EEG synchronization in mild cognitive impairment and Alzheimer's disease

OBJECTIVES: To compute the synchronization likelihood of multichannel electroencephalogram (EEG) data in Alzheimer (AD) patients, subjects with mild cognitive impairment (MCI) and subjects with subjective memory complaints (SC). MATERIAL AND METHODS: EEGs (200 Hz sample frequency; 21 channels; average reference) were recorded in 10 AD patients (two males; age 76.2; SD 9.36; range 59-86), 17 subjects with MCI (eight males; age 77.41; SD 6.25; range 62-88) and 20 subjects with SCI (11 males; age 68.9; SD 12.96; range: 51-89). The synchronization likelihood, a novel type of coherence measure, was computed, comparing each channel with all other channels, for the 2-6, 6-10, 10-14, 14-18, 18-22 and 22-50 Hz band. RESULTS: The synchronization likelihood was significantly decreased in the 14-18 and 18-22 Hz band in AD patients compared with both MCI subjects and healthy controls. Lower beta band synchronization correlated with lower Mini-Mental state examination (MMSE) scores. CONCLUSION: Loss of beta band synchronization occurs early in mildly affected AD patients and correlates with cognitive impairment.     

Complexity of functional connectivity networks in mild cognitive impairment subjects during a working memory task

ObjectivesThe objective is to study the changes of brain activity in patients with mild cognitive impairment (MCI). Using magneto-encephalogram (MEG) signals, the authors investigate differences of complexity of functional connectivity network between MCI and normal elderly subjects during a working memory task.MethodsMEGs are obtained from 18 right handed patients with MCI and 19 age-matched elderly participants without cognitive impairment used as the control group. The brain networks’ complexities are measured by Graph Index Complexity (C_r) and Efficiency Complexity (C_e).ResultsThe results obtained by both measurements show complexity of functional networks involved in the working memory function in MCI subjects is reduced at alpha and theta bands compared with subjects with control subjects, and at the theta band this reduction is more pronounced in the whole brain and intra left hemisphere.ConclusionsC_e would be a better measurement for showing the global differences between normal and MCI brains compared with C_r.SignificanceThe high accuracy of the classification shows C_e at theta band can be used as an index for assessing deficits associated with working memory, a good biomarker for diagnosis of MCI.     

Event-related desynchronization/synchronization during an auditory-verbal working memory task in mild Parkinson's disease.

OBJECTIVE: Event-related desynchronization (ERD) and synchronization (ERS) were studied during an auditory-verbal working memory task in patients suffering from Parkinson's disease (PD). METHODS: PD patients (n=7, mean age 59) at a mild stage of the disease volunteered in the study. A group of healthy subjects (n=10, mean age 61) served as control group. ERD and ERS of the 1-25 Hz EEG frequencies were studied using wavelet transforms during memory encoding and retrieval. RESULTS: Both groups performed equally well on the memory task. Statistically significant differences in ERD/ERS responses were observed in posterior electrodes during encoding of the memory set due to the fact that alpha ( approximately 10-15 Hz) ERS was elicited in the controls, but not in the PD group. In broad frequency bands ( approximately 6-25 Hz) ERD responses were observed in both groups during memory retrieval. A pre-stimulus alpha ERS seen in the control group was absent in the PD group. CONCLUSIONS: The results of this preliminary study indicate that Parkinson's disease might affect brain oscillatory responses in the alpha frequency range in the encoding phase of auditory-verbal working memory. SIGNIFICANCE: The ERD/ERS patterns may reflect neurophysiological alterations in the processes underlying working memory deficits in PD.     

Altered EEG microstate dynamics in mild cognitive impairment and Alzheimer's disease

ObjectiveResting-state EEG microstate is a promising neurophysiological tool to explore the temporal dynamics of cognitive activity. Till now, the microstate syntax is far from being fully understood in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). We aim to investigate the possible explanation for the alterations of transition probabilities in microstate syntax between different stages of cognitive impairment.MethodsThe artefact-corrected resting-state EEG in patients with MCI (n = 46), AD (n = 43) and healthy controls (HC, n = 43) were used for microstate analysis. Four microstates were labeled A-D according to the study (Koenig et al., 2002).ResultsMicrostate duration, occurrence and coverage showed overall differences between HC, MCI and AD. Duration and coverage B increased significantly in AD compared with HC and MCI. Coverage C decreased significantly in AD compared with MCI. Microstate syntax had specialized single transitions in MCI and AD. Transitions between symmetrical (C and D) and asymmetrical (A and B) classes showed a decreased pattern. It was only in MCI that an increased transition from A to C was found and only in AD an increased transition from A to B was found. Besides, a negative spearman’s correlation was found between the transition probability from A to B and Mini-Mental State Examination (MMSE) scores.ConclusionAltered resting-state EEG microstates in particular specialized single transitions in microstate syntax were showed in MCI and AD.SignificanceFor the first time, we discovered which single transitions between pairs of microstates play an important role in microstate syntax in different stages of cognitive impairment.     

