Resting State Abnormalities of the Default Mode Network in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

Published on Jan 1, 2019in Journal of Alzheimer's Disease3.909
· DOI :10.3233/JAD-180847
Lisa T. Eyler47
Estimated H-index: 47
(UCSD: University of California, San Diego),
Jeremy A. Elman15
Estimated H-index: 15
(UCSD: University of California, San Diego)
+ 13 AuthorsWilliam S. Kremen70
Estimated H-index: 70
(UCSD: University of California, San Diego)
BACKGROUND: Large-scale brain networks such as the default mode network (DMN) are often disrupted in Alzheimer's disease (AD). Numerous studies have examined DMN functional connectivity in those with mild cognitive impairment (MCI), a presumed AD precursor, to discover a biomarker of AD risk. Prior reviews were qualitative or limited in scope or approach. OBJECTIVE: We aimed to systematically and quantitatively review DMN resting state fMRI studies comparing MCI and healthy comparison (HC) groups. METHODS: PubMed was searched for relevant articles. Study characteristics were abstracted and the number of studies showing no group difference or hyper- versus hypo-connnectivity in MCI was tallied. A voxel-wise (ES-SDM) meta-analysis was conducted to identify regional group differences. RESULTS: Qualitatively, our review of 57 MCI versus HC comparisons suggests substantial inconsistency; 9 showed no group difference, 8 showed MCI > HC and 22 showed HC > MCI across the brain, and 18 showed regionally-mixed directions of effect. The meta-analysis of 31 studies revealed areas of significant hypo- and hyper-connectivity in MCI, including hypoconnectivity in the posterior cingulate cortex/precuneus (z = -3.1, p < 0.0001). Very few individual studies, however, showed patterns resembling the meta-analytic results. Methodological differences did not appear to explain inconsistencies. CONCLUSIONS: The pattern of altered resting DMN function or connectivity in MCI is complex and variable across studies. To date, no index of DMN connectivity qualifies as a useful biomarker of MCI or risk for AD. Refinements to MCI diagnosis, including other biological markers, or longitudinal studies of progression to AD, might identify DMN alterations predictive of AD risk.
Figures & Tables
📖 Papers frequently viewed together
2 Citations
1 Citations
6 Authors (Huijie Li, ..., Xi-Nian Zuo)
86 Citations
#1Xin GaoH-Index: 3
#2Xiaowen Xu (Tongji University)H-Index: 3
Last. Rui LiH-Index: 1
view all 6 authors...
Functional brain network (FBN) provides an effective biomarker for understanding brain activation patterns and a diagnostic criterion for neurodegenerative diseases detections. Unfortunately, it still remains challenges to estimate the biologically meaningful or discriminative FBNs accurately, because of the poor quality of functional magnetic resonance imaging data or our limited understanding of human brain. In this study, a novel FBN estimation model based on group similarity prior was propos...
5 CitationsSource
#1Avinash Chandra ('KCL': King's College London)H-Index: 5
#2George Dervenoulas ('KCL': King's College London)H-Index: 5
view all 4 authors...
Research utilizing magnetic resonance imaging (MRI) has been crucial to the understanding of the neuropathological mechanisms behind and clinical identification of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). MRI modalities show patterns of brain damage that discriminate AD from other brain illnesses and brain abnormalities that are associated with risk of conversion to AD from MCI and other behavioural outcomes. This review discusses the application of various MRI techniques to...
31 CitationsSource
#1Mark W. Logue (BU: Boston University)H-Index: 33
#2Matthew S. Panizzon (UCSD: University of California, San Diego)H-Index: 35
Last. William S. Kremen (UCSD: University of California, San Diego)H-Index: 70
view all 14 authors...
Author(s): Logue, MW; Panizzon, MS; Elman, JA; Gillespie, NA; Hatton, SN; Gustavson, DE; Andreassen, OA; Dale, AM; Franz, CE; Lyons, MJ; Neale, MC; Reynolds, CA; Tu, X; Kremen, WS | Abstract: Early identification of younger, non-demented adults at elevated risk for Alzheimer's disease (AD) is crucial because the pathological process begins decades before dementia onset. Toward that end, we showed that an AD polygenic risk score (PRS) could identify mild cognitive impairment (MCI) in adults who w...
54 CitationsSource
#1Enyan YuH-Index: 4
#2Zhengluan LiaoH-Index: 2
Last. Zhongxiang DingH-Index: 8
view all 14 authors...
