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.

CSF proteomic profiles of neurodegeneration biomarkers in Alzheimer's disease.

INTRODUCTION: We aimed to unravel the underlying pathophysiology of the neurodegeneration (N) markers neurogranin (Ng), neurofilament light (NfL), and hippocampal volume (HCV), in Alzheimer's disease (AD) using cerebrospinal fluid (CSF) proteomics. METHODS: Individuals without dementia were classified as A+ (CSF amyloid beta [Aß]42), T+ (CSF phosphorylated tau181), and N+ or N- based on Ng, NfL, or HCV separately. CSF proteomics were generated and compared between groups using analysis of covariance. RESULTS: Only a few individuals were A+T+Ng-. A+T+Ng+ and A+T+NfL+ showed different proteomic profiles compared to A+T+Ng- and A+T+NfL-, respectively. Both Ng+ and NfL+ were associated with neuroplasticity, though in opposite directions. Compared to A+T+HCV-, A+T+HCV+ showed few proteomic changes, associated with oxidative stress. DISCUSSION: Different N markers are associated with distinct neurodegenerative processes and should not be equated. N markers may differentially complement disease staging beyond amyloid and tau. Our findings suggest that Ng may not be an optimal N marker, given its low incongruency with tau pathophysiology. HIGHLIGHTS: In Alzheimer's disease, neurogranin (Ng)+, neurofilament light (NfL)+, and hippocampal volume (HCV)+ showed differential protein expression in cerebrospinal fluid. Ng+ and NfL+ were associated with neuroplasticity, although in opposite directions. HCV+ showed few proteomic changes, related to oxidative stress. Neurodegeneration (N) markers may differentially refine disease staging beyond amyloid and tau. Ng might not be an optimal N marker, as it relates more closely to tau.

Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study.

INTRODUCTION: We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration. METHODS: We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF-AD) study using the EPIC array. RESULTS: We identified Bonferroni-significant differential methylation associated with CSF YKL-40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL-40 levels correlating with plasma YKL-40 levels. A co-localization analysis showed shared genetic variants underlying YKL-40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co-methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development. DISCUSSION: We conducted the most comprehensive epigenome-wide association study (EWAS) of AD-relevant CSF biomarkers to date. Future work should explore the relationship between YKL-40 genotype, DNA methylation, and protein levels in the brain. HIGHLIGHTS: Blood DNA methylation was assessed in the EMIF-AD MBD study. Epigenome-wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)-relevant cerebrospinal fluid (CSF) biomarker measures. Five Bonferroni-significant loci were associated with YKL-40 levels and seven with neurofilament light chain (NfL). DNA methylation in YKL-40 co-localized with previously reported genetic variation. DNA methylation potentially mediates the effect of single-nucleotide polymorphisms (SNPs) in YKL-40 on CSF protein levels.

Blood-based multivariate methylation risk score for cognitive impairment and dementia.

INTRODUCTION: The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection. METHODS: In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in independent dementia cohorts. RESULTS: We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (P = 2.0 × 10-3). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)-Learning = 2.47) and Parkinson's disease (hazard ratio for MCI/dementia = 2.59). DISCUSSION: Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk. HIGHLIGHTS: We used whole blood DNA methylation as a surrogate for 14 dementia risk factors. Created a multivariate methylation risk score for predicting cognitive impairment. Emphasized the role of machine learning and omics data in predicting dementia. The score predicts cognitive impairment development at the population level.

Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer's disease CSF profile of neuronal injury and inflammation.

Alzheimer's disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (ß-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on NfL and YKL-40, indicators of neuronal injury and inflammation. Four genes were associated with this PC: IFFO1, DTNB, NLRC3, and SLC22A10. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2 and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB, NLRC3, and SLC22A10 heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2 and CASZ1 were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.

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.

Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits.

INTRODUCTION: Despite increasing evidence of a role of rare genetic variation in the risk of Alzheimer's disease (AD), limited attention has been paid to its contribution to AD-related biomarker traits indicative of AD-relevant pathophysiological processes. METHODS: We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808). RESULTS: Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively. DISCUSSION: The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets.

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.

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.

Longitudinal Cognitive and Physical Training Effectiveness in MCI, Based on the Experience of the Alzheimer's Hellas Day Care Centre.

This study assesses the effectiveness of a multicomponent Longitudinal Cognitive Training (CT) program plus physical exercise (PE) for people with Mild Cognitive Impairment (MCI). 155 people with MCI, completed a 3 years (3Y) CT+PE, whilst 133 were control. Neuropsychological assessment was performed at baseline and 3 years later, whilst CT+PE had additional annual assessments. According to the results, the 3Y CT+PE outperformed control in cognitive abilities (p < 0.002), and Activities of Daily Living (ADL) (p < 0.001), stabilized their functional performances between 1st and 2nd year, but worsened in working and verbal memory between 2nd and 3 rd year (p < 0.002). Control deteriorated in cognitive functions (p < 0.001) and ADL (p < 0.001) after 3 years, whilst 1.33% of the experimental and 13.53% of the control group progressed to dementia (p < 0.001). Longitudinal CT+PE improves cognitive performance and ADL in MCI and delay the progression to dementia.

