Exploring the disruptions of the neurophysiological organization in Alzheimer's disease: An integrative approach.

BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD) is a neurological disorder that impairs brain functions associated with cognition, memory, and behavior. Noninvasive neurophysiological techniques like magnetoencephalography (MEG) and electroencephalography (EEG) have shown promise in reflecting brain changes related to AD. These techniques are usually assessed at two levels: local activation (spectral, nonlinear, and dynamic properties) and global synchronization (functional connectivity, frequency-dependent network, and multiplex network organization characteristics). Nonetheless, the understanding of the organization formed by the existing relationships between these levels, henceforth named neurophysiological organization, remains unexplored. This work aims to assess the alterations AD causes in the resting-state neurophysiological organization. METHODS: To that end, three datasets from healthy controls (HC) and patients with dementia due to AD were considered: MEG database (55 HC and 87 patients with AD), EEG1 database (51 HC and 100 patients with AD), and EEG2 database (45 HC and 82 patients with AD). To explore the alterations induced by AD in the relationships between several features extracted from M/EEG data, association networks (ANs) were computed. ANs are graphs, useful to quantify and visualize the intricate relationships between multiple features. RESULTS: Our results suggested a disruption in the neurophysiological organization of patients with AD, exhibiting a greater inclination towards the local activation level; and a significant decrease in the complexity and diversity of the ANs (p-value ¡ 0.05, Mann-Whitney U-test, Bonferroni correction). This effect might be due to a shift of the neurophysiological organization towards more regular configurations, which may increase its vulnerability. Moreover, our findings support the crucial role played by the local activation level in maintaining the stability of the neurophysiological organization. Classification performance exhibited accuracy values of 83.91%, 73.68%, and 72.65% for MEG, EEG1, and EEG2 databases, respectively. CONCLUSION: This study introduces a novel, valuable methodology able to integrate parameters characterize different properties of the brain activity and to explore the intricate organization of the neurophysiological organization at different levels. It was noted that AD increases susceptibility to changes in functional neural organization, suggesting a greater ease in the development of severe impairments. Therefore, ANs could facilitate a deeper comprehension of the complex interactions in brain function from a global standpoint.

Connectivity-based Meta-Bands: A new approach for automatic frequency band identification in connectivity analyses.

The majority of electroencephalographic (EEG) and magnetoencephalographic (MEG) studies filter and analyse neural signals in specific frequency ranges, known as "canonical" frequency bands. However, this segmentation, is not exempt from limitations, mainly due to the lack of adaptation to the neural idiosyncrasies of each individual. In this study, we introduce a new data-driven method to automatically identify frequency ranges based on the topological similarity of the frequency-dependent functional neural network. The resting-state neural activity of 195 cognitively healthy subjects from three different databases (MEG: 123 subjects; EEG1: 27 subjects; EEG2: 45 subjects) was analysed. In a first step, MEG and EEG signals were filtered with a narrow-band filter bank (1 Hz bandwidth) from 1 to 70 Hz with a 0.5 Hz step. Next, the connectivity in each of these filtered signals was estimated using the orthogonalized version of the amplitude envelope correlation to obtain the frequency-dependent functional neural network. Finally, a community detection algorithm was used to identify communities in the frequency domain showing a similar network topology. We have called this approach the "Connectivity-based Meta-Bands" (CMB) algorithm. Additionally, two types of synthetic signals were used to configure the hyper-parameters of the CMB algorithm. We observed that the classical approaches to band segmentation are partially aligned with the underlying network topologies at group level for the MEG signals, but they are missing individual idiosyncrasies that may be biasing previous studies, as revealed by our methodology. On the other hand, the sensitivity of EEG signals to reflect this underlying frequency-dependent network structure is limited, revealing a simpler frequency parcellation, not aligned with that defined by the "canonical" frequency bands. To the best of our knowledge, this is the first study that proposes an unsupervised band segmentation method based on the topological similarity of functional neural network across frequencies. This methodology fully accounts for subject-specific patterns, providing more robust and personalized analyses, and paving the way for new studies focused on exploring the frequency-dependent structure of brain connectivity.

