Alterations in Dynamic Functional Connectivity in Individuals With Subjective Cognitive Decline.

Qian Chen,Jiaming Lu,Wen Zhang,Wenqian Chen,Xin Li,Bing Zhang,Yi Sun,Xin Zhang,Zhao Qing

doi:10.3389/fnagi.2021.646017

Abstract

Purpose: To investigate the dynamic functional connectivity (DFC) and static parameters of graph theory in individuals with subjective cognitive decline (SCD) and the associations of DFC and topological properties with cognitive performance.Methods: Thirty-three control subjects and 32 SCD individuals were enrolled in this study, and neuropsychological evaluations and resting-state functional magnetic resonance imaging scanning were performed. Thirty-three components were selected by group independent component analysis to construct 7 functional networks. Based on the sliding window approach and k-means clustering, distinct DFC states were identified. We calculated the temporal properties of fractional windows in each state, the mean dwell time in each state, and the number of transitions between each pair of DFC states. The global and local static parameters were assessed by graph theory analysis. The differences in DFC and topological metrics, and the associations of the altered neuroimaging measures with cognitive performance were assessed.Results: The whole cohort demonstrated 4 distinct connectivity states. Compared to the control group, the SCD group showed increased fractional windows and an increased mean dwell time in state 4, characterized by hypoconnectivity both within and between networks. The SCD group also showed decreased fractional windows and a decreased mean dwell time in state 2, dominated by hyperconnectivity within and between the auditory, visual and somatomotor networks. The number of transitions between state 1 and state 2, between state 2 and state 3, and between state 2 and state 4 was significantly reduced in the SCD group compared to the control group. No significant differences in global or local topological metrics were observed. The altered DFC properties showed significant correlations with cognitive performance.Conclusion: Our findings indicated DFC network reconfiguration in the SCD stage, which may underlie the early cognitive decline in SCD subjects and serve as sensitive neuroimaging biomarkers for the preclinical detection of individuals with incipient Alzheimer's disease.

Highlights

Individuals with subjective cognitive decline (SCD), a selfperceived worsening of cognitive function without objectively detected deficits, have been considered at higher risk of developing Alzheimer’s disease (AD) dementia in the future compared to those without cognitive complaints (Reisberg et al, 2010; Jessen et al, 2014)
No significant differences in terms of age, gender, or years of education were found between the SCD and normal controls (NCs) groups
Increased switches between distinct dynamic functional connectivity (FC) states may contribute to better language ability. These findings provide evidence that altered dynamic functional brain organization is linked to cognitive function, which may further serve as the neural substrates underlying cognitive decline in the SCD stage

Summary

Introduction

Individuals with subjective cognitive decline (SCD), a selfperceived worsening of cognitive function without objectively detected deficits, have been considered at higher risk of developing Alzheimer’s disease (AD) dementia in the future compared to those without cognitive complaints (Reisberg et al, 2010; Jessen et al, 2014). Cognitive impairment could be partly attributable to altered functional coupling in brain-wide networks, and previous studies have reported aberrant FC and disrupted brain networks in AD dementia and MCI patients (Delli Pizzi et al, 2019; Franzmeier et al, 2019). Altered FC could be the neural basis underlying early cognitive decline and serve as an objective imaging marker to identify preclinically at-risk AD patients

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