Differences in functional brain connectivity alterations associated with cerebral amyloid deposition in amnestic mild cognitive impairment

Abstract

Despite potential implications for the early detection of impending Alzheimer's disease (AD), very little is known about the differences of large-scale brain networks between amnestic mild cognitive impairment (aMCI) with high cerebral amyloid-beta protein (Aβ) deposition (i.e., aMCI+) and aMCI with no or very little Aβ deposition (i.e., aMCI-). We first aimed to extend the current literature on altering intrinsic functional connectivity (FC) of the default mode network (DMN) and salience network (SN) from cognitively normal (CN) to AD dementia. Second, we further examined the differences of the DMN and the SN between aMCI-, aMCI+, and CN. Forty-three older adult (12 CN, 10 aMCI+, 10 aMCI-, and 11 AD dementia) subjects were included. All participants received comprehensive clinical and neuropsychological assessment, resting-state functional magnetic resonance imaging, structural MRI, and Pittsburgh compound-B-PET scans. FC data were preprocessed using multivariate exploratory linear optimized decomposition into independent components of FMRIB's Software Library. Group comparisons were carried out using the "dual-regression" approach. In addition, to verify presence of gray matter volume changes with intrinsic functional network alterations, voxel-based morphometry was performed on the acquired T1-weighted data. As expected, AD dementia participants exhibited decreased FC in the DMN compared to CN (particularly in the precuneus and cingulate gyrus). The degree of alteration in the DMN in aMCI+ compared to CN was intermediate to that of AD. In contrast, aMCI- exhibited increased FC in the DMN compared to CN (primarily in the precuneus) as well as aMCI+. In terms of the SN, aMCI- exhibited decreased FC compared to both CN and aMCI+ particularly in the inferior frontal gyrus. FC within the SN in aMCI+ and AD did not differ from CN. Compared to CN, aMCI- showed atrophy in bilateral superior temporal gyri whereas aMCI+ showed atrophy in right precuneus. The results indicate that despite the similarity in cross-sectional cognitive features, aMCI- has quite different functional brain connectivity compared to aMCI+.

Keywords: amnestic mild cognitive impairment; amyloid-beta deposition; brain functional connectivity; default mode network; salience network.

Figure 1

(A) Illustration of the default mode network (DMN) regions derived from group independent component analysis (ICA). The DMN component identified by meta-ICA analysis included the posterior cingulate cortex, precuneus, medical prefrontal cortex, lateral parietal regions, lateral temporal regions, and bilateral medial temporal regions (p < 0.001). (B) Illustration of the salience network (SN) regions derived from group independent component analysis (ICA). The SN component identified by meta-ICA analysis included the anterior cingulate cortex, presupplementary motor area, and anterior insula (p < 0.001).

Figure 2

Brain regions displaying significant differences (in red) in the default mode network (DMN) between the groups using voxel-wise comparisons (p < 0.005, uncorrected for multiple comparisons) masked by the overall average DMN in yellow (p < 0.001, uncorrected). Results are superimposed on the MNI-152 T1 1-mm brain template.

Figure 3

Brain regions displaying significant differences (in red) in the salience network (SN) between the groups using voxel-wise comparisons (p < 0.005, uncorrected for multiple comparisons) marked by the overall average SN in yellow (p < 0.001, uncorrected). Results are superimposed on the MNI-152 T1 1-mm brain template.

Figure 4

Statistical parametric maps showing the results of analysis of covariance of VBM at p < 0.005 (uncorrected). Brain regions displaying significant differences in brain volume are shown in red between (A) CN and aMCI−, and between (B) CN and aMCI+. Results are superimposed using the cortex_20484.surf template in SPM8. The peak voxels of clusters meeting the p < 0.001 (uncorrected) cluster-wise criterion for the contrasts are listed in Table 4.