The discrimination of early Alzheimer’s disease (AD) and its prodromal form (i.e., mild cognitive impairment, MCI) from cognitively healthy control (HC) subjects is crucial since the treatment is more effective in the first stages of the dementia. The aim of our study is to evaluate the usefulness of a methodology based on electroencephalography (EEG) to detect AD and MCI. EEG rhythms were recorded from 37 AD patients, 37 MCI subjects and 37 HC subjects. Artifact-free trials were analyzed by means of several spectral and nonlinear features: relative power in the conventional frequency bands, median frequency, individual alpha frequency, spectral entropy, Lempel–Ziv complexity, central tendency measure, sample entropy, fuzzy entropy, and auto-mutual information. Relevance and redundancy analyses were also conducted through the fast correlation-based filter (FCBF) to derive an optimal set of them. The selected features were used to train three different models aimed at classifying the trials: linear discriminant analysis (LDA), quadratic discriminant analysis (QDA) and multi-layer perceptron artificial neural network (MLP). Afterwards, each subject was automatically allocated in a particular group by applying a trial-based majority vote procedure. After feature extraction, the FCBF method selected the optimal set of features: individual alpha frequency, relative power at delta frequency band, and sample entropy. Using the aforementioned set of features, MLP showed the highest diagnostic performance in determining whether a subject is not healthy (sensitivity of 82.35% and positive predictive value of 84.85% for HC vs. all classification task) and whether a subject does not suffer from AD (specificity of 79.41% and negative predictive value of 84.38% for AD vs. all comparison). Our findings suggest that our methodology can help physicians to discriminate AD, MCI and HC.

Objective . The aim of this study was to evaluate the effect of electroencephalographic (EEG) volume conduction in different measures of functional connectivity and to characterize the EEG coupling alterations at the different stages of dementia due to Alzheimer’s disease (AD). Approach . Magnitude squared coherence ( MSCOH ), imaginary part of coherence ( iCOH ), lagged coherence ( lagCOH ), amplitude envelope correlation ( AEC ), synchronization likelihood ( SL ), phase lag index ( PLI ), phase locking value ( PLV ), and corrected imaginary PLV ( ciPLV ) were applied to: (i) synthetic signals generated with a Kuramoto-based model of several coupled oscillators; and (ii) a resting-state EEG database of real recordings from 51 cognitively healthy controls, 51 mild cognitive impairment (MCI) subjects, 51 mild AD (AD _mil ) patients, 50 moderate AD (AD _mod ) patients, and 50 severe AD (AD _sev ) patients. Main results . Our results using synthetic signals showed that PLI was the least affected parameter by spurious influences in a simulated volume conduction environment. Results using real EEG recordings showed that spontaneous activity of MCI patients is characterized by a significant coupling increase in the band. As dementia progresses, this increase in the band became more pronounced, and a significant widespread decrease in band appeared at the last stage of dementia. Significance . Our results revealed that the estimation of functional EEG connectivity using PLI could reduce the bias introduced by the spurious influence of volume conduction, and it could increase the insight into the underlying brain dynamics at different stages of the AD continuum.

Alzheimer’s Disease (AD) represents the most prevalent form of dementia and is considered a major health problem due to its high prevalence and its economic costs. An accurate characterization of the underlying neural dynamics in AD is crucial in order to adopt effective treatments. In this regard, mild cognitive impairment (MCI) is an important clinical entity, since it is a risk-state for developing dementia. In the present study, coupling patterns of 111 resting-state electroencephalography (EEG) recordings were analyzed. Specifically, we computed Cross-Approximate Entropy (Cross-ApEn) and Cross-Sample Entropy (Cross-SampEn) of 37 patients with dementia due to AD, 37 subjects with MCI and 37 healthy control (HC) subjects. Our results showed that Cross-SampEn outperformed Cross-ApEn, revealing higher number of significant connections among the three groups (Kruskal-Wallis test, FDR-corrected p-values < 0.05). AD patients exhibited statically significant lower dissimilarity values at alpha and beta1 frequency bands compared to HC. MCI is also characterized by a global decrease of dissimilarity in all bands, being only significant at beta1. These differences shows that beta band might play a significant role in the identification of early stages of AD. Clinically, the brain alterations and neural mechanisms involved in cognitive decline may be explained by the loss of acetylcholine, long-distance association fibers or gray matter volume. Our results suggest that Cross-SampEn could increase the insight into brain dynamics at different AD stages. Consequently, it may contribute to develop early AD biomarkers, potentially useful as diagnostic information.

Objective . The aim of this study was to solve one of the current limitations for the characterization of the brain network in the Alzheimer’s disease (AD) continuum. Nowadays, frequency-dependent approaches have reached contradictory results depending on the frequency band under study, tangling the possible clinical interpretations. Approach . To overcome this issue, we proposed a new method to build multiplex networks based on canonical correlation analysis (CCA). Our method determines two basis vectors using the source and electrode-level frequency-specific network parameters for a reference group, and then project the results for the rest of the groups into these hyperplanes to make them comparable. It was applied to: (i) synthetic signals generated with a Kuramoto-based model; and (ii) a resting-state electroencephalography (EEG) database formed by recordings from 51 cognitively healthy controls, 51 mild cognitive impairment subjects, 51 mild AD patients, 50 moderate AD patients, and 50 severe AD patients. Main results . Our results using synthetic signals showed that the interpretation of the proposed CCA-based multiplex parameters (multiplex strength, multiplex characteristic path length and multiplex clustering coefficient) can be analogous to their frequency-specific counterparts, as they displayed similar behaviors in terms of average connectivity, integration, and segregation. Findings using real EEG recordings revealed that dementia due to AD is characterized by a significant increase in average connectivity, and by a loss of integration and segregation. Significance . We can conclude that CCA can be used to build multiplex networks based from frequency-specific results, summarizing all the available information and avoiding the limitations of possible frequency-specific conflicts. Additionally, our method supposes a novel approach for the construction and analysis of multiplex networks during AD continuum.

Brain waves, measured by electroencephalography (EEG), are a powerful tool in the investigation of neurophysiological traits and a noninvasive and cost-effective alternative in the diagnostic of some neurological diseases. In order to identify novel Quantitative Trait Loci (QTLs) for brain wave relative power (RP), we collected resting state EEG data in five frequency bands (δ, θ, α, β1, and β2) and genome-wide data in a cohort of 105 patients with late onset Alzheimer’s disease (LOAD), 41 individuals with mild cognitive impairment and 45 controls from Iberia, correcting for disease status. One novel association was found with an interesting candidate for a role in brain wave biology, CLEC16A (C-type lectin domain family 16), with a variant at this locus passing the adjusted genome-wide significance threshold after Bonferroni correction. This finding reinforces the importance of immune regulation in brain function. Additionally, at a significance cutoff value of 5 × 10⁻⁶, 18 independent association signals were detected. These signals comprise brain expression Quantitative Loci (eQTLs) in caudate basal ganglia, spinal cord, anterior cingulate cortex and hypothalamus, as well as chromatin interactions in adult and fetal cortex, neural progenitor cells and hippocampus. Moreover, in the set of genes showing signals of association with brain wave RP in our dataset, there is an overrepresentation of loci previously associated with neurological traits and pathologies, evidencing the pleiotropy of the genetic variation modulating brain function.