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Occipital sources of resting-state electroencephalographic (EEG) alpha rhythms are abnormal, at the group level, in patients with amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here, we evaluated the hypothesis that amplitude of these occipital sources is related to neurodegeneration in occipital lobe as measured by magnetic resonance imaging. Resting-state eyes-closed EEG rhythms were recorded in 45 healthy elderly (Nold), 100 MCI, and 90 AD subjects. Neurodegeneration of occipital lobe was indexed by weighted averages of gray matter density, estimated from structural MRIs. EEG rhythms of interest were alpha 1 (8-10.5 Hz) and alpha 2 (10.5-13 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography. Results showed a positive correlation between occipital gray matter density and amplitude of occipital alpha 1 sources in Nold, MCI, and AD subjects as a whole group (r = 0.3, p = 0.000004, N = 235). Furthermore, there was a positive correlation between the amplitude of occipital alpha 1 sources and cognitive status as revealed by Mini Mental State Examination score across all subjects (r = 0.38, p = 0.000001, N = 235). Finally, amplitude of occipital alpha 1 sources allowed a moderate classification of individual Nold and AD subjects (sensitivity: 87.8%; specificity: 66.7%; area under the receiver operating characteristic curve: 0.81). These results suggest that the amplitude of occipital sources of resting-state alpha rhythms is related to AD neurodegeneration in occipital lobe along pathologic aging.

Here we presented a single electroencephalographic (EEG) marker for a neurophysiological assessment of Alzheimer's disease (AD) patients already diagnosed by current guidelines. The ability of the EEG marker to classify 127 AD individuals and 121 matched cognitively intact normal elderly (Nold) individuals was tested. Furthermore, its relationship to AD patients' cognitive status and structural brain integrity was examined. Low-resolution brain electromagnetic tomography (LORETA) freeware estimated cortical sources of resting state eyes-closed EEG rhythms. The EEG marker was defined as the ratio between the activity of parieto-occipital cortical sources of delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms. Results showed 77.2% of sensitivity in the recognition of the AD individuals; 65% of specificity in the recognition of the Nold individuals; and 0.75 of area under the receiver-operating characteristic curve. Compared to the AD subgroup with the EEG maker within one standard deviation of the Nold mean (EEG-), the AD subgroup with EEG+ showed lower global cognitive status, as revealed by Mini-Mental State Evaluation score, and more abnormal values of white-matter and cerebrospinal fluid normalized volumes, as revealed by structural magnetic resonance imaging. We posit that cognitive and functional status being equal, AD patients with EEG+ should receive special clinical attention due to a neurophysiological "frailty". EEG+ label can be also used in clinical trials (i) to form homogeneous groups of AD patients diagnosed by current guidelines and (ii) as end-point to evaluate intervention effects.

Acetylcholinesterase inhibitors (AChEIs) are the most widely used symptomatic treatment for mild to severe Alzheimer's disease (AD) patients, while N-methyl-d-aspartic acid (NMDA) receptor antagonist memantine is licensed for use in moderate to severe AD patients. In this article, the effect of these compounds on resting state eyes-closed electroencephalographic (EEG) rhythms in AD patients is reviewed to form a knowledge platform for the European Innovative Medicine Initiative project "PharmaCog" (IMI Grant Agreement No. 115009) aimed at developing innovative translational models for drug testing in AD. Indeed, quite similar EEG experiments and the same kind of spectral data analysis can be performed in animal models of AD and in elderly individuals with prodromal or manifest AD. Several studies have shown that AChEIs affect both resting state EEG rhythms and cognitive functions in AD patients. After few weeks of successful treatment, delta (0-3 Hz) or theta (4-7 Hz) rhythms decrease, dominant alpha rhythms (8-10 Hz) increase, and cognitive functions slightly improve. Beneficial effects of these rhythms and cognitive functions were also found in AD responders to the long-term successful treatment (i.e. 6-12 months). In contrast, only one study has explored the long-term effects of memantine on EEG rhythms in AD patients, showing reduced theta rhythms. The present review enlightens the expected effects of AChEIs on resting state EEG rhythms in AD patients as promising EEG markers for the development of translational protocols both within the PharmaCog project and for wider use.

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.