Patterns of longitudinal subcortical atrophy over one year in amnestic mild cognitive impairment and its impact on cognitive performance: a preliminary study.

Background/aim: Amnestic mild cognitive impairment (aMCI) is a risk factor for dementia, and thus, it is of interest to enlighten specific brain atrophy patterns in aMCI patients. We aim to define the longitudinal atrophy pattern in subcortical structures and its effect on cognition in patients with aMCI. Materials and methods: Twenty patients with aMCI and 20 demographically matched healthy controls with baseline and longitudinal structural magnetic resonance imaging scans and neuropsychological assessments were studied. The algorithm FIRST (FMRIB's integrated registration and segmentation tool) was used to obtain volumes of subcortical structures (thalamus, putamen, caudate nucleus, nucleus accumbens, globus pallidus, hippocampus, and amygdala). Correlations between volumes and cognitive performance were assessed. Results: Compared with healthy controls, aMCI demonstrated subcortical atrophies in the hippocampus (p = 0.001), nucleus accumbens (p = 0.003), and thalamus (p = 0.003) at baseline. Significant associations were found for the baseline volumes of the thalamus, nucleus accumbens, and hippocampus with memory, the thalamus with visuospatial skills. Conclusion: aMCI demonstrated subcortical atrophies associated with cognitive deficits. The thalamus, nucleus accumbens, and hippocampus may provide additional diagnostic information for aMCI.

Taxonomically-related Word Pairs Evoke both N400 and LPC at Long SOA in Turkish.

Semantic priming in Turkish was examined in 36 right-handed healthy participants in a delayed lexical decision task via taxonomic relations using EEG. Prime-target relations included related- unrelated- and pseudo-words. Taxonomically related words at long stimulus onset asynchrony (SOA) were shown to modulate N400 and late positive component (LPC) amplitudes. N400 semantic priming effect in the time window of 300-500 ms was the largest for pseudo-words, intermediate for semantically-unrelated targets, and smallest for semantically-related targets as a reflection of lexical-semantic retrieval. This finding contributes to the ERP literature showing how remarkably universal the N400 brain potential is, with similar effects across languages and orthography. The ERP data also revealed different influences of related, unrelated, and pseudo-word conditions on the amplitude of the LPC. Attention scores and mean LPC amplitudes of related words in parietal region showed a moderate correlation, indicating LPC may be related to "relationship-detection process".

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study.

INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.

Semantic and phonemic verbal fluency tests: Normative data for the Turkish population.

Semantic and phonemic verbal fluency tests are widely used neuropsychological assessments of executive functions and language skills and are easy to administer. The aim of this study was to determine the impact of age, education, and gender on semantic and phonemic verbal fluency tests and to establish normative data for Turkish adults aged between 18 and 86 years. The results revealed significant main effects of age and education on all subscores of verbal fluency tests. Furthermore, an interaction effect between age and education was observed on semantic fluency and letter K fluency scores. While no significant differences were found among the 18-29, 30-39, and 40-49 age groups in any of the subscores, performance on the tests decreased with increasing age. Significant differences were observed among all education groups in all subscores. No main or interaction effects of gender were found on any subscore. These normative data could prove useful in clinical and research settings for the assessment of cognitive impairment.

