Abstract
PurposeAlzheimer’s disease (AD) and mild cognitive impairment (MCI) are characterized by both aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). However, the effect of AD/MCI on the coupling between regional neural activity (measured by regional fluorodeoxyglucose imaging (rFDG)) and inter-regional FC (measured by resting-state functional magnetic resonance imaging (rs-fMRI)) is poorly understood.MethodsWe scanned 19 patients with MCI, 33 patients with AD, and 26 healthy individuals by simultaneous FDG-PET/rs-fMRI and assessed rFDG and inter-regional FC metrics (i.e., clustering coefficient and degree centrality). Next, we examined the potential moderating effect of disease status (MCI or AD) on the link between rFDG and inter-regional FC metrics using hierarchical moderated multiple regression analysis. We also tested this effect by considering interaction between disease status and inter-regional FC metrics, as well as interaction between disease status and rFDG.ResultsOur findings revealed that both rFDG and inter-regional FC metrics were disrupted in MCI and AD. Moreover, AD altered the relationship between rFDG and inter-regional FC metrics. In particular, we found that AD moderated the effect of inter-regional FC metrics of the caudate, parahippocampal gyrus, angular gyrus, supramarginal gyrus, frontal pole, inferior temporal gyrus, middle frontal, lateral occipital, supramarginal gyrus, precuneus, and thalamus on predicting their rFDG. On the other hand, AD moderated the effect of rFDG of the parietal operculum on predicting its inter-regional FC metric.ConclusionOur findings demonstrated that AD decoupled the link between regional neural activity and functional segregation and global connectivity across particular brain regions.
Highlights
Alzheimer’s disease (AD) and mild cognitive impairment (MCI), a syndrome at risk for AD, are characterized by progressive cognitive dysfunctions due to neuronal loss and reduced overall neural activity, which can be indirectly quantified through fluorodeoxyglucose-positron emissionThis article is part of the Topical Collection on Neurology – DementiaChristian Sorg and Masoud Tahmasian contributed to this work.Extended author information available on the last page of the article tomography (FDG-PET) [1]
Comparing regional glucose metabolism (rFDG) between groups, we found significantly reduced metabolism in the default mode network (DMN) areas including the bilateral posterior cingulate cortex, angular gyri, left parahippocampal gyrus, left middle frontal cortex, and left precuneus cortex in AD patients compared to healthy control (HC) subjects
We found hypometabolism in the bilateral middle and inferior temporal gyri, bilateral lateral occipital gyri, bilateral angular gyri, and caudate in MCI patients compared to HC subjects (Fig. 1(a), SI-Table 1)
Summary
Extended author information available on the last page of the article tomography (FDG-PET) [1]. As 80% of neural metabolic activity is dedicated to synaptic signaling [4], intrinsic functional connectivity (FC) measured by resting-state functional magnetic resonance imaging (rs-fMRI) might indicate a conjugate in-/decreased blood oxygenation level–dependent (BOLD) signaling between the brain regions. Topological features of these FC networks can be modeled through graph theory analyses, in which brain regions are considered “nodes,” and FC between them as “edges” of the graph [5]. The effect of AD/MCI on the coupling between regional neural activity and inter-regional
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