Assessing the cognitive decline of people in the spectrum of AD by monitoring their activities of daily living in an IoT-enabled smart home environment: a cross-sectional pilot study.

Introduction: Assessing functional decline related to activities of daily living (ADLs) is deemed significant for the early diagnosis of dementia. As current assessment methods for ADLs often lack the ability to capture subtle changes, technology-based approaches are perceived as advantageous. Specifically, digital biomarkers are emerging, offering a promising avenue for research, as they allow unobtrusive and objective monitoring. Methods: A study was conducted with the involvement of 36 participants assigned to three known groups (Healthy Controls, participants with Subjective Cognitive Decline and participants with Mild Cognitive Impairment). Participants visited the CERTH-IT Smart Home, an environment that simulates a fully functional residence, and were asked to follow a protocol describing different ADL Tasks (namely Task 1 - Meal, Task 2 - Beverage and Task 3 - Snack Preparation). By utilizing data from fixed in-home sensors installed in the Smart Home, the identification of the performed Tasks and their derived features was explored through the developed CARL platform. Furthermore, differences between groups were investigated. Finally, overall feasibility and study satisfaction were evaluated. Results: The composition of the ADLs was attainable, and differentiation among the HC group compared to the SCD and the MCI groups considering the feature "Activity Duration" in Task 1 - Meal Preparation was possible, while no difference could be noted between the SCD and the MCI groups. Discussion: This ecologically valid study was determined as feasible, with participants expressing positive feedback. The findings additionally reinforce the interest and need to include people in preclinical stages of dementia in research to further evolve and develop clinically relevant digital biomarkers.

Discriminant Potential of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in Greek Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment.

Background: Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is a widely used screening tool for detecting older adults with Alzheimer's disease among their cognitively healthy peers. A previous study in Greek population showed that ADAS-Cog-Greek (G) is a valid tool and can identify people with Alzheimer's disease from older adult control group; however, there is no current data about whether ADAS-Cog can differentiate older adults with mild cognitive impairment (MCI) from those who have subjective cognitive decline (SCD). Objective: The current study aimed to examine the discriminant potential of ADAS-Cog-G in Greek older adults who meet the criteria for SCD or MCI. Methods: Four hundred eighty-two community-dwelling older adults, visitors of the Greek Alzheimer Association and Related Disorders, were enrolled in the current study. One hundred seventy-six of them met the criteria for SCD and three hundred six had MCI. Results: Path analysis applied to the data showed that age, as well as educational level affected ADAS-Cog-G performance. Results showed that the cut-off scores, which better discriminate people with SCD from MCI as well as their sensitivity and specificity values, were extracted in participants with high educational level (13 educational years<) and mainly under the age of 75 years. Conclusions: The current study provided evidence concerning the discriminant potential of ADAS-Cog-G to differentiate older adults with SCD from those with MCI in the Greek population, and therefore contributes to the relevant literature on the field.

Predictors of Nursing Home Placement in a Cohort of European People with Alzheimer's Disease and Other Dementia Cases Enrolled in SCU-B or Non SCU-B Centers: The RECage Study.

Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease. Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up. Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility. The tertiary objective of the study was to assess the possible role of the SCU-B in delaying NHP. We assessed the relationship of the baseline characteristics with NHP by means of univariate analysis followed by Cox's multivariate model. Results: Patients' mean age was 78.1 years, 54.9% were women. Diagnosis mean age was 75.4 (±8.32) years; the main diagnosis was Alzheimer's disease (296; 58.4%). During follow-up, 96 (18.9%) patients died and 153 (30.1%) were institutionalized without a statistically significant difference between the two cohorts (p = 0.9626). The mean NHP time was 902 (95% CI: 870-934). The multivariable analysis without death as a competing risk retained four independent predictors of NHP: age increase (hazard ratio (HR) = 1.023, 95% CI: 1.000-1.046), patient education level increase (HR = 1.062, 95% CI: 1.024-1.101), Neuropsychiatric Inventory total increase (HR = 1.018; 95% CI: 1.011-1.026), and total Mini-Mental State Examination as a favorable factor (HR = 0.948, 95% CI: 0.925-0.971). Gender (females versus males: HR = 1.265, 95% CI: 0.899-1.781) was included in the final Cox's model for adjusting the estimates for. Conclusions: Our data partially agree with the predictors of NHP in literature including the effect of high education level. No caregivers' factors were statistically significant. Clinical trial registration: NCT03507504.

The Effects of Pomegranate Seed Oil on Mild Cognitive Impairment.