Functional magnetic resonance imaging study during resting state and visual oddball task in mild cognitive impairment.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is a transitional state between normal aging and dementia, and identifying early biomarkers is crucial for disease detection and intervention. Functional magnetic resonance imaging (fMRI) has the potential to identify changes in neural activity in MCI. METHODS: We investigated neural activity changes in the visual network of the aMCI patients (n:20) and healthy persons (n:17) using resting-state fMRI and visual oddball task fMRI. We used independent component analysis to identify regions of interest and compared the activity between groups using a false discovery rate correction. RESULTS: Resting-state fMRI revealed increased activity in the areas that have functional connectivity with the visual network, including the right superior and inferior lateral occipital cortex, the right angular gyrus and the temporo-occipital part of the right middle temporal gyrus (p-FDR = 0.008) and decreased activity in the bilateral thalamus and caudate nuclei, which are part of the frontoparietal network in the aMCI group (p-FDR = 0.002). In the visual oddball task fMRI, decreased activity was found in the right frontal pole, the right frontal orbital cortex, the left superior parietal lobule, the right postcentral gyrus, the right posterior part of the supramarginal gyrus, the right superior part of the lateral occipital cortex, and the right angular gyrus in the aMCI group. CONCLUSION: Our results suggest the alterations in the visual network are present in aMCI patients, both during resting-state and task-based fMRI. These changes may represent early biomarkers of aMCI and highlight the importance of assessing visual processing in cognitive impairment. However, future studies with larger sample sizes and longitudinal designs are needed to confirm these findings.

Validity, Reliability and Normative Data of the Stroop Test Çapa Version. / Stroop Testi Çapa Formu’nun Geçerlik-Güvenirlik ve Norm Çalismasi.

OBJECTIVE: The Stroop test Çapa version does not have normative data, despite its extensive use in clinical and research settings to assess executive functions. The aim of the present study was to test the validity and reliability of the Stroop test Çapa version and to establish stratified normative data in individuals aged between 18-83 years. METHOD: The norm determination phase of the study included 541 healthy participants, stratified by age, education, and gender. The relative contributions of the demographic variables on the completion times of Stroop subtests were assessed with multiple linear regression analysis. The main effects of age, education and gender variables and of interactions between these on the completion times of subtests were investigated with 6x3x2 ANOVA design. In addition, the concurrent validity, test-retest reliability and internal consistency of the test were examined. RESULTS: Multiple linear regression models that included age and education accounted for 23-42% of the completion time variances of all subtests. In the factorial ANOVA, main effects, as well as interaction effects of age and education were found on all subtests. For all Stroop subtests, the completion times were the shortest for the individuals in the 18-29 age group with the highest education level and longest for the individuals in the 70-83 age group with the lowest education level. The test demonstrated acceptable internal consistency and high test-retest reliability. CONCLUSION: Normative data of the Stroop Test Çapa Version were provided for the assessment of executive functions in young and middleaged adults and elderly population.

Resting-state electroencephalographic delta rhythms may reflect global cortical arousal in healthy old seniors and patients with Alzheimer's disease dementia.

Extending Basar's theory of event-related EEG oscillations, here we hypothesize that even in quiet wakefulness, transient increases in delta rhythms may enhance global cortical arousal as revealed by the desynchronization of alpha rhythms in normal (Nold) seniors with some derangement in Alzheimer's disease dementia (ADD). Clinical and EEG datasets in 100 ADD and 100 Nold individuals matched as demography, education, and gender were taken from an international archive. Standard delta (< 4 Hz) and alpha1 (8-10.5 Hz) bands were used for the main analysis, while alpha2 (10.5-13 Hz), theta (4-8 Hz), beta1 (13-20 Hz), beta2 (20-35 Hz), and gamma (35-40 Hz) served as controls. In the interpretation, the higher the alpha1 power (density), the lower that arousal. As expected, when compared to the Nold group, the ADD group showed higher global (scalp) power density at the delta-theta band and lower global power density at the alpha-beta bands. As novel findings, we observed that: (1) in the Nold group, the global delta and alpha1-2 power were negatively and linearly correlated; (2) in the ADD group, this correlation was just marginal; and (3) in both Nold and AD groups, the EEG epochs with the highest delta power (median value for stratification) were associated with the lowest global alpha1 power. This effect was related to eLORETA freeware solutions showing maximum alpha1 source activations in posterior cortical regions. These results suggest that even in quiet wakefulness, delta and alpha rhythms are related to each other, and ADD partially affects this cross-band neurophysiological mechanism.

Abnormalities of resting-state EEG in patients with prodromal and overt dementia with Lewy bodies: Relation to clinical symptoms.

