Distinct Disruptive Patterns of Default Mode Subnetwork Connectivity Across the Spectrum of Preclinical Alzheimer's Disease

Chen Xue; Baoyu Yuan; Yingying Yue; Jiani Xu; Siyu Wang; Meilin Wu; Nanxi Ji; Xingzhi Zhou; Yilin Zhao; Jiang Rao; Wenjie Yang; Chaoyong Xiao; Jiu Chen

doi:10.3389/fnagi.2019.00307

Distinct Disruptive Patterns of Default Mode Subnetwork Connectivity Across the Spectrum of Preclinical Alzheimer's Disease

Front Aging Neurosci. 2019 Nov 13:11:307. doi: 10.3389/fnagi.2019.00307. eCollection 2019.

Authors

Chen Xue^{1

2}, Baoyu Yuan³, Yingying Yue⁴, Jiani Xu², Siyu Wang², Meilin Wu², Nanxi Ji², Xingzhi Zhou², Yilin Zhao², Jiang Rao^{5

6}, Wenjie Yang^{5

6}, Chaoyong Xiao^{1

6}, Jiu Chen^{2

6}

Affiliations

¹ Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
² Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, China.
³ Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
⁴ Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
⁵ Department of Rehabilitation, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
⁶ Institute of Brain Functional Imaging, Nanjing Medical University, Nanjing, China.

Abstract

Background: The early progression continuum of Alzheimer's disease (AD) has been considered to advance through subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI). Altered functional connectivity (FC) in the default mode network (DMN) is regarded as a hallmark of AD. Furthermore, the DMN can be divided into two subnetworks, the anterior and posterior subnetworks. However, little is known about distinct disruptive patterns in the subsystems of the DMN across the preclinical AD spectrum. This study investigated the connectivity patterns of anterior DMN (aDMN) and posterior DMN (pDMN) across the preclinical AD spectrum. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in the DMN subnetworks in 20 healthy controls (HC), eight SCD, 11 naMCI, and 28 aMCI patients. Moreover, a correlation analysis was used to examine associations between the altered connectivity of the DMN subnetworks and the neurocognitive performance. Results: Compared to the HC, SCD patients showed increased FC in the bilateral superior frontal gyrus (SFG), naMCI patients showed increased FC in the left inferior parietal lobule (IPL), and aMCI patients showed increased FC in the bilateral IPL in the aDMN; while SCD patients showed decreased FC in the precuneus, naMCI patients showed increased FC in the left middle temporal gyrus (MTG), and aMCI patients also showed increased FC in the right middle frontal gyrus (MFG) in the pDMN. Notably, the FC between the ventromedial prefrontal cortex (vmPFC) and the left MFG and the IPL in the aDMN was associated with episodic memory in the SCD and aMCI groups. Interestingly, the FC between the posterior cingulated cortex (PCC) and several regions in the pDMN was associated with other cognitive functions in the SCD and naMCI groups. Conclusions: This study demonstrates that the three preclinical stages of AD exhibit distinct FC alternations in the DMN subnetworks. Furthermore, the patient group data showed that the altered FC involves cognitive function. These findings can provide novel insights for tailored clinical intervention across the preclinical AD spectrum.

Keywords: amnestic mild cognitive impairment; default mode network; functional connectivity; non-amnestic mild cognitive impairment; subjective cognitive decline.