Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 44, Issue 2, Pages 493-505Publisher
IOS PRESS
DOI: 10.3233/JAD-141872
Keywords
Aging; APOE epsilon 4; functional connectivity; magnetoencephalography; mild cognitive impairment; source analysis
Categories
Funding
- Spanish Ministry of Science and Economy [PSI2009-14415-C03-01, PSI2012-38375-C03-01]
- National Institute of Health Carlos III [PI10/01585]
- Spanish Ministry of Science and Innovation [BES-2010-036469]
- Ministry of Education (FPU) [AP-2008-00175, AP2010-1317]
- PICATA predoctoral fellowship of the Moncloa Campus of International Excellence (UCM-UPM)
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The apolipoprotein E (APOE) epsilon 4 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 epsilon 4 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 epsilon 4 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 epsilon 4 allele carriers. Several of these results correlated with cognitive decline and neuropsychological performance. The present study characterizes how the APOE epsilon 4 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.
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