Quantification of the robustness of functional neural networks: application to the characterization of Alzheimer's disease continuum.

Objective.Brain connectivity networks are usually characterized in terms of properties coming from the complex network theory. Using new measures to summarize the attributes of functional connectivity networks can be an important step for their better understanding and characterization, as well as to comprehend the alterations associated with neuropsychiatric and neurodegenerative disorders. In this context, the main objective of this study was to introduce a novel methodology to evaluate network robustness, which was subsequently applied to characterize the brain activity in the Alzheimer's disease (AD) continuum.Approach.Functional connectivity networks were built using 478 electroencephalographic and magnetoencephalographic resting-state recordings from three different databases. These functional connectivity networks computed in the conventional frequency bands were modified simulating an iterative attack procedure using six different strategies. The network changes caused by these attacks were evaluated by means of Spearman's correlation. The obtained results at the conventional frequency bands were aggregated in a correlation surface, which was characterized in terms of four gradient distribution properties: mean, variance, skewness, and kurtosis.Main results.The new proposed methodology was able to consistently quantify network robustness. Our results showed statistically significant differences in the inherent ability of the network to deal with attacks (i.e. differences in network robustness) between controls, mild cognitive impairment subjects, and AD patients for the three different databases. In addition, we found a significant correlation between mini-mental state examination scores and the changes in network robustness.Significance.To the best of our knowledge, this is the first study which assesses the robustness of the functional connectivity network in the AD continuum. Our findings consistently evidence the loss of network robustness as the AD progresses for the three databases. Furthermore, the changes in this complex network property may be related with the progressive deterioration in brain functioning due to AD.

High Frequential Resolution Networks: Considerations on a New Functional Brain Connectivity Framework.

Connectivity analyses are widely used to assess the interaction brain networks. This type of analyses is usually conducted considering the well-known classical frequency bands: delta, theta, alpha, beta, and gamma. However, this parcellation of the frequency content can bias the analyses, since it does not consider the between-subject variability or the particular idiosyncrasies of the connectivity patterns that occur within a band. In this study, we addressed these limitations by introducing the High Frequential Resolution Networks (HFRNs). HFRNs were constructed, using a narrow-bandwidth FIR bank filter of 1 Hz bandwidth, for two different connectivity metrics (Amplitude Envelope Correlation, AEC, and Phase Lag index, PLI) and for 3 different databases of MEG and EEG recordings. Results showed a noticeable similarity between the frequential evolution of PLI, AEC, and the Power Spectral Density (PSD) from MEG and EEG signals. Nonetheless, some technical remarks should be considered: (i) results at the gamma band should exclude the frequency range around 50 Hz due to abnormal connectivity patterns, consequence of the previously applied 50 Hz notch-filter; (ii) HFRNs patterns barely vary with the connection distance; and (iii) a low sampling frequency can exert a remarkable influence on HFRNs. To conclude, we proposed a new framework to perform connectivity analyses that allow to further analyze the frequency-based distribution of brain networks.

Clinical Informatics Training During Emergency Medicine Residency: The University of Michigan Experience.

Clinical informatics (CI) is a rich field with longstanding ties to resident education in many clinical specialties, although a historic gap persists in emergency medicine. To address this gap, we developed a CI track to facilitate advanced training for senior residents at our 4-year emergency medicine residency. We piloted an affordable project-based approach with strong ties to operational leadership at our institution and describe specific projects and their outcomes. Given the relatively low cost, departmental benefit, and unique educational value, we believe that our model is generalizable to many emergency medicine residencies. We present a pathway to defining a formal curriculum using Kern's framework.

