Altered functional connectivity strength in informant-reported subjective cognitive decline: A resting-state functional magnetic resonance imaging study

Abstract

Introduction: Informant-reported subjective cognitive decline (iSCD) has been associated with a higher risk of conversion to dementia, but the findings of whole brain functional connectivity strength (FCS) changes in iSCD are limited.

Methods: The sample comprised 39 participants with iSCD and 39 age- and sex- matched healthy controls. The global absolute (aFCS) and relative functional connectivity strengths were estimated using weighted degree centrality and the z-scores of the weighted degree centrality respectively. FreeSurfer was used for measuring cortical thickness.

Results: The aFCS was lower in iSCD primarily in left medial superior frontal, left precuneus, left parietal, right cuneus, and bilateral calcarine; while relative functional connectivity strength was higher in posterior cingulate cortex/precuneus compared with healthy controls. No significant differences in cortical thickness were observed.

Discussion: There are detectable changes of FCS in iSCD, with the precuneus possibly playing a compensatory role. FCS could therefore have a potential role to serve as one of the earliest neuroimaging markers of neurodegenerative disease.

Keywords: Aging; Functional connectivity strength; Preclinical Alzheimer's disease; Precuneus; Subjective cognitive decline.

Fig. 1

Spatial FCS patterns of iSCD and healthy controls. Prominent hubs were indicated by colors in iSCD (left) and healthy controls (right) (two-tailed Gaussian random field (GRF) correction voxel level: P < .005; cluster level: P < .05). The color bars indicate T-statistic. Abbreviations: iSCD, informant-reported subjective cognitive decline; HC, healthy controls; FCS, functional connectivity strength.

Fig. 2

The aFCS difference maps between iSCD and healthy controls. Participants with iSCD showed significantly decreased aFCS compared with the healthy controls (10,000 random permutations, cluster-defining threshold: P ≤ .01, FWE-corrected: P ≤ .05). No significantly increased aFCS was found in iSCD. The color bars indicate T-statistic, and regions with blue colors indicate lower values in iSCD. Abbreviations: iSCD, informant-reported subjective cognitive decline; aFCS, absolute functional connectivity strength.

Fig. 3

The rFCS difference maps between iSCD and healthy controls. (A) Box plot for the group comparison in mean rFCS. Box plot shows that the mean rFCS values in iSCD are significantly higher than that of in healthy controls. (B) Sagittal view of the rFCS differences between groups. The rFCS values in iSCD were higher than healthy controls in precuneus/posterior cingulate cortex (10,000 random permutations for two-sample t test, cluster-defining threshold: P ≤ .01, FWE-corrected: P ≤ .05). The hot colors indicate the higher T values in iSCD. Abbreviations: iSCD, informant-reported subjective cognitive decline; rFCS, relative functional connectivity strength.

Fig. 4

The intergroup FCS differences without/with GM volume as covariates. (A) The aFCS analysis. The left and the right are the aFCS differences without or with GM volume as covariates respectively. Both of the analysis had same significantly altered regions located in left precuneus (BA5/7), left occipital (BA19), left cuneus (BA18/19) and left calcarine (BA17/19) (two-tailed GRF correction, voxel level: P < .005; cluster level: P < .05). (B)The rFCS analysis. The left and the right are the rFCS differences without or with GM volume as covariates respectively. Similarly, both of the analysis had same significantly altered regions located in precuneus/PCC (BA7/31) (two-tailed GRF correction, voxel level: P < .005; cluster level: P < .05). The color bars indicate T-statistic. Abbreviations: iSCD, informant-reported subjective cognitive decline; aFCS, absolute functional connectivity strength; rFCS, relative functional connectivity strength; GM, gray matter.