Microstructure changes in whiter matter relate to cognitive impairment in Wilson's disease.

Ting Dong,An-Qin Wang,Ming-Cai Wu,Chun-Jun Kuang,Peng Huang,Chun-Sheng Xu,Juan Zhang,Zhi-Ling Gao,Wen-Ming Yang

doi:10.1042/bsr20181651

Abstract

Purpose: Wilson’s disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain. The purpose of the present study was to evaluate the relationship between the damaged white matter and the impaired cognitive function in WD patients. Materials and methods: Thirty WD adolescents and thirty age- and sex-matched healthy controls (HC) were enrolled. All subjects had received brain MRI, including conventional and diffusion-tensor imaging (DTI) scans. The DTI parameter of fractional anisotropy (FA) was calculated by diffusion kurtosis estimator software. The t test was used to compare the differences between two groups. The correlation between cognitive function and whiter matter disorders were analyzed by linear regression. The results of FA parameter and MD parameter intergroup analysis were both corrected with False Discovery Rate (FDR) simulations by SPSS. Results: WD adolescents showed significantly lower scores of time-based prospective memory (TBPM) and verbal fluency test (VFT) compared with HC. We found significantly higher FA in the right thalamus, right lentiform nucleus, left thalamus, left lentiform nucleus, and brain stem in WD adolescents. Besides, WD adolescents exhibited significantly lower FA in right cerebellum and cingulum and left middle frontal lobe compared with controls (P<0.05). There were significantly negative correlations between FA in bilateral lentiform and thalamus and cognitive impairment in WD adolescents (P<0.05). Conclusion: The whiter matter of WD adolescents was impaired and mainly distributed in subcortical brain regions. The impaired cognitive function was affected by the damaged whiter matter. The present study may be helpful for recognition and understanding of WD.

Highlights

Wilson’s disease (WD), known as progressive hepatolenticular degeneration, is a genetic disorder commonly supposed due to a mutation of gene ATP7B responsible for copper metabolism, and usually occurs in children
A total of 30 WD adolescents and 30 healthy controls (HC) were enrolled in the present study
There were no significant differences between WD and HC groups in age, gender, and education levels (P>0.05, Table 1)

Summary

Introduction

Wilson’s disease (WD), known as progressive hepatolenticular degeneration, is a genetic disorder commonly supposed due to a mutation of gene ATP7B responsible for copper metabolism, and usually occurs in children. Routine MRI is usually used in its diagnosis, that exhibits symmetrical T2 hyperintensity or mixed intensity in caudate nuclei, thalami, pons putamina, or globi pallida [3,4,5,6]. Some types of WD do not have significant signs in the MRI method, and more accurate quantitative measurement could be applied, such as diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI) [7,8]. Fractional anisotropy (FA) is the main parameter of DTI, which is usually applied to identify the microstructural abnormalities in whiter matter. DTI has been applied to assess the microstructure of thalamus and evaluate diffusion abnormalities in the white matter regions in WD patients [9]

Objectives

Methods

Results

Conclusion