Nodal Global Efficiency in Front-Parietal Lobe Mediated Periventricular White Matter Hyperintensity (PWMH)-Related Cognitive Impairment.

Haifeng Chen,Yun Xu,Dan Yang,Lei Ye,Mengdi Guo,Lili Huang,Caimei Luo,Qing Ye,Bing Zhang,Mengchun Li,Ruomeng Qin

doi:10.3389/fnagi.2019.00347

Abstract

White matter hyperintensity (WMH) is widely observed in the elderly population and serves as a key indicator of cognitive impairment (CI). However, the underlying mechanism remains to be elucidated. Herein, we investigated the topological patterns of resting state functional networks in WMH subjects and the relationship between the topological measures and CI. A graph theory-based analysis was employed in the resting-state functional magnetic resonance scans of 112 subjects (38 WMH subjects with cognitive impairment without dementia (CIND), 36 WMH subjects with normal cognition and 38 healthy controls (HCs), and we found that WMH-CIND subjects displayed decreased global efficiency at the levels of the whole brain, specific subnetworks [fronto-parietal network (FPN) and cingulo-opercular network (CON)] and certain nodes located in the FPN and CON, as well as decreased local efficiency in subnetworks. Our results demonstrated that nodal global efficiency in frontal and parietal regions mediated the impairment of information processing speed related to periventricular WMH (PWMH). Additionally, we performed support vector machine (SVM) analysis and found that altered functional efficiency can identify WMH-CIND subjects with high accuracy, sensitivity and specificity. These findings suggest impaired functional networks in WMH-CIND individuals and that decreased functional efficiency may be a feature of CI in WMH subjects.

Highlights

Cerebral small vessel disease (CSVD) is a group of clinical syndromes arising from impaired blood circulation in cerebral arterioles, small perforating arteries, capillaries and small veins in the brain
We found significantly decreased global efficiency in White matter hyperintensities (WMH)-cognitive impairment without dementia (CIND) subjects compared with HCs at sparsities of 0.06∼0.35 (P < 0.05, uncorrected) and WMH-NC subjects at sparsities of 0.06∼0.35 (P < 0.05, uncorrected), but no significant differences were found between HCs and WMH-NC subjects
We found that the association between PWMH volume and the Trail Making Test-A (TMT-A) score was significantly mediated by nodal global efficiency in the right dorsal frontal cortex (DFC) in the fronto-parietal network (FPN) (Figure 5A)

Summary

Introduction

Cerebral small vessel disease (CSVD) is a group of clinical syndromes arising from impaired blood circulation in cerebral arterioles, small perforating arteries, capillaries and small veins in the brain. Increasing evidences have confirmed that WMH burden can lead to CI in executive function and information processing speed and associated with increased risk of dementia (Van Dijk et al, 2008; Sudo et al, 2013). WMH is very common in elderly subjects with normal cognition, and a portion of these individuals do not develop CI (Lampe et al, 2019). The association between enlarged perivascular space and cognition in CSVD is conflicting (Hurford et al, 2014; Yao et al, 2014). These findings suggest that the structural lesions of CSVD are not always associated with CI.

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