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Patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8-12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid-tau biomarkers in ADMCI patients. An international database provided clinical-demographic-rsEEG datasets for cognitively unimpaired older (Healthy; N = 45), ADMCI (N = 70), and noADMCI (N = 45) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. Posterior rsEEG alpha source activities were reduced in the ADMCI group compared not only to the Healthy group but also to the noADMCI group ( p < 0.001). Negative associations between the CSF phospho-tau and total tau levels and posterior rsEEG alpha source activities were observed in the ADMCI group ( p < 0.001), whereas those with CSF amyloid beta 42 levels were marginal. These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through rsEEG alpha rhythms are mainly affected by brain tauopathy in ADMCI patients.

Are posterior resting-state electroencephalographic (rsEEG) alpha rhythms sensitive to the Alzheimer's disease mild cognitive impairment (ADMCI) progression at a 6-month follow-up? Clinical, cerebrospinal, neuroimaging, and rsEEG datasets in 52 ADMCI and 60 Healthy old seniors (equivalent groups for demographic features) were available from an international archive (www.pdwaves.eu). The ADMCI patients were arbitrarily divided into two groups: REACTIVE and UNREACTIVE, based on the reduction (reactivity) in the posterior rsEEG alpha eLORETA source activities from the eyes-closed to eyes-open condition at ≥ -10% and -10%, respectively. 75% of the ADMCI patients were REACTIVE. Compared to the UNREACTIVE group, the REACTIVE group showed (1) less abnormal posterior rsEEG source activity during the eyes-closed condition and (2) a decrease in that activity at the 6-month follow-up. These effects could not be explained by neuroimaging and neuropsychological biomarkers of AD. Such a biomarker might reflect abnormalities in cortical arousal in quiet wakefulness to be used for clinical studies in ADMCI patients using 6-month follow-ups., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: SOMI (Stages of Objective Memory Impairment) is a novel classification that identifies six stages of memory decline in Alzheimer's Disease (AD) using the Free and Cued Selective Reminding Test (FCSRT). However, the relationship between SOMI stages and brain metabolism remains unexplored. This study aims to investigate the metabolic correlates of SOMI stages using FDG-PET in Mild Cognitive Impairment due to AD (MCI-AD) and early AD patients., Methods: One hundred twenty-nine-patients (99 aMCI-AD and 30 AD), and 42 healthy controls (HCs) (MMSE = 29.2 ± .8; age:69.1 ± 8.6 years; education:10.7 ± 3.8 years) who underwent an extensive neuropsychological battery including FCSRT and brain FDG-PET were enrolled. According to their clinical relevance and available sample sizes, SOMI-4 (N = 24 subjects; MMSE score:26.6 ± 2.6: age:75.4 ± 3.2; education:9.9 ± 4.5) and SOMI-5 groups (N = 97; MMSE:25.3 ± 2.6; age:73.9 ± 5.8; education:9.4 ± 4.1) were investigated., Results: Compared to HCs, SOMI-4 showed hypometabolism in the precuneus, medial temporal gyrus bilaterally, right pecuneus and angular gyrus. SOMI-5 exhibited broader hypometabolism, extending to the left posterior cingulate and medial frontal gyrus bilaterally. The conjunction analysis revealed overlapping areas in the precuneus, medial temporal gyrus bilaterally, and in the right angular gyrus and cuneus. The disjunction analysis identified SOMI-5 specific hypometabolism encompassing left inferior temporal gyrus, uncus and parahippocampal gyrus, and medial frontal gyrus bilaterally (p < .001, p-value (FWE) < .05)., Discussion: SOMI-4 relates to posterior hypometabolism, while SOMI-5 to more extensive hypometabolism further encompassing frontal cortices, suggesting SOMI as a biologically relevant classification system of memory decline., Conclusion: Memory decline staged with SOMI is associated with hypometabolism spreading in amnesic MCI-AD/AD, suggesting its usefulness as a clinical marker of increasing neurodegeneration., Competing Interests: Declaration of competing interest Dr. Pardini reports research support from Novartis and Nutricia and speakers fees from GEBiogen and Merk. Dr. Arnaldi reports speakers fee from Fidia. Dr. Morbelli reports speakers fees GE. All other authors do not report significant conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Abnormalities in cortical sources of resting-state eyes closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10-20 montage) with 19 scalp electrodes characterized Alzheimer's disease (AD) from preclinical to dementia stages. An intriguing rsEEG application is the monitoring and evaluation of AD progression in large populations with few electrodes in low-cost devices. Here we evaluated whether the above-mentioned abnormalities can be observed from fewer scalp electrodes in patients with mild cognitive impairment due to AD (ADMCI). Clinical