Exploring the Alterations in the Distribution of Neural Network Weights in Dementia Due to Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder which has become an outstanding social problem. The main objective of this study was to evaluate the alterations that dementia due to AD elicits in the distribution of functional network weights. Functional connectivity networks were obtained using the orthogonalized Amplitude Envelope Correlation (AEC), computed from source-reconstructed resting-state eletroencephalographic (EEG) data in a population formed by 45 cognitive healthy elderly controls, 69 mild cognitive impaired (MCI) patients and 81 AD patients. Our results indicated that AD induces a progressive alteration of network weights distribution; specifically, the Shannon entropy (SE) of the weights distribution showed statistically significant between-group differences (p < 0.05, Kruskal-Wallis test, False Discovery Rate corrected). Furthermore, an in-depth analysis of network weights distributions was performed in delta, alpha, and beta-1 frequency bands to discriminate the weight ranges showing statistical differences in SE. Our results showed that lower and higher weights were more affected by the disease, whereas mid-range connections remained unchanged. These findings support the importance of performing detailed analyses of the network weights distribution to further understand the impact of AD progression on functional brain activity.

Abnormal meta-state activation of dynamic brain networks across the Alzheimer spectrum.

The characterization of the distinct dynamic functional connectivity (dFC) patterns that activate in the brain during rest can help to understand the underlying time-varying network organization. The presence and behavior of these patterns (known as meta-states) have been widely studied by means of functional magnetic resonance imaging (fMRI). However, modalities with high-temporal resolution, such as electroencephalography (EEG), enable the characterization of fast temporally evolving meta-state sequences. Mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) have been shown to disrupt spatially localized activation and dFC between different brain regions, but not much is known about how they affect meta-state network topologies and their network dynamics. The main hypothesis of the study was that MCI and dementia due to AD alter normal meta-state sequences by inducing a loss of structure in their patterns and a reduction of their dynamics. Moreover, we expected that patients with MCI would display more flexible behavior compared to patients with dementia due to AD. Thus, the aim of the current study was twofold: (i) to find repeating, distinctly organized network patterns (meta-states) in neural activity; and (ii) to extract information about meta-state fluctuations and how they are influenced by MCI and dementia due to AD. To accomplish these goals, we present a novel methodology to characterize dynamic meta-states and their temporal fluctuations by capturing aspects based on both their discrete activation and the continuous evolution of their individual strength. These properties were extracted from 60-s resting-state EEG recordings from 67 patients with MCI due to AD, 50 patients with dementia due to AD, and 43 cognitively healthy controls. First, the instantaneous amplitude correlation (IAC) was used to estimate instantaneous functional connectivity with a high temporal resolution. We then extracted meta-states by means of graph community detection based on recurrence plots (RPs), both at the individual- and group-level. Subsequently, a diverse set of properties of the continuous and discrete fluctuation patterns of the meta-states was extracted and analyzed. The main novelty of the methodology lies in the usage of Louvain GJA community detection to extract meta-states from IAC-derived RPs and the extended analysis of their discrete and continuous activation. Our findings showed that distinct dynamic functional connectivity meta-states can be found on the EEG time-scale, and that these were not affected by the oscillatory slowing induced by MCI or dementia due to AD. However, both conditions displayed a loss of meta-state modularity, coupled with shorter dwell times and higher complexity of the meta-state sequences. Furthermore, we found evidence that meta-state sequencing is not entirely random; it shows an underlying structure that is partially lost in MCI and dementia due to AD. These results show evidence that AD progression is associated with alterations in meta-state switching, and a degradation of dynamic brain flexibility.

Descriptive Analysis of Extubations Performed in an Emergency Department-based Intensive Care Unit.