Many functional magnetic resonance imaging (fMRI) studies have indicated that Granger causality analysis (GCA) is a suitable method for revealing causal effects between brain regions. The purpose of the present study was to identify neuroimaging biomarkers with a high sensitivity to amnestic mild cognitive impairment (aMCI). The resting-state fMRI data of 30 patients with Alzheimer’s disease (AD), 14 patients with aMCI, and 18 healthy controls (HC) were evaluated using GCA. This study focused on...
25 CitationsSource
#1Yi-Wen Zhang (CAS: Chinese Academy of Sciences)H-Index: 2
#1Yi-Wen Zhang (CAS: Chinese Academy of Sciences)H-Index: 2
Last. Xi-Nian ZuoH-Index: 63
view all 13 authors...
Alterations in both local and remote connectivity were reported in amnestic mild cognitive impairment (aMCI) patients but rarely in the same group of patients. In the present study, we employed a novel resting-state functional magnetic resonance imaging (rfMRI) connectome index, regional functional homogeneity on the 2-dimensional cortical surface, to detect full-cortex vertex-wise changes of the local rfMRI connectivity in 32 aMCI patients compared with 40 healthy controls. We further used the ...
8 CitationsSource
#1Enyan YuH-Index: 2
#1Enyan YuH-Index: 3
Last. Zhongxiang DingH-Index: 8
view all 7 authors...
Background: Impaired functional connectivity in the default mode network (DMN) is supposedly involved in Alzheimer’s disease (AD) progression. The posterior cingulate cortex (PCC) might be an imaging marker for monitoring AD progression. Objective: To investigate the alterations in the directed functional connectivity between the PCC and whole brain in patients with AD, patients with mild cognitive impairment (MCI), and healthy controls. Methods: A total of 116 enrolled participants were divided...
22 CitationsSource
#1Francesco BarbanH-Index: 12
#2Matteo ManciniH-Index: 11
Last. Marco BozzaliH-Index: 60
view all 16 authors...
Alzheimer’s disease (AD) alters the functional connectivity of the default mode network (DMN) but also the topological properties of the functional connectome. Cognitive training (CT) is a tool to slow down AD progression and is likely to impact on functional connectivity. In this pilot study, we aimed at investigating brain functional changes after a period of CT and active control (AC) in a group of 26 subjects with mild AD (mAD), 26 with amnestic mild cognitive impairment (aMCI), and a contro...
19 CitationsSource
#1Zan Wang (SEU: Southeast University)H-Index: 14
#2Zhengjia Dai (McGovern Institute for Brain Research)H-Index: 20
Last. Zhijun Zhang (SEU: Southeast University)H-Index: 54
view all 9 authors...
Whether and how the apolipoprotein E (APOE) e4 genotype specifically modulates brain network connectivity in patients with amnestic mild cognitive impairment (aMCI) remain largely unknown. Here, we employed resting-state (‘task-free’) functional MRI and network centrality approaches to investigate local (degree centrality, DC) and global (eigenvector centrality, EC) functional integrity in the whole-brain connectome in 156 older adults, including 66 aMCI patients (27 e4-carriers and 39 non-carri...
11 CitationsSource
#1Srikala Bharath (National Institute of Mental Health and Neurosciences)H-Index: 12
#2Himanshu Joshi (National Institute of Mental Health and Neurosciences)H-Index: 3
Last. Mathew Varghese (National Institute of Mental Health and Neurosciences)H-Index: 20
view all 8 authors...
Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using vo...
16 CitationsSource
#1Andrew C. McKinnon (Macquarie University)H-Index: 6
#2Shantel L. Duffy (USYD: University of Sydney)H-Index: 16
Last. Sharon L. Naismith (USYD: University of Sydney)H-Index: 69
view all 11 authors...
Background: Sleep disturbance is prevalent in MCI, and is a risk factor for cognitive deterioration. Objective: To identify functional connectivity deficits in the default mode network (DMN) in patients with mild cognitive impairment (MCI) and sleep disturbance, relative to MCIs with intact sleep. Methods: Participants comprised 47 adults aged 55 years and over, recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. This sample contained 15 controls and 3...
12 CitationsSource
Cited By16
#2Geetanjali MurariH-Index: 5
Last. Linda Mah (U of T: University of Toronto)H-Index: 12
view all 8 authors...
BACKGROUND Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer's disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. OBJECTIVE To examine the association between SCD and pDMN network connectivity with medial temporal lobe (MTL) regions using resting-state functional magn...
#1Jiyeon Lee (KU: Korea University)H-Index: 7
#2Wonjun Ko (KU: Korea University)H-Index: 4
Last. Heung-Il Suk (KU: Korea University)H-Index: 28
view all 4 authors...