and rsEEG data acquired in hospital settings (10-20 montage) from 75 ADMCI participants and 70 age-, education-, and sex-matched normal elderly controls (Nold) were available in an Italian-Turkish archive (PDWAVES Consortium; www.pdwaves.eu). Standard spectral fast fourier transform (FFT) analysis of rsEEG data for individual delta, theta, and alpha frequency bands was computed from 6 monopolar scalp electrodes to derive bipolar C3-P3, C4-P4, P3-O1, and P4-O2 markers. The ADMCI group showed increased delta and decreased alpha power density at the C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels compared to the Nold group. Increased theta power density for ADMCI patients was observed only at the C3-P3 bipolar channel. Best classification accuracy between the ADMCI and Nold individuals reached 81% (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from six posterior bipolar channels characterized ADMCI status. These results may pave the way toward diffuse clinical applications in health monitoring of dementia using low-cost EEG systems with a strict number of electrodes in lower- and middle-income countries.

Please modify the Abstract as follows:Here we tested if the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms from the eye-closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer's disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems.We used clinical, demographical, and rsEEG datasets in 28 older adults (Healthy), 42 DLB, and 48 ADD participants. The eLORETA freeware was used to estimate cortical rsEEG sources.Results showed a substantial (> -10%) reduction in the posterior alpha activities during the eyes-open condition in 24 Healthy, 26 ADD, and 22 DLB subjects. There were lower reductions in the posterior alpha activities in the ADD and DLB groups than in the Healthy group. That reduction in the occipital region was lower in the DLB than in the ADD group.These results suggest that DLB patients may suffer from a greater alteration in the neural synchronization mechanisms regulating vigilance in occipital cortical systems compared to ADD patients., Competing Interests: Disclosure statement None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the present retrospective and exploratory study, we tested the hypothesis that sex may affect cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer's disease and mild cognitive impairment (ADMCI). Datasets in 69 ADMCI and 57 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands and fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into matched females and males. The sex factor affected the magnitude of rsEEG source activities in the Nold seniors. Compared with the males, the females were characterized by greater alpha source activities in all cortical regions. Similarly, the parietal, temporal, and occipital alpha source activities were greater in the ADMCI-females than the males. Notably, the present sex effects did not depend on core genetic (APOE4), neuropathological (Aβ42/phospho-tau ratio in the cerebrospinal fluid), structural neurodegenerative and cerebrovascular (MRI) variables characterizing sporadic AD-related processes in ADMCI seniors. These results suggest the sex factor may significantly affect neurophysiological brain neural oscillatory synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms to regulate cortical arousal during quiet vigilance., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Patients with amnesic mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show a "slowing" of cortical resting-state eyes-closed electroencephalographic (rsEEG) rhythms. Some of them also show subclinical, non-convulsive, and epileptiform EEG activity (EEA) with an unclear relationship with that "slowing.", Objective: Here we tested the hypothesis that the "slowing" of rsEEG rhythms is related to EEA in ADMCI patients., Methods: Clinical and instrumental datasets in 62 ADMCI patients and 38 normal elderly (Nold) subjects were available in a national archive. No participant had received a clinical diagnosis of epilepsy. The eLORETA freeware estimated rsEEG cortical sources. The area under the receiver operating characteristic curve (AUROCC) indexed the accuracy of eLORETA solutions in the classification between ADMCI-EEA and ADMCI-noEEA individuals., Results: EEA was observed in 15% (N = 8) of the ADMCI patients. The ADMCI-EEA group showed: 1) more abnormal Aβ42 levels in the cerebrospinal fluid as compared to the ADMCI-noEEA group and 2) higher temporal and occipital delta (<4 Hz) rsEEG source activities as compared to the ADMCI-noEEA and Nold groups. Those source activities showed moderate accuracy (AUROCC = 0.70-0.75) in the discrimination between ADMCI-noEEA versus ADMCI-EEA individuals., Conclusion: It can be speculated that in ADMCI-EEA patients, AD-related amyloid neuropathology may be related to an over-excitation in neurophysiological low-frequency (delta) oscillatory mechanisms underpinning cortical arousal and quiet vigilance.

