Structural and Functional Disruption of Salience Network in Distinguishing Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment

Abstract

Salience network (SN), playing a vital role in advanced cognitive function, is regarded to be impaired in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI). The purpose of the study was to explore the importance of structural and functional features of SN in the diagnosis of SCD and aMCI. Structural and resting-state functional magnetic resonance imaging were collected from SCD, aMCI, and healthy control (HC). Cortex thickness, gray matter (GM) volume, spontaneous brain activity, functional connectivity (FC) within SN, and its relationship with cognitive function were analyzed. Moreover, the receiver operating characteristic analysis was performed to assess diagnostic efficacy of altered indictors for SCD and aMCI. Compared to HC, both SCD and aMCI showed decreased GM volume, decreased spontaneous brain activity, and increased FC within SN, while aMCI showed additional decreased cortex thickness. Furthermore, the altered FC in SCD and aMCI was significantly correlated with cognitive function. Particularly, the best-fitting classification models of SCD and aMCI were based on the combined multiple indicators. In conclusion, structure and function of SN were disrupted in SCD and aMCI, which involved in cognitive decline. The combined multiple indicators of SN provided powerful biomarkers for the diagnosis of SCD and aMCI.

Differential Abnormality in Functional Connectivity Density in Preclinical and Early-Stage Alzheimer's Disease

“…A mediation analysis revealed that indirect FCs between the hippocampus and other brain areas were mediated by the PHG (Ward et al, 2014 ), which may be one of the reasons for the different results of the two indicators. Existing rs-fMRI studies on patients with SCD have been more concerned with exploring the significance of general functional connectivity alterations (Liang et al, 2020 ; Xue et al, 2021 ), and this is the first report of specific alterations of the lrFCD in the hippocampus of patients with SCD. We hypothesized that this specific elevation was also a manifestation of functional compensation and could become a specific biomarker that distinguishes SCD from normal aging.…”

“…Among them, eight participants were excluded due to excessive head motion (cumulative translation or rotation of > 3.0 mm or 3.0°). According to previous studies (Wang et al, 2021 ; Xue et al, 2021 ), a total of 194 participants, including 59 aMCI, 57 SCD, and 78 HC, were eventually included after strict exclusion. Detailed information about inclusive and exclusive criteria is summarized in the Supplementary Material .…”

“…A comprehensive neuropsychological assessment covering general cognitive function and four cognitive domains, including episodic memory (EM), executive function (EF), visuospatial function (VF), and information processing speed (IPS), was conducted among the participants (Chen et al, 2020 ; Wang et al, 2021 ; Xue et al, 2021 ; Xu et al, 2021 ). All evaluations were performed by two experienced neuropsychologists (Dr. Chen and Song).…”

“…Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) have been recognized as the preclinical and prodromal stages of Alzheimer's disease (AD), respectively (Rabin and Smart, 2017 ; Hadjichrysanthou et al, 2020 ). SCD is used to describe the condition of elderly people who perceive their cognitive function to be impaired despite the absence of verifiable neuropsychological dysfunction, whereas aMCI refers to individuals who experience memory loss with or without a decline in other cognitive abilities (Xue et al, 2021 ). Accumulating evidence has suggested that both of them have a high probability of progressing to AD (Rabin and Smart, 2017 ; Hadjichrysanthou et al, 2020 ).…”

“…The gFCD of a voxel reflects functional coupling throughout the brain, whereas the lFCD presents local changes, and the lrFCD presents functional integration between voxels that are not adjacent to each other (Tomasi, 2010 ). Different metrics can describe different characteristics of a functional hub (Tomasi, 2010 ), and multiscale assessment can be more accurate in disease identification (Liu et al, 2018 ; Xue et al, 2021 ). Previous studies have shown dramatic changes in FCD in patients with neuropsychological diseases (Zhuo et al, 2014 ; Zhang et al, 2015 , 2016 ).…”