Decreased theta event-related synchronization during working memory activation is associated with progressive mild cognitive impairment

BACKGROUND: Among the different quantitative electroencephalographic markers, theta activity is known to reflect neural resources involved in memory processes and directed attention. Previous studies suggested that synchronization likelihood analysis in theta-band frequency might be a sensitive method to identify early alterations of neuronal networks in mild cognitive impairment (MCI). METHODS: We report here a longitudinal study of 24 MCI patients with theta event-related synchronization (ERS) analysis during the n-back working memory task and neuropsychological follow-up after 1 year. Statistical analysis included analysis of variance and logistic regression to assess the relationship between cognitive decline and theta ERS. RESULTS: Upon follow-up, 13 MCI patients showed progressive MCI and 11 remained stable. In both groups, the phasic increase in theta amplitude after stimulus presentation did not depend on working memory load and electrode sites. Progressive MCI cases displayed significantly lower theta ERS power over all electrode sites compared to stable MCI cases. Theta ERS was significantly related to the cognitive outcome explaining 15.5% of its variability. In terms of MCI classification, the best combination of sensitivity and specificity was 0.87 and 0.60, respectively, with an area under the corresponding receiver operating characteristic curve reaching 76%. CONCLUSIONS: The present data indicate that a decrease in the early phasic theta ERS power during working memory activation may predict cognitive decline in MCI. This phenomenon is not related to working memory load but may reflect the presence of early deficits in directed attention-related neural circuits in MCI.     

EEG alpha synchronization and functional coupling during top-down processing in a working memory task

Electroencephalogram (EEG) alpha (around 10 Hz) is the dominant rhythm in the human brain during conditions of mental inactivity. High amplitudes as observed during rest usually diminish during cognitive effort. During retention of information in working memory, however, power increase of alpha oscillations can be observed. This alpha synchronization has been interpreted as cortical idling or active inhibition. The present study provides evidence that during top-down processing in a working memory task, alpha power increases at prefrontal but decreases at occipital electrode sites, thereby reaching a state in which alpha power and frequency become very similar over large distances. Two experimental conditions were compared. In the first, visuospatial information only had to be retained in memory whereas the second condition additionally demanded manipulation of the information. During the second condition, stronger alpha synchronization at prefrontal sites and larger occipital alpha suppression was observed as compared to that for pure retention. This effect was accompanied by assimilation of prefrontal and occipital alpha frequency, stronger functional coupling between prefrontal and occipital brain areas, and alpha latency shifts from prefrontal cortex to primary visual areas, possibly indicating the control of posterior cortical activation by anterior brain areas. An increase of prefrontal EEG alpha amplitudes, which is accompanied by a decrease at posterior sites, thus may not be interpreted in terms of idling or "global" inhibition but may enable a tight functional coupling between prefrontal cortical areas, and thereby allows the control of the execution of processes in primary visual brain regions.     

Alzheimer's disease and mild cognitive impairment

As our society ages, age-related diseases assume increasing prominence as both personal and public health concerns. Disorders of cognition are particularly important in both regards, and Alzheimer's disease is by far the most common cause of dementia of aging. In 2000, the prevalence of Alzheimer's disease in the United States was estimated to be 4.5 million individuals, and this number has been projected to increase to 14 million by 2050. Although not an inevitable consequence of aging, these numbers speak to the dramatic scope of its impact. This article focuses on Alzheimer's disease and the milder degrees of cognitive impairment that may precede the clinical diagnosis of probable Alzheimer's disease, such as mild cognitive impairment.     

