Influence of the APOE ε4 Allele and Mild Cognitive Impairment Diagnosis in the Disruption of the MEG Resting State Functional Connectivity in Sources Space

Abstract

The apolipoprotein E (APOE) ε4 allele constitutes the major genetic risk for the development of late onset Alzheimer's disease (AD). However, its influence on the neurodegeneration that occurs in early AD remains unresolved. In this study, the resting state magnetoencephalography(MEG) recordings were obtained from 27 aged healthy controls and 36 mild cognitive impairment (MCI) patients. All participants were divided into carriers and non-carriers of the ε4 allele. We have calculated the functional connectivity (FC) in the source space along brain regions estimated using the Harvard-Oxford atlas and in the classical bands. Then, a two way ANOVA analysis (diagnosis and APOE) was performed in each frequency band. The diagnosis effect consisted of a diminished FC within the high frequency bands in the MCI patients, affecting medial temporal and parietal regions. The APOE effect produced a decreased long range FC in delta band in ε4 carriers. Finally, the interaction effect showed that the FC pattern of the right frontal-temporal region could be reflecting a compensatory/disruption process within the ε4 allele carriers. Several of these results correlated with cognitive decline and neuropsychological performance. The present study characterizes how the APOE ε4 allele and MCI status affect the brain's functional organization by analyzing the FC patterns in MEG resting state in the sources space. Therefore a combination of genetic, neuropsychological, and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration.

Precuneus Failures in Subjects of the PSEN1 E280A Family at Risk of Developing Alzheimer’s Disease Detected Using Quantitative Electroencephalography

“…The Alpha-3, which is close to our Alpha-2, is also higher in young subjects and lower in old subjects [65]. The Apolipoprotein E (ApoE) ε4 allele is the greatest genetic susceptibility factor for AD and has been studied in carriers with AD and MCI using EEG [66][67][68][69][70], having been also reported anomalies for Alpha and Theta band at resting state related to slowing of EEG [71,72]. To our knowledge, only one study has used EEG in subjects within a wide range of age (18-56 years), including young asymptomatic carriers [65].…”

Healthy and Pathological Brain Aging: From the Perspective of Oscillations, Functional Connectivity, and Signal Complexity

“…The influence of APOE4 on aging and neurodegeneration has also been explored with MEG, reporting decreased long-range functional connectivity in slow frequencies in APOE 4 carriers, where frontal and temporal connections were particularly compromised [71]. …”

MEG Beamformer-Based Reconstructions of Functional Networks in Mild Cognitive Impairment

“…Several resting-state electroencephalography (EEG) and magnetoencephalography (MEG) studies have found decreases in functional connectivity, especially in higher frequency bands (i.e., alpha and beta bands), in MCI patients compared to healthy controls (Moretti et al, 2008; Gómez et al, 2009; López et al, 2014b; Cuesta et al, 2015). This change in synchronization pattern is quite similar to that described for AD patients (Stam and van Dijk, 2002; Jeong, 2004; Stam et al, 2006), although increased connectivity has also been described for AD involving posterior brain regions (Stam et al, 2006; Alonso et al, 2011).…”