Intrinsic Brain Activity Alterations in Patients With Mild Cognitive Impairment-to-Normal Reversion: A Resting-State Functional Magnetic Resonance Imaging Study From Voxel to Whole-Brain Level.

Qili Hu,Zhou Xie,Xize Jia,Yunfei Li,Guofeng Huang,Xiaohu Zhao,Qianqian Wang,Linlin Zhan,Xiaomei Lin

doi:10.3389/fnagi.2021.788765

Abstract

Mild cognitive impairment (MCI) reversion refers to patients with MCI who revert from MCI to a normal cognitive state. Exploring the underlying neuromechanism of MCI reverters may contribute to providing new insights into the pathogenesis of Alzheimer’s disease and developing therapeutic interventions. Information on patients with MCI and healthy controls (HCs) was collected from the Alzheimer’s Disease Neuroimaging Initiative database. We redefined MCI reverters as patients with MCI whose logical memory scores changed from MCI to normal levels using the logical memory criteria. We explored intrinsic brain activity alterations in MCI reverters from voxel, regional, and whole-brain levels by comparing resting-state functional magnetic resonance imaging metrics of the amplitude of low-frequency of fluctuation (ALFF), the fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) between MCI reverters and HCs. Finally, partial correlation analyses were conducted between cognitive scale scores and resting-state functional magnetic resonance imaging metrics of brain regions, revealing significant group differences. Thirty-two patients with MCI from the Alzheimer’s Disease Neuroimaging Initiative database were identified as reverters. Thirty-seven age-, sex-, and education-matched healthy individuals were also enrolled. At the voxel level, compared with the HCs, MCI reverters had increased ALFF, fALFF, and PerAF in the frontal gyrus (including the bilateral orbital inferior frontal gyrus and left middle frontal gyrus), increased PerAF in the left fusiform gyrus, and decreased ALFF and fALFF in the right inferior cerebellum. Regarding regional and whole-brain levels, MCI reverters showed increased ReHo in the left fusiform gyrus and right median cingulate and paracingulate gyri; increased DC in the left inferior temporal gyrus and left medial superior frontal; decreased DC in the right inferior cerebellum and bilateral insular gyrus relative to HCs. Furthermore, significant correlations were found between cognitive performance and neuroimaging changes. These findings suggest that MCI reverters show significant intrinsic brain activity changes compared with HCs, potentially related to the cognitive reversion of patients with MCI. These results enhance our understanding of the underlying neuromechanism of MCI reverters and may contribute to further exploration of Alzheimer’s disease.

Highlights

Alzheimer’s disease (AD), accounting for 60–80% of all dementia cases, is an irreversible neurodegenerative disease that causes progressive problems with memory, judgment, orientation, and other functions (Dai and He, 2014)
We identified significant intrinsic brain activity changes in mild cognitive impairment (MCI) reverters compared to healthy controls (HCs) on different scales
Our study indicates that amplitude of low-frequency of fluctuation (ALFF), fractional amplitude of low-frequency of fluctuation (fALFF), and degree centrality (DC) values in the cerebellum consistently decreased in MCI reverters compared to HCs

Summary

Introduction

Alzheimer’s disease (AD), accounting for 60–80% of all dementia cases, is an irreversible neurodegenerative disease that causes progressive problems with memory, judgment, orientation, and other functions (Dai and He, 2014). With an elevated risk of progression to AD (Busse et al, 2006; Petersen et al, 2009; Belleville et al, 2011; Buschert et al, 2011), mild cognitive impairment (MCI) is generally considered a transitional state between normal cognitive functioning and dementia. Research on this mental state has recently increased. Patients with MCI may progress to dementia, maintain stability, or revert to normal (Petersen et al, 2009); most studies have mainly focused on studying MCI-to-dementia or MCI-stable populations and have made considerable contributions in identifying individuals at high risk of developing dementia (Li et al, 2021; Pyun et al, 2021). Further exploration of the neural basis of MCI reverters may contribute to providing new insights into the pathogenesis of AD and developing specific pharmacologic and nonpharmacologic interventions

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