Hippocampal morphology and autobiographic memory in mild cognitive impairment and Alzheimer's disease

Autobiographical memory (AM) comprises memories of one's own past that are characterized by a sense of subjective time and autonoetic awareness. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. However, little is known on the association between cerebral alterations and AM in mild cognitive impairment (MCI) and AD. In the current study, patients with AD or MCI and healthy controls underwent high-resolution magnetic resonance imaging (MRI) and neuropsychological testing including semi-structured assessment of semantic and episodic AM of distinct lifetime periods. In MRI analysis, FSL-FIRST was used to automatically ascertain volume and shape of the hippocampal formation. Episodic, but not semantic AM loss was associated with morphological changes of the hippocampus, primarily involving the left hemisphere. According to shape analyses, these associations referred to regionally specific rather than global atrophy of the hippocampus. Our study demonstrates that loss of episodic AM early in the course of AD is associated with regionally confined hippocampal atrophy, thus supporting the multiple trace theory for the role of the hippocampus in episodic AM. Our findings are not only relevant for the understanding of memory function, but may also contribute to facilitating the early diagnosis of AD.     

Phenotypic regional functional imaging patterns during memory encoding in mild cognitive impairment and Alzheimer's disease

BackgroundReliable blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) phenotypic biomarkers of Alzheimer’s disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature.MethodsA series of random-effects activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based on a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis.ResultsALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal control subjects across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe, specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal control subjects.ConclusionsALE consistencies broadly support the presence of frontal compensatory activity, medial temporal lobe activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective predisease condition. Taken together, these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD.     

The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.     

Gender-specificities in Alzheimer's disease and mild cognitive impairment

Background Amnestic Mild Cognitive Impairment (MCI) is a condition with an increased risk for developing Alzheimer's disease (AD). Presently, gender differences are neglected in the assessment of MCI and AD. Methods We examined verbal and visuospatial episodic memory in 143 subjects diagnosed as healthy controls (HC; N = 48, Mini-Mental State Examination (MMSE) 29.2 ± 1.0 (mean ± standard deviation)), MCI (N = 43,MMSE 28.5 ± 1.4), and AD (N = 49, MMSE 25.1 ± 2.2). Findings Female HC and MCI subjects performed better on verbal episodic memory tasks than males. In contrast, visuospatial episodic memory was better in male than female AD patients. Conclusions We interpret the results in light of a genderspecific cognitive reserve and conclude that the gender-specificity of neuropsychological performance needs to be accounted for in clinical diagnosis of Alzheimer’s disease.     

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.     

Resting EEG sources correlate with attentional span in mild cognitive impairment and Alzheimer's disease

Previous evidence has shown that resting delta and alpha electroencephalographic (EEG) rhythms are abnormal in patients with Alzheimer's disease (AD) and its potential preclinical stage (mild cognitive impairment, MCI). Here, we tested the hypothesis that these EEG rhythms are correlated with memory and attention in the continuum across MCI and AD. Resting eyes-closed EEG data were recorded in 34 MCI and 53 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). These sources were correlated with neuropsychological measures such as Rey list immediate recall (word short-term memory), Rey list delayed recall (word medium-term memory), Digit span forward (immediate memory for digits probing focused attention), and Corsi span forward (visuo-spatial immediate memory probing focused attention). A statistically significant negative correlation (Bonferroni corrected, P < 0.05) was observed between Corsi span forward score and amplitude of occipital or temporal delta sources across MCI and AD subjects. Furthermore, a positive correlation was shown between Digit span forward score and occipital alpha 1 sources (Bonferroni corrected, P < 0.05). These results suggest that cortical sources of resting delta and alpha rhythms correlate with neuropsychological measures of immediate memory based on focused attention in the continuum of MCI and AD subjects.     

Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer's disease: a pilot study

Our aim was to assess the potential of navigated transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) responses in studying neuronal reactivity and cortical connectivity in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). We studied 14 right-handed subjects: five patients with AD, five patients with MCI and four healthy controls. Fifty TMS-pulses at an intensity of 110% of individually determined motor threshold were delivered to the hand area of primary motor cortex (M1) with navigated brain stimulation (NBS). Spreading of primary NBS-evoked neuronal activity was monitored with a compatible 60-channel EEG, and analyzed in time, frequency and spatial-domains. We found significantly reduced TMS-evoked P30 (time-locked response 30 ms after the magnetic stimulation) in the AD subjects. This reduction was seen in the temporo-parietal area ipsilateral to stimulation side as well as in the contralateral fronto-central cortex corresponding to the sensorimotor network, which is anatomically interconnected with the stimulated M1. In addition, there was a significant decrease in the N100 amplitude in the MCI subjects when compared with the control subjects. Thus, the combination of NBS and EEG revealed prominent changes in functional cortical connectivity and reactivity in the AD subjects. This pilot study suggests that the method may provide a novel tool for examining the degree and progression of dementia.     

