Abstract

Despite the severe social burden caused by Alzheimer’s disease (AD), no drug than can change the disease progression has been identified yet. The structural brain network research provides an opportunity to understand physiological deterioration caused by AD and its precursor, mild cognitive impairment (MCI). Recently, persistent homology has been used to study brain network dynamics and characterize the global network organization. However, it is unclear how these parameters reflect changes in structural brain networks of patients with AD or MCI. In this study, our previously proposed persistent features and various traditional graph-theoretical measures are used to quantify the topological property of white matter (WM) network in 150 subjects with diffusion tensor imaging (DTI). We found significant differences in these measures among AD, MCI, and normal controls (NC) under different brain parcellation schemes. The decreased network integration and increased network segregation are presented in AD and MCI. Moreover, the persistent homology-based measures demonstrated stronger statistical capability and robustness than traditional graph-theoretic measures, suggesting that they represent a more sensitive approach to detect altered brain structures and to better understand AD symptomology at the network level. These findings contribute to an increased understanding of structural connectome in AD and provide a novel approach to potentially track the progression of AD.

Highlights

  • Alzheimer’s disease (AD) [1] is a common neurodegenerative disease in the elderly

  • This study introduces a novel perspective of persistent homology that confirms the increased segregation in AD structural networks

  • The widely-used automated anatomical labeling atlas with 90 regions (AAL90) [38] was severed as the second parcellation, and the last parcellation subdivided each of the regions of DK68 atlas into four sub-regions according to a parcellation division algorithm [39,40], producing an atlas with 272 regions (DK272)

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Summary

Introduction

Alzheimer’s disease (AD) [1] is a common neurodegenerative disease in the elderly. Clinical manifestations are mainly memory dysfunction and cognitive decline. Understanding the physiological deterioration caused by AD and MCI provides an opportunity to develop future drugs and predict AD onset [2,3]. The human brain is interconnected by a large number of neurons through synapses, forming a highly complex network system that realizes various intelligent behaviors of human beings. Within these neural networks, even minor mutations can cause serious diseases [4]. WM brain network research provides a chance to understand how abnormal structural connections can lead to cognitive and behavioral deficits in these patients

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