co morbidity and neuroimaging in alzheimer s disease

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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 Alzheimer's 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 participant's generic cognitive status. The deterioration of the network's 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

Pseudocyesis as a healing mechanism for psychological trauma

Pseudocyesis, a rare condition characterized by clinical signs and symptoms of pregnancy except for the actual existence of a fetus, is a somatic symptom disorder associated with a variety of biological, psychological and social factors. The present report aims to present the case of a 45-year old patient with pseudocyesis from a psychodynamic perspective. According to a psychodynamic perspective and based on patient’s history, pseudocyesis functioned as a mental healing mechanismfor the trauma of long-standing infertility, the trauma of eight unsuccessful and painful in vitro fertilization attempts and above all, the trauma of finally giving birth to a non-healthy child

Greek high phenolic early harvest extra virgin olive oil reduces the over-excitation of information-flow based on dominant coupling mode model in patients with mild cognitive impairment: an EEG resting-state validation approach

Background:Extra virgin olive oil (EVOO) constitutes a natural compound with high protection over cognitive function that could positively alter brain dynamics and the mixture of within and between-frequency connectivity. Objective:The balance of cross-frequency coupling over within-frequency coupling can build a nonlinearity index (NI) that encapsulates the over-excitation of information flow between brain areas and across experimental time. The present study investigated for the very first time how the Greek High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) versus Moderate Phenolic (MP-EVOO) and Mediterranean Diet (MeDi) intervention in people with mild cognitive impairment (MCI) could affect their spontaneous EEG dynamic connectivity. Methods:Forty-three subjects (14 in MeDi, 16 in MP-EVOO, and 13 in HP-EH-EVOO) followed an EEG resting-state recording session (eyes-open and closed) before and after the treatment. Following our dominant coupling mode model, we built a dynamic integrated dynamic functional connectivity graph that tabulates the functional strength and the dominant coupling mode model of every pair of brain areas. Results:Signal spectrum within 1–13 Hz and theta/beta ratio have decreased in the HP-EH-EVOO group in the eyes-open condition. The intervention improved the FI D oCM across groups and conditions but was more prominent in the HP-EH-EVOO group (p <  0.001). Finally, we revealed a significant higher post-intervention reduction of NI (ΔNITotal and α ) for the HP-EH-EVOO compared to the MP-EVOO and MeDi groups (p <  0.0001). Conclusion:Long-term intervention with HP-EH-EVOO reduced the over-excitation of information flow in spontaneous brain activity and altered the signal spectrum of EEG rhythms

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Εfficacy of computer-based interventions in mild cognitive impairment subjects stratified by gene polymorphisms

