White matter integrity mediates the associations between white matter hyperintensities and cognitive function in patients with silent cerebrovascular diseases

Jing Chen; Anyan Ge; Ying Zhou; Yuanyuan Ma; Shaoping Zhong; Caizhong Chen; Weibin Shi; Jing Ding; Xin Wang

doi:10.1111/cns.14015

White matter integrity mediates the associations between white matter hyperintensities and cognitive function in patients with silent cerebrovascular diseases

CNS Neurosci Ther. 2023 Jan;29(1):412-428. doi: 10.1111/cns.14015. Epub 2022 Nov 22.

Authors

Jing Chen¹, Anyan Ge¹, Ying Zhou², Yuanyuan Ma¹, Shaoping Zhong¹, Caizhong Chen³, Weibin Shi⁴, Jing Ding¹, Xin Wang^{1

5}

Affiliations

¹ Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Neurology, XiaMen Branch, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Health Examination Center, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Department of the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science，Institutes of Brain Science, Fudan University, Shanghai, China.

Abstract

Objective: To evaluate the relationships between cognitive function and white matter hyperintensity volume (WMHV) in patients with silent cerebrovascular disease and to investigate whether white matter integrity or brain atrophy play a role in this association.

Methods: Automated Fiber Quantification and Voxel- based morphometry were used to track and identify the integrity of 20 well-defined white matter tracts and to measure the gray matter volume (GMV). A linear regression model was applied for examining the associations between cognitive function and WMHV and mediation analysis was used to identify the roles of white matter integrity or GMV in the influence of WMHV on cognitive function.

Results: Two hundred and thirty-six individuals were included for analysis. Executive function was linearly associated with fractional anisotropy (FA) of the right interior frontal occipital fasciculus (IFOF) (β = 0.193; 95% CI, 0.126 to 1.218) and with WMHV (β = -0.188; 95% CI, -0.372 to -0.037). Information processing speed was linearly associated with WMHV (β = -0.357; 95% CI, -0.643 to -0.245), FA of the right anterior thalamic radiation (ATR) (β = 0.207; 95% CI, 0.116 to 0.920), and FA of the left superior longitudinal fasciculus (SLF) (β = 0.177; 95% CI, 0.103 to 1.315). The relationship between WMHV and executive function was mediated by FA of the right IFOF (effect size = -0.045, 95% CI, -0.015 to -0.092). Parallel mediation analysis showed that the association between WMHV and information processing speed was mediated by FA of the right ATR (effect size = -0.099, 95% CI, -0.198 to -0.038) and FA of the left SLF (effect size = -0.038, 95% CI, -0.080 to -0.003).

Conclusion: These findings suggest a mechanism by which WMH affects executive function and information processing speed by impairing white matter integrity. This may be helpful in providing a theoretical basis for rehabilitation strategies of cognitive function in patients with silent cerebrovascular diseases.

Keywords: diffusion tensor imaging; execution function; information processing speed; mediation analysis; white matter hyperintensities.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anisotropy
Brain / diagnostic imaging
Cerebrovascular Disorders* / complications
Cerebrovascular Disorders* / diagnostic imaging
Cognition
Diffusion Tensor Imaging
Executive Function
Humans
White Matter* / diagnostic imaging