Subclinical epileptiform activity during sleep in Alzheimer's disease and mild cognitive impairment

ObjectiveRecent findings suggested that subclinical epileptiform activity is prevalent during sleep in a significant proportion of Alzheimer’s Disease (AD) patients. The aims of our study were: (A) comparing the frequency of subclinical epileptiform activity during the sleep in a sample diagnosed with ‘probable’ AD and Mild Cognitive Impairment (MCI) due to AD, and in healthy subjects; (B) evaluating epileptiform EEG activity as a function of different sleep stages within a well-controlled polysomnographic setting.MethodsWe prospectively enrolled 50 ‘probable’ AD patients (73 ± 7.0 years) and 50 subjects with MCI due to AD (72 ± 6.7 years) without history of seizures, comparing them with 50 controls (69 ± 6.7 years). Patients underwent to a full-night video-PSG.ResultsSubclinical epileptiform activity was detected in 6.38% of ‘probable’ AD patients, 11.63% of MCI due to AD subjects and 4.54% of controls (p = 0.43). The comparisons between the three groups for the frequency of epileptiform activity did not reach statistically significant differences neither for total sleep nor for any sleep period considered.ConclusionsOur study shows that, when controlling for sleep stages and the influence of psychoactive drugs, AD patients and MCI due to AD subjects do not exhibit a higher frequency of epileptiform discharges during sleep compared to healthy subjects.SignificanceSubclinical epileptiform activity during sleep does not discriminate ‘probable’ AD from MCI due to AD and healthy controls.     

Event-related. EEG desynchronization and synchronization during an auditory memory task

Event-related desynchronization (ERD) and synchronization (ERS) of the lower (8–10 Hz) and upper (10–12 Hz) alpha bands of background EEG were studied in 10 subjects during an auditory memory scanning paradigm. Each experimental trial started with the presentation of a visual warning signal, after which an auditory 4-vowel memory set was presented for memorization. Thereafter the probe, a fifth vowel, was presented and identified by the subject as belonging or not belonging to the memorized set. In 50% of the cases, the probe was among the previously presented memory set. The presentation of the memory set elicited a significant ERS in the both alpha frequency bands. In contrast, the presentation of the probe elicited a significant bilateral ERD in both alpha frequency bands studied. The results suggest that the ERD phenomenon is closely associated with higher cortical processes such as memory functions rather than with auditory stimulus processing per se. Event-related desynchronization provides a potentially valuable tool for studying cortical activity during cognitive processing in the auditory stimulus modality.     

Subjective memory complaints in Chinese subjects with mild cognitive impairment and early Alzheimer's disease

BACKGROUND: Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia. However, there is inconsistent opinion as to the validity of subjective memory complaints as a criterion for diagnosis. OBJECTIVE: This study aimed to examine the potential significance of applying a short memory questionnaire in the assessment of Chinese subjects with MCI and early dementia. METHODS: Three hundred and six ambulatory Chinese subjects were recruited. Each participant completed a short memory questionnaire. They were also assessed with the Chinese versions of the mini-mental state examination (CMMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), category verbal fluency test (CVFT) and span tests. Severity of cognitive impairment was evaluated using the Clinical Dementia Rating (CDR); subjects with CDR 0.5 were further classified into MCI not demented (MCIND) and MCI possible incipient dementia (MCIID) depending on the subscale scores of CDR. RESULTS: An increasing frequency of memory complaints with increasing CDR was observed (Kruskal Wallis test, chi square = 21.29, df 3, p < 0.001). With a cutoff of 3 or more memory complaints, the memory questionnaire demonstrated a sensitivity of 65.3% and 70.4% in identifying subjects with incipient and early dementia respectively. Significant associations between memory complaints and most cognitive test performance were found (Spearman's correlations, p < 0.01). Logistic regression analysis revealed that educational level, the memory questionnaire, ADAS-Cog total and delayed recall scores were significant predictors of MCIID status. CONCLUSIONS: The findings suggested that a short memory questionnaire is useful in the screening of MCI, particularly in subjects who already present with subtle functioning disturbances. Subjective memory complaints were significant correlated with objective performance of memory functions, reflecting the usefulness of memory complaints in the assessment of MCI.     

Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment

The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction.