaired (CU; median age: 65 years, range: 50 to 89) and 51 mildly cognitively impaired (MCI; median age: 72, range: 53 to 89) individuals with available amyloid (18F-flutementamol) PET and FLAIR-weighted images. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each participant's white matter was segmented into 38 parcels, and WMH volume was calculated in each parcel. Correlated principal component analysis was applied to the parceled WMH data to determine patterns of WMH covariation. Adjusted and unadjusted linear regression models were used to investigate associations of component scores with comorbidities and AD-related factors. Using multiple linear regression, we tested whether WMH component scores predicted cognitive performance.ResultsPrincipal component analysis identified four WMH components that broadly describe FLAIR signal hyperintensities in posterior, periventricular, and deep white matter regions, as well as basal ganglia and thalamic structures. In CU individuals, hypertension was associated with all patterns except the periventricular component. MCI individuals showed more diverse associations. The posterior and deep components were associated with renal disorders, the periventricular component was associated with increased amyloid, and the subcortical gray matter structures was associated with sleep disorders, endocrine/metabolic disorders, and increased amyloid. In the combined sample (CU + MCI), the main effects of WMH components were not associated with cognition but predicted poorer episodic memory performance in the presence of increased amyloid. No interaction between hypertension and the number of comorbidities on component scores was observed.ConclusionOur study underscores the significance of understanding the regional distribution patterns of WMHs and the valuable insights that risk factors can offer regarding their underlying causes. Moreover, patterns of hyperintensities in periventricular regions and deep gray matter structures may have more pronounced cognitive implications, especially when amyloid pathology is also present.

Dataset Information

Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people.

Background

Methods

Results

Conclusions

Publications

Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people.

Similar Datasets

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