Affiliations: [a] Departamento de Psiquiatría, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain | [b] Laboratorio de Neurociencia Cognitiva y Computacional. Centro de Tecnología Biomédica, Universidad Politécnica de Madrid y Universidad Complutense de Madrid, Madrid, Spain | [c] Departamento de Estadística e Investigación Operativa, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain | [d] Servicio de Geriatría, Hospital Clínico San Carlos, Madrid, Spain | [e] Departamento de Psicología Básica II, Facultad de Psicología, Universidad Complutense de Madrid, Madrid, Spain | [f] Departamento de Psicología Básica I, Facultad de Psicología, Universidad Complutense de Madrid, Madrid, Spain
Correspondence:
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Correspondence to: Alberto Fernández, PhD, Departamento de Psiquiatría y Psicología Médica. Facultad de Medicina, Universidad Complutense de Madrid, Avda, Spain. Tel.: +34 913942296; Fax: +34 913941503; E-mail: aferlucas@med.ucm.es.
Abstract: New diagnostic criteria for Alzheimer's disease (AD) stress the role of in vivo biomarkers. Neurophysiological markers are usually not considered as such criteria, although theoretical and practical reasons would justify them. In order to assess the value of neurophysiology as an AD biomarker, whole-head magnetoencephalographic (MEG) resting state recordings were obtained from 35 AD patients, 23 mild cognitive impairment (MCI) patients, and 24 healthy controls. The AD group was further split into two groups differing in severity according to the GDS/FAST criteria. A Minimum Norm Estimation procedure was utilized to estimate the cortical origin of slow brain oscillatory activity in the delta band (2–4 Hz). Eight regions of interest (ROIs) discriminated between AD patients and controls. Delta current density (DCD) in all ROIs showed a significant negative correlation with cognitive status (p < 0.001). DCD values in posterior parietal, occipital, prerolandic, and precuneus cortices distinguished reliably between MCI patients, AD patients with different severity scores, and controls. Importantly, an increase of DCD in right parietal cortex and precuneus indexed the transition from MCI to mild dementia and from mild to more severe dementia. MEG delta mapping might be a serious candidate for a “neural degeneration” marker of AD reflecting dysfunctional synaptic transmission. More importantly, the localization of DCD values is in line with functional imaging markers of AD. However, MEG delta mapping is a totally non-invasive technique that directly measures neural activity. We propose that individuals with enhanced DCD in posterior parietal and precuneus cortices are at risk of progression to full dementia.
