Characterizing Brain Iron Deposition in Patients with Subcortical Vascular Mild Cognitive Impairment Using Quantitative Susceptibility Mapping: A Potential Biomarker.

Yawen Sun,Mengqiu Cao,Wenwei Cao,Jianrong Xu,Yan Zhou,Yao Wang,Qun Xu,Yong Zhang,Weina Ding,Xin Ge,Xu Han

doi:10.3389/fnagi.2017.00081

Abstract

The presence and pattern of iron accumulation in subcortical vascular mild cognitive impairment (svMCI) and their effects on cognition have rarely been investigated. We aimed to examine brain iron deposition in svMCI subjects using quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the correlation between brain iron deposition and the severity of cognitive impairment as indicated by z-scores. We recruited 20 subcortical ischemic vascular disease (SIVD) patients who fulfilled the criteria for svMCI. The control group comprised 19 SIVD patients without cognitive impairment. The SIVD and control groups were matched based on age, gender, and years of education. Both groups underwent QSM using a 3.0T MRI system. Susceptibility maps were reconstructed from in vivo data, which were acquired with a three-dimensional spoiled gradient recalled sequence. Then, regions of interest were drawn manually on the map of each subject. The inter-group differences of susceptibility values were explored in deep gray matter nuclei, including the bilateral pulvinar nucleus of the thalamus, head of caudate nucleus, globus pallidus, putamen, hippocampus, substantia nigra, and red nucleus. The correlations between regional iron deposition and composite z-score, memory z-score, language z-score, attention-executive z-score and visuospatial z-score were assessed using partial correlation analysis, with patient age and gender as covariates. Compared with the control, the svMCI group had elevated susceptibility values within the bilateral hippocampus and right putamen. Furthermore, the susceptibility value in the right hippocampus was negatively correlated with memory z-score and positively correlated with language z-score. The susceptibility value in the right putamen was negatively correlated with attention-executive z-score in the svMCI group. However, composite z-score were unrelated to susceptibility values. Our results suggest that brain iron deposition has clinical relevance as a biomarker for cognition. In addition, our results highlight the importance of iron deposition in understanding svMCI-associated cognitive deficits in addition to conventional MRI markers.

Highlights

Vascular dementia (VaD) is clinically characterized by stepwise progression, fluctuating course, and predominant deterioration of intelligence with the relative preservation of personality
In accordance with the criteria suggested by Galluzzi et al (2005), subcortical ischemic vascular disease (SIVD) was defined as subcortical white matter hyperintensities (WMHs) that are visible on T2-weighted imaging with at least one lacunar infarct
The subcortical vascular mild cognitive impairment (svMCI) patients and control groups displayed no difference in terms of visuospatial z-score

Summary

Introduction

Vascular dementia (VaD) is clinically characterized by stepwise progression, fluctuating course, and predominant deterioration of intelligence with the relative preservation of personality. VaD is the second most common form of dementia after Alzheimer’s disease (AD) and places an enormous burden on society (Erkinjuntti, 1999). Subcortical vascular dementia (SVaD), a small vessel disease (SVD), constitutes approximately half of VaD cases (Yoshitake et al, 1995). Most studies have involved patients in the prodromal stage of AD, referred to as the amnestic mild cognitive impairment (aMCI). It is clinically important to focus on subcortical vascular mild cognitive impairment (svMCI), which is a prodromal stage of SVaD and distinctive from aMCI (Lee et al, 2014), since management of risk factors and drug treatment could prevent the evolution of svMCI to SVaD (Seo et al, 2010). Finding potential biomarkers for early diagnosis and relating these biomarkers to cognitive measurements before the onset of clinical deterioration are urgent matters

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