Mild cognitive impairment (MCI) can be defined as the condition between healthy aging and dementia. Apolipoprotein E ε4 allele and TREM2 (R47H) are known as genetic risk factors for Alzheimer's Disease (AD). Computer-based training programs seem to improve the cognitive performance of the elderly. This study investigates the effects of different computer-based interventions and the impact of genetic risk factors on the outcomes. The study also aims to investigate the long-term effects of different non-pharmacological interventions in 2 years. The research will try to determine whether there are differences in training outcomes based on genotype and which training program can postpone further cognitive decline and dementia onset. Three hundred thirty-three participants >60 years old were split into three different training programs (a. combined physical and cognitive training, b. cognitive training, c. physical training) through an elderly-friendly training web-based platform and a passive control group. Additionally, one hundred fifty-nine MCI subjects were assessed with Fullerton test to evaluate the impact of the computerized Physical Exercise via "Exergaming" on the functional fitness of MCI older adults in general but also depending on the presence of genetic risk factors. Every participant underwent an extensive neuropsychological evaluation before and after the interventions, blood tests, and brain imaging. Also, a blood sample was taken for DNA testing. All the interventions resulted in multiple statistically significant cognitive benefits. The APOE ε4-carriers present an improvement resistance. The follow-ups' analysis showed that most of the training beneficial effects on the neuropsychological scores were retained 24 months post-training even for the resistant APOE ε4-carriers. The positive impact of physical exercise on functional fitness was statistically significant for APOE ε4-carriers and non-carriers, and it was also retained six months post-training. The prevalence of the polymorphism R47H of the TREM2 gene in our study was 1% (3/300); therefore, it was not possible to identify the effects of its presence. We suggest that the continuous, combined Cognitive and Physical Training via "Exergaming" may achieve long-term benefits for the high-risk MCI ΑPOE ε4+ subgroup. The polymorphism R47H of the TREM2 gene was found to be very rare in Greek MCI patients, and it was assessed for the first time in this study.Η Ήπια νοητική Διαταραχή (ΗΝΔ) θεωρείται ως η ενδιάμεση κλινική κατάσταση μεταξύ του φυσιολογικού γήρατος και της άνοιας. Το αλλήλιο ε4 της Απολιποπρωτεΐνης Ε (APOE) και ο πολυμορφισμός R47H του γονιδίου TREM2 είναι γνωστοί γενετικοί παράγοντες κινδύνου για τη Νόσο Alzheimer (NA). Μη φαρμακευτικές παρεμβάσεις με τη χρήση νέων τεχνολογιών φαίνεται πως μπορούν να βελτιώσουν την νοητική επίδοση των ηλικιωμένων. Οι επιδράσεις διαφορετικών παρεμβάσεων με τη χρήση νέων τεχνολογιών και η επίδραση της παρουσίας των γενετικών επιβαρυντικών πολυμορφισμών διερευνώνται στα πλαίσια της παρούσας διατριβής. Η μελέτη στόχο έχει να διερευνήσει την αποτελεσματικότητα των παρεμβάσεων με τη χρήση νέων τεχνολογιών σε βάθος χρόνου διετίας, παρουσία γενετικών παραγόντων κινδύνου. Καθώς και να διερευνήσει πιθανή υπεροχή κάποιας παρέμβασης στην αναστολή εξέλιξης της νόσου. Τριακόσιοι τριανταπέντε συμμετέχοντες ηλικίας >60 ετών χωρίστηκαν σε τρεις διαφορετικές ομάδες παρέμβασης (α. συνδυασμός νοητικής και σωματικής άσκησης, β. νοητικής άσκησης και γ. σωματικής άσκησης) που διενεργήθηκαν μέσω ειδικού λογισμικού διαδικτυακά και μια παθητική ομάδα ελέγχου. Επιπλέον, εκατόν πενήντα επτά ασθενείς με ΗΝΔ εκτιμήθηκαν μέσω της λειτουργικής σωματομετρικής κλίμακας Fullerton, προκειμένου να διερευνηθεί επιμέρους η επίδραση της σωματικής άσκησης μέσω νέων τεχνολογιών στη σωματική κατάσταση των ηλικιωμένων παρουσία γενετικών παραγόντων κινδύνου. Όλοι οι συμμετέχοντες υποβλήθηκαν σε εκτενή νευροψυχολογική εκτίμηση, πριν και μετά την παρέμβαση, αιματολογικό και απεικονιστικό έλεγχο ενώ λήφθηκε και δείγμα για το γενετικό έλεγχο. Όλες οι παρεμβάσεις κατέδειξαν στατιστικά σημαντική βελτίωση σε πολλαπλές νευροψυχολογικές δοκιμασίες στο σύνολο των συμμετεχόντων. Ωστόσο, οι φορείς του APOE ε4 δεν είχαν στατιστικά σημαντική βελτίωση ως άμεσο αποτέλεσμα μετά το πέρας της παρέμβασης. Οι επανεκτιμήσεις των ασθενών 24 μήνες μετά το πέρας της παρέμβασης κατέδειξαν ότι το όφελος των παρεμβάσεων διατηρείται, εν μέρει, 2 χρόνια μετά και μάλιστα είναι εμφανής η αναστολή της εξέλιξης και στους φορείς του APOE ε4. Επιπλέον η βελτίωση των σωματομετρικών μεταβλητών μέσω της σωματικής άσκησης ήταν στατιστικά σημαντική τόσο στους φορείς του APOE ε4 όσο και στους μη φορείς. Το θετικό αυτό αποτέλεσμα διατηρήθηκε και 6 μήνες μετά την παρέμβαση. Ο επιπολασμός του R47H του γονιδίου TREM2 ήταν μόλις 1% (3/300), και ως εκ τούτου δεν ήταν εφικτή η μελέτη της επίδρασης της παρουσίας του στις υπό μελέτη παραμέτρους. Η συνδυασμένη νοητική και σωματική άσκηση με τη χρήση νέων τεχνολογιών (Exergaming), μπορεί να επιφέρει θετικές επιδράσεις στη νοητική και σωματική κατάσταση των ασθενών με ΗΝΔ, ακόμη και των γενετικά επιβαρυμένων με το γονίδιο ΑPOE ε4. Ο πολυμορφισμός R47H του γονιδίου TREM2, είναι πολύ σπάνιος στον ελληνικό πληθυσμό με ΗΝΔ όπως εκτιμήθηκε για πρώτη φορά από την παρούσα μελέτη

Electroencephalogram and Alzheimer’s Disease: Clinical and Research Approaches

Alzheimer’s 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

A Novel Connectome-based Electrophysiological Study of Subjective Cognitive Decline Related to Alzheimer’s Disease by Using Resting-state High-density EEG EGI GES 300

Aim: To investigate for the first time the brain network in the Alzheimer&rsquo;s disease (AD) spectrum by implementing a high-density electroencephalography (HD-EEG - EGI GES 300) study with 256 channels in order to seek if the brain connectome can be effectively used to distinguish cognitive impairment in preclinical stages. Methods: Twenty participants with AD, 30 with mild cognitive impairment (MCI), 20 with subjective cognitive decline (SCD) and 22 healthy controls (HC) were examined with a detailed neuropsychological battery and 10 min resting state HD-EEG. We extracted correlation matrices by using Pearson correlation coefficients for each subject and constructed weighted undirected networks for calculating clustering coefficient (CC), strength (S) and betweenness centrality (BC) at global (256 electrodes) and local levels (29 parietal electrodes). Results: One-way ANOVA presented a statistically significant difference among the four groups at local level in CC [F (3, 88) = 4.76, p = 0.004] and S [F (3, 88) = 4.69, p = 0.004]. However, no statistically significant difference was found at a global level. According to the independent sample t-test, local CC was higher for HC [M (SD) = 0.79 (0.07)] compared with SCD [M (SD) = 0.72 (0.09)]; t (40) = 2.39, p = 0.02, MCI [M (SD) = 0.71 (0.09)]; t (50) = 0.41, p = 0.004 and AD [M (SD) = 0.68 (0.11)]; t (40) = 3.62, p = 0.001 as well, while BC showed an increase at a local level but a decrease at a global level as the disease progresses. These findings provide evidence that disruptions in brain networks in parietal organization may potentially represent a key factor in the ability to distinguish people at early stages of the AD continuum. Conclusions: The above findings reveal a dynamically disrupted network organization of preclinical stages, showing that SCD exhibits network disorganization with intermediate values between MCI and HC. Additionally, these pieces of evidence provide information on the usefulness of the 256 HD-EEG in network construction