Abstract

Deficits in episodic memory (EM) are a hallmark clinical symptom of patients with amnestic mild cognitive impairment (aMCI). Impairments in executive function (EF) are widely considered to exacerbate memory deficits and to increase the risk of conversion from aMCI to Alzheimer's disease (AD). However, the specific mechanisms underlying the interaction between executive dysfunction and memory deficits in aMCI patients remain unclear. Thus, the present study utilized resting-state functional magnetic resonance imaging (fMRI) scans of the EF network and the EM network to investigate this relationship in 79 aMCI patients and 119 healthy controls (HC). The seeds were obtained from the results of a regional homogeneity (ReHo) analysis. Functional connectivity (FC) within the EM network was determined using a seed in the right retrosplenial cortex (RSC), and FC within EF network was assessed using seeds in the right dorsolateral prefrontal cortex (DLPFC). There was a significant negative correlation between EM scores and EF scores in both the aMCI and HC groups. Compared to the HC group, aMCI patients had reduced right RSC connectivity but enhanced right DLPFC connectivity. The overlapping brain regions between the EM and EF networks were associated with FC in the right inferior parietal lobule (IPL) in the right RSC network, and in the bilateral middle cingulate cortex (MCC) and left IPL in the right DLPFC network. A mediation analysis revealed that the EF network had an indirect positive effect on EM performance in the aMCI patients. The present findings provide new insights into the neural mechanisms underlying the interaction between impaired EF and memory deficits in aMCI patients and suggest that the EF network may mediate EM performance in this population.

Highlights

  • It has been proposed that amnesic mild cognitive impairment is a condition of intermediate symptomatology that represents the cognitive changes between normal aging and very early dementia in populations at high risk of Alzheimer’s disease (AD) [1]

  • In the dorsolateral prefrontal cortex (DLPFC) network, the amnesic mild cognitive impairment (aMCI) group showed increased Functional connectivity (FC) in the left anterior central gyrus (ACG), left supplementary motor area (SMA), bilateral middle cingulate cortex (MCC), and caudate nucleus compared to the healthy controls (HC) group

  • The mediation analyses revealed that the connectivity between the right DLPFC and bilateral MCC mediated the association between executive function (EF) and episodic memory (EM) in patients with aMCI. These findings indicate that the effects of EF on EM performance in aMCI patients may be explained by two mechanisms: the direct effect of EF on EM or www.impactjournals.com/oncotarget an indirect pathway mediated via the effects of EF on the DLPFC network

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Summary

Introduction

It has been proposed that amnesic mild cognitive impairment (aMCI) is a condition of intermediate symptomatology that represents the cognitive changes between normal aging and very early dementia in populations at high risk of Alzheimer’s disease (AD) [1]. It is well known that deficits in episodic memory (EM) are a hallmark clinical symptom of aMCI [2, 3], and it has been consistently demonstrated that the simultaneous existence of impaired executive function (EF) may be present in these patients [4,5,6,7]. Memory function is facilitated by the medial temporal lobe (MTL) system but is supported by a distributed network, www.impactjournals.com/oncotarget in the DMN [19]. Structural and functional imaging studies have consistently established that the retrosplenial cortex (RSC) and the posterior cingulate cortex (PCC) are the main hubs connecting with the MTL and that the prefrontal cortex (PFC) plays a central role in processing EM [20,21,22]

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