Liberating older adults from the bonds of vascular risk factors: What is their impact on financial capacity in amnestic mild cognitive impairment?

BACKGROUND: There is a pressing need to clarify whether vascular risk factors (VRFs) are related to the heterogeneous cognitive performance found in mild cognitive impairment (MCI) and whether the number of VRFs relates to financial capacity impairment in patients with amnestic MCI (aMCI). METHODS: A total of 112 participants were divided into three groups: patients with single-domain aMCI, patients with multiple-domain aMCI, and healthy controls (HCs), while taking into consideration whether participants had a diagnosis of one VRF or disease, or more than one VRF or disease. Patients with aMCI with VRFs (one and more than one VRF) and HCs did not differ significantly in age, education, and sex. Mini-Mental State Examination, 15-item Geriatric Depression Scale, and Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS) were administered to all groups. RESULTS: Diagnosis (P <0.001) and VRFs (P = 0.006) showed significant main effects on LCPLTAS but no interaction (P = 0.654). Patients with aMCI with high vascular burden were more frequently of the multiple-domain subtype, whereas patients with no vascular burden were more frequently of the single-domain subtype. A larger vascular burden is correlated with lower LCPLTAS scores. DISCUSSION: Vascular burden plays an important role in the heterogeneity of aMCI by impairing financial capacity.

Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer's disease pathophysiology.

BACKGROUND: Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics. METHODS: Individuals were classified based on CSF amyloid beta (Aß)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed. RESULTS: A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus. CONCLUSION: The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD.

Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

Frontotemporal dementia and financial capacity: facing the Cerberus of overestimation or underestimation?

OBJECTIVE: This study investigates the performance of people with frontotemporal dementia (FTD) on objective assessment of financial capacity with comparison to the estimation of financial capacity by both people themselves and their caregivers. METHOD: FTD patients and healthy (age/gender/education-matched) controls from Greece underwent cognitive assessment (memory, attention, executive functioning, visuospatial skills, verbal functions), emotional (anxiety, depression), and financial capacity assessment (Legal Capacity for Property Law Transactions Assessment Scale-LCPLTAS). Additionally, they self-reported on their financial performance and a third-party living with the older participants for both groups reported their estimates of financial performance and their anxiety and depression levels. RESULTS: Financial capacity in FTD patients is severely impaired compared to controls, but caregivers of FTD patients tend to overestimate the patients' financial performance, a finding that is not related to the caregivers' depression and anxiety levels or other demographics. FTD patients overestimate their financial capacity. CONCLUSION: FTD may have significant impact on financial capacity, but people with FTD tend to overestimate their own financial capacity. This study also indicates that families and caregivers tend to overestimate financial capacity in people with FTD. This has implications for the assessment and care planning of people with FTD in clinical settings.

Catastrophe Theory Applied to Neuropsychological Data: Nonlinear Effects of Depression on Financial Capacity in Amnestic Mild Cognitive Impairment and Dementia.

Financial incapacity is one of the cognitive deficits observed in amnestic mild cognitive impairment and dementia, while the combined interference of depression remains unexplored. The objective of this research is to investigate and propose a nonlinear model that explains empirical data better than ordinary linear ones and elucidates the role of depression. Four hundred eighteen (418) participants with a diagnosis of amnestic MCI with varying levels of depression were examined with the Geriatric Depression Scale (GDS-15), the Functional Rating Scale for Symptoms of Dementia (FRSSD), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). Cusp catastrophe analysis was applied to the data, which suggested that the nonlinear model was superior to the linear and logistic alternatives, demonstrating depression contributes to a bifurcation effect. Depressive symptomatology induces nonlinear effects, that is, beyond a threshold value sudden decline in financial capacity is observed. Implications for theory and practice are discussed.

Longitudinal Study of Depression on Amnestic Mild Cognitive Impairment and Financial Capacity.

