Elsevier

Behavioural Brain Research

Volume 223, Issue 2, 1 October 2011, Pages 388-394
Behavioural Brain Research

Research report
Abnormal functional connectivity in patients with vascular cognitive impairment, no dementia: A resting-state functional magnetic resonance imaging study

https://doi.org/10.1016/j.bbr.2011.05.006Get rights and content

Abstract

The functional connectivity (FC) method was used to investigate the changes in the resting state of patients with vascular cognitive impairment, no dementia (VCIND). Resting-state functional magnetic resonance images (fMRIs) were acquired from 16 patients with subcortical ischemic vascular disease (SIVD) who fulfilled the criteria for VCIND, as well as 18 age- and sex-matched subjects with SIVD with no cognitive impairment (control group). Posterior cingulate cortex connectivity was gathered by investigating synchronic low-frequency fMRI signal fluctuations with a temporal correlation method. Compared with the control group, the patients showed FC decrease in the left middle temporal gyrus, the left anterior cingulate/left middle frontal gyrus, the right caudate, the right middle frontal gyrus, and the left medial frontal gyrus/paracentral lobule. There were also some regions that showed increased connectivity. These regions included the right inferior temporal gyrus, the left middle temporal gyrus, the left precentral gyrus, and the left superior parietal lobule. Our findings revealed the change in resting-state patterns of neuronal activity in patients with VCIND. This change may be caused by subcortical white matter lesions that destroyed direct and indirect fiber tract connectivity across the cerebral white matter and influenced the cortical FC and hypoperfusion resulted from small vascular disease. The results of the increased connectivity may be evoked by the compensatory recruitment and plasticity mechanism. Our findings suggest that the simplicity and noninvasiveness of this method makes it a potential tool to help thoroughly understand the pathogenesis of VCIND.

Highlights

► The FC method was used to detect the change in the resting state of VCIND patients. ► Posterior cingulated cortex connectivity was gathered in VCIND and control groups. ► White matter lesions destroyed fiber connectivity and lead to decreased of FC. ► Increased connectivity maybe evoked by the compensatory and plasticity mechanism. ► It maybe a potential tool to help thoroughly understand the pathogenesis of VCIND.

Introduction

In developing countries, the incidence of dementia has been predicted to increase at an alarming rate in the near future [1]. Vascular cognitive impairment (VCI) has been defined as cognitive impairment evoked by or associated with vascular causes [2]. It has been classified into three subtypes: vascular dementia (VaD), Alzheimer's disease (AD) with a vascular component, and vascular cognitive impairment, no dementia (VCIND) [3]. O’Brien et al. [4] proposed that people with VCI have a specific cognitive profile: memory is preserved and executive function is impaired, which is different from AD. The pathophysiology of VCI continues to be investigated; subcortical ischemic vascular disease (SIVD), a more homogeneous subtype of cerebral vascular disease, is considered one of the major causes of VCI [5]. Considering its common occurrence, cost, and possible preventability, VCI remains of interest to clinicians and researchers [6].

Neuroimaging in VCIND shows a pattern of vascular lesions similar to, but less severe than the changes observed in VaD [7]. Pathology includes evidence of leukoaraiosis and white matter infarction [8], [9], with mild hippocampal and entorhinal cortex atrophy relative to the level seen in mild cognitive impairment or AD [7]. Previous studies tried to find some special manifestation to aid early detection, to discriminate the neuropathology, to estimate the prognosis, and to monitor disease progression or treatment response in patients with VCI and VCIND, but research is hampered by the clinical and pathological heterogeneity of VCI and the presence of pathology. Several imaging techniques have been used to investigate the structural and functional change in the brains of patients with VCI and/or VCIND. These techniques include magnetic resonance imaging (MRI) [10], [7], [11], magnetic resonance spectroscopy (MRS) [12], diffusion-weighted imaging [13], and diffusion tensor imaging (DTI) [14], [15], [16]. The techniques search for specific MRI abnormalities, such as the distribution and severity of the white matter hyperintensities and the clinical significance of the parameters derived from MRS and DTI [10], [7], [11], [12], [13], [14], [15], [16].

The default-mode network (DMN) has been extensively used in the study of psychiatric and neurological disorders in recent years. A number of resting-state functional MRI (fMRI) studies on psychiatric and neurological disorders have applied functional connectivity (FC) as an analytical approach [17], [18]. FC refers to interregional cooperation that can be represented by a synchrony of low-frequency fluctuations in signal at cerebral blood oxygen level-dependent (BOLD) fMRI. A number of studies suggest that the posterior cingulate cortex (PCC) plays an essential role in spatial orientation, self-appraisal, and internal monitoring, as well as memory processing [19]. In addition, PCC is commonly identified as a critical node in the traditional DMN [20]. Given that the PCC is the seed region most commonly used in studies of the default network, the PCC was used as the region of interest (ROI) to study its altered connections with other brain regions.

The DMN could be affected by neuropsychiatric disorders [17], [18], and some researchers suggested that the cause of the small vessel disease-related cognitive decline may lie in a disruption and disconnection of the frontal–subcortical pathways [21]. Furthermore, vascular disease can reduce cerebral blood flow (CBF) [22], which may influence the BOLD fMRI signal. So we hypothesize that FC will dissociate within the default networks associated with the PCC in the VCIND patients, and the difference may contribute to the understanding of the pathogenesis of VCIND.

Section snippets

Subjects

Patients with SIVD were recruited from a stroke or transient ischemic attack (TIA) clinic. SIVD is defined as subcortical white matter hyperintensity on T2-weighted images on MRI with at least one lacunar infarct. All participants received baseline evaluation, including complete sociodemographic and clinical (cognitive, behavioral, neurological, functional, and physical) data collection. Patient histories were collected from knowledgeable informants, usually from their spouses. All patients

Demography and neuropsychological test

Demographic characteristics and main neuropsychological information are showed in Table 1. No significant differences in age, gender, and education were found between the two groups. Compared with the control group, Z-scores were significantly lower in the VCIND group.

PCC connectivity: within-group analysis

Within-group analysis was performed with the SPM5 random-effects one-sample t-test. With a p-value < 0.01 [false discovery rate (FDR)–corrected] and an extent threshold of 54 voxels, the PCC connectivity maps in both groups included

Discussion

SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk factor for developing dementia; it seems to contribute specifically to the deterioration of psychomotor speed, executive control, and global cognitive function [5], [6]. The cause of the small vessel disease-related cognitive symptoms, including the psychomotor slowing and the executive deficits, may lie in a disruption and disconnection of the frontal–subcortical

Acknowledgments

This research was supported by the Shanghai Leading Academic Discipline Project (Project No. S30203), particularly the study design and collection, analysis, and interpretation of data, as well as in the writing of the report and the decision to submit the paper for publication.

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