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

The default mode network (DMN) is often disrupted in Alzheimer's disease (AD), and many studies have examined DMN connectivity in people with mild cognitive impairment (MCI), a presumed AD precursor, to find a biomarker of AD risk. This systematic review and meta-analysis of 57 MCI versus healthy comparison studies found substantial inconsistency: 9 showed no group difference, 8 showed hyperconnectivity in MCI, 22 showed hypoconnectivity, and 18 showed regionally mixed directions. The meta-analysis of 31 studies revealed significant hypo- and hyperconnectivity in MCI, including hypoconnectivity in the posterior cingulate cortex/precuneus. Very few individual studies matched the meta-analytic pattern, and methodological differences did not explain the inconsistencies. No index of DMN connectivity currently qualifies as a useful biomarker of MCI or AD risk.

Study at a glance

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.