OBJECTIVES: Amnestic mild cognitive impairment (aMCI) among other cognitive deficits also includes impairments in financial capacity, but so far the role of depression in time has not been examined. We aimed to examine the hypothesis that individuals with aMCI and comorbid worsening depression levels would demonstrate greater deficits in financial capacity atone year in relation to multiple-domain aMCI patients with stable levels of depression, aMCI patients without depression and healthy individuals. METHODS: Ninety-six Greek women and 24 men aged 54 and older (multiple-domain aMCI with, stable and increased levels of depression at one year, aMCI without depressive symptoms, and cognitively intact elders with and without depression) were examined with the Mini-mental State Examination (MMSE), the Geriatric Depression Scale (GDS-15), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). RESULTS: Bootstrapped ANCOVA was implemented. Multiple-domain aMCI patients' performance regarding financial capacity is severely impaired when depression co-exists, resembling the performance of patients with mild Alzheimer's disease, and it declines further when depression deteriorates. CONCLUSIONS: Findings contribute to the limited evidence in financial capacity assessment when depression co-exists showing that higher depressive symptom scores are associated with reduced financial capacity scores and deterioration of depressive symptomatology worsens not only general cognitive outcome, but financial capacity in particular. CLINICAL IMPLICATIONS: Proactive care for individuals with depression is needed as this condition severely influences financial capacity in aMCI.

Greek Adaptation of the Positive Aspects of Caregiving (PAC) Scale in Dementia Caregivers.

Objectives: The aim of the present study is to validate the Positive Aspects of Caregiving (PAC) scale in Greek informal family caregivers of patients with dementia, in order to assess its psychometric properties.Methods: Two hundred and forty-seven dementia caregivers completed the Greek version of the PAC (G-PAC) scale in correlation with the following psychometric tools, the Beck Depression Scale, the Zarit Burden Interview (ZBI), the Beck Anxiety Inventory (BAI), the Quality of Life-AD (QoL-AD), the Perceived Stress Scale (PSS), and the Neuropsychiatric Inventory (NPI). Caregivers were included in the study after they had been initially informed of its purpose and completed the informed consent.Results: The Principal Component Analysis (PCA) extracted two factors for the G-PAC, which is also in agreement with the original version, which is Enriching Life and Affirming Self. Concurrent validity suggested significant correlations between G-PAC and behavioral and psychological symptoms of dementia and with perceived stress. In regard to the reliability measures, the results showed that the G-PAC scale has very good internal reliability and high levels of test-retest reliability.Conclusions: The scale is a both valid and reliable tool, and therefore it can be used to assess the positive aspects of caregiving in dementia caregivers.Clinical implications: The development of positive psychology measures in dementia care can be regarded as the cornerstone of the psychotherapeutic interventions addressed to caregivers, and therefore helping them to adapt better in their caregiving role.

Mild Alzheimer Disease, Financial Capacity, and the Role of Depression: Eyes Wide Shut?

The aim of this study was to assess whether comorbid depression in patients with mild Alzheimer disease (AD) can influence financial capacity. The sample comprised 109 participants divided into 4 groups: mild AD with and without depressive symptoms, and cognitive normal elderly with and without depression. Participants were examined using a number of neuropsychological tests, with an emphasis on the Mini-Mental State Examination, the 15-item Geriatric Depression Scale, and the Legal Capacity for Property Law Transactions Assessment Scale. Financial capacity ascertained as performance in the Legal Capacity for Property Law Transactions Assessment Scale in the group of mild AD patients was severely impaired when depression coexisted, thus clearly differentiating the mild AD group from mild AD with comorbid depression.

Vascular Dementia, Depression, and Financial Capacity Assessment.

We still know little about financial capacity, which consists of multiple cognitive domains as well as specific skills, and the influence of depression in patients with vascular dementia (VaD). Participants were divided into 4 groups: (1) VaD with and (2) without depressive symptoms, (3) nondemented elders with and (4) without depression. The participants were examined with the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS-15), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). The findings extend earlier work in other groups of older patients and indicate that VaD patients' performance in cognitive functioning and financial capacity is severely impaired, while there is a statistically significant difference between depressed and nondepressed VaD patients. Thus, depression negatively influences financial capacity. Depression and mood disorders should be considered in future capacity research with older adults and with larger VaD populations.

Unraveling Ariadne's Thread Into the Labyrinth of aMCI: Depression and Financial Capacity.

BACKGROUND: People with amnestic mild cognitive impairment (aMCI) face many daily challenges as memory loss is their predominant cognitive impairment. OBJECTIVES: This study examined whether financial capacity can be influenced by comorbid depression in patients with multiple-domain aMCI. MATERIALS AND METHODS: The participants included 120 patients in 4 groups: multiple-domain aMCI with and without depressive symptoms, and nondemented elders with and without depression. Participants were examined with the Mini-Mental State Examination, the 15-item Geriatric Depression Scale, and the Legal Capacity for Property Law Transactions Assessment Scale. RESULTS: The findings extend earlier work in other groups of older patients and indicate that the performance of patients with multiple-domain aMCI in cognitive functioning and financial capacity is severely impaired when depression coexists, resembling the performance of patients with mild Alzheimer disease. CONCLUSIONS: The results support special care for individuals with depression as this condition severely influences financial capacity in aMCI.