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.
Highlights
Mild cognitive impairment (MCI), which is divided into amnestic mild cognitive impairment and non-amnestic mild cognitive impairment, is regarded as the intermediate stage between healthy aging and dementia
In the groups consisting of subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), the analysis showed that the altered functional connectivity (FC) between the ventromedial prefrontal cortex (vmPFC) and the left inferior parietal lobule (IPL) in the anterior DMN (aDMN) is negatively correlated with episodic memory (r = −0.5002, p = 0.0019), while the altered FC between the vmPFC and the left middle temporal gyrus (MTG) is positively correlated with episodic memory (r = 0.6419, p = < 0.0001)
The present study indicates that the SCD group showed increased FC in the aDMN and decreased FC in the posterior DMN (pDMN), while the non-amnestic mild cognitive impairment (naMCI) and aMCI groups showed increased FC both in the aDMN and the pDMN
Summary
Mild cognitive impairment (MCI), which is divided into amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI; Grundman et al, 2004; Kim et al, 2015; Makovac et al, 2018), is regarded as the intermediate stage between healthy aging and dementia. Converging evidence suggests that the development of AD may partly progress through a continuum from SCD to MCI and eventually to AD (Berger-Sieczkowski et al, 2019). This could mean that SCD, naMCI, and aMCI can be considered as a spectrum of preclinical AD, which may have a different topography of pathological involvement during different disease stages. 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). This study investigated the connectivity patterns of anterior DMN (aDMN) and posterior DMN (pDMN) across the preclinical AD spectrum
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