INTRODUCTION: Extubation of appropriate patients in the emergency department (ED) may be a strategy to avoid preventable or short-stay intensive care unit (ICU) admissions, and could allow for increased ventilator and ICU bed availability when demand outweighs supply. Extubation is infrequently performed in the ED, and a paucity of outcome data exists. Our objective was to descriptively analyze characteristics and outcomes of patients extubated in an ED-ICU setting. METHODS: We conducted a retrospective observational study at an academic medical center in the United States. Adult ED patients extubated in the ED-ICU from 2015-2019 were retrospectively included and analyzed. RESULTS: We identified 202 patients extubated in the ED-ICU; 42% were female and median age was 60.86 years. Locations of endotracheal intubation included the ED (68.3%), outside hospital ED (23.8%), and emergency medical services/prehospital (7.9%). Intubations were performed for airway protection (30.2%), esophagogastroduodenoscopy (27.7%), intoxication/ingestion (17.3%), respiratory failure (13.9%), seizure (7.4%), and other (3.5%). The median interval from ED arrival to extubation was 9.0 hours (interquartile range 6.2-13.6). One patient (0.5%) required unplanned re-intubation within 24 hours of extubation. The attending emergency physician (EP) at the time of extubation was not critical care fellowship trained in the majority (55.9%) of cases. Sixty patients (29.7%) were extubated compassionately; 80% of these died in the ED-ICU, 18.3% were admitted to medical-surgical units, and 1.7% were admitted to intensive care. Of the remaining patients extubated in the ED-ICU (n = 142, 70.3%), zero died in the ED-ICU, 61.3% were admitted to medical-surgical units, 9.9% were admitted to intensive care, and 28.2% were discharged home from the ED-ICU. CONCLUSION: Select ED patients were safely extubated in an ED-ICU by EPs. Only 7.4% required ICU admission, whereas if ED extubation had not been pursued most or all patients would have required ICU admission. Extubation by EPs of appropriately screened patients may help decrease ICU utilization, including when demand for ventilators or ICU beds is greater than supply. Future research is needed to prospectively study patients appropriate for ED extubation.

Characterization of the dynamic behavior of neural activity in Alzheimer's disease: exploring the non-stationarity and recurrence structure of EEG resting-state activity.

OBJECTIVE: Mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) have been shown to induce perturbations to normal neuronal behavior and disrupt neuronal networks. Recent work suggests that the dynamic properties of resting-state neuronal activity could be affected by MCI and AD-induced neurodegeneration. The aim of the study was to characterize these properties from different perspectives: (i) using the Kullback-Leibler divergence (KLD), a measure of non-stationarity derived from the continuous wavelet transform; and (ii) using the entropy of the recurrence point density ([Formula: see text]) and the median of the recurrence point density ([Formula: see text]), two novel metrics based on recurrence quantification analysis. APPROACH: KLD, [Formula: see text] and [Formula: see text] were computed for 49 patients with dementia due to AD, 66 patients with MCI due to AD and 43 cognitively healthy controls from 60 s electroencephalographic (EEG) recordings with a 10 s sliding window with no overlap. Afterwards, we tested whether the measures reflected alterations to normal neuronal activity induced by MCI and AD. MAIN RESULTS: Our results showed that frequency-dependent alterations to normal dynamic behavior can be found in patients with MCI and AD, both in non-stationarity and recurrence structure. Patients with MCI showed signs of patterns of abnormal state recurrence in the theta (4-8 Hz) and beta (13-30 Hz) frequency bands that became more marked in AD. Moreover, abnormal non-stationarity patterns were found in MCI patients, but not in patients with AD in delta (1-4 Hz), alpha (8-13 Hz), and gamma (30-70 Hz). SIGNIFICANCE: The alterations in normal levels of non-stationarity in patients with MCI suggest an initial increase in cortical activity during the development of AD. This increase could possibly be due to an impairment in neuronal inhibition that is not present during later stages. MCI and AD induce alterations to the recurrence structure of cortical activity, suggesting that normal state switching during rest may be affected by these pathologies.