Purpose: To investigate brain functional correlates of mild cognitive impairment (MCI) in idiopathic REM sleep behavior disorder (iRBD)., Methods: Thirty-nine consecutive iRBD patients, 17 with (RBD-MCI, 73.6±6.5 years), and 22 without (RBD-NC, 69.6±6.1 years) MCI underwent neuropsychological assessment, 18 F-FDG-PET, and 123 I-FP-CIT-SPECT as a marker of nigro-striatal dopaminergic function. Forty-two healthy subjects (69.6±8.5 years) were used as control for 18 F-FDG-PET analysis. Brain metabolism was compared between the three groups by univariate analysis of variance. Post hoc comparison between RBD-MCI and RBD-NC was performed to investigate the presence of an MCI-related volume of interest (MCI-VOI). Brain functional connectivity was explored by interregional correlation analysis (IRCA), using the whole-brain normalized MCI-VOI uptake as the independent variable. Moreover, the MCI-VOI uptake was correlated with 123 I-FP-CIT-SPECT specific-to-non displaceable binding ratios (SBR) and neuropsychological variables. Finally, the MCI-VOI white matter structural connectivity was analyzed by using a MRI-derived human atlas., Results: The MCI-VOI was characterized by a relative hypometabolism involving precuneus and cuneus (height threshold p<0.0001). IRCA (height threshold p<0.0001) revealed a brain functional network involving regions in frontal, temporal, parietal, and occipital lobes, thalamus, caudate, and red nuclei in iRBD patients. In controls, the network was smaller and involved temporal, occipital, cingulate cortex, and cerebellum. Moreover, MCI-VOI metabolism was correlated with verbal memory (p=0.01), executive functions (p=0.0001), and nigro-putaminal SBR (p=0.005). Finally, MCI-VOI was involved in a white matter network including cingulate fasciculus and corpus callosum., Conclusion: Our data suggest that cuneus/precuneus is a hub of a large functional network subserving cognitive function in iRBD.

In normal old (Nold) and Alzheimer's disease (AD) persons, a high cognitive reserve (CR) makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here, we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu-) educational attainment subgroups, were available in an Italian-Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. As compared to the Nold-Edu- subgroup, the Nold-Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI-Edu- subgroup, the ADMCI-Edu+ subgroup displayed lower alpha source activations topographically widespread. Furthermore, the 2 ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray-white matter measures, and neuropsychological scores. The current findings suggest that a high CR may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: To investigate clinical and dopaminergic pre-synaptic brain imaging characteristics of subjects with idiopathic rapid eye movement (REM) behavior disorder (iRBD) and mild cognitive impairment (MCI), and to evaluate the combined predictive value of risk factors for short-term conversion to synucleinopathy., Method: In sum, 44 polysomnography (PSG)-confirmed iRBD patients (68.5 ± 7.2 years; 38 males) underwent 123 I-FP-CIT-SPECT, comprehensive neuropsychological evaluation, clinical examination and clinical follow-up every six months (30.6 ± 21.5 months). Step-wise logistic regression was applied to identify those features discriminating iRBD patients with (iRBD-MCI; n = 14) and without MCI (normal cognition [NC], iRBD-NC; n = 30). The risk of neurodegeneration was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional-hazards analysis, adjusting for age, gender and education. A generalized linear model (GLM) was applied to define the best combination of risk factors predicting conversion at follow-up., Results: At baseline, patients with iRBD-MCI showed reduced striatal dopamine transporter (DAT) specific to non-displaceable binding ratio (SBR) and more constipation compared with iRBD-NC patients (p < 0.0001). During the follow-up, 10 patients (22.7%) develop an overt synucleinopathy. GLM analysis showed that patients with orthostatic hypotension, non-motor experiences of daily living, reduced putaminal DAT-SPECT SBR, and cognitive impairment in verbal memory/visuoconstruction abilities were at higher risk of phenoconversion (Hazard Ratio [HR] 26.05; Sensitivity 90%; Specificity 100%; Accuracy 97.73%; Positive Predictive Value 100%; Negative Predictive Value 97.14%)., Conclusions: iRBD-MCI patients showed a more severe dopaminergic neuroimaging and clinical phenotype. Combining clinical and neuroimaging markers allowed to achieve excellent ability in identifying iRBD patients at high risk of developing a synucleinopathy within about three years from diagnosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: In relaxed adults, staying in quiet wakefulness at eyes closed is related to the so-called resting state electroencephalographic (rsEEG) rhythms, showing the highest amplitude in posterior areas at alpha frequencies (8-13 Hz)., Objective: Here we tested the hypothesis that age may affect rsEEG alpha (8-12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with mild cognitive impairment due to Alzheimer's disease (ADMCI)., Methods: Clinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals (matched for demography, education, and gender) were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles)., Results: As compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. On the contrary, in relation to the younger ADMCI subgroups, the older one displayed a lesser reduction in those rhythms. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions revealed by neuroimaging, and clinical and neuropsychological scores., Conclusion: The present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier versus later onset of the AD.

Objective: Here we tested if cortical sources of resting state electroencephalographic (rsEEG) rhythms may differ in sub-groups of patients with prodromal and overt dementia with Lewy bodies (DLB) as a function of relevant clinical symptoms., Methods: We extracted clinical, demographic and rsEEG datasets in matched DLB patients (N = 60) and control Alzheimer's disease (AD, N = 60) and healthy elderly (Nold, N = 60) seniors from our international database. The eLORETA freeware was used to estimate cortical rsEEG sources., Results: As compared to the Nold group, the DLB and AD groups generally exhibited greater spatially distributed delta source activities (DLB > AD) and lower alpha source activities posteriorly (AD > DLB). As compared to the DLB "controls", the DLB patients with (1) rapid eye movement (REM) sleep behavior disorders showed lower central alpha source activities (p < 0.005); (2) greater cognitive deficits exhibited higher parietal and central theta source activities as well as higher central, parietal, and occipital alpha source activities (p < 0.01); (3) visual hallucinations pointed to greater parietal delta source activities (p < 0.005)., Conclusions: Relevant clinical features were associated with abnormalities in spatial and frequency features of rsEEG source activities in DLB patients., Significance: Those features may be used as neurophysiological surrogate endpoints of clinical symptoms in DLB patients