Background: In recent years, there has been a growing interest, supported by many experimental and clinical studies, about the benefits of pomegranate in preventing various pathologic conditions, including brain neurodegeneration. The pomegranate seed oil (PSO) contains high levels of fatty acids that have antioxidant and anti-inflammatory properties. Objective: Due to the lack of clinical trials, the aim of the present study was to investigate the effects of PSO on cognition of people with mild cognitive impairment (MCI). Methods: Eighty people with the diagnosis of MCI were randomized forty to take 5 drops of PSO and follow the Mediterranean Diet (MeDi) and forty just followed MeDi. All were examined with an extensive neuropsychological assessment before and after one year of treatment. Results: The results showed that the participants who took the PSO had statistically significantly better global cognition (p = 0.004), verbal episodic memory (p = 0.009), and processing and executive functions (p < 0.001) in contrast with the participants who did not take it. Conclusions: In conclusion, the PSO can be beneficial for people with MCI as it is helpful for some important cognitive domains. As PSO is a natural product that does not burden the human body, it can be used by people with MCI and be a significant and promising part of holistic approaches for the prevention of dementia.

A Semantic Framework to Detect Problems in Activities of Daily Living Monitored through Smart Home Sensors.

Activities of daily living (ADLs) are fundamental routine tasks that the majority of physically and mentally healthy people can independently execute. In this paper, we present a semantic framework for detecting problems in ADLs execution, monitored through smart home sensors. In the context of this work, we conducted a pilot study, gathering raw data from various sensors and devices installed in a smart home environment. The proposed framework combines multiple Semantic Web technologies (i.e., ontology, RDF, triplestore) to handle and transform these raw data into meaningful representations, forming a knowledge graph. Subsequently, SPARQL queries are used to define and construct explicit rules to detect problematic behaviors in ADL execution, a procedure that leads to generating new implicit knowledge. Finally, all available results are visualized in a clinician dashboard. The proposed framework can monitor the deterioration of ADLs performance for people across the dementia spectrum by offering a comprehensive way for clinicians to describe problematic behaviors in the everyday life of an individual.

What goes wrong with the perceptions of elder financial abuse? Data from older adults, healthcare professionals and students from Greece.

This study examines what healthcare professionals, students and older adults believe about elder financial abuse in Greece. Participants responded to two vignettes by choosing which characteristics indicate elder financial abuse. Greeks are less likely to perceive financial exploitation when the perpetrator is a close family member, but are more likely to recognize it when perpetrated by paid caregivers or more distant (male) relatives. Signing over the victim's property to another is less likely to be perceived as elder abuse than is the taking of money from bank accounts, even though the property is often worth more than what is taken from the account. Although there are some differences in perception between healthcare professionals and others in Greek society, these (and other anomalies) make it difficult to accurately report and prevent elder financial abuse in Greece.

Correction: Ethical challenges of using remote monitoring technologies for clinical research: A case study of the role of local research ethics committees in the RADAR-AD study.

[This corrects the article DOI: 10.1371/journal.pone.0285807.].

A Protocol for the Development and Assessment of a Non-Pharmacological Intervention Designed to Improve Cognitive Skills of Adults with Intellectual Disabilities: A Mixed Method Design.

Aim: This paper describes the steps of a protocol for developing and assessing a non-pharmacological intervention, specifically a Serious Game, with the goal of improving eight cognitive skills in adults with Intellectual Disabilities. Serious games that focus on one deficit and/or are restricted to one disorder have been developed to improve the cognitive skills of people with Intellectual Disabilities. There is a lack of a single tool that targets various cognitive skills as well as a broader spectrum of disorders. Purpose: The presentation of the protocol which describes the steps of developing a new Serious Game that will be evaluated in a randomised control trial intervention. Participants and Methods: The protocol is divided into three stages: identification of cognitive deficits and development of the Serious Game, randomised control trial intervention- follow up assessment, and evaluation of the Serious Game by trainers and caregivers. The participants of the intervention are adults with Intellectual Disabilities. Results: The protocol's results are expected to cover the development of a new Serious Game for specific cognitive functions of a mixed group of adults with Intellectual Disabilities, evaluating the structure and content of the game through neuropsychological assessments for participants and specific questionnaires for trainers and caregivers, evaluating the improvement of specific cognitive abilities in participants in the intervention; and measuring the possible improvement of the quality of life and social interaction of people with Intellectual Disabilities. Conclusion: This is the first study to develop a protocol and implement and assess this new Serious Game. This Serious Game is expected to assist people with Intellectual Disabilities in cognitive and social aspects.

Resilience in Mild Cognitive Impairment (MCI): Examining the Level and the Associations of Resilience with Subjective Wellbeing and Negative Affect in Early and Late-Stage MCI.

