Abnormal functional connectivity of the default mode network in remitted late-onset depression

Background: The functional neural network model has been a major method used to investigate mechanisms of neuropsychopathy. There is considerable evidence that late-onset depression (LOD) is the prodrome, or the early clinical manifestation, of Alzheimer's disease (AD). The default mode network (DMN) is one of the neural networks that can be used to explore the complex relationships between depressive symptoms, episodic memory deficits and other cognitive impairments. To date, no study has directly linked the DMN to LOD while focusing on episodic memory and the influence of apolipoprotein E4 (APOE4), a major genetic risk factor for AD in LOD patients.

Methods: In total, 33 remitted LOD (rLOD) patients and 33 elderly controls underwent fMRI scanning using low-frequency BOLD signal imaging during the resting state and during an episodic memory task. Furthermore, function-based functional connectivities (FCs) in the region of interesting (ROI) (posterior cingulate cortex (PCC) of the DMN) were analysed to explore interactions between disease states, task states and genetic risk factors (APOE4).

Results: Compared to healthy control subjects (HC), the FCs between the PCC and the right medial temporal lobe of the rLOD patients were significantly stronger during rest (p<0.005) and significantly weaker (p<0.05) during performance of the task. The mode of change from rest to task performance in the HC was in contrast to the mode of change in the rLOD patients. The FCs of the rLOD patients without APOE4 were significantly increased (p<0.05) in the resting state, but the rLOD patients who carried APOE4 showed a trend toward decreased FCs.

Limitations: The sample size was small. While the study was cross-sectional, we did not differentiate between the various types of antidepressants the patients used, which may have had different effects on cognitive function, especially on episodic memory.

Conclusion: Our results suggested that rLOD might be the prodrome, or the early clinical manifestation, of AD and that rLOD patients with APOE4 showed an increased risk for episodic memory decline and AD.