in future cross-validation prospective studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Compared with Alzheimer's disease (AD), Parkinson's disease (PD) shows peculiar clinical manifestations related to vigilance (i.e., executive cognitive deficits and visual hallucinations) that may be reflected in resting-state electroencephalographic rhythms. To test this hypothesis, clinical and resting-state electroencephalographic rhythms in age-, sex-, and education-matched PD patients (N = 136) and Alzheimer's disease patients (AD, N = 85), and healthy older participants (Nold, N = 65), were available from an international archive. Electroencephalographic sources were estimated by eLORETA software. The results are as follows: (1) compared to the Nold participants, the AD and PD patients showed higher widespread delta source activities (PD > AD) and lower posterior alpha source activities (AD > PD); (2) the PD patients with the most pronounced motor deficits exhibited very low alpha source activities in widespread cortical regions; (3) the PD patients with the strongest cognitive deficits showed higher alpha source activities in widespread cortical regions; and (4) compared to the PD patients without visual hallucinations, those with visual hallucinations were characterized by higher posterior alpha sources activities. These results suggest that in PD patients resting in quiet wakefulness, abnormalities in cortical neural synchronization at alpha frequencies are differently related to cognitive, motor, and visual hallucinations. Interestingly, parallel PD neuropathological processes may have opposite effects on cortical neural synchronization mechanisms generating cortical alpha rhythms in quiet wakefulness., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The reduction of background activity and the increase of low-frequency powers on electroencephalogram (EEG) correlate with cognitive impairment and have been suggested to be underpinned by cholinergic deficit. We aimed to investigate the ratio between α and θ band power (α/θ ratio), as a synoptic index of quantitative EEG (qEEG) slowing-down, in a peculiar group of patients with mild cognitive impairment (MCI) due to an early-stage Lewy body disease (MCI-LBD), as compared to de novo PD patients without cognitive impairment (PD-MOT), to patients with MCI due to Alzheimer's disease (MCI-AD), and to healthy controls (HC)., Methods: Twelve patients with MCI-LBD (8 males; mean age 74.8 ± 3.6), 11 PD-MOT, 11 MCI-AD and 24 HC subjects undergoing qEEG were matched for gender, age, and education. Following logarithmic transformation, the α/θ ratio was compared among groups and brain regions by repeated measures ANOVA, also exploring group*regions interactions., Results: A significant effect of group (p = 0.0003), regions (p = 0.0001), and group*regions interaction (p = 0.0001) on the α/θ ratio was observed. At post-hoc analysis, α/θ ratio was significantly lower in MCI-LBD (p = 0.001) and in PD-MOT (p = 0.02) compared to HC, and in MCI-LBD than MCI-AD (p = 0.05). No significant differences were found between MCI-AD and HC, as well as between MCI-LBD and PD-MOT., Conclusion: The α/θ power ratio as a synoptic index of EEG background slowing-down could be a simple and easy-to-use qEEG index which might indirectly mirror a cholinergic failure, useful to pick-up those MCI patients at higher risk of developing a Lewy-body disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Previous evidence has shown different resting-state eyes-closed electroencephalographic delta (<4 Hz) and alpha (8-10.5 Hz) source connectivity in subjects with dementia due to Alzheimer's (ADD) and Lewy body (DLB) diseases. The present study tested if the same differences may be observed in the prodromal stages of mild cognitive impairment (MCI). Here, clinical and resting-state eyes-closed electroencephalographic data in age-, gender-, and education-matched 30 ADMCI, 23 DLBMCI, and 30 healthy elderly (Nold) subjects were available in our international archive. Mini-Mental State Evaluation (MMSE) score was matched in the ADMCI and DLBMCI groups. The eLORETA freeware estimated delta and alpha source connectivity by the tool called lagged linear connectivity (LLC). Area under receiver operating characteristic curve (AUROCC) indexed the classification accuracy among individuals. Results showed that widespread interhemispheric and intrahemispheric LLC solutions in alpha sources were abnormally lower in both MCI groups compared with the Nold group, but with no differences were found between the 2 MCI groups. AUROCCs of LLC solutions in alpha sources exhibited significant accuracies (0.72-0.75) in the discrimination of Nold versus ADMCI-DLBMCI individuals, but not between the 2 MCI groups. These findings disclose similar abnormalities in ADMCI and DLBMCI patients as revealed by alpha source connectivity. It can be speculated that source connectivity mostly reflects common cholinergic impairment in prodromal state of both AD and DLB, before a substantial dopaminergic derangement in the dementia stage of DLB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We hypothesized that dopamine neuromodulation might affect cortical excitability in Parkinson's disease (PD) patients set in quiet wakefulness, as