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

Article type: Research Article

Authors: Cuesta, Pablo^{a; b; c; *} | Garcés, Pilar^{a; c} | Castellanos, Nazareth P.^d | López, Maria Eugenia^{a; b} | Aurtenetxe, Sara^a | Bajo, Ricardo^a | Pineda-Pardo, José Angel^a | Bruña, Ricardo^a | Marín, Antonio García^e | Delgado, Marisa^f | Barabash, Ana^{g; h} | Ancín, Inés^{g; h} | Cabranes, Jose Antonio^{g; h} | Fernandez, Alberto^{a; h; i} | del Pozo, Francisco^a | Sancho, Miguel^c | Marcos, Alberto^{h; j} | Nakamura, Akinori^k | Maestú, Fernando^{a; b; h}

Affiliations: [a] Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain | [b] Department of Basic Psychology II, Complutense University of Madrid, Spain | [c] Department of Applied Physics III, Faculty of Physics, Complutense University of Madrid, Madrid, Spain | [d] Institute of Psychiatry, King's College London, London, UK | [e] Memory Decline Prevention Center, Ayuntamiento de Madrid, Spain | [f] Seniors Center of the District of Chamartin, Madrid, Spain | [g] Laboratory of Psychoneuroendocrinology and Molecular Genetics, Biomedical Research Foundation, Clínico San Carlos Hospital, Madrid, Spain | [h] Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain | [i] Department of Psychiatry, Faculty of Medicine, Complutense University of Madrid, Spain | [j] Neurology Department, San Carlos University Hospital, Madrid, Spain | [k] Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Japan

Correspondence: [*] Correspondence to: Pablo Cuesta Prieto, Laboratory of Cognitive and Computational Neuroscience (UCM-UPM), Centre for Biomedical Technology (CTB), Campus de Montegancedo s/n, Pozuelo de Alarcón, 28223 Madrid, Spain. Tel.: +34914524900/Extn.: 1779; Fax: +34913941503; E-mail: [email protected].

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.

Keywords: Aging, APOE ε4, functional connectivity, magnetoencephalography, mild cognitive impairment, source analysis

DOI: 10.3233/JAD-141872

Journal: Journal of Alzheimer's Disease, vol. 44, no. 2, pp. 493-505, 2015