Default Mode, Executive Function, and Language Functional Connectivity Networks are Compromised in Mild Alzheimer´s Disease

Abstract

Alzheimer's disease (AD) is characterized by mental and cognitive problems, particularly with memory, language, visuospatial skills (VS), and executive functions (EF). Advances in the neuroimaging of AD have highlighted dysfunctions in functional connectivity networks (FCNs), especially in the memory related default mode network (DMN). However, little is known about the integrity and clinical significance of FNCs that process other cognitive functions than memory. We evaluated 22 patients with mild AD and 26 healthy controls through a resting state functional MRI scan. We aimed to identify different FCNs: the DMN, language, EF, and VS. Seed-based functional connectivity was calculated by placing a seed in the DMN (posterior cingulate cortex), language (Broca's and Wernicke's areas), EF (right and left dorsolateral prefrontal cortex), and VS networks (right and left associative visual cortex). We also performed regression analyses between individual connectivity maps for the different FCNs and the scores on cognitive tests. We found areas with significant decreases in functional connectivity in patients with mild AD in the DMN and Wernicke's area compared with controls. Increased connectivity in patients was observed in the EF network. Regarding multiple linear regression analyses, a significant correlation was only observed between the connectivity of the DMN and episodic memory (delayed recall) scores. In conclusion, functional connectivity alterations in mild AD are not restricted to the DMN. Other FCNs related to language and EF may be altered. However, we only found significant correlations between cognition and functional connectivity in the DMN and episodic memory performance.

IC‐P‐034: Mediation of Episodic Memory Performance by The Executive Function Network in Patients with Amnestic Mild Cognitive Impairment: A Resting‐State Functional MRI Study

“…Converging evidence from our research group and others indicates that ReHo is altered in the RSC in the EM network [3,19,41,56] and in the DLPFC in the EF network [4,6,37,57] in aMCI patients. Therefore, it was reasonable for the present study to utilize a new approach to analyze FC that employed the ReHo results as the seed ROIs.…”

“…Findings from our research group and other studies suggest that brain regions with altered ReHo in patients with aMCI are located in structures associated with the EM [3,19,41,56] and EF [4,6,37,57] networks and include regions such as the hippocampus, PCC/precuneus (PCu), right inferior parietal lobule (IPL), DLPFC, and ventromedial prefrontal cortex (VMPFC) [58][59][60][61]. Therefore, the present study computed ReHo values to identify regions with abnormal local connectivity in a group of aMCI patients relative to healthy controls (HC).…”

“…It is also well established that the prefrontal and parietal regions are crucial aspects of the EF system [37][38][39][40][41]. Using probabilistic independent component analyses or seed-based correlation analyses, several fMRI studies have demonstrated that the fronto-parietal EF network includes the dorsolateral PFC (DLPFC), anterior cingulate cortex (ACC), supplementary motor area (SMA), and orbitofrontal cortex (OFC) [42,43].…”

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels

“…Fewer studies, however, have investigated the functional abnormalities of task-positive RSNs. Results showing, for example, disrupted connectivity in the salience (SAL), 1 executive control (ECN) 2 and language networks (LN), 3 among others, show us that the deleterious effects of Alzheimer disease extend well beyond the regions included in the DMN.…”

Differences and the Relationship in Default Mode Network Intrinsic Activity and Functional Connectivity in Mild Alzheimer's Disease and Amnestic Mild Cognitive Impairment

“…Many studies have shown that functional connectivity in the default mode network (DMN) is impaired in AD patients (Agosta et al, 2012;Greicius et al, 2004;Xia et al, 2014), probably contributing to cognitive and clinical symptoms (Balthazar et al, 2014;Weiler et al, 2014). The function of DMN is not completely understood, but is generally considered a distributed system for self-related cognitive activity that is activated when a person is not focused on activities directed to the external environment (Buckner et al, 2008;Menon, 2011).…”