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The regional specificity of hippocampal abnormalities in late-life depression (LLD) has been demonstrated in previous studies. In this study, we sought to examine the functional connectivity (FC) patterns of hippocampal subregions in remitted late-onset depression (rLOD), a special subtype of LLD. Fourteen rLOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ∼21 months of follow-up. Each hippocampus was divided into three parts, the cornu ammonis (CA), the dentate gyrus, and the subicular complex, and then six seed-based hippocampal subregional networks were established. Longitudinal changes of the six networks over time were directly compared between the rLOD and control groups. From baseline to follow-up, the rLOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus (PCC/PCUN), but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex (bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area). Further correlative analyses revealed that the longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test (r = 0.624, P = 0.017) and the Digit Span Test (r = 0.545, P = 0.044) scores in the rLOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in rLOD patients.

Altered functional connectivity networks of hippocampal subregions in remitted late-onset depression: a longitudinal resting-state study