Aberrant intra- and inter-network connectivity architectures in Alzheimer’s disease and mild cognitive impairment

Abstract

Alzheimer’s disease (AD) patients and those with high-risk mild cognitive impairment are increasingly considered to have dysfunction syndromes. Large-scale network studies based on neuroimaging techniques may provide additional insight into AD pathophysiology. The aim of the present study is to evaluate the impaired network functional connectivity with the disease progression. For this purpose, we explored altered functional connectivities based on previously well-defined brain areas that comprise the five key functional systems [the default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL), sensorimotor network (SMN)] in 35 with AD and 27 with mild cognitive impairment (MCI) subjects, compared with 27 normal cognitive subjects. Based on three levels of analysis, we found that intra- and inter-network connectivity were impaired in AD. Importantly, the interaction between the sensorimotor and attention functions was first attacked at the MCI stage and then extended to the key functional systems in the AD individuals. Lower cognitive ability (lower MMSE scores) was significantly associated with greater reductions in intra- and inter-network connectivity across all patient groups. These profiles indicate that aberrant intra- and inter-network dysfunctions might be potential biomarkers or predictors of AD progression and provide new insight into AD pathophysiology.

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

“…Our work in turn, suggests that this connectivity is damaged in patients with Alzheimer disease, aligning with the findings of previous research reporting loss of correlation between the SAL and ECN in patients with Alzheimer disease 5 and even in those with aMCI. 1 Although the present study did not find statistically significant results for the aMCI group, functional connectivity disruptions within 7 and between 1,7 networks in these patients have been reported previously in the literature. Our lack of significant results for patients with aMCI could be due to the heterogeneity of the sample (early v. late aMCI), different cognitive reserve levels, which is known to influence the functional connectivity of networks, 24 or our different methodological approach.…”

“…Even individuals at risk for Alzheimer disease (i.e., those with amnestic mild cognitive impairment [aMCI]) have been shown to have disruptions between the SAL and both the ECN and DMN 1 as well as between the dorsal attention (DAN) and sensorimotor networks. 7 Moreover, intercorrelations between the DMN and DAN, between the DMN and sensorimotor network and between the ECN and sensorimotor network have been reported to be reduced with increasing Alzheimer disease severity. 8 The spatial distribution of the DMN has a striking overlap with the burden of amyloid β (Aβ )-pathology in patients with Alzheimer disease, 9 which has been suggested to be a possible explanation for the connectivity disruption involving this network.…”

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

“…Tested as a whole, patients exhibit lower DMN connectivity than controls, see (Wang et al., 2015; Lee et al., 2016) and their references. The “canonical” pattern of the DMN is the precuneus, superior lateral parietal lobes, and the ACC.…”

“…Analyses of AD‐related functional brain network differences associated with the DMN but not part of the DMN report changes in superior parietal and occipital regions (Agosta et al., 2012; Lee et al., 2016). These findings are consistent with those in resting and visual fMRI studies that report affected visual functioning accompanied by differences in the visual cortices (Alegret et al., 2010; Lehmann et al., 2013; Wang et al., 2015; Zhang et al., 2010) and the idea that deviations from the typical pathology, such as the involvement of functionally specific brain regions, drive the variation in neurodegenerative variation in AD.…”

Resting-State Functional Connectivity Changes Associated with Visuospatial Cognitive Deficits in Patients with Mild Alzheimer Disease

“…Hypoconnectivity within DMN is possibly due to early amyloid deposition in regions with high metabolism (posterior cingulate-precuneus complex within the DMN) [13,14]. Reduced rsFC within DMN is observed in patients with presymptomatic AD (mild cognitive impairment) and cognitively normal elders with amyloid deposition [15,16,17,18]. As rsFC of DMN is correlated with cognitive functions, DMN hypoconnectivity may reflect the core pathophysiology underlying verbal memory deficits in AD [15,16,18], while hyperconnectivity within the EN is attributed to compensatory mechanisms secondary to primary hypoconnectivity [13,14].…”