Source Analysis of Spontaneous Magnetoencephalograpic Activity in Healthy Aging and Mild Cognitive Impairment: Influence of Apolipoprotein E Polymorphism

Article type: Research Article

Authors: Cuesta, Pablo^{a; b; c} | Barabash, Ana^{d; e} | Aurtenetxe, Sara^a | Garcés, Pilar^{a; c} | López, María Eugenia^{a; b} | Bajo, Ricardo^a | Llanero-Luque, Marcos^f | Ancín, Inés^{d; e} | Cabranes, José Antonio^{d; e} | Marcos, Alberto^{e; g} | Sancho, Miguel^c | Nakamura, Akinori^h | Maestú, Fernando^{a; b; e} | Fernandez, Alberto^{a; e; i; *}

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, Madrid, Spain | [c] Department of Applied Physics III, Faculty of Physics, Complutense University of Madrid, Madrid, Spain | [d] Laboratory of Psychoneuroendocrinology and Molecular Genetics, Biomedical Research Foundation, Clínico San Carlos Hospital, Madrid, Spain | [e] Institute of Sanitary Investigation [IdISSC], San Carlos University Hospital, Madrid, Spain | [f] Centre for Prevention of Cognitive Impairment, Ayuntamiento de Madrid, Spain | [g] Neurology Department, San Carlos University Hospital, Madrid, Spain | [h] Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Japan | [i] Department of Psychiatry, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain

Correspondence: [*] Correspondence to: Alberto Fernández, PhD, Department of Psychiatry, Faculty of Medicine, Complutense University of Madrid and 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.: +34913942296; Fax: +34913941503; E-mail: aferlucas@med.ucm.es.

Abstract: The apolipoprotein E (APOE) ε4 allele is a genetic risk factor for the development of late-onset Alzheimer's disease (AD), which affects cholinergic system functioning. The association between reduced cholinergic levels and increase of magnetoencephalographic (MEG) low-frequency has been used to explain spectral changes found in AD patients. However, the investigation in predementia stages is scarce. We obtained MEG recordings from 25 aged controls and 36 mild cognitive impairment (MCI) patients during a resting-state condition. According to their APOE genotype, MCIs and controls were subdivided in carriers and non-carriers of the ε4 allele. Sources of spectral variations in these groups were calculated through beamforming. MCI patients exhibited a significant increase of relative power within the low-frequency domain, accompanied by a power decrease within the high-frequency range. APOEε4 carriers showed an increased relative power in the 4.5–6.5 Hz frequency range over frontal lobes. The power increase observed in controls carrying ε4 was significantly higher as compared with MCI non-carriers, while MCI carriers exhibited the highest relative power within the 4.5–6.5 Hz range. Higher power values within the low-frequency ranges correlated with a poorer cognitive performance in MCIs and controls. Our investigation demonstrates that APOEε4 affects resting-state activity to an extent that makes it more proximate to the pattern observed in early stages of AD. Therefore, a combination of genetic 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, APOEε4, magnetoencephalography, mild cognitive impairment, relative power, source analysis

DOI: 10.3233/JAD-140633

Journal: Journal of Alzheimer's Disease, vol. 43, no. 1, pp. 259-273, 2015