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

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.

Altered Patterns of Phase Position Connectivity in Default Mode Subnetwork of Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment

“…Hence, the altered regions we found might involve in language cognitive disorder, and pDMN first appears abnormal connections compared to aDMN, which might suggest that the aDMN and pDMN have different manifestations in the early stages of AD. We found that both aMCI and SCD groups showed a prominent region in SFG that is connected to DMN subnetworks, and according to the previous research that the altered functional connectivity between the pDMN and the SFG might be a compensatory response of brain (Xue et al, 2019). We assume that the aberrant PPC in SFG connected to the DMN may also be caused by the brain's compensation.…”

“…Interestingly, compared to patients with SCD, DMN subnetworks in aMCI group showed obvious differences in right SFGMP and left MFGOP belonging to FG. In previous studies, aMCI group showed more widespread topological changes involving the frontal lobes (Barban et al, 2017), and aberrant connectivity was also found in patients with SCD between DMN and FG due to cognitive impairment (Xue et al, 2019). Besides, an increasing trend of values of amplitude of low-frequency fluctuation (ALFF) and fractional ALFF were detected in FG (Yang et al, 2018).…”

“…Besides, according to the recent report, there have identified that the non-parametric permutation test with Threshold-Free Cluster Enhancement (TFCE) can effectively achieve a good balance between family wise error (FWE) rate and reliability (Chen et al, 2018). Therefore, permutation test associated with TFCE, all integrated into PLAM module of DPABI, were employed as the method of multiple comparisons of this work, and we set cluster size >10 voxels (270 mm 3 , p < 0.05) as a prominent cluster (Xue et al, 2019).…”

“…Moreover, the seed-based method was conducted to analyze the altered PPC of DMN subnetworks. To identify the seed regions about aDMN and pDMN, 10-mm spherical regions of interest in aDMN (MNI space: 0, 52, −6) and pDMN (MNI space: 0, −53, 26) were adopted in our work (Zhang and Raichle, 2010;Xue et al, 2019). Collectively, we applied phase position synchronization generated by HT to investigate the altered connectivity between the DMN subnetworks and the whole brain, and aim to explore the relationship between the aberrant regions and cognitive function.…”

Altered Patterns of Functional Connectivity and Causal Connectivity in Salience Subnetwork of Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment

“…Previous study has identified that the non-parametric permutation test with Threshold-Free Cluster Enhancement (TFCE) can strike a good and strict balance between familywise error rate and reliability . Consequently, permutation tests with TFCE, implemented in PLAM within DPABI, were utilized to perform multiple comparisons in this work, and then a cluster size > 10 voxels (270 mm 3 ) was adopted as the significant cluster, and the significance level was set at 0.05 (Xue C. et al, 2019).…”