Greek High Phenolic Early Harvest Extra Virgin Olive Oil Reduces the Over-Excitation of Information-Flow Based on Dominant Coupling Mode (DoCM) 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 FIDoCM 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.

The pleiotropic beneficial intervention of olive oil intake on the Alzheimer's disease onset via fibrinolytic system.

The daily consumption of Extra Virgin Olive Oil (EVOO) in Mediterranean nutrition is tightly associated with lower frequency of many diseases' appearance, including Alzheimer's disease (AD). Fibrinolytic system is already assumed to be involved in AD pathophysiology through various factors, especially plasminogen activator inhibitor-1 (PAI-1), a2-antiplasmin (α2ΑP) and tissue plasminogen activator (tPA). We, here, present a biochemical study, as a continuation of a clinical trial of a cohort of 84 participants, focusing on the pleiotropic effect of the annual EVOO consumption on the fibrinolytic factors of Mild Cognitive Impairment (MCI) patients. The levels of all these fibrinolytic factors, measured by Enzyme-Linked Immunosorbent Assay (ELISA) method, were reduced in the serum of MCI patients annually administered with EVOO, versus not treated MCI patients, as well as AD patients. The well-established AD hallmarks (Aß1-40 and Aß1-42 species, tau, and p-tau) of MCI patients' group, annually administered with EVOO, were restored to levels equal to those of the cognitively-healthy group; in contrast to those patients not being administered, and their AD hallmarks levels increased at the end of the year. Moreover, one of the EVOO annual consumption multimodal effects on the MCI patients focused on the levels of an oxidative stress trademark, malondialdehyde (MDA), which displayed also a visible quenching; On the other hand, an increase exhibited in the MCI patients not consuming EVOO one year after, was attributed to the lack of the EVOO anti-oxidative properties. These outcomes are exploitable towards the establishment of natural products like EVOO, as a preventive remedy fighting this neurodegenerative disorder, AD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03362996 MICOIL gov Identifier: NCT03362996.

A Comparison of Traditional and Serious Game-Based Digital Markers of Cognition in Older Adults with Mild Cognitive Impairment and Healthy Controls.

BACKGROUND: Electroencephalography (EEG) has been used to assess brain activity while users are playing an immersive serious game. OBJECTIVE: To assess differences in brain activation as measured with a non-intrusive wearable EEG device, differences in game performance and correlations between EEG power, game performance and global cognition, between cognitively impaired and non-impaired older adults, during the administration of a novel self-administered serious game-based test, the Virtual Supermarket Test (VST). METHODS: 43 older adults with subjective cognitive decline (SCD) and 33 older adults with mild cognitive impairment (MCI) were recruited from day centers for cognitive disorders. Global cognition was assessed with the Montreal Cognitive Assessment (MoCA). Brain activity was measured with a non-intrusive wearable EEG device in a resting state condition and while they were administered the VST. RESULTS: During resting state condition, the MCI group showed increased alpha, beta, delta, and theta band power compared to the SCD group. During the administration of the VST, the MCI group showed increased beta and theta band power compared to the SCD group. Regarding game performance, alpha, beta, delta, and theta rhythms were positively correlated with average duration, while delta rhythm was positively correlated with mean errors. MoCA correlated with alpha, beta, delta, and theta rhythms and with average game duration and mean game errors indicating that elevated EEG rhythms in MCI may be associated with an overall cognitive decline. CONCLUSION: VST performance can be used as a digital biomarker. Cheap commercially available wearable EEG devices can be used for obtaining brain activity biomarkers.

Restoration of BMI1 levels after the administration of early harvest extra virgin olive oil as a therapeutic strategy against Alzheimer's disease.

Even though Alzheimer's disease (AD) is the most common cause of dementia, the mechanisms governing the establishment and progression of the disease remain largely unknown. Here, we investigated the implication of the neuroprotective protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) in AD and the possibility to reverse the onset of the disease through the administration of extra virgin olive oil (EVOO) in Mild Cognitive Impairment (MCI) patients. For this purpose, we utilized a wide bank of MCI patient samples to examine the potential effects of EVOO. We found that while EVOO treatment increases BMI1 levels, p53 levels drop in MCI patient serum after EVOO treatment for 12 months. Additionally, AD-related biomarkers (p-tau, Aß1-42 and Aß1-42/Aß-40 ratio) return to normal levels after administration of EVOO in MCI patients for 12 months. Moreover, we show that upon EVOO administration, BMI1-upregulation correlates with reduction of oxidative stress and inflammatory responses. In conclusion, we provide clinical trial evidence to confirm that restoration of BMI1 activity through EVOO administration in MCI patients constitutes a potential therapeutic approach against neurodegeneration leading to AD.

A Randomized Clinical Trial of Greek High Phenolic Early Harvest Extra Virgin Olive Oil in Mild Cognitive Impairment: The MICOIL Pilot Study.

