Patients with geriatric depression exhibit a spectrum of symptoms ranging from mild to severe cognitive impairment which could potentially lead to the development of Alzheimer’s disease (AD). The aim of the study is to assess the alterations of the default mode network (DMN) in remitted geriatric depression (RGD) patients and whether it could serve as an underlying neuropathological mechanism associated with the risk of progression of AD.

Cross-sectional study.

A total of 154 participants, comprising 66 RGD subjects (which included 27 patients with comorbid amnestic mild cognitive impairment [aMCI] and 39 without aMCI [RGD]), 45 aMCI subjects without a history of depression (aMCI), and 43 matched healthy comparisons (HC), were recruited.

All participants completed neuropsychological tests and underwent resting-state functional magnetic resonance imaging (fMRI). Posterior cingulate cortex (PCC)-seeded DMN functional connectivity (FC) along with cognitive function were compared among the four groups, and correlation analyses were conducted.

In contrast to HC, RGD, aMCI, and RGD-aMCI subjects showed significant impairment across all domains of cognitive functions except for attention. Furthermore, compared with HC, there was a similar and significant decrease in PCC-seed FC in the bilateral medial superior frontal gyrus (M-SFG) in the RGD, aMCI, and RGD-aMCI groups.

The aberrations in rsFC of the DMN were associated with cognitive deficits in RGD patients and might potentially reflect an underlying neuropathological mechanism for the increased risk of developing AD. Therefore, altered connectivity in the DMN could serve as a potential neural marker for the conversion of geriatric depression to AD.

Neuroimaging studies have shown that major depressive disorder is associated with altered activity patterns of the default-mode network (DMN). In this study, we sought to investigate the topological organization of the DMN in patients with remitted geriatric depression (RGD) and whether RGD patients would be more likely to show disrupted topological configuration of the DMN during the resting-state.

Thirty-three RGD patients and thirty-one healthy control participants underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans. The functional connectivity (FC) networks were constructed by thresholding Pearson correlation metrics of the DMN regions defined by group independent component analysis, and their topological properties (e.g. small-world and network efficiency) were analyzed using graph theory-based approaches.

Relative to the healthy controls, the RGD patients showed decreased FC in the posterior regions of the DMN (i.e. the posterior cingulate cortex/precuneus, angular gyrus, and middle temporal gyrus). Furthermore, the RGD patients showed abnormal global topology of the DMN (i.e. increased characteristic path length and reduced global efficiency) when compared with healthy controls. Importantly, significant correlations between these network measures and cognitive performance indicated their potential use as biomarkers of cognitive dysfunction in RGD.

The present study indicated disrupted FC and topological organization of the DMN in the context of RGD, and further implied their contribution to cognitive deficits in RGD patients.