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Meta-Analysis
. 2019;70(1):107-120.
doi: 10.3233/JAD-180847.

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

Lisa T Eyler  1   2 , Jeremy A Elman  1 , Sean N Hatton  1   3 , Sarah Gough  1 , Anna K Mischel  1 , Donald J Hagler  4 , Carol E Franz  1 , Anna Docherty  5 , Christine Fennema-Notestine  1   4 , Nathan Gillespie  6 , Daniel Gustavson  1 , Michael J Lyons  7 , Michael C Neale  6 , Matthew S Panizzon  1 , Anders M Dale  3   4 , William S Kremen  1   8
Affiliations
Meta-Analysis

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

Lisa T Eyler et al. J Alzheimers Dis. 2019.

Abstract

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.

Keywords: Alzheimer’s disease; default mode network; functional connectivity; mild cognitive impairment; posterior cingulate cortex; resting state functional magnetic resonance imaging.

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Figures

Figure 1
Figure 1
PRISMA flow diagram of review process.
Figure 2
Figure 2
Significant clusters from the meta-analysis of studies comparing DMN resting state connectivity between those with mild cognitive impairment (MCI) and healthy comparison (HC) participants. Warm-colored clusters are regions where the studies indicated greater/more positive correlation strength among those with MCI compared to HC. Cool-colored clusters are regions where the studies indicated lower/less positive correlation strength in MCI compared to HC.
Figure 3
Figure 3
Number of studies out of 24 that showed a non-zero effect in each voxel. Locations of significant clusters from the meta-analysis are indicated with black outlines. The color scale indicates the number of studies with significant non-zero effects, not the effect size.
See this image and copyright information in PMC

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