Structural and functional differences in the brains of patients with MCI with and without depressive symptoms and their relations with Alzheimer's disease: an MRI study

Abstract

Background: The mild cognitive impairment (MCI) stage among elderly individuals is very complex, and the level of diagnostic accuracy is far from ideal. Some studies have tried to improve the 'MCI due to Alzheimer's disease (AD)' classification by further stratifying these patients into subgroups. Depression-related symptoms may play an important role in helping to better define the MCI stage in elderly individuals.

Objective: In this work, we explored functional and structural differences in the brains of patients with nondepressed MCI (nDMCI) and patients with MCI with depressive symptoms (DMCI), and we examined how these groups relate to AD atrophy patterns and cognitive functioning.

Methods: Sixty-five participants underwent MRI exams and were divided into four groups: cognitively normal, nDMCI, DMCI, and AD. We compared the regional brain volumes, cortical thickness, and white matter microstructure measures using diffusion tensor imaging among groups. Additionally, we evaluated changes in functional connectivity using fMRI data.

Results: In comparison to the nDMCI group, the DMCI patients had more pronounced atrophy in the hippocampus and amygdala. Additionally, DMCI patients had asymmetric damage in the limbic-frontal white matter connection. Furthermore, two medial posterior regions, the isthmus of cingulate gyrus and especially the lingual gyrus, had high importance in the structural and functional differentiation between the two groups.

Conclusion: It is possible to differentiate nDMCI from DMCI patients using MRI techniques, which may contribute to a better characterization of subtypes of the MCI stage.

Keywords: Alzheimer's Disease; depressive disorders; mild cognitive impairment; neuroimaging.

Figure 1:

Normalized brain volumes (mean ± standard deviation) of the right/left hippocampus, amygdala, lingual gyrus, and the isthmus of the cingulate gyrus are expressed as a percentage of the intracranial volume for the CN, nDMCI, DMCI, and AD groups. Significant differences (P < 0.05) are marked as follows: a when different from the CN group; b when different from the nDMCI group; c when different from the DMCI group; and d when different from the AD group.

Figure 2:

Correlation between the right lingual gyrus volume and scores on the GDS. The blue line represents the linear regression between the data, with the Pearson correlation coefficient and the P value of this association being indicated in the upper right.

Figure 3:

Cortical thickness values (mean ± standard deviation) of the entorhinal cortex and lingual gyrus for the CN, nDMCI, DMCI, and AD groups. Significant differences (P < 0.05) are marked as follows: a when different from the CN group; b when different from the nDMCI group; c when different from the DMCI group; and d when different from the AD group.

Figure 4:

Fractional anisotropy (FA) and RD (mean ± standard deviation) of the uncinate fasciculus for the CN, nDMCI, DMCI, and AD groups. Significant differences (P < 0.05) are marked as follows: a when different from the CN group; b when different from the nDMCI group; c when different from the DMCI group; and d when different from the AD group.

Figure 5:

Elements represent connections that were significantly different (P false discovery rate < 0.05) in the group comparison. The lower diagonal shows connections with higher FC in the CN compared to the nDMCI, DMCI, and AD groups. The upper diagonal shows connections with higher FC in the CN, nDMCI, and DMCI groups than in the AD group. Regions: 1–2 middle frontal gyrus L/R (MFG), 3–4 rectus L/R (REC), 5–6 insula L/R (INS), 7–8 anterior cingulate L/R (ACG), 9–10 posterior cingulate L/R (PCG), 11–12 hippocampus L/R (HIP), 13–14 parahippocampal gyrus L/R (PHG), 15–16 amygdala L/R (AMYG), 17–18 lingual gyrus L/R (LING), 19–20 supramarginal L/R (SMG), 21–22 angular L/R (ANG), 23–24 precuneus L/R (PCUN), 25–26 thalamus L/R (THA), and 27–28 temporal pole L/R (TPO). NS = no statistical significance.