Elsevier

Ageing Research Reviews

Volume 35, May 2017, Pages 12-21
Ageing Research Reviews

Review
Aberrant spontaneous low-frequency brain activity in amnestic mild cognitive impairment: A meta-analysis of resting-state fMRI studies

https://doi.org/10.1016/j.arr.2016.12.001Get rights and content

Highlights

  • We performed a meta-analysis of ALFF changes in 14 datasets on aMCI.

  • Widespread aberrant regional spontaneous brain activity was observed in aMCI.

  • The aberrant regions involved in the default mode, salience, and visual networks.

  • GM volume corrections partly influenced the results of the ALFF analysis.

Abstract

Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have provided strong evidence of abnormal spontaneous brain activity in amnestic mild cognitive impairment (aMCI). However, the conclusions have been inconsistent. A meta-analysis of whole-brain rs-fMRI studies that measured differences in the amplitude of low-frequency fluctuations (ALFF) between aMCI patients and healthy controls was conducted using the Seed-based d Mapping software package. Twelve studies reporting 14 datasets were included in the meta-analysis. Compared to healthy controls, patients with aMCI showed decreased ALFFs in the bilateral precuneus/posterior cingulate cortices, bilateral frontoinsular cortices, left occipitotemporal cortex, and right supramarginal gyrus and increased ALFFs in the right lingual gyrus, left middle occipital gyrus, left hippocampus, and left inferior temporal gyrus. A meta-regression analysis demonstrated that the increased severity of cognitive impairment in aMCI patients was associated with greater decreases in ALFFs in the cuneus/precuneus cortices. Our comprehensive meta-analysis suggests that aMCI is associated with widespread aberrant regional spontaneous brain activity, predominantly involving the default mode, salience, and visual networks, which contributes to understanding its pathophysiology.

Introduction

Amnestic mild cognitive impairment (aMCI) is a syndrome defined by objective memory impairment without dementia, adjusted for age, with essentially preserved general cognitive functions and intact functional activities (Petersen, 2004). The aMCI syndrome carries a substantial risk for developing dementia or Alzheimer’s disease (AD) (Petersen et al., 2001b), with the annual rate of conversion from aMCI to dementia and/or AD at 11.7% (Mitchell and Shiri-Feshki, 2009). Early detection of individuals at the prodromal stage of dementia is of dramatically increasing importance. Although the pathophysiology of aMCI is yet to be determined, brain structural impairments and functional alterations have been suggested to play critical roles (Pihlajamaki et al., 2009). Gray matter (GM) atrophy in aMCI patients was identified in the bilateral amygdala and hippocampus extending to the left medial temporal lobe, left superior temporal gyrus, left thalamus, and precuneus cortices extending to the dorsal cingulate cortex (Nickl-Jockschat et al., 2012). Relative to healthy controls, MCI patients showed aberrant brain activation mainly in regions involved in the default mode, frontoparietal, visual, ventral attention, and somatomotor networks in task-based functional magnetic resonance imaging (fMRI) studies (Li et al., 2015).

However, findings from task-based fMRI studies may be confounded by differences in the experimental design of the studies and in the tasks themselves (Bennett and Miller, 2010). In the last decade, resting-state fMRI (rs-fMRI) has emerged as a promising approach to explore intrinsic brain activity and functional connectivity networks (Barkhof et al., 2014, Sheline and Raichle, 2013). Rs-fMRI can be easily implemented without any task or stimulus, which avoids any variability due to the task (Chao-Gan and Yu-Feng, 2010). The amplitude of low frequency fluctuations (ALFF) technique reveals regional spontaneous synchronous neural activity during rs-fMRI studies (Zuo et al., 2010). The ALFF technique was found to be reliable and useful in characterizing the intrinsic or spontaneous brain activity in patients with aMCI or AD (Cha et al., 2015, Wang et al., 2011). Although the findings from the ALFF studies in aMCI were encouraging, the conclusions were inconsistent. Most of the studies identified both decreased and increased ALFFs in aMCI patients relative to healthy controls (Cai et al., 2016, Han et al., 2012, Jia et al., 2015, Ni et al., 2016, Yin et al., 2014, Zhao et al., 2014, Zhou et al., 2014, Zhuang et al., 2012). However, some studies only detected decreased ALFFs (Cha et al., 2015, Liang et al., 2014). In addition, the affected brain regions observed in these studies were diverse (Cai et al., 2016, Cha et al., 2015, Han et al., 2012, Jia et al., 2015, Liang et al., 2014, Ni et al., 2016, Yin et al., 2014, Zhao et al., 2014, Zhou et al., 2014, Zhuang et al., 2012). Therefore, the objective of this current study was to perform a meta-analysis of the existing literature to identify the most replicable results. This is expected not only to enable a more precise understanding of the pathophysiology of aMCI but also to contribute to the identification of potential biomarkers for prevention and intervention in this disorder.

Section snippets

Data sources and study selection

Studies were comprehensively searched in the PubMed and Embase databases from January 2000–15 May 2016, using the keywords “mild cognitive impairment” OR “MCI”; AND “amplitude of low frequency fluctuations” OR “ALFF”. The reference lists of the included studies and relevant review articles were searched for additional studies. Studies were eligible for our meta-analysis if they satisfied the following conditions: (1) the patients met the diagnostic criteria for aMCI (Petersen et al., 2001a,

Included studies and sample characteristics

After initial assessment of the 38 relevant documents arising from the search strategy, 24 rs-fMRI studies that investigated ALFF differences between aMCI patients and healthy controls were obtained. Eleven studies were excluded because 7 studies did not use a whole brain analysis (Bai et al., 2011a) or did not report the whole brain stereotactic coordinates (Han et al., 2011, Jing et al., 2012, Li et al., 2014, Mascali et al., 2015, Weiler et al., 2014, Zhou et al., 2015) and 4 had overlapping

Discussion

Using the SDM method, this quantitative meta-analysis of whole-brain ALFF analyses demonstrated consistent differences between aMCI patients and healthy controls. The aberrant ALFF regions identified in the meta-analysis are predominantly involved in the default mode network (the bilateral precuneus/PCC, right supramarginal gyrus, and left hippocampus), the salience network (the bilateral frontoinsular cortices), and the visual network (the right lingual gyrus, left middle occipital gyrus, left

Conclusions

Using the SDM method, the current meta-analysis demonstrates that aMCI is associated with widespread abnormalities of regional spontaneous brain activity, predominantly involving the default mode, salience, and visual networks. These findings provide useful insights for understanding the underlying pathophysiology of brain dysfunction in aMCI. Future longitudinal studies should investigate whether the identified pattern of spontaneous brain activity could serve as an early marker for AD. In

Role of funding source

This research was supported by the National Natural Science Foundation of China (81230026, 81171085, 81601161), the Natural Science Foundation (BL2012013) and the Bureau of Health (LJ201101) of Jiangsu Province of China.

Acknowledgements

We thank Dr. Joaquim Radua for his kind suggestions.

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