Encefalopatía inducida por metronidazol: descripción de un caso con hallazgos radiológicos y anatomopatológicos / Metronidazole-induced encephalopathy: description of a case with radiological and anatomopathological Findings

Introducción. El metronidazol es un antibiótico ampliamente conocido y utilizado. En casos excepcionales puede producir como efecto adverso un cuadro de encefalopatía con unas lesiones características en la resonancia magnética, localizadas generalmente en el cerebelo y el esplenio del cuerpo calloso. La incidencia y la patogenia se desconocen. La suspensión del tratamiento habitualmente resuelve los síntomas y normaliza la resonancia magnética en pocas semanas. Debido al habitual buen pronóstico, los hallazgos anatomopatológicos son excepcionales. Se presenta un caso clínico con los hallazgos radiológicos sugestivos de la encefalopatía inducida por metronidazol y, de forma excepcional, se aportan los hallazgos anatomopatológicos. Caso clínico. Mujer de 72 años, con enfermedad de Crohn grave, que meses más tarde de iniciar tratamiento con metronidazol presentó de forma lentamente progresiva bradipsiquia y dificultad para caminar hasta llegar al coma. En la resonancia magnética mostraba características imágenes hiperintensas en T2 en el cuerpo calloso, y los núcleos rojos y dentados. Mejoró al suspender el metronidazol, pero posteriormente desarrolló una sepsis y falleció. En la autopsia se observó reblandecimiento del núcleo rojo y, microscópicamente, necrosis celular y desmielinización. Conclusión. Con la publicación de la información clínica, radiológica y anatomopatológica de este caso se pretende fomentar el conocimiento de esta infrecuente causa tratable de encefalopatía subaguda y aportar datos que ayuden a aclarar su patogenia

Introduction. Metronidazole is a widely known and used antibiotic. In exceptional cases, an encephalopathy with characteristic lesions on magnetic resonance imaging (MRI), usually located in the cerebellum and splenium of the corpus callosum, may be an adverse effect. The incidence and pathogenesis are unknown. The suspension of the treatment usually resolves the symptoms and normalizes the MRI in a few weeks. Due to the usual good prognosis, the anatomopathological findings are exceptional. We present a clinical case with the radiological findings suggestive of metronidazole-induced encephalopathy and, exceptionally, we provide the anatomopathological findings. Case report. A 72 years-old woman with severe Crohn’s disease who, months after starting treatment with metronidazole, presented a slowly progressing bradypsychia and difficulty walking until she came to coma. In MRI it showed hyperintense images in T2 in the corpus callosum, red and dentate nuclei. He improved by stopping metronidazole but later developed sepsis and died. At autopsy, softening of the red nucleus was observed and, microscopically, cell necrosis and demyelination. Conclusion. With the publication of the clinical, radiological and anatomopathological information of our case we intend to promote the knowledge of this infrequent treatable cause of subacute encephalopathy and provide data that help to clarify its pathogenesis

Characterizing the fluctuations of dynamic resting-state electrophysiological functional connectivity: reduced neuronal coupling variability in mild cognitive impairment and dementia due to Alzheimer's disease.

OBJECTIVE: The characterization of brain functional connectivity is a helpful tool in the study of the neuronal substrates and mechanisms that are altered in Azheimer's disease (AD) and mild cognitive impairment (MCI). Recently, there has been a shift towards the characterization of dynamic functional connectivity (dFC), discarding the assumption of connectivity stationarity during the resting-state. The majority of these studies have been performed with functional magnetic resonance imaging recordings, with only a small subset being based on magnetoencephalography/electroencephalography (MEG/EEG). However, only these modalities enable the characterization of potentially fast brain dynamics, which is mandatory for an accurate understanding of the transmission and processing of neuronal information. The aim of this study was to characterize the dFC of resting-state EEG activity in AD and MCI. APPROACH: Three measures: the phase lag index (PLI), leakage-corrected magnitude squared coherence (MSCOH) and leakage-corrected amplitude envelope correlation (AEC) were computed for 45 patients with dementia due to AD, 51 subjects with MCI due to AD and 36 cognitively healthy controls. All measures were estimated in epochs of 60 s using a sliding window approach. An epoch length of 15 s was used to provide reliable results. We tested whether the observed PLI, MSCOH and AEC fluctuations reflected actual variations in functional connectivity, as well as whether between-group differences could be found. MAIN RESULTS: We found dFC using PLI, MSCOH and AEC, with AEC having the highest number of statistically significant connections, followed by MSCOH and PLI. Furthermore, a significant reduction in AEC dFC for patients with AD compared to controls was found in the alpha (8-13 Hz) and beta-1 (13-30 Hz) bands. SIGNIFICANCE: Our results suggest that patients with AD (and MCI subjects to a lesser degree) show less variation in neuronal connectivity during resting-state, supporting the notion that dFC can be found at the EEG time scale and is abnormal in the MCI-AD continuum. Measures of dFC have the potential of being used as biomarkers of AD. Moreover, they could also suggest that AD resting-state networks may operate at a state of low firing activity induced by the observed reduction in coupling strength. Furthermore, the statistically significant correlation between dFC and relative power in the beta-1 band could be related to pathologically high levels of neural activity inducing a loss of dFC. These findings show that the stability of neuronal coupling is affected in AD and MCI.

