Negative affective burden is associated with higher resting-state functional connectivity in subjective cognitive decline

Abstract

Subjective cognitive decline (SCD), as expressed by older adults, is associated with negative affect, which, in turn, is a likely risk factor for Alzheimer's Disease (AD). This study assessed the associations between negative affective burden, cognitive functioning, and functional connectivity in networks vulnerable to AD in the context of SCD. Older participants (60-90 years) with SCD (n = 51) and healthy controls (n = 50) were investigated in a cross-sectional study. Subclinical negative affective burden, quantified through a composite of self-reported negative affective factors, was related to cognitive functioning (self-perceived and objective) and functional connectivity. Seed-to-voxel analyses were carried out in default mode network (DMN) and salience network (SAL) nodes using resting-state functional magnetic resonance imaging. Greater negative affective burden was associated with lower self-perceived cognitive functioning and lower between-network functional connectivity of DMN and SAL nodes in the total sample. In addition, there was a significant moderation of SCD status. Greater negative affective burden related to higher functional connectivity within DMN (posterior cingulate-to-precuneus) and within SAL (anterior cingulate-to-insula) nodes in the SCD group, whereas in controls the inverse association was found. We show that negative affective burden is associated with functional brain alterations in older adults, regardless of SCD status. Specifically in the SCD phenotype, greater negative affective burden relates to higher functional connectivity within brain networks vulnerable to AD. Our findings imply that negative affective burden should be considered a potentially modifiable target for early intervention.

Figure 1

Effect of negative affective burden on functional connectivity. (a,b) Main effects of the negative affective burden composite on functional connectivity. For the Default Mode Network (a, PCC seed), greater negative affective burden was associated with higher coupling between the PCC and the left middle frontal gyrus (MFG). For the Salience Network (b, ACC seed), greater negative affective burden was associated with lower functional connectivity between the ACC and the precuneus (PCUN). (c,d) Interactions between the negative affective burden composite and subjective cognitive decline (SCD) group status on functional connectivity. Greater negative affective burden was associated with higher regional functional connectivity in the SCD group and with lower regional functional connectivity in the healthy control (HC) group. For the Default Mode Network (c, PCC seed), brain regions included the cingulate gyrus/PCUN and for the Salience Network (d, ACC seed) the left central opercular/insular cortex (COIN). (a–d) Maps were displayed with a voxel-level threshold of p < 0.005 and a cluster-level threshold of p < 0.05 FDR-corrected. Individual relationships were illustrated using scatterplots with fitted regression, shaded areas indicate 95% confidence intervals and dots represent individual functional connectivity values extracted from significant clusters of the voxel-wise regression analyses. Standardized beta values (β) are presented for main (a,b) and interaction effects (c,d). ACC anterior cingulate cortex, FC functional connectivity, FDR false discovery rate, HC healthy controls, PCC posterior cingulate cortex, SCD subjective cognitive decline.