Neural correlates associated with cognitive decline in late-life depression

Abstract

Objectives: Persistent cognitive impairment (PCI) after remission of depressive symptoms is a major adverse outcome of late-life depression (LLD). The purpose of this study was to examine neural substrates associated with PCI in LLD.

Design: Longitudinal study.

Setting: Outpatient depression treatment study at Duke University.

Participants: Twenty-three patients with LLD completed a 2-year follow-up study, and were in a remitted or partially remitted state at Year 2.

Methods: At first entry to the study (Year 0), all participants had a functional magnetic resonance imaging scan while performing an emotional oddball task. For the purpose of this report, the primary functional magnetic resonance imaging outcome was brain activation during target detection, which is a measure of executive function. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery was used to assess cognitive status yearly, and the Montgomery-Åsberg Depression Rating Scale was used to assess severity of depression at Year 0 and every 6 months thereafter for 2 years. We investigated changes in brain activation at Year 0 associated with PCI over 2 years.

Results: Patients with PCI at the 2-year follow-up date had significantly decreased activation at Year 0 in the dorsal anterior cingulate cortex, hippocampus, inferior frontal cortex, and insula compared to non-PCI patients.

Conclusions: Our results suggest individuals who have LLD with PCI have decreased activation in the similar neural networks associated with the development of Alzheimer disease among nondepressed individuals. Measuring neural activity in these regions in individuals with LLD may help identify patients at-risk for cognitive impairment.

Figure 1

Brain regions showing significantly reduced activation in the PCI group compared with the non-PCI group. dACC=dorsal anterior cingulate, dmPFC=dorsomedial prefrontal cortex, HC=hippocampal complex, IFC=inferior frontal cortex, IPC=inferior parietal cortex.

Figure 2

Brain regions revealing a linear correlation between brain activation to targets and cognitive decline measured by the change in CERAD TS (Year 2- Year 0). dACC= dorsal anterior cingulate cortex, HC=hippocampal complex, IFC=inferior frontal cortex, IPC=inferior parietal cortex, PCC=posterior cingulate cortex.

Figure 3

The Brain maps illustrating the overlapped brain regions showing significantly reduced activation in the PCI group compared with the non-PCI group and meanwhile the activations significantly correlated with the degree of cognitive decline based on the conjunction analysis. The plots illustrating the relationship of brain activation in the hippocampus with cognitive function at Year 0 (left) and with the degree of cognitive decline over the two years (right). Mid-CC: middle cingulate cortex, HC= hippocampal complex, IPC=inferior parietal cortex,

Figure 4

Brain regions revealing a linear correlation between brain activation to targets with cognitive function as measured by CERAD TS at Year 0. The image inside the white box (lower right) illustrates the overlapping voxels from three analyses: 1) activations that were correlated with cognitive function at Year 0 (green), 2) activations that were correlated with cognitive decline over the two years (purple), and 3) the regions which significantly distinguished the PCI and non-PCI groups (red). The overlapping voxels among the three analyses are in white, where the arrowhead is pointed. The overlapping voxels between analyses 1) and 3) are indicated in yellow. dACC=dorsal anterior cingulate, dmPFC=dorsomedial prefrontal cortex, IPC=inferior parietal cortex.