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.

Abnormal cortical neural synchronization mechanisms in quiet wakefulness are related to motor deficits, cognitive symptoms, and visual hallucinations in Parkinson's disease patients: an electroencephalographic study.

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.

The difference of mild cognitive impairment in Parkinson's disease from amnestic mild cognitive impairment: Deeper power decrement and no phase-locking in visual event-related responses.

Event-related oscillatory responses reflect the cognitive status in many neuropsychiatric conditions including mild cognitive impairment (MCI). In this study, a total of 30 patients with amnestic MCI (aMCI) and 25 patients with MCI of Parkinson's disease (PD-MCI) were compared with 28 aged-, gender-, education-matched healthy control (HC) participants using visual event-related delta, theta, alpha oscillatory responses by methods of event-related spectral perturbation and inter-trial coherence. PD-MCI and aMCI groups commonly share a decreased theta power, but all electrophysiological deviations from the controls were more prominent in PD-MCI than aMCI in all frequency bands. Additionally, decreased phase-locking in all studied frequency bands was encountered only in PD-MCI group, but it was preserved in aMCI. These findings indicate that visual networks in PD-MCI are more severely affected than aMCI. Reduced phase-locking in PD-MCI may possibly relate to dysfunctioning subcortical modulating centers that take a role in the generation of event-related responses.

Mild cognitive impairment in Parkinson's disease is associated with decreased P300 amplitude and reduced putamen volume.

OBJECTIVE: Functional and structural brain alterations of cognitively normal Parkinson's disease (PD-CN) and Parkinson's disease mild cognitive impairment (PD-MCI) patients were investigated using event-related potentials (ERP) P300 and volumetric magnetic resonance imaging (MRI) parameters. METHODS: Twenty three patients with PD-CN, 21 with PD-MCI, and 23 demographically-matched healthy controls were included. EEGs were recorded using a visual oddball task and mean amplitude and peak latency values of P300 were measured. Gray matter volumes (GMV) of thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens were obtained using FMRIB Integrated Registration and Segmentation Tool. Correlations among P300, subcortical GMV and cognitive performances were assessed. RESULTS: PD-CN patients demonstrated reduced P300 amplitudes compared to healthy controls. PD-MCI patients had lower P300 amplitudes than both PD-CN patients and controls and reduced volumes of the putamen compared to controls. Both putamen volumes and P300 amplitudes showed moderate associations with executive functions. CONCLUSIONS: Our findings support that P300 amplitude may be a useful marker for the detection of preclinical changes before the appearance of cognitive and structural deterioration in PD, as shown by decreased frontal P300 amplitudes in PD-CN. The reduction further spread to centro-parietal areas in PD-MCI patients, which was accompanied by lower putamen volumes. SIGNIFICANCE: This study is the first to report on changes in ERP P300 amplitude and subcortical volume in well-matched samples of PD-CN, PD-MCI and healthy controls.

Impairment in recognition of emotional facial expressions in Alzheimer's disease is represented by EEG theta and alpha responses.

Behavioral studies have shown that the recognition of facial expressions may be impaired in patients with Alzheimer's disease (AD). The identification and recognition of a facial expression might be represented by event-related brain oscillations. The present study aims to analyze EEG event-related oscillations and determine the electrophysiological indicators of impaired facial expression recognition in AD patients. EEGs of 30 healthy controls and 30 AD patients were recorded during their perception of three different facial expressions (angry, happy, neutral). Event-related power spectrum and phase locking were analyzed in the theta (4-7) and alpha (8-13 Hz) frequency bands with the EEGLAB open toolbox. There was a significant facial Expression × Group interaction (p < 0.05) for the theta power spectrum; the healthy control group had higher theta power than the AD group during the perception of angry facial expressions (p < 0.05). There was a significant hemisphere difference between the two groups (p < 0.05). There was a right hemisphere alpha power dominance in healthy subjects. However, AD patients did not have this alpha power asymmetry. The present study, for the first time in the literature, presents the electrophysiological indicators of impaired recognition of facial expression in AD patients. The current study could be a basis for future studies that will analyze emotional processing in different kinds of dementia patients, and this study may have provided indicators of electrophysiological correlates of behavioral problems observed in clinical practice.

