Abstract

The subjective cognitive decline (SCD) may last for decades prior to the onset of dementia and has been proposed as a risk population for development to amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Disruptions of functional connectivity and causal connectivity (CC) in the salience network (SN) are generally perceived as prominent hallmarks of the preclinical AD. Nevertheless, the alterations in anterior SN (aSN), and posterior SN (pSN) remain unclear. Here, we hypothesized that both the functional connectivity (FC) and CC of the SN subnetworks, comprising aSN and pSN, were distinct disruptive in the SCD and aMCI. We utilized resting-state functional magnetic resonance imaging to investigate the altered FC and CC of the SN subnetworks in 28 healthy controls, 23 SCD subjects, and 29 aMCI subjects. In terms of altered patterns of FC in SN subnetworks, aSN connected to the whole brain was significantly increased in the left orbital superior frontal gyrus, left insula lobule, right caudate lobule, and left rolandic operculum gyrus (ROG), whereas decreased FC was found in the left cerebellum superior lobule and left middle temporal gyrus when compared with the HC group. Notably, no prominent statistical differences were obtained in pSN. For altered patterns of CC in SN subnetworks, compared to the HC group, the aberrant connections in aMCI group were separately involved in the right cerebellum inferior lobule (CIL), right supplementary motor area (SMA), and left ROG, whereas the SCD group exhibited more regions of aberrant connection, comprising the right superior parietal lobule, right CIL, left inferior parietal lobule, left post-central gyrus (PG), and right angular gyrus. Especially, SCD group showed increased CC in the right CIL and left PG, whereas the aMCI group showed decreased CC in the left pre-cuneus, corpus callosum, and right SMA when compared to the SCD group. Collectively, our results suggest that analyzing the altered FC and CC observed in SN subnetworks, served as impressible neuroimaging biomarkers, may supply novel insights for designing preclinical interventions in the preclinical stages of AD.

Highlights

  • Alzheimer disease (AD) is a chronic neurodegenerative disorder presented in elderly individuals with conspicuous decline in cognitive deterioration and lapse of memory (Huang et al, 2019; Wessels et al, 2019; Zhang et al, 2019)

  • One-way analysis of variance (ANOVA) presented the significant differences on age (F = 8.248, p = 0.016), Mini-Mental State Examination (MMSE) score (F = 9.129, p < 0.01), and CDR score (F = 68.98, p < 0.01)

  • The region where the subjective cognitive decline (SCD) group patients showed decreased functional connectivity (FC) in the left middle temporal gyrus (MTG) in SCD compared to the healthy controls (HCs) group was similar to that in the amnestic mild cognitive impairment (aMCI) group compared to the SCD group, yet only the former FC was reduced, and the latter FC was increased

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Summary

Introduction

Alzheimer disease (AD) is a chronic neurodegenerative disorder presented in elderly individuals with conspicuous decline in cognitive deterioration and lapse of memory (Huang et al, 2019; Wessels et al, 2019; Zhang et al, 2019). The SN, which is typically involved in detecting stimulus salience, is a large-scale brain network within the human brain (Cai et al, 2019). It can be spilt into anterior SN (aSN) and posterior SN (pSN) and is primarily anchored in frontoinsular cortices and dorsal anterior cingulate cortex (dACC) (Menon and Uddin, 2010). For the aMCI subjects, the FC of the SN-centered model [includes SN, DMN, executive control network (ECN)] is impaired compared to the patients with AD, and these alterations in SN-centered model may result in a decline in cognitive disorder (Aguirre et al, 2019).

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