Anthoula Tsolaki

Gains in cognition through combined cognitive and physical training: the role of training dosage and severity of neurocognitive disorder.

Physical as well as cognitive training interventions improve specific cognitive functions but effects barely generalize on global cognition. Combined physical and cognitive training may overcome this shortcoming as physical training may facilitate the neuroplastic potential which, in turn, may be guided by cognitive training. This study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n = 237) or a passive control group (n = 85). Training group participants were allocated to different training dosages ranging from 24 to 110 potential sessions. In a pre-post-test design, global cognition was assessed by averaging standardized performance in working memory, episodic memory and executive function tests. The intervention group increased in global cognition compared to the control group, p = 0.002, Cohen’s d = 0.31. Exploratory analysis revealed a trend for less benefits in participants with more severe NCD, p = 0.08 (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d = 0.04). In participants without dementia, we found a dose-response effect of the potential number and of the completed number of training sessions on global cognition, p = 0.008 and p = 0.04, respectively. The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials.

Functional disorganization of small-world brain networks in mild Alzheimer's Disease and amnestic Mild Cognitive Impairment: an EEG study using Relative Wavelet Entropy (RWE)

Previous neuroscientific findings have linked Alzheimers Disease (AD) with less efficient information processing and brain network disorganization. However, pathological alterations of the brain networks during the preclinical phase of amnestic Mild Cognitive Impairment (aMCI) remain largely unknown. The present study aimed at comparing patterns of the detection of functional disorganization in MCI relative to Mild Dementia (MD). Participants consisted of 23 cognitively healthy adults, 17 aMCI and 24 mild AD patients who underwent electroencephalographic (EEG) data acquisition during a resting-state condition. Synchronization analysis through the Orthogonal Discrete Wavelet Transform (ODWT), and directional brain network analysis were applied on the EEG data. This computational model was performed for networks that have the same number of edges (N = 500, 600, 700, 800 edges) across all participants and groups (fixed density values). All groups exhibited a small-world (SW) brain architecture. However, we found a significant reduction in the SW brain architecture in both aMCI and MD patients relative to the group of Healthy controls. This functional disorganization was also correlated with the participants generic cognitive status. The deterioration of the networks organization was caused mainly by deficient local information processing as quantified by the mean cluster coefficient value. Functional hubs were identified through the normalized betweenness centrality metric. Analysis of the local characteristics showed relative hub preservation even with statistically significant reduced strength. Compensatory phenomena were also evident through the formation of additional hubs on left frontal and parietal regions. Our results indicate a declined functional network organization even during the prodromal phase. Degeneration is evident even in the preclinical phase and coexists with transient network reorganization due to compensation.

A Decision-Support Framework for Promoting Independent Living and Ageing Well

Artificial intelligence and decision support systems offer a plethora of health monitoring capabilities in ambient assisted living environment. Continuous assessment of health indicators for elderly people living on their own is of utmost importance, so as to prolong their independence and quality of life. Slow varying, long-term deteriorating health trends are not easily identifiable in seniors. Thus, early sign detection of a specific condition, as well as, any likely transition from a healthy state to a pathological one are key problems that the herein proposed framework aims at resolving. Statistical process control concepts offer a personalized approach toward identification of trends that are away from the atypical behavior or state of the seniors, while fuzzy cognitive maps knowledge representation and inference schema have proved to be efficient in terms of disease classification. Geriatric depression is used as a case study throughout the paper, so to prove the validity of the framework, which is planned to be pilot tested with a series of lone-living seniors in their own homes.

Brain source localization of MMN, P300 and N400: Aging and gender differences

The localization of neuronal generators during an ERP study, using a high-density electroencephalogram (HD-EEG) equipment was made on three Evoked Related Potential (ERP) components, i.e., the Mismatch Negativity (MMN), the P300 and the N400. Furthermore, the ERP characteristics, their field distribution and the area of their maximum field intensity were extracted and compared between young and elderly, as well as between females and males. A two tone oddball experiment was conducted, involving 27 young adults and 18 elderly, healthy and right handed, and HD-EEG data were acquired. These data were then subjected to auditory ERPs extraction and thorough statistical analysis. The derived experimental results revealed significant age-related differences to both the latencies and the amplitudes of the MMN and the P300 and the topographic distribution of the HD-EEG amplitudes. Additionally, a shift in the maximum intensities from frontal to temporal lobe with aging appeared in the case of the P300, whereas no effect was observed for the MMN component. No statistical significant differences (p>0.05) due to age was found in N400 characteristics. Finally, gender-related differences were significant in the response time of the subjects, finding males response faster. The level and the location of the maximum intensity of sources also differed between genders, especially in young subjects. These findings justify the enhanced potential of HD-EEG data to accurately reflect the age and gender dependencies at the three components of simple auditory ERPs and pave the way for the investigation of neurodegenerative pathologies, such as the Alzheimers disease.

Electroencephalogram and Alzheimer’s Disease: Clinical and Research Approaches

Alzheimers disease (AD) is a neurodegenerative disorder that is characterized by cognitive deficits, problems in activities of daily living, and behavioral disturbances. Electroencephalogram (EEG) has been demonstrated as a reliable tool in dementia research and diagnosis. The application of EEG in AD has a wide range of interest. EEG contributes to the differential diagnosis and the prognosis of the disease progression. Additionally such recordings can add important information related to the drug effectiveness. This review is prepared to form a knowledge platform for the project entitled “Cognitive Signal Processing Lab,” which is in progress in Information Technology Institute in Thessaloniki. The team tried to focus on the main research fields of AD via EEG and recent published studies.

Brain source localization of MMN and P300 ERPs in mild cognitive impairment and Alzheimer's disease: a high-density EEG approach

Alzheimers disease is the most common neurodegenerative disease of Western societies, suggesting the need for early diagnosis, even in preclinical stages. In this vein, the localization of neuronal generators of event-related potential (ERP) components, that is, the mismatch negativity and the P300, based on high-density electroencephalogram data, was explored as a means to enhance their sensitivity as markers of preclinical Alzheimers disease (AD). A 2-tone oddball experiment was conducted, involving 21 healthy elderly, 21 mild cognitive impairment, and 21 mild AD patients, while high-density electroencephalogram data were recorded. The results revealed longer latencies of both mismatch negativity and P300 and slower and far less accurate responses as neurodegeneration progressed. Standardized low-resolution electromagnetic tomography revealed that source differences between healthy and mild cognitive impairment and healthy and AD patients for both ERP components were present in the same Brodmann area independently of the ERP and the stage of cognitive decline. This finding indicates an early change of source activation related to cognitive performance and may be used to improve the diagnostic and prognostic value of ERPs.

Cognitive MMN and P300 in mild cognitive impairment and Alzheimer's disease: A high density EEG-3D vector field tomography approach.

Precise preclinical detection of dementia for effective treatment and stage monitoring is of great importance. Miscellaneous types of biomarkers, e.g., biochemical, genetic, neuroimaging, and physiological, have been proposed to diagnose Alzheimers disease (AD), the usual suspect behind manifested cognitive decline, and mild cognitive impairment (MCI), a neuropathology prior to AD that does not affect cognitive functions. Event related potential (ERP) methods constitute a non-invasive, inexpensive means of analysis and have been proposed as sensitive biomarkers of cognitive impairment; besides, various ERP components are strongly linked with working memory, attention, sensory processing and motor responses. In this study, an auditory oddball task is employed, to acquire high density electroencephalograhy recordings from healthy elderly controls, MCI and AD patients. The mismatch negativity (MMN) and P300 ERP components are then extracted and their relationship with neurodegeneration is examined. Then, the neural activation at these components is reconstructed using the 3D vector field tomography (3D-VFT) inverse solution. The results reveal a decline of both ERPs amplitude, and a statistically significant prolongation of their latency as cognitive impairment advances. For the MMN, higher brain activation is usually localized in the inferior frontal and superior temporal gyri in the controls. However, in AD, parietal sites exhibit strong activity. Stronger P300 generators are mostly found in the frontal lobe for the controls, but in AD they often shift to the temporal lobe. Reduction in inferior frontal source strength and the switch of the maximum intensity area to parietal and superior temporal sites suggest that these areas, especially the former, are of particular significance when neurodegenerative disorders are investigated. The modulation of MMN and P300 can serve to produce biomarkers of dementia and its progression, and brain imaging can further contribute to the diagnostic efficiency of ERPs.

Five-year biomarker progression variability for Alzheimer's disease dementia prediction: Can a complex instrumental activities of daily living marker fill in the gaps?

Biomarker progressions explain higher variability in cognitive decline than baseline values alone. This study examines progressions of established biomarkers along with a novel marker in a longitudinal cognitive decline.

Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial

There is evidence to suggest the efficacy of Crocus (saffron) in the management of cognitive decline. This study examined the efficacy of Crocus in patients with amnesic and multi domain MCI (aMCImd). The participants included 17 patients on Crocus and 18 on a waiting list, who were examined with a short neuropsychological battery, MRI 3T, while some patients were examined via 256-channel electroencephalogram (HD-EEG) at baseline and after 12 months. The results showed that patients on Crocus had improved Mini-Mental State Examination scores (p = 0.015), while the control group deteriorated. Also, MRI, EEG, and ERP showed improvement in specific domains. This led us to conclude that Crocus is a good choice for management of aMCImd.

Age Effect in Human Brain Responses to Emotion Arousing Images: The EEG 3D-Vector Field Tomography Modeling Approach

Understanding of the brain responses to emotional stimulation remains a great challenge. Studies on the aging effect in neural activation report controversial results. In this paper, pictures of two classes of facial affect, i.e., anger and fear, were presented to young and elderly participants. High-density 256-channel EEG data were recorded and an innovative methodology was used to map the activated brain state at the N170 event-related potential component. The methodology, namely 3D Vector Field Tomography, reconstructs the electrostatic field within the head volume and requires no prior modeling of the individuals brain. Results showed that the elderly exhibited greater N170 amplitudes, while age-based differences were also observed in the topographic distribution of the EEG recordings at the N170 component. The brain activation analysis was performed by adopting a set of regions of interest. Results on the maximum activation area appeared to be emotion-specific; the anger emotional conditions induced the maximum activation in the inferior frontal gyrus, while fear activated more the superior temporal gyrus. The approach used here shows the potential of the proposed computational model to reveal the age effect on the brain activation upon emotion arousing images, which could be further transferred to the design of assistive clinical applications.