Electrophysiological evidence of altered facial expressions recognition in Alzheimer's disease: A comprehensive ERP study.

OBJECTIVES: The present study aims to evaluate the amplitude and latency of event-related potentials (ERPs) P100, N170, VPP and N230 in individuals with Alzheimer's disease (AD) compared to healthy elderly controls, using a passive viewing task of emotional facial expressions. METHODS: Twenty-four individuals with mild to moderate AD and 23 demographically matched healthy elderly controls were included in the study. ERP P100, N170, VPP and N230 amplitude and latency values were compared between groups. RESULTS: The categorization of emotional facial expressions was intact; yet, increased P100 amplitude and latency, decreased N170 amplitude, and increased VPP amplitude were observed in AD compared to controls. Increased N230 amplitude and latency were observed in response to angry expressions, while neutral expressions elicited decreased amplitude and latency. CONCLUSIONS: Increased P100 amplitude and latency may reflect reduced amygdala volume and disruptions in the visual system, while decreased N170 and increased VPP amplitudes may reflect impaired perceptual processing, mitigated by a greater involvement of prefrontal areas for task performance in AD. SIGNIFICANCE: This study is the first to report a complex pattern of ERPs to emotional facial expressions in individuals with AD.

Abnormalities of functional cortical source connectivity of resting-state electroencephalographic alpha rhythms are similar in patients with mild cognitive impairment due to Alzheimer's and Lewy body diseases.

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.

Levodopa may affect cortical excitability in Parkinson's disease patients with cognitive deficits as revealed by reduced activity of cortical sources of resting state electroencephalographic rhythms.

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.

Electrophysiological and neuropsychological outcomes of severe obstructive sleep apnea: effects of hypoxemia on cognitive performance.

Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized with upper airway obstructions. Some studies showed cognitive and electrophysiological changes in patients with OSAS; however, contradictory results were also reported. The purpose of the present study was twofold: (1) to investigate cognitive changes in severe OSAS patients by using neuropsychological tests and electrophysiological methods together, (2) to investigate influence of hypoxemia levels on cognition. Fifty-four severe OSAS patients and 34 age-, gender- and education matched healthy subjects were participated. OSAS patients were further divided into two subgroups according to minimum oxygen saturation levels. All participants underwent a detailed neuropsychological test battery. A classical visual oddball task was used to elicit ERP P300 and mean P300 amplitudes were measured from Fz, Cz and Pz electrode sites. OSAS patients showed reduced mean P300 amplitudes up to 43-51% on all electrode sites compared to healthy controls. Subgroup analysis revealed significant differences in neuropsychological test scores between healthy controls and high hypoxemia OSAS group, as well as between low and high hypoxemia groups. Moreover, both low and high hypoxemia OSAS groups had lower P300 amplitudes compared with healthy controls. P300 amplitudes showed a gradual decline in parallel with increasing hypoxemia severity; however, the difference between high and low hypoxemia OSAS groups did not reach significance. Moderate correlations were found between sleep parameters, neuropsychological test scores and P300 amplitudes. These results suggest that electrophysiological measures could be better indicators of cognitive changes than neuropsychological tests in OSAS, particularly in mildly affected patients.

Functional cortical source connectivity of resting state electroencephalographic alpha rhythms shows similar abnormalities in patients with mild cognitive impairment due to Alzheimer's and Parkinson's diseases.

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.

Abnormalities of resting-state functional cortical connectivity in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study.

