Abstract

The purpose of our study was to investigate whether the whole-brain functional connectivity pattern exhibits disease severity-related alterations in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Resting-state functional magnetic resonance imaging data were acquired in 27 MCI subjects, 35 AD patients, and 27 age- and gender-matched subjects with normal cognition (NC). Interregional functional connectivity was assessed based on a predefined template which parcellated the brain into 90 regions. Altered whole-brain functional connectivity patterns were identified via connectivity comparisons between the AD and NC subjects. Finally, the relationship between functional connectivity strength and cognitive ability according to the mini-mental state examination (MMSE) was evaluated in the MCI and AD groups. Compared with the NC group, the AD group exhibited decreased functional connectivities throughout the brain. The most significantly affected regions included several important nodes of the default mode network and the temporal lobe. Moreover, changes in functional connectivity strength exhibited significant associations with disease severity-related alterations in the AD and MCI groups. The present study provides novel evidence and will facilitate meta-analysis of whole-brain analyses in AD and MCI, which will be critical to better understand the neural basis of AD.

Highlights

  • It has been estimated that more than 81.1 million individuals will suffer from dementia by 2040, and Alzheimer’s disease (AD) will account for the underlying pathology in the majority of these cases [1]

  • The present results demonstrated that the identified impaired connectivity strengths in the Mild cognitive impairment (MCI) patients were located between those of the normal cognitive subjects and AD patients (Figures 2(d)–2(f)) and that most of the identified functional connectivity strengths were significantly correlated with cognitive variables in the patient groups (Figure 4)

  • The present data-driven whole-brain functional connectivity study demonstrated that brain functional connectivity patterns are significantly impaired in AD/MCI patients

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Summary

Introduction

It has been estimated that more than 81.1 million individuals will suffer from dementia by 2040, and Alzheimer’s disease (AD) will account for the underlying pathology in the majority of these cases [1]. MCI is thought to be the prodromal stage of dementia; in particular, the amnestic subtype of MCI carries a very high risk of progression to AD [2]. The past decade has witnessed great progress in restingstate functional magnetic resonance imaging (rs-fMRI), which is based on the measurement of spontaneous lowfrequency fluctuations of blood oxygen level-dependent (BOLD) signals [3]. The correlations/similarities of these types of fluctuations among various brain regions have been thought to represent the interregional functional connectivity [4]. Convergent evidence identified via rs-fMRI has suggested that alterations in functional connectivity/networks are prevalent in AD and MCI [5,6,7,8,9,10,11,12,13,14]. The previous literature has suggested that AD/MCI is a disconnection syndrome [15,16,17]

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