Characterization of EEG Resting-state Activity in Alzheimer's Disease by Means of Recurrence Plot Analyses.

The main objective of this study was to characterize EEG resting-state activity in 55 Alzheimer's disease (AD) patients and 29 healthy controls by means of TREND, a measure based on recurrence quantification analysis. TREND was computed from 60-second recordings of consecutive EEG activity, divided into non-overlapping windows of length 1, 2, 3, 5, 10, 15, 20 and 60 seconds. This measure was computed in the conventional EEG frequency bands (delta, theta, alpha, beta-1, beta-2 and gamma). The parameters delay (τ) and embedding dimension (m) were first optimized for every window size and frequency band under study. These embedding parameters proved to be frequency-dependent. Furthermore, 10 s epochs were set as the minimum length required to avoid spurious results. Statistically significant differences between both groups were found (p <; 0.05, Mann-Whitney U-test). The groups showed differences in TREND in the theta (4-8 Hz), beta1 (13-19 Hz) and beta-2 (19-30 Hz) frequency bands. Our results using TREND suggest that AD disrupts resting-state neural dynamics. Furthermore, these findings indicate that AD induces a frequency-dependent pattern of alterations in the non-stationarity levels of resting-state neural activity.

Analysis of Volume Conduction Effects on Different Functional Connectivity Metrics: Application to Alzheimer's Disease EEG Signals.

The aim of this study was to evaluate the effect of volume conduction on different connectivity metrics: Amplitude Envelope Correlation (AEC), Phase Lag Index (PLI), and Magnitude Squared Coherence (MSCOH). These measures were applied to: (i) a synthetic model of 64 coupled oscillators; and (ii) a resting-state EEG database of 72 patients with dementia due to Alzheimer's disease (AD) and 37 cognitively healthy controls. Our results revealed that AEC and PLI are weakly influenced by the simulated volume conduction compared to MSCOH, although the three metrics are not immune to this effect. Furthermore, results with real EEG recordings showed that AD patients are characterized by an AEC increase in δ frequency band and widespread connectivity decreases in α and ß1 bands. These coupling changes reflect the abnormalities in spontaneous EEG activity of AD patients and might provide further insights into the underlying brain dynamics associated with this disorder.

Measuring Alterations of Spontaneous EEG Neural Coupling in Alzheimer's Disease and Mild Cognitive Impairment by Means of Cross-Entropy Metrics.

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 statistically significant lower similarity values at θ and ß1 frequency bands compared to HC. MCI is also characterized by a global decrease of similarity in all bands, being only significant at ß1. These differences shows that ß band might play a significant role in the identification of early stages of AD. 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.

Assessment of EEG Connectivity Patterns in Mild Cognitive Impairment Using Phase Slope Index.

