Fiber Connectivity Density in Cerebral Small-Vessel Disease Patients With Mild Cognitive Impairment and Cerebral Small-Vessel Disease Patients With Normal Cognition.

Chengxia Liu,Shiqi Yang,Zhenxiong Wang,Yihao Yao,Wenhao Zhu,Yuanyuan Qin,Defeng Wang,Wenzhen Zhu,Pan Sun,Xiangyu Tang,Lin Shi,Shun Zhang

doi:10.3389/fnins.2020.00083

Abstract

Abnormal structural connectivity of cerebral small-vessel disease (CSVD) is associated with cognitive impairment. But the different characteristics of structural connectivity have not been elucidated in early CSVD patients. The current study aimed to investigate the potential differences of structural connectivity in CSVD patients with mild cognitive impairment (MCI) and CSVD patients with normal cognition. Twenty-two CSVD patients with MCI, 34 CSVD patients with normal cognition, and 35 controls, who were age, sex, and education matched underwent diffusion tensor imaging and high resolution T1-weighted imaging. Clinical characteristics, lacunar infarct volume, white matter hyperintensity (WMH) volume, and global atrophy were quantitatively evaluated. Maps of fiber connectivity density (FiCD) were constructed and compared across groups in vertex levels. Pearson correlation was used to estimate the imaging–clinical relationships with control of general characteristics. CSVD patients with MCI had higher lesion load of WMH and lacunar infarcts, and correspondingly lower global FiCD value than CSVD patients with normal cognition (P < 0.01). Lacunar infarct (r = −0.318, P < 0.01) and WMH (r = −0.400, P < 0.01), but not global atrophy, age, or sex, were significantly correlated with the global FiCD value. CSVD patients with normal cognition showed decreased FiCD value mainly in the prefrontal areas (P < 0.01 with Monte Carlo correction). Compared with CSVD patients with normal cognition, CSVD patients with MCI showed significantly decreased FiCD value in enlarged frontal and parietal areas (P < 0.01 with Monte Carlo correction). Inter-group comparisons showed regional enhanced impairment of connectivity density in CSVD patients with MCI in the left superior frontal gyrus, the left precuneus, and the orbital part of the right inferior frontal gyrus (P < 0.01 with Monte Carlo correction). Regional FiCD value of frontal and parietal areas was associated with the cognitive function (P < 0.01). In conclusion, cognitively normal CSVD patients already have disruptions of structural connectivity. The extent and intensity of connectivity disruptions in frontal and parietal areas may underlie the mechanism of cognitive impairment in CSVD. Fiber connectivity density measurements may be helpful for quantitative description of structural cortical connectivity.

Highlights

White matter hyperintensity of presumed vascular origin is one of the major imaging features of cerebral small-vessel disease (CSVD) (Wardlaw et al, 2013)
The exclusion criteria were: (1) age < 55 years; (2) severe systemic diseases, neurodegenerative diseases (e.g., Alzheimer’s disease), and severe psychiatric diseases; (3) subjects without formal liberal education to ensure the accuracy of neuropsychological assessments; (4) any physical disorders that could lead to abnormal cognitive performance; (5) subjects with transient ischemic attack within 3 months or lacunar infarcts observed as hyperintensities on diffusion weighted imaging (DWI) images were excluded to avoid any acute effects on neuropsychological assessments
We found that CSVD patients with normal cognition had impairment of structural connectivity mainly in the prefrontal cortex

Summary

INTRODUCTION

White matter hyperintensity of presumed vascular origin is one of the major imaging features of CSVD (Wardlaw et al, 2013). Graph analyses using DTI have found associations between the disruptions of structural network connectivity and the cognitive impairment in CSVD patients (Lawrence et al, 2014; Tuladhar et al, 2016). It is found that the preferential disruptions of cortical connectivity in central brain areas may contribute to the development of cognitive impairment in CSVD patients (Tuladhar et al, 2017). Over 10% of asymptomatic elderly people have confluent WMH on MRI (O’Sullivan, 2008) It is yet not clear whether there are potential disruptions of structural connectivity associated with WMH in CSVD patients with normal cognition. The entire cerebral cortex is typically parcelated into dozens of anatomical areas which are defined as network nodes (Tzourio-Mazoyer et al, 2002) It is a well-established parcelation scheme, the most optimal parcelation scale remains to be determined.

Participants

RESULTS

ETHICS STATEMENT