Disrupted small-world brain networks in moderate Alzheimer's disease: a resting-state FMRI study.

Xiaohu Zhao,Tianzi Jiang,Xiangbin Wang,Qihao Guo,Hong Jiang,Bing Liu,Peijun Wang,Qian Xi,Yong Liu,Olaf Sporns

doi:10.1371/journal.pone.0033540

Abstract

The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD). However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI) of carefully selected moderate AD patients and normal controls (NCs). Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients.

Highlights

Alzheimer’s disease (AD) is the leading cause of intellectual impairment in the elderly worldwide [1,2,3]
We focused on moderate AD patients to directly investigate the hypothesis that the brain network of AD is characterized by the disruption of efficient smallworld topological properties based on resting-state functional magnetic resonance imaging (fMRI) data
Exploratory study of gene effect To investigate the potential effect of apolipoprotein E (ApoE) genotype on network topological properties, we evaluated the differences between the normal controls (NCs) ApoE42 group and the AD ApoE42 and ApoE4+ groups and those between the AD ApoE42 and ApoE4+ groups using a two-sample two-tailed t-test for each value over a wide range of connection densities (P,0.05)

Summary

Introduction

Alzheimer’s disease (AD) is the leading cause of intellectual impairment in the elderly worldwide [1,2,3]. The most commonly recognized symptom is an inability to acquire new memories, such as difficulty in recalling recently observed facts, which is commonly referred to as the loss of episodic memory. Extensive cognitive impairments begin to manifest, including language breakdown and long-term memory loss. Most brain functions deteriorate, leading to death. The neural basis underlying the functional damage is not yet fully understood. Recent studies based on multimodal imaging have provided evidence supporting the notion of AD as a disconnection syndrome [4,5,6]

Objectives

Methods

Results

Discussion

Conclusion