Mild cognitive impairment (MCI) is a pathology characterized by an abnormal cognitive state. MCI patients are considered to be at high risk for developing dementia. The aim of this study is to characterize the changes that MCI causes in the patterns of brain information flow. For this purpose, spontaneous EEG activity from 41 MCI patients and 37 healthy controls was analyzed by means of an effective connectivity measure: the phase slope index (PSl). Our results showed statistically significant decreases in PSI values mainly at delta and alpha frequency bands for MCI patients, compared to the control group. These abnormal patterns may be due to the structural changes in the brain suffered by patients: decreased hippocampal volume, atrophy of the medial temporal lobe, or loss of gray matter volume. This study suggests the usefulness of PSI to provide further insights into the underlying brain dynamics associated with MCI.

Detection of maltreatment of people with dementia in Spain: usefulness of the Caregiver Abuse Screen (CASE).

The objective of our study is to validate the Caregiver Abuse Screen (CASE) as an instrument for detecting the maltreatment of people with dementia in Spain. In total, 326 informal caregivers of people with different types of dementia were interviewed in several cities in northwest Spain. The caregivers were selected from outpatient neurology clinics and associations of relatives of people with Alzheimer's disease and other dementias. A comprehensive sociodemographic questionnaire was administered to all participants, and several standardized scales were used to assess burden, anxiety, depression, social support and resilience. The "Psychological Aggression" and "Physical Assault" dimensions of the Revised Conflicts Tactics Scale were used as risk factors of caregivers' maltreatment for the construct validation. To establish the probability of maltreatment, a latent class analysis was carried out according to the item responses obtained from the CASE. The internal consistency (Cronbach's alpha) of the CASE was 0.71. The construct validity was explored through factorial analysis, and we found that two dimensions of CASE-i.e., interpersonal abuse and neglect/dependency-explained 62.5% of the variability. According to the latent class probabilities, 20.4% of participants were categorized as possible abusers and 21.4% as non-abusers. The optimal maltreatment cutoff point was six points on the CASE. The validation of the CASE provides us a brief and easy instrument for detecting possible cases of maltreatment of Spanish people with dementia.

Automated Multiclass Classification of Spontaneous EEG Activity in Alzheimer's Disease and Mild Cognitive Impairment.

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.

Bispectral analysis of spontaneous EEG activity from patients with moderate dementia due to Alzheimer's disease.

Dementia due to Alzheimer's disease (AD) is a common disorder with a great impact on the patients' quality of life. The aim of this pilot study was to characterize spontaneous electroencephalography (EEG) activity in dementia due to AD using bispectral analysis. Five minutes of EEG activity were recorded from 17 patients with moderate dementia due to AD and 19 age-matched controls. Bispectrum results revealed that AD patients are characterized by an increase of phase coupling at low frequencies in comparison with controls. Additionally, some bispectral features calculated from the bispectrum showed significant differences between both groups (p <; 0.05, Mann-Whitney U test with Bonferroni's correction). Finally, a stepwise logistic regression analysis with a leave-one-out cross-validation procedure was used for classification purposes. An accuracy of 86.11% (sensitivity = 88.24%; specificity =84.21%) was achieved. This study suggests the usefulness of bispectral analysis to provide further insights into the underlying brain dynamics associated with AD.

Phase-amplitude coupling analysis of spontaneous EEG activity in Alzheimer's disease.

This study was aimed at exploring phase-amplitude coupling (PAC) patterns of neural activity in dementia due to Alzheimer's disease (AD). For this task, five minutes of spontaneous electroencephalographic (EEG) activity from 22 patients with mild AD and 16 cognitively healthy controls were studied. To assess PAC patterns, phase-locking value was computed between the phase of low frequencies and the power of high frequencies within each sensor. Our results showed that high-frequency gamma power is phase-locked to the alpha peak in EEG signals. Furthermore, statistically significant differences (p<;0.05, permutation test) between patients with mild AD and elderly controls were observed at the lower left temporo-parietal area, suggesting that early stages of AD elicit a region-specific decrease of PAC in the neural activity.