Impaired Structural Network Properties Caused by White Matter Hyperintensity Related to Cognitive Decline.

Dan Yang,Yun Xu,Meijuan Zhang,Caimei Luo,Pengfei Shao,Lili Huang,Junyi Ma,Mengchun Li,Hengheng Xu,Ruomeng Qin,Bing Zhang

doi:10.3389/fneur.2020.00250

Abstract

Purpose: There is a high correlation between white matter hyperintensity (WMH) and cognitive impairment (CI) in elderly people. However, not all WMH will develop into CI, and the potential mechanism of WMH-related CI is still unclear. This study aimed to investigate the topological properties of white matter structural network in WMH-related CI.Methods: Forty-one WMH subjects with CI (WMH-CI), 42 WMH subjects without CI (WMH-no-CI), and 52 elderly healthy controls (HC) were recruited. Diffusion tensor imaging (DTI) fiber tractography and graph theoretical analysis were applied to construct the structural network. We compared network properties and clinical features among the three groups. Multiple linear regression analysis was performed to investigate the relationships among WMH volumes, impaired network properties, and cognitive functions in the WMH-CI group.Results: Compared with the controls, both WMH groups showed decreased network strength, global efficiency, and increased characteristic path length (Lp) at the level of the whole brain. The WMH-CI group displayed more profound impairments of nodal efficiency and nodal path length (NLp) within multiple regions including precentral, cingulate, and medial temporal gyrus. The disrupted network properties were associated with CI and WMH burdens in the WMH-CI group. Furthermore, a mediation effect of NLp in the left inferior frontal gyrus was observed for the association between periventricular WMH (PWMH) and memory deficit.Conclusions: Brain structural network in WMH-CI is significantly disturbed, and this disturbance is related to the severity of WMH and CI. Increased NLp in the left opercular part of inferior frontal gyrus (IFGoperc.L) was shown to be a mediation framework between PWMH and WMH-related memory, which shed light on investigating the underlying mechanisms of CI caused by WMH.

Highlights

White matter hyperintensity (WMH), presented as high signal lesions on T2-weighted or fluid-attenuated inversion recovery (FLAIR) sequence, is frequently seen in elderly individuals [1]
There were no differences in gender, education years, vascular risk factors, the number of lacunars and cerebral microbleeds, and Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) scores among the three groups except for ages, cognitive functions, and WMH volumes (P < 0.05)
When analyzing the relationships between WMH and nodal network properties, we found that total white matter hyperintensity (TWMH) and deep white matter hyperintensity (DWMH) were positively associated with nodal path length (NLp) of precentral gyrus (PreCG).R, left opercular part of inferior frontal gyrus (IFGoperc.L), left precuneus (PCUN.L), and middle temporal gyrus (MTG).R

Summary

Introduction

White matter hyperintensity (WMH), presented as high signal lesions on T2-weighted or fluid-attenuated inversion recovery (FLAIR) sequence, is frequently seen in elderly individuals [1]. One plausible rationale is that WMH burden can result in cognitive decline through making the previously connected cortex atrophy [10,11,12] Another possible mechanism is that WMH can disrupt white matter fibers and connectivity which play crucial roles in the information transportation of cortical– cortical or cortical–subcortical regions independent of cortical atrophy [13, 14]. All these rationales were proposed based on studies of cerebral small vessel disease (CSVD) cohort [15, 16].

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