The current study examines the relationship between the cognitive state of participants [healthy-early mild cognitive impairment (MCI)-late MCI], some subjective wellbeing factors (positive emotions, engagement, positive relationships, meaning in life, accomplishment, and negative emotions), and negative psychological outcomes (depression, anxiety, stress), as well as psychological resilience. We expected that people with advanced MCI would perceive increased negative psychological outcomes, poorer psychological resilience, and lower levels of subjective wellbeing in contrast to early MCI and healthy participants. The study involved 30 healthy, 31 early, and 28 late MCI individuals. A series of questionnaires have been applied to assess the aforementioned constructs. To examine the hypotheses of the study, path analysis (EQS program) was applied. Results showed that early MCI persons maintain the same levels of positive emotions and feelings of accomplishment with healthy peers. Late-stage patients present those feelings in a diminished form, which adversely impacts psychological resilience. Individuals with early and late MCI exhibit negative emotions and stress that impact their resilience; however, those with early MCI experience greater stress, negative emotions, depression, and anxiety. These findings may be utilized to design psychological interventions for resilience enhancement and support brain health in elderly adults who are at risk of neurodegeneration.

Ethical challenges of using remote monitoring technologies for clinical research: A case study of the role of local research ethics committees in the RADAR-AD study.

INTRODUCTION: Clinical research with remote monitoring technologies (RMTs) has multiple advantages over standard paper-pencil tests, but also raises several ethical concerns. While several studies have addressed the issue of governance of big data in clinical research from the legal or ethical perspectives, the viewpoint of local research ethics committee (REC) members is underrepresented in the current literature. The aim of this study is therefore to find which specific ethical challenges are raised by RECs in the context of a large European study on remote monitoring in all syndromic stages of Alzheimer's disease, and what gaps remain. METHODS: Documents describing the REC review process at 10 sites in 9 European countries from the project Remote Assessment of Disease and Relapse-Alzheimer's Disease (RADAR-AD) were collected and translated. Main themes emerging in the documents were identified using a qualitative analysis approach. RESULTS: Four main themes emerged after analysis: data management, participant's wellbeing, methodological issues, and the issue of defining the regulatory category of RMTs. Review processes differed across sites: process duration varied from 71 to 423 days, some RECs did not raise any issues, whereas others raised up to 35 concerns, and the approval of a data protection officer was needed in half of the sites. DISCUSSION: The differences in the ethics review process of the same study protocol across different local settings suggest that a multi-site study would benefit from a harmonization in research ethics governance processes. More specifically, some best practices could be included in ethical reviews across institutional and national contexts, such as the opinion of an institutional data protection officer, patient advisory board reviews of the protocol and plans for how ethical reflection is embedded within the study.

A Confirmatory and an Exploratory Factor Analysis of the Cohen-Mansfield Agitation Inventory (CMAI) in a European Case Series of Patients with Dementia: Results from the RECage Study.

BACKGROUND: One of the most widely used instruments for assessing agitation in dementia patients is the Cohen-Mansfield Agitation Inventory (CMAI), nevertheless no global score has been proposed. The aim of this study is: (a) to conduct a confirmatory (CFA) and exploratory factor analysis (EFA) of CMAI on people with dementia and Psychological and Behavioral Symptoms (BPSD), and (b) to propose an alternative structure, based on clinical criteria including all CMAI items. METHODS: Confirmatory and exploratory factor analyses were carried out on the CMAI 29 items administered at baseline to 505 patients with dementia (PwD) and BPSD enrolled in the international observational RECage study. RESULTS: The three-factor structure has not been confirmed by the CFA, whilst the EFA was carried out respectively on 25 items disregarding 4 items with a prevalence ≤5% and then on 20 items disregarding 9 items with a prevalence ≤10%. The four-factor structure explaining 56% of the variance comprised Physically Aggressive behavior, Verbally Aggressive behavior, Physically non-aggressive behavior, and Physically and verbally aggressive behavior. CONCLUSIONS: A new grouping of all items according to a clinical criterion is proposed, allowing for a more sensible evaluation of the symptoms leading to better differentiation.

In the Hands of Hypnos: Associations between Sleep, Cognitive Performance and Financial Capacity in aMCI and Mild AD.

Objective The aim of this monocentric observational study is to assess whether sleep disorders can predict financial capacity in single-and multiple-domain aMCI (amnestic Mild Cognitive Impairment), mild Alzheimer's Disease (AD), and healthy controls. Methods Older participants from Northern Greece were examined with several neuropsychological tests, including Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). Sleep duration and quality were based on caregiver/family members' reports in the Sleep Disorders Inventory (SDI). Results These preliminary findings coming from 147 participants indicate for the first time that apart from MMSE, complex cognitive functions, such as financial capacity may be also directly linked to the frequency of sleep-disturbed behaviours as indicated by SDI frequency questions, both in aMCI and mild AD. Discussion An urgency for further investigation of the neglected sleep factor should be added in financial capacity assessment protocols.

Making Pre-screening for Alzheimer's Disease (AD) and Postoperative Delirium Among Post-Acute COVID-19 Syndrome (PACS) a National Priority: The Deep Neuro Study.

SARS-CoV-2 effects on cognition are a vibrant area of active research. Many researchers suggest that COVID-19 patients with severe symptoms leading to hospitalization sustain significant neurodegenerative injury, such as encephalopathy and poor discharge disposition. However, despite some post-acute COVID-19 syndrome (PACS) case series that have described elevated neurodegenerative biomarkers, no studies have been identified that directly compared levels to those in mild cognitive impairment, non-PACS postoperative delirium patients after major non-emergent surgery, or preclinical Alzheimer's disease (AD) patients that have clinical evidence of Alzheimer's without symptoms. According to recent estimates, there may be 416 million people globally on the AD continuum, which include approximately 315 million people with preclinical AD. In light of all the above, a more effective application of digital biomarker and explainable artificial intelligence methodologies that explored amyloid beta, neuronal, axonal, and glial markers in relation to neurological complications in-hospital or later outcomes could significantly assist progress in the field. Easy and scalable subjects' risk stratification is of utmost importance, yet current international collaboration initiatives are still challenging due to the limited explainability and accuracy to identify individuals at risk or in the earliest stages that might be candidates for future clinical trials. In this open letter, we propose the administration of selected digital biomarkers previously discovered and validated in other EU-funded studies to become a routine assessment for non-PACS preoperative cognitive impairment, PACS neurological complications in-hospital, or later PACS and non-PACS improvement in cognition after surgery. The open letter also includes an economic analysis of the implications for such national-level initiatives. Similar collaboration initiatives could have existing pre-diagnostic detection and progression prediction solutions pre-screen the stage before and around diagnosis, enabling new disease manifestation mapping and pushing the field into unchartered territory.

Eliciting brain waves of people with cognitive impairment during meditation exercises using portable electroencephalography in a smart-home environment: a pilot study.

Objectives: Meditation imparts relaxation and constitutes an important non-pharmacological intervention for people with cognitive impairment. Moreover, EEG has been widely used as a tool for detecting brain changes even at the early stages of Alzheimer's Disease (AD). The current study investigates the effect of meditation practices on the human brain across the AD spectrum by using a novel portable EEG headband in a smart-home environment. Methods: Forty (40) people (13 Healthy Controls-HC, 14 with Subjective Cognitive Decline-SCD and 13 with Mild Cognitive Impairment-MCI) participated practicing Mindfulness Based Stress Reduction (Session 2-MBSR) and a novel adaptation of the Kirtan Kriya meditation to the Greek culture setting (Session 3-KK), while a Resting State (RS) condition was undertaken at baseline and follow-up (Session 1-RS Baseline and Session 4-RS Follow-Up). The signals were recorded by using the Muse EEG device and brain waves were computed (alpha, theta, gamma, and beta). Results: Analysis was conducted on four-electrodes (AF7, AF8, TP9, and TP10). Statistical analysis included the Kruskal-Wallis (KW) nonparametric analysis of variance. The results revealed that both states of MBSR and KK lead to a marked difference in the brain's activation patterns across people at different cognitive states. Wilcoxon Signed-ranks test indicated for HC that theta waves at TP9, TP10 and AF7, AF8 in Session 3-KK were statistically significantly reduced compared to Session 1-RS Z = -2.271, p = 0.023, Z = -3.110, p = 0.002 and Z = -2.341, p = 0.019, Z = -2.132, p = 0.033, respectively. Conclusion: The results showed the potential of the parameters used between the various groups (HC, SCD, and MCI) as well as between the two meditation sessions (MBSR and KK) in discriminating early cognitive decline and brain alterations in a smart-home environment without medical support.

The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia - Six-Month Follow-Up.

