Specifically progressive deficits of brain functional marker in amnestic type mild cognitive impairment

Abstract

Background: Deficits of the default mode network (DMN) have been demonstrated in subjects with amnestic type mild cognitive impairment (aMCI) who have a high risk of developing Alzheimer's disease (AD). However, no longitudinal study of this network has been reported in aMCI. Identifying links between development of DMN and aMCI progression would be of considerable value in understanding brain changes underpinning aMCI and determining risk of conversion to AD.

Methodology/principal findings: Resting-state fMRI was acquired in aMCI subjects (n = 26) and controls (n = 18) at baseline and after approximately 20 months follow up. Independent component analysis was used to isolate the DMN in each participant. Differences in DMN between aMCI and controls were examined at baseline, and subsequent changes between baseline and follow-up were also assessed in the groups. Posterior cingulate cortex/precuneus (PCC/PCu) hyper-functional connectivity was observed at baseline in aMCI subjects, while a substantial decrement of these connections was evident at follow-up in aMCI subjects, compared to matched controls. Specifically, PCC/PCu dysfunction was positively related to the impairments of episodic memory from baseline to follow up in aMCI group.

Conclusions/significance: The patterns of longitudinal deficits of DMN may assist investigators to identify and monitor the development of aMCI.

Figure 1. Validation of the ICA approach in aMCI subjects and healthy controls.

Images showed the DMN in aMCI group and controls group at baseline and follow up, separately. Significant consistency between these studies is demonstrated across the majority of clusters including the posterior cingulated cortex, precuneus, inferior parietal lobule, prefrontal cortex, ventral anterior cingulate cortex, lateral temporal cortex. Thresholds were set at a corrected P<0.05, determined by Monte Carlo simulation.

Figure 2. Groups × time points ANOVA of DMN IC functional connectivity.

Thresholds were set at a corrected P<0.05, determined by Monte Carlo simulation.

Figure 3

(1). Comparison to controls group at baseline, aMCI group showed increased functional connectivity of DMN IC in a  =  bilateral PCC/PCu. (2). A comparison between the longitudinal changes between aMCI group and controls group, showing a greater decrement in functional connectivity of DMN IC in the aMCI group, particularly in PCC/PCu, and another region was d  =  right anterior cingulate/ medial frontal gyrus. In addition, the longitudinal increased functional connectivity of the prefrontal cortex was observed at follow up in aMCI subjects compared with controls, including b  =  left superior frontal gyrus/ middle frontal gyrus, c  =  right superior frontal gyrus/ middle frontal gyrus, e  =  left middle frontal gyrus and f  =  left inferior frontal gyrus. Thresholds were set at a corrected P<0.05, determined by Monte Carlo simulation. (3) Overlap regions (PCC/Pcu) between baseline changes and longitudinal changes of DMN IC were observed in aMCI group compared to controls. (4) Hyper-functional connectivity between the PCC/PCu (overlap regions) and mean DMN IC in baseline aMCI subjects, and significant hypo-connections of these regions were in follow-up aMCI subjects, whilst controls only showed a light decreases at the longitudinal period. * P<0.05 (0.046); ** P<0.001(0.000). (5) Correlative analysis: within the aMCI group, the decreases of functional connectivity between PCC/PCu and mean DMN IC were positively related to the impairments of episodic memory (AVLT-delayed recall scores, r = 0.462, P = 0.018, two-tailed) from baseline to follow up. It should be noted that the raw scores of AVLT-delayed recall for each subject was transformed to z scores.