Regional amyloid burden and intrinsic connectivity networks in cognitively normal elderly subjects

Abstract

Although previous studies demonstrated decreased functional connectivity in the default mode network in the cognitively normal older adults with amyloid burden, effects of amyloid burden in the other large-scale intrinsic connectivity networks are not yet clear. The aim of this study was to investigate the distinctive association pattern of amyloid-β deposition on the three large-scale intrinsic connectivity networks (the default mode network, salience network and central executive network) in older adults with normal cognition. Fifty-six older adults with normal cognition underwent functional magnetic resonance imaging and were dichotomized using 11C-labelled Pittsburgh compound B positron emission tomography imaging into subjects with (PiB+; n=27) and without (PiB-; n=29) detectable amyloid burden. We found that the functional connectivities of (i) the default mode network were greater; (ii) the salience network were not different; and (iii) the central executive network were lower in the Pittsburgh compound B positive group, compared with the Pittsburgh compound B negative group. Anterior cingulate cortex Pittsburgh compound B retention was negatively correlated with the functional connectivities of the posterior default mode network, and positively correlated with fronto-parietal functional connectivity (within the central executive network) in the Pittsburgh compound B positive group. The anti-correlation strength between the default mode network and the central executive network was negatively correlated with the anterior cingulate cortex Pittsburgh compound B levels. Additionally, significant group × episodic memory interactions with functional connectivities in the posterior default mode network, and the frontal default mode network were observed. Our results of aberrant default mode network functional connectivity and distinctive correlation patterns between the Pittsburgh compound B retention in the anterior cingulate cortex and functional connectivities in the default mode network and central executive network in the Pittsburgh compound B positive group might reflect a detrimental effect of amyloid retention on functional changes in the course of Alzheimer's disease progression.

Keywords: amyloid imaging; functional MRI; large scale intrinsic networks; normal older adults.

Figure 1

PiB retention among the cognitively normal subjects without amyloid burden (PiB−) and with amyloid burden (PiB+). Group comparison results between the PiB+ and PiB− groups using (A) region of interest (P < 0.05, Holm-Bonferroni corrected for multiple comparisons) and (B) voxel-wise (P < 0.05, FDR corrected for multiple comparisons) analyses. The standardized uptake value ratio levels in the PiB+ were significantly increased compared with the PiB− group. SUVR = standardized uptake value ratio; ACC = anterior cingulate cortex; FRC = frontal cortex; LTC = lateral temporal cortex; MTC = medial temporal cortex; PAR = parietal cortex; PRC = precuneus cortex. *Significant P < 0.05, Bonferroni corrected for multiple comparisons.

Figure 2

Spatial maps of the resting state ICN of interest identified by independent component analysis of all subjects. (A) The DMN; (B) the SN; and (C) the CEN.

Figure 3

Statistical maps of voxel-wise analysis results of independent component analysis. (A) Group differences between the PiB+ and PiB− group. (B) Correlation analysis between the PiB level and functional connectivity in the PiB+ group. (C) Left: Regional DMN functional connectivity showing significant interaction between the group and episodic memory performances. Right: Correlation analysis between episodic memory performances and functional connectivity in the PiB+ group. All P-values were FDR corrected for multiple comparisons (P < 0.05). FC = functional connectivity; EM = episodic memory.

Figure 4

(A) Group analysis results of the inter-ICN functional connectivity indicating no significant inter-ICN functional connectivity differences between the PiB+ and the PiB−groups. (B) Association between the inter-ICN functional connectivity and the anterior cingulate cortex standardized uptake value ratio in the PiB+ group indicating significant positive correlations between the anterior cingulate cortex standardized uptake value ratio and the DMN-CEN inter-ICN functional connectivity (r = 0.52, Holm-Bonferroni corrected P < 0.05) in the PiB+ group. (C) Single subject blood oxygen level-dependent time series for the DMN (blue) and the CEN (green). Note anti-correlations between the DMN and the CEN as evidenced by significant correlation coefficient (r = −0.41 Holm-Bonferroni corrected P < 0.05). FC = functional connectivity; ACC = anterior cingulate cortex; BOLD = blood oxygen level-dependent; NS = not significant; SUVR = standardized uptake value ratio.