OBJECTIVES: To investigate the beneficial outcomes of giving cannabidiol (CBD) 3% over a six-month period in the BPSD, the management of which is a crucial issue for everyday clinical praxis and to compare the progress in BPSD of patients who receive Cannabidiol 3% with those who follow usual medical treatment (UMT) in everyday clinical praxis. METHODS: A total of 20 PwD with severe BPSD were recruited from the database of Alzheimer Hellas with NPI score >30. Ten of them were assigned to UMT, while ten were assigned to a six-month treatment with CBD drops. The follow-up assessment was performed with NPI, both clinically and by structured telephone interview. RESULTS: The follow-up assessment with NPI showed significant improvement of the BPSD in all our patients who received CBD, and no or limited improvement in the second group, regardless of the underlying neuropathology of dementia. CONCLUSIONS: We suggest that CBD may be a more effective and safe choice for managing BPSD than the typical intervention. Future large randomized clinical trials are needed to re-assure these findings. CLINICAL IMPLICATIONS: Healthcare professionals should consider incorporating CBD 3% into their practices to reduce BPSD in PwD. Regular assessments are necessary to ensure long-term effectiveness.

Masitinib for mild-to-moderate Alzheimer's disease: results from a randomized, placebo-controlled, phase 3, clinical trial.

BACKGROUND: Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB09004 evaluated masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate dementia due to probable Alzheimer's disease (AD). METHODS: Study AB09004 was a randomized, double-blind, two parallel-group (four-arm), placebo-controlled trial. Patients aged ≥50 years, with clinical diagnosis of mild-to-moderate probable AD and a Mini-Mental State Examination (MMSE) score of 12-25 were randomized (1:1) to receive masitinib 4.5 mg/kg/day (administered orally as two intakes) or placebo. A second, independent parallel group (distinct for statistical analysis and control arm), randomized patients (2:1) to masitinib at an initial dose of 4.5 mg/kg/day for 12 weeks that was then titrated to 6.0 mg/kg/day, or equivalent placebo. Multiple primary outcomes (each tested at a significance level of 2.5%) were least-squares mean change from baseline to week 24 in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), or the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL). Safety for each masitinib dose level was compared against a pooled placebo population. RESULTS: Masitinib (4.5 mg/kg/day) (n=182) showed significant benefit over placebo (n=176) according to the primary endpoint of ADAS-cog, -1.46 (95% CI [-2.46, -0.45]) (representing an overall improvement in cognition) versus 0.69 (95% CI [-0.36, 1.75]) (representing increased cognitive deterioration), respectively, with a significant between-group difference of -2.15 (97.5% CI [-3.48, -0.81]); p<0.001. For the ADCS-ADL primary endpoint, the between-group difference was 1.82 (97.5% CI [-0.15, 3.79]); p=0.038 (i.e., 1.01 (95% CI [-0.48, 2.50]) (representing an overall functional improvement) versus -0.81 (95% CI [-2.36, 0.74]) (representing increased functional deterioration), respectively). Safety was consistent with masitinib's known profile (maculo-papular rash, neutropenia, hypoalbuminemia). Efficacy results from the independent parallel group of titrated masitinib 6.0 mg/kg/day versus placebo (n=186 and 91 patients, respectively) were inconclusive and no new safety signal was observed. CONCLUSIONS: Masitinib (4.5 mg/kg/day) may benefit people with mild-to-moderate AD. A confirmatory study has been initiated to substantiate these data. TRIAL REGISTRATION: EudraCT: 2010-021218-50. CLINICALTRIALS: gov : NCT01872598.

Stressful life events, general cognitive performance, and financial capacity in healthy older adults and Alzheimer's disease patients.

BACKGROUND: The influence of stressful life events on general cognition and for the first time on financial capacity performance of patients with a diagnosis of Alzheimer's disease (AD) and in healthy controls (HC) is assessed. METHODS: A total of 268 participants (122 patients and 146 HCs with similar demographics) were examined with a number of neuropsychological tests, including Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), and Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS) for measuring financial capacity. The life change unit (LCU) method was also used. RESULTS: HCs reported more stressful events than AD patients before the onset of the disease as the LCU load was higher for them (51.80 vs. 27.50), but in both groups the level of LCU load was far below 100, which is the threshold suggested for the induction of a psychosomatic disorder. The most frequently reported life event for AD patients was increased family arguments (n = 45/122), followed by increase in responsibilities (n = 32/122) and financial difficulties (n = 29/122), while the HC group reported problems within the family (n = 56/146), change in health status (n = 32/146), and a death of a beloved family member (n = 27/146). Regressions indicate no causal role for recent life events in the etiopathogenesis of AD, but an influence only of MMSE and diagnosis on financial capacity. CONCLUSIONS: Stressful life events do not seem to be important in financial capacity and relevant vulnerability to financial exploitation for either HCs or AD patients; therefore clinicians should not consider them per se as a possible aggravating factor for financial deficits.