Previous evidence showed abnormal posterior sources of resting-state delta (<4 Hz) and alpha (8-12 Hz) rhythms in patients with Alzheimer's disease with dementia (ADD), Parkinson's disease with dementia (PDD), and Lewy body dementia (DLB), as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis of additional abnormalities in functional cortical connectivity computed in those sources, in ADD, considered as a "disconnection cortical syndrome", in comparison with PDD and DLB. Resting-state eyes-closed electroencephalographic (rsEEG) rhythms had been collected in 42 ADD, 42 PDD, 34 DLB, and 40 normal healthy older (Nold) participants. Exact low-resolution brain electromagnetic tomography (eLORETA) freeware estimated the functional lagged linear connectivity (LLC) from rsEEG cortical sources in delta, theta, alpha, beta, and gamma bands. The area under receiver operating characteristic (AUROC) curve indexed the classification accuracy between Nold and diseased individuals (only values >0.7 were considered). Interhemispheric and intrahemispheric LLCs in widespread delta sources were abnormally higher in the ADD group and, unexpectedly, normal in DLB and PDD groups. Intrahemispheric LLC was reduced in widespread alpha sources dramatically in ADD, markedly in DLB, and moderately in PDD group. Furthermore, the interhemispheric LLC in widespread alpha sources showed lower values in ADD and DLB than PDD groups. At the individual level, AUROC curves of LLC in alpha sources exhibited better classification accuracies for the discrimination of ADD versus Nold individuals (0.84) than for DLB versus Nold participants (0.78) and PDD versus Nold participants (0.75). Functional cortical connectivity markers in delta and alpha sources suggest a more compromised neurophysiological reserve in ADD than DLB, at both group and individual levels.

Abnormalities of Resting State Cortical EEG Rhythms in Subjects with Mild Cognitive Impairment Due to Alzheimer's and Lewy Body Diseases.

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.

Increased long distance event-related gamma band connectivity in Alzheimer's disease.

BACKGROUND: Brain oscillatory responses can be used for non-invasive analyses of cortico-cortical connectivity, local neuronal synchronization, and coherence of oscillations in many neuropsychiatric conditions including Alzheimer's disease (AD). In the present paper, we examine sensory-evoked and event-related gamma coherences elicited by visual stimuli in three sub-gamma bands in two sub-groups of patients with AD (i.e., acetylcholinesterase-inhibitor treated and untreated) and healthy controls. METHODS: We studied a total of 39 patients with probable mild AD (according to NINCDS-ADRDA criteria) who had been sub-divided into untreated (n = 21) and treated (n = 18) (patients either on cholinergic monotherapy or combined therapy with memantine) AD groups, and 21 age-, gender-, and education-matched healthy elderly controls. A simple flash visual paradigm was applied for the acquisition of sensory-evoked coherences. Event-related coherences were elicited using a classical visual oddball paradigm. Both sensory-evoked and event-related gamma coherences were calculated for long-distance intrahemispheric pairs for three frequency ranges: 25-30 Hz, 30-35 Hz, and 40-48 Hz in post-stimulus 0-800 ms duration. The long-distance intrahemispheric pairs from both sides were fronto-parietal, fronto-temporal, fronto-temporoparietal, fronto-occipital, centro-occipital and parieto-occipital. RESULTS: The sensory-evoked or event-related gamma coherences revealed that both treated and untreated AD patients had significantly increased values compared to healthy controls in all three sub-gamma bands. Moreover, the treated AD patients demonstrated significantly higher fronto-parietal gamma coherences during both sensory stimulation and oddball paradigm and lower occipito-parietal coherences during oddball paradigm in comparison to untreated AD patients. CONCLUSION: The present study demonstrated that an increase of gamma coherences was present in response to both visual sensory and cognitive stimulation in AD patients in all gamma sub-bands. Therefore, gamma oscillatory activity seems to be fundamental in brain functions at both the sensory and cognitive levels. The increase of gamma coherence values was not due to cholinergic treatment to any significant extent, as both treated and untreated AD patients had increased gamma coherence values compared to healthy controls. The use of coherence values reflecting brain connectivity holds potential for neuroimaging of AD and understanding brain dynamics related to the effects of medication.