Background: Dementia is a priority for global public health. The management of behavioral and psychological symptoms of dementia (BPSD) is one of the highest ongoing challenges and needs new approaches. The special care unit for people with dementia and BPSD (SCU-B) is viewed in this context as a further medical intervention. Aim: this study aims to explore SCU-B units in order to describe their main characteristics in relation to different implementation contexts, identify the characteristics of their replicability, and examine the social innovation elements promoted by SCU-B units. Method: This qualitative study is based on focus groups (FGs) and interviews involving nine international centers. Five of the centers have a memory clinic unit and SCU-B, compared with six that only have a memory clinic unit. A total number of 18 FGs were held, which altogether involved 164 participants. All data were transcribed verbatim and analyzed by means of a content analysis and a SWOT (strengths, weaknesses, opportunities, and threats) analysis. Results: The qualitative analysis offers a vision of the SCU-B model as an innovative care unit for BPSD, promoting social innovation in the long-term care (LTC) sector. This system mainly targets people with dementia and BPSD and their informal caregivers but encourages collaboration between dementia care stakeholders at the micro and meso levels. Conclusions: Specific characteristics of the country’s LTC systems and the organization of specialized units are determinants for the success of the SCU-B experience. The replicability of the entire SCU-B model was considered low; however, the implementation of single elements composing the SCU-B model may foster innovation. This study provides relevant suggestions on how to implement the SCU-B unit and innovative solutions for dementia care.

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.

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, A beta 1-42 and A beta 1-42/AP-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.

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 (alpha 2 Alpha P) 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 (A beta 1-40 and A beta 1-42 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.

Background: Alzheimer’s disease (AD) is the most common type of dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain; amyloid beta 1-42 is a marker of amyloid plaques, while total and phosphorylated tau are markers of NFT formation. Additional biomarkers associated with disease pathogenesis are needed, for better prognosis, more specific diagnosis, prediction of disease severity and progression and for improved patient classification in clinical trials. The aim of the present study was to evaluate brain-specific proteins as potential biomarkers of progression of AD. Methods: Overall, 30 candidate proteins were quantified in cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment (MCI) and mild, moderate and severe AD dementia (n=101) using mass spectrometry-based selected reaction monitoring assays. ELISA was used for neuronal pentraxin receptor-1 (NPTXR) confirmation. Results: The best discrimination between MCI and more advanced AD stages (moderate and severe dementia) was observed for protein NPTXR (area under the curve, AUC=0.799). A statistically different abundance of this protein was observed between the two groups, with severe AD patients having progressively lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort that included Open Peer Review

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.

OBJECTIVEAlthough Mediterranean diet is connected with longevity and lower rate of many disorders including Alzheimer's disease (AD), the effect of olive oil, which is the principal component of the Mediterranean diet, on fibrinolytic system related to AD and especially on plasminogen activator inhibitor-1 (PAI-1) and a2-antiplasmin in aged participants are not yet examined. This study was performed on 108 aged participants allocated into 5 groups: Mild Cognitive Impairment (MCI) (36) patients subjected to 1-year therapy with extra virgin olive oil (EVOO), MCI without therapy patients (26), MCI without therapy 1-year later patients (11), AD patients (30) and healthy individuals (16). Hypothesis/Purpose: To examine the effect of EVOO therapy on the fibrinolytic factors PAI-1 and a2-antiplasmin, on hallmarks of AD, tau and Aβ amyloid fragments and on an oxidative stress biomarker, MDA in the serum of MCI patients aiming to be exploited as a future preventive therapy.RESULTSUsing ELISA method, the levels of both fibrinolytic factors PAI-1 and a2- antiplasmin in the serum of MCI patients were reduced notably in the EVOO treated patients versus the control group and were lower than those of all other groups. For better determination of AD from other pathological conditions the ratio Aβ1-42/Aβ1-40 was measured in serum of all participants. The more lessened the ratio is, the more cognitive impairment is observed in patients. The MCI group with one-year EVOO therapy displayed a ratio similar to this of healthy individuals. Moreover, patients with EVOO therapy showed decreased tau protein levels in comparison with all the other groups. The levels of the oxidative stress's biomarker, malondialdehyde (MDA) showed a significant decrease in MCI patients subjected to EVOO therapy revealing the involvement of the beneficial antioxidative properties of EVOO in the progression of AD.CONCLUSIONWe demonstrated that EVOO therapy may prevent the risk of patients with MCI to progress to AD via decreasing fibrinolytic factors PAI-1 and a2 antiplasmin that reflecting in the diminution of the hallmarks proteins of AD, tau and Aβ amyloid as well and in a biomarker of oxidative stress, MDA.