BACKGROUND: Extra virgin olive oil (EVOO) constitutes a natural compound with high protection over cognitive function. OBJECTIVE: To investigate for the first time the effect of Greek High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) versus Moderate Phenolic (MP-EVOO) and Mediterranean Diet (MeDi) in people with mild cognitive impairment (MCI). METHODS: We conducted a randomized prospective study so as to examine the HP-EH-EVOO and MP-EVOO versus MeDi in MCI. Genetic predisposition (APOEɛ4) to Alzheimer's disease (AD) was tested and an extensive neuropsychological battery was administered at baseline and after 12 months. Each participant was randomized and assigned one of three groups: 1) Group 1 received the HP-EH-EVOO (50 mL/day); 2) Group 2 received the MP-EVOO (50 mL/day), and 3) Group 3 received only the MeDi instructions. RESULTS: Better follow-up performance was found in Group 1 compared to Group 2 and Group 3 in the almost all cognitive domains. Moreover, Group 2 showed also significant improvement compared to Group 3 in ADAS-cog (p = 0.001) and MMSE (p = 0.05), whereas Group 3 exhibited worse or similar to baseline performance in almost all domains. In particular, Group 1 and Group 2 had better outcomes with regards to ADAS-cog (p = 0.003), Digit Span (p = 0.006), and Letter fluency (p = 0.003). Moreover, there was a significant difference (p = 0.001) in the presence of APOEɛ4 between the Groups 1 and 2 versus Group 3. CONCLUSION: Long-term intervention with HP-EH-EVOO or MP-EVOO was associated with significant improvement in cognitive function compared to MeDi, independent of the presence of APOEɛ4.

Detection of Mild Cognitive Impairment in an At-Risk Group of Older Adults: Can a Novel Self-Administered Serious Game-Based Screening Test Improve Diagnostic Accuracy?

BACKGROUND: Literature supports the use of serious games and virtual environments to assess cognitive functions and detect cognitive decline. This promising assessment method, however, has not yet been translated into self-administered screening instruments for pre-clinical dementia. OBJECTIVE: The aim of this study is to assess the performance of a novel self-administered serious game-based test, namely the Virtual Supermarket Test (VST), in detecting mild cognitive impairment (MCI) in a sample of older adults with subjective memory complaints (SMC), in comparison with two well-established screening instruments, the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). METHODS: Two groups, one of healthy older adults with SMC (N = 48) and one of MCI patients (N = 47) were recruited from day centers for cognitive disorders and administered the VST, the MoCA, the MMSE, and an extended pencil and paper neuropsychological test battery. RESULTS: The VST displayed a correct classification rate (CCR) of 81.91% when differentiating between MCI patients and older adults with SMC, while the MoCA displayed of CCR of 72.04% and the MMSE displayed a CCR of 64.89%. CONCLUSION: The three instruments assessed in this study displayed significantly different performances in differentiating between healthy older adults with SMC and MCI patients. The VST displayed a good CCR, while the MoCA displayed an average CCR and the MMSE displayed a poor CCR. The VST appears to be a robust tool for detecting MCI in a population of older adults with SMC.

Web-Based Intervention Effects on Mild Cognitive Impairment Based on Apolipoprotein E Genotype: Quasi-Experimental Study.

BACKGROUND: Apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and mild cognitive impairment (MCI). Computer-based training programs can improve cognitive performance in elderly populations. However, the effects of computer-based interventions on MCI APOE ε4 carriers have never been studied before. OBJECTIVE: The effects of different web-based interventions and the APOE isoform-specific differences in training outcomes are investigated. METHODS: Using a quasi-experimental study design, 202 participants with MCI aged 60 years and older took part in three different intervention programs (physical and cognitive [Long-Lasting Memories, or LLM], cognitive [Active Control, or AC], or physical intervention [Physical Training Control, or PTC]) via an innovative information and communication technologies exergaming platform. Participants in each interventional group were subdivided into APOE ε4 carriers and non-APOE ε4 carriers. All participants underwent an extensive neuropsychological evaluation before and after the training, blood tests, and brain imaging. RESULTS: All interventions resulted in multiple statistically significant cognitive benefits after the intervention. Verbal learning (California Verbal Learning Test: immediate recall test score-LLM: P=.04; AC: P<.001), working memory (digit span forward and backward test scores-AC: P=.03; PTC: P=.02 and P=.006, respectively), and long-term memory (California Verbal Learning Test: delayed recall test score-LLM: P=.02; AC: P=.002; and PTC: P=.02) were improved. There was no statistically significant difference among the intervention effects. APOE ε4 presence moderates intervention effects as the LLM intervention improved only their task-switching processing speed (Trail Making Test, Part B: P=.03) and the PTC intervention improved only the working memory (digit span backward: P=.03). No significant performance alteration was noted for the APOE ε4+ cognitive AC training group. CONCLUSIONS: None of the applied interventions could be identified as the optimal one; it is suggested, however, that combined cognitive and physical training and physical training via exergaming may be more effective for the high-risk MCI ΑPOE ε4+ subgroup.