revealed by resting state eyes-closed electroencephalographic (rsEEG) rhythms at alpha frequencies (8-12 Hz). Clinical and rsEEG rhythms in PD with dementia (N = 35), PD with mild cognitive impairment (N = 50), PD with normal cognition (N = 35), and normal (N = 50) older adults were available from an international archive. Cortical rsEEG sources were estimated by exact low-resolution brain electromagnetic tomography. Compared with the normal older group, the PD groups showed reduced occipital alpha sources and increased widespread delta (<4 Hz) sources. Widespread frontal and temporal alpha sources exhibited an increase in PD with dementia compared with PD with mild cognitive impairment and PD with normal cognition groups, as function of dopamine depletion severity, typically greater in the former than the latter groups. A daily dose of levodopa induced a widespread reduction in cortical delta and alpha sources in a subgroup of 13 PD patients under standard chronic dopaminergic regimen. In PD patients in quiet wakefulness, alpha cortical source activations may reflect an excitatory effect of dopamine neuromodulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Graph theory analysis on resting state electroencephalographic rhythms disclosed topological properties of cerebral network. In Alzheimer's disease (AD) patients, this approach showed mixed results. Granger causality matrices were used as input to the graph theory allowing to estimate the strength and the direction of information transfer between electrode pairs. The number of edges (degree), the number of inward edges (in-degree), of outgoing edges (out-degree) were statistically compared among healthy controls, patients with mild cognitive impairment due to AD (AD-MCI) and AD patients with mild dementia (ADD) to evaluate if degree abnormality could involve low and/or high degree vertices, the so called hubs, in both prodromal and over dementia stage. Clustering coefficient and local efficiency were evaluated as measures of network segregation, path length and global efficiency as measures of integration, the assortativity coefficient as a measure of resilience. Degree, in-degree and out-degree values were lower in AD-MCI and ADD than the control group for non-hubs and hubs vertices. The number of edges was preserved for frontal electrodes, where patients' groups showed an additional hub in F3. Clustering coefficient was lower in ADD compared with AD-MCI in the right occipital electrode, and it was positively correlated with mini mental state examination. Local and global efficiency values were lower in patients' than control groups. Our results show that the topology of the network is altered in AD patients also in its prodromal stage, begins with the reduction of the number of edges and the loss of the local and global efficiency.

Objective: This study tested the hypothesis that markers of functional cortical source connectivity of resting state eyes-closed electroencephalographic (rsEEG) rhythms may be abnormal in subjects with mild cognitive impairment due to Alzheimer's (ADMCI) and Parkinson's (PDMCI) diseases compared to healthy elderly subjects (Nold)., Methods: rsEEG data had been collected in ADMCI, PDMCI, and Nold subjects (N = 75 for any group). eLORETA freeware estimated functional lagged linear connectivity (LLC) from rsEEG cortical sources. Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Nold and MCI individuals., Results: Posterior interhemispheric and widespread intrahemispheric alpha LLC solutions were abnormally lower in both MCI groups compared to the Nold group. At the individual level, AUROC curves of LLC solutions in posterior alpha sources exhibited moderate accuracies (0.70-0.72) in the discrimination of Nold vs. ADMCI-PDMCI individuals. No differences in the LLC solutions were found between the two MCI groups., Conclusions: These findings unveil similar abnormalities in functional cortical connectivity estimated in widespread alpha sources in ADMCI and PDMCI. This was true at both group and individual levels., Significance: The similar abnormality of alpha source connectivity in ADMCI and PDMCI subjects might reflect common cholinergic impairment., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The present study tested the hypothesis that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and dementia with Lewy bodies (DLBMCI) as compared to cognitively normal elderly (Nold) subjects. Clinical and rsEEG data in 30 ADMCI, 23 DLBMCI, and 30 Nold subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) score was matched between the ADMCI and DLBMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROCC) classified these sources across individuals. Compared to Nold, IAF showed marked slowing in DLBMCI and moderate in ADMCI. Furthermore, the posterior alpha 2 and alpha 3 source activities were more abnormal in the ADMCI than the DLBMCI group, while widespread delta source activities were more abnormal in the DLBMCI than the ADMCI group. The posterior delta and alpha sources correlated with the MMSE score and correctly classified the Nold and MCI individuals (area under the ROCC >0.85). In conclusion, the ADMCI and DLBMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test the clinical validity of these rsEEG markers.