Research investigating treatments and interventions for cognitive decline and Alzheimer's disease (AD) suffer due to difficulties in accurately identifying individuals at risk of AD in the pre-symptomatic stages of the disease. There is an urgent need for better identification of such individuals in order to enable earlier treatment and to properly stage and stratify participants for clinical trials and intervention studies. Although some biological measures (biomarkers) can identify Alzheimer's-related changes before significant changes in cognitive function occur, such biomarkers are not ideal as they are only able to place individuals in rudimentary stages of the disease/cognitive decline and sometimes mistakenly diagnose individuals. Two tests, based on real-world functioning, which have been used to screen for pre-symptomatic AD are dual-task walking tests and day-out tasks. A multisite clinical trial financed by the European Institute for Innovation & Technology (EIT), the Global Brain Health Institute and Alzheimer's Association USA aimed to validate a novel digital biomarker of cognitive decline, the Altoida ADPS app. A group of pre-identified healthy older adults that can be described as high-risk and individuals in prodromal stages of AD (n=410) were being studied for a period of 36 months on the basis of 6 domains (Demographics, Aβ and Tau, MRI, Cognition, APOE status). The ADPS Neuro Motor Index (NMI) was included as a secondary outcome measure of cognitive ability and real-world function. ADPS is administrable by means of a tablet in less than 10 minutes and tracks 250 real-world metrics, while the individual places three-dimensional virtual objects in a real environment with their subsequent recovery after a distraction task. ADPS demonstrated high test-retest reliability and was able to accurately discriminate between healthy controls, high-risk individuals and prodromal stages of AD. It could also differentiate between people with mild cognitive impairment who convert to AD and those who don't and correlated with existing measures of cognitive function and biomarkers. ADPS is rapid, ecological and cheaper than current neuropsychological tests and, in case of complete validation as a tool to assist physicians in real-world clinical settings, opens the doors to large-scale population screening for the early detection of cognitive impairment.

Background: Alzheimer’s disease (AD) is the most common type of dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain; amyloid beta 1-42 is a marker of amyloid plaques, while total and phosphorylated tau are markers of NFT formation. Additional biomarkers associated with disease pathogenesis are needed, for better prognosis, more specific diagnosis, prediction of disease severity and progression and for improved patient classification in clinical trials. The aim of the present study was to evaluate brain-specific proteins as potential biomarkers of progression of AD. Methods: Overall, 30 candidate proteins were quantified in cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment (MCI) and mild, moderate and severe AD dementia (n=101) using mass spectrometry-based selected reaction monitoring assays. ELISA was used for neuronal pentraxin receptor-1 (NPTXR) confirmation. Results: The best discrimination between MCI and more advanced AD stages (moderate and severe dementia) was observed for protein NPTXR (area under the curve, AUC=0.799). A statistically different abundance of this protein was observed between the two groups, with severe AD patients having progressively lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort that included controls, MCI and AD patients. Conclusions: We conclude that NPTXR protein in CSF is a novel potential biomarker of AD progression and could have important utility in assessing treatment success in clinical trials.

Background: Alzheimer’s disease (AD) is the most common type of dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain; amyloid beta 1-42 is a marker of amyloid plaques, while total and phosphorylated tau are markers of NFT formation. Additional biomarkers associated with disease pathogenesis are needed, for better prognosis, more specific diagnosis, prediction of disease severity and progression and for improved patient classification in clinical trials. The aim of the present study was to evaluate brain-specific proteins as potential biomarkers of progression of AD. Methods: Overall, 30 candidate proteins were quantified in cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment (MCI) and mild, moderate and severe AD dementia (n=101) using mass spectrometry-based selected reaction monitoring assays. ELISA was used for neuronal pentraxin receptor-1 (NPTXR) confirmation. Results: The best discrimination between MCI and more advanced AD stages (moderate and severe dementia) was observed for protein NPTXR (area under the curve, AUC=0.799). A statistically different abundance of this protein was observed between the two groups, with severe AD patients having progressively lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort that included controls, MCI and AD patients. Conclusions: We conclude that NPTXR protein in CSF is a novel potential biomarker of AD progression and could have important utility in assessing treatment success in clinical trials.