Brain Topological Changes in Subjective Cognitive Decline and Associations with Amyloid Stages

Abstract

This study examined how amyloid burden affects structural and functional brain network topology in subjective cognitive decline (SCD), a risk condition for Alzheimer's disease (AD). Functional and structural brain networks were analyzed in 100 individuals with SCD and 86 normal controls (NC; both sexes included) using resting-state functional MRI and diffusion tensor imaging. Topological properties of brain networks were evaluated as indicators of information exchange efficiency and network robustness. Amyloid burden in 55 SCD participants was measured using amyloid PET imaging and a frequency-based staging method, which defined global and regional amyloid burden for four anatomical stages. Compared with NC, individuals with SCD exhibited increased functional nodal efficiency and structural nodal betweenness in the left anterior and median cingulate gyri, with no differences in network-level properties. Amyloid staging revealed four cortical divisions: Stage 1, fusiform and lateral temporal gyri; Stage 2, occipital areas; Stage 3, default mode network (DMN), midline brain, and lateral frontotemporal areas; and Stage 4, the remaining cortex. The global and regional amyloid burdens of each cortical stage were positively associated with the node-level properties of a set of DMN hubs, with the left anterior and posterior cingulate gyri being congruently associated with all amyloid stages. These findings suggest that amyloid burden continuously influences network adaptations through DMN hubs, irrespective of local proximity to pathology. Increased nodal properties in cortical hubs may reflect heightened information-processing demands during early amyloid deposition in this population at risk for AD.

Keywords: DTI; amyloid PET; amyloid staging; graph theory; resting fMRI; subjective cognitive decline.

Figure 1.

Topological differences and correlations in SCD. A, Altered node-level topological properties in SCD versus NC; left, increased fNE; right, altered sNB; regions showing significant effects were mapped onto the brain surface with the BrainNet Viewer (Xia et al., 2015); see Extended Data Table S1 for abbreviations. B, Bar plots for node-level topological property changes in the left anterior cingulate gyrus (ACG.L) and the left median cingulate gyrus (DCG.L); C, Positive correlations between SCD characteristics and the sNB in ACG.L. *p < 0.05, FDR-corrected.

Figure 2.

Staging of amyloid deposition and network hub involvement in SCD. A, Results of the frequency-based amyloid staging. Frequency of ROI-level amyloid positivity across SCD participants on a color scale from magenta (highest) to yellow (lowest). The 39 ROI pairs are merged into four larger anatomical divisions. B, Bar plots showed the ROI-level amyloid positivity frequency. The color scale showed the frequency ranges: yellow (division 4, <10%), green (division 3, 10–30%), blue (division 2, 30–50%), and magenta (division 1, >50%). The circles and the rhombuses above the frequency bars indicate the hub regions within the structural or functional network, respectively. The solid circles and rhombuses represent the bilateral hubs, while the half-solid circles and rhombuses represent the unilateral hubs. See Extended Data Table S1 for abbreviations.

Figure 3.

Correlational analysis of amyloid burden and nodal topology in SCD. Pearson's correlations between global and regional amyloid load (global SUVr and regional SUVr values of Anatomical Divisions 1–4) and node-level topological properties. A, fNE; B, C, sNB. *p < 0.05, FDR-corrected. L, left; R, right; PCG, posterior cingulate gyrus; ACG, anterior cingulate gyrus; PoCG, postcentral gyrus.