The aim of this retrospective and exploratory study was that the cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and Parkinson's disease (PDMCI) as compared to healthy subjects. Clinical and rsEEG data of 75 ADMCI, 75 PDMCI, and 75 cognitively normal elderly (Nold) subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) was matched between the ADMCI and PDMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROC) classified these sources across individuals. Results showed that compared to the Nold group, the posterior alpha2 and alpha3 source activities were more abnormal in the ADMCI than the PDMCI group, while the parietal delta source activities were more abnormal in the PDMCI than the ADMCI group. The parietal delta and alpha sources correlated with MMSE score and correctly classified the Nold and diseased individuals (area under the ROC = 0.77-0.79). In conclusion, the PDMCI and ADMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test these rsEEG markers for clinical applications and drug discovery.

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Cortical sources of resting state electroencephalographic (EEG) rhythms are abnormal in subjects with mild cognitive impairment (MCI). Here, we tested the hypothesis that these sources in amnesic MCI subjects further deteriorate over 1 year. To this aim, the resting state eyes-closed EEG data were recorded in 54 MCI subjects at baseline (Mini Mental State Examination I = 26.9; standard error [SE], 0.2) and at approximately 1-year follow-up (13.8 months; SE, 0.5; Mini Mental State Examination II = 25.8; SE, 0.2). As a control, EEG recordings were also performed in 45 normal elderly and in 50 mild Alzheimer's disease subjects. 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), and beta2 (20-30 Hz). Cortical EEG sources were estimated using low-resolution brain electromagnetic tomography. Compared with the normal elderly and mild Alzheimer's disease subjects, the MCI subjects were characterized by an intermediate power of posterior alpha1 sources. In the MCI subjects, the follow-up EEG recordings showed a decreased power of posterior alpha1 and alpha2 sources. These results suggest that the resting state EEG alpha sources were sensitive-at least at the group level-to the cognitive decline occurring in the amnesic MCI group over 1 year, and might represent cost-effective, noninvasive and widely available markers to follow amnesic MCI populations in large clinical trials., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We evaluated the brain metabolic correlates of main indexes of a widely used word list learning test, the Rey Auditory Verbal Memory Test (RAVLT), in a group of elderly subjects with memory complaints. Fifty-four subjects (age: 72.02 ± 7.45; Mini-Mental State Examination (MMSE) score: 28.9 ± 1.24) presenting at a memory clinic complaining of memory deficit, but not demented, and thirty controls (age: 71.87 ± 7.08; MMSE score: 29.1 ± 1.1) were included. Subjects with memory complaints included both patients with (amnestic mild cognitive impairment, aMCI) and without (subjective memory complaints, SMC) impairment on memory tests. All subjects underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), analyzed with statistical parametric. Patients with aMCI but not those with SMC showed the expected posterior cingulate-precuneus and parietal hypometabolism as compared to controls. Correlation was determined for between four indexes of the RAVLT and brain metabolism. The results show a significant correlation between the delayed recall score and metabolism in posterior cingulate gyrus of both hemispheres and in left precuneus, as well as between a score of long-term percent retention and metabolism in left posterior cingulate gyrus, precuneus, and orbitofrontal areas. These correlations survived correction for age, education, and MMSE score. No correlation was found between immediate or total recall scores and glucose metabolism. These data show the relevant role of posterior cingulate-precuneus and orbitofrontal cortices in retention and retrieval of de-contextualized verbal memory material in a group of elderly subjects with memory complaints and shed light on the topography of synaptic dysfunction in these subjects, overlapping that found in the earliest stages of Alzheimer-type neurodegeneration.