Abstract Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely adopted to investigate functional abnormalities in brain diseases. Rs-fMRI data is unsupervised in nature because the psychological and neurological labels are coarse-grained, and no accurate region-wise label is provided along with the complex co-activities of multiple regions. To the best of our knowledge, most studies regarding univariate group analysis or multivariate pattern recognition for brain disease ...
#1Borcuk C (UDS: University of Strasbourg)
#2Céline Héraud (UDS: University of Strasbourg)H-Index: 5
Last. Mathis C
view all 13 authors...
A critical challenge in current research on AD is to clarify the relationship between early neuropathology and network dysfunction associated to the emergence of subtle memory alterations which announce disease onset. In the present work, the new generation AppNL-F/MAPT double knock in (dKI) model was used to evaluate early stages of AD. The initial step of tau pathology was restricted to the perirhinal-entorhinal region, sparing the hippocampus. This discrete neuropathological sign was associat...
#1Qianqian Zhang (SEU: Southeast University)
#2Qing Wang (SEU: Southeast University)H-Index: 6
Last. Chunming Xie (SEU: Southeast University)H-Index: 25
view all 13 authors...
Objective: To investigate variation in the characteristics of regional Cerebral Blood Flow (rCBF), brain activity and intrinsic Function Connectivity (FC) across the Alzheimer’s Disease Spectrum (ADS). Methods: The study recruited 20 individuals in each of the following categories; Alzheimer’s Disease (AD), Mild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD) and healthy normal (HC). All the participants completed the 3.0T resting-state functional magnetic resonance imaging and ar...
Last. Xingfu Zhao (Nanjing Medical University)H-Index: 2
view all 5 authors...
Background and Objective: Current evidence suggests that abnormalities within the default-mode network (DMN) play a key role in the broad-scale cognitive problems that characterize mild cognitive impairment (MCI). However, little is known about the alterations of DMN network homogeneity (NH) in MCI. Methods: Resting-state functional magnetic resonance imaging scans (rs-fMRI) were collected from 38 MCI patients and 69 healthy controls matched for age, gender, and education. NH approach was employ...
#1Jin Li (HEU: Harbin Engineering University)H-Index: 6
#2Chenyuan Bian (HEU: Harbin Engineering University)H-Index: 1
Last. Hong Liang (HEU: Harbin Engineering University)H-Index: 4
view all 6 authors...
OBJECTIVE The characterization of functional brain network is crucial to understanding the neural mechanisms associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Some studies have shown that graph theoretical analysis could reveal changes of the disease-related brain networks by thresholding edge weights. But the choice of threshold depends on ambiguous cognitive conditions, which leads to the lack of interpretability. Recently, persistent homology (PH) was proposed to r...
#1Giuseppe Sarli (University of Sheffield)H-Index: 1
#1Giuseppe Sarli (Sapienza University of Rome)H-Index: 3
Last. Annalena Venneri (University of Sheffield)H-Index: 49
view all 6 authors...
Background: The association between regional volumes and resting-state functional networks was tested within the default-mode network (DMN), influenced by Alzheimer pathology, salience network (Sal...
1 CitationsSource
#1Lingyan Liang (Xida: Guangxi University)H-Index: 3
#2Yueming Yuan (SZU: Shenzhen University)H-Index: 2
Last. Demao DengH-Index: 1
view all 12 authors...
BACKGROUND The brain's dynamic spontaneous neural activity and dynamic functional connectivity (dFC) are both important in supporting cognition, but how these two types of brain dynamics evolve and co-evolve in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remain unclear. The aim of the present study was to investigate recurrent and concurrent patterns of two types of dynamic brain states correlated with cognitive decline. METHODS The present study analyzed resting-state...
#1Jaime D Mondragón (UMCG: University Medical Center Groningen)H-Index: 4
#2Natasha M. Maurits (UMCG: University Medical Center Groningen)H-Index: 41
view all 4 authors...
Abstract Alzheimer’s continuum biological profiles (A+T-N-, A+T+N-, A+T-N+, and A+T+N+) were established in the 2018 National Institute on Aging and Alzheimer's Association (NIA-AA) research framework for Alzheimer’s disease (AD). We aim to assess the relation between AT(N) biomarker profiles and brain functional connectivity (FC) and assess the neural correlates of anosognosia. We assessed local functional coupling and between-network connectivity through between-group intrinsic local correlati...
#1Shumei Li (German Center for Neurodegenerative Diseases)H-Index: 1
#2Marcel Daamen (German Center for Neurodegenerative Diseases)
Last. Henning Boecker (University Hospital Bonn)H-Index: 12
view all 37 authors...
BACKGROUND Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework. OBJECTIVE This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially fo...