Search results for: Alzheimer's dementia

Authors: Sara Sahraoui

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This research studied the effect of Alzheimer's disease (AD) on language information processing in subjects with Alzheimer’s disease (AD) who were bilingual (French and dialectical Arabic). The results show a disorder of certain semantic aspects of their mother tongue (L1). On the other hand, grammatical levels appeared to be relatively unaffected in oral speech in L1 but were disturbed in the second language (L2). In consequence, we constructed a cognitive-language stimulation protocol for bilingual patients (PSCLAB) to respond to this disorder. The efficacy of this protocol in terms of rehabilitation was assessed in 30 such patients through discourse analysis carried out before and after initiating the protocol. The results show that cognitive/language training using the PSCLAB appears to improve the language behaviour of bilingual patients with AD. However, this survey study aims to verify the satisfaction of patients’ relatives with the results of cognitive language training by PSCLAB. We developed a brief instrument to measure the satisfaction of family members. The results report that the patient's relatives are satisfied with the results of cognitive training by PSCLAB.

Keywords: satisfaction, Alzheimer's disease, rehabilitation, levels language

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Authors: Linyi Fan, C.J. Schumaker

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Background: Biomedical efforts to treat Alzheimer’s disease (AD) have typically produced mixed to poor results, while more lifestyle-focused treatments such as exercise may fare better than existing biomedical treatments. A few promising studies have indicated that activities of daily life (ADL) may be a useful way of predicting AD. However, the existing cross-sectional studies fail to show how functional-related issues such as ADL in early years predict AD and how social factors influence health either in addition to or in interaction with individual risk factors. This study would helpbetterscreening and early treatments for the elderly population and healthcare practice. The findings have significance academically and practically in terms of creating positive social change. Methodology: The purpose of this quantitative historical, correlational study was to examine the relationship between early years’ ADL and the development of AD in later years. The studyincluded 4,526participantsderived fromRAND HRS dataset. The Health and Retirement Study (HRS) is a longitudinal household survey data set that is available forresearchof retirement and health among the elderly in the United States. The sample was selected by the completion of survey questionnaire about AD and dementia. The variablethat indicates whether the participant has been diagnosed with AD was the dependent variable. The ADL indices and changes in ADL were the independent variables. A four-step multilevel regression model approach was utilized to address the research questions. Results: Amongst 4,526 patients who completed the AD and dementia questionnaire, 144 (3.1%) were diagnosed with AD. Of the 4,526 participants, 3,465 (76.6%) have high school and upper education degrees,4,074 (90.0%) were above poverty threshold. The model evaluatedthe effect of ADL and change in ADL on onset of AD in late years while allowing the intercept of the model to vary by level of education. The results suggested that the only significant predictor of the onset of AD was changes in early years’ ADL (b = 20.253, z = 2.761, p < .05). However, the result of the sensitivity analysis (b = 7.562, z = 1.900, p =.058), which included more control variables and increased the observation period of ADL, are not supported this finding. The model also estimated whether the variances of random effect vary by Level-2 variables. The results suggested that the variances associated with random slopes were approximately zero, suggesting that the relationship between early years’ ADL were not influenced bysociodemographic factors. Conclusion: The finding indicated that an increase in changes in ADL leads to an increase in the probability of onset AD in the future. However, this finding is not support in a broad observation period model. The study also failed to reject the hypothesis that the sociodemographic factors explained significant amounts of variance in random effect. Recommendations were then made for future research and practice based on these limitations and the significance of the findings.

Keywords: alzheimer’s disease, epidemiology, moderation, multilevel modeling

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Authors: Frederick Huie, Lauren Fusfeld, William Burchenal, Scott Howell, Alyssa McVey, Thomas F. Goss

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Alzheimer’s Disease (AD) is a degenerative brain disease characterized by memory loss and cognitive decline that presents a substantial economic burden for patients and health insurers in the US. This study evaluates the payer budget impact of the DISCERN™ test in the diagnosis and management of patients with symptoms of dementia evaluated for AD. DISCERN™ comprises three assays that assess critical factors related to AD that regulate memory, formation of synaptic connections among neurons, and levels of amyloid plaques and neurofibrillary tangles in the brain and can provide a quicker, more accurate diagnosis than tests in the current diagnostic pathway (CDP). An Excel-based model with a three-year horizon was developed to assess the budget impact of DISCERN™ compared with CDP in a Medicare Advantage plan with 1M beneficiaries. Model parameters were identified through a literature review and were verified through consultation with clinicians experienced in diagnosis and management of AD. The model assesses direct medical costs/savings for patients based on the following categories: •Diagnosis: costs of diagnosis using DISCERN™ and CDP. •False Negative (FN) diagnosis: incremental cost of care avoidable with a correct AD diagnosis and appropriately directed medication. •True Positive (TP) diagnosis: AD medication costs; cost from a later TP diagnosis with the CDP versus DISCERN™ in the year of diagnosis, and savings from the delay in AD progression due to appropriate AD medication in patients who are correctly diagnosed after a FN diagnosis.•False Positive (FP) diagnosis: cost of AD medication for patients who do not have AD. A one-way sensitivity analysis was conducted to assess the effect of varying key clinical and cost parameters ±10%. An additional scenario analysis was developed to evaluate the impact of individual inputs. In the base scenario, DISCERN™ is estimated to decrease costs by $4.75M over three years, equating to approximately $63.11 saved per test per year for a cohort followed over three years. While the diagnosis cost is higher with DISCERN™ than with CDP modalities, this cost is offset by the higher overall costs associated with CDP due to the longer time needed to receive a TP diagnosis and the larger number of patients who receive a FN diagnosis and progress more rapidly than if they had received appropriate AD medication. The sensitivity analysis shows that the three parameters with the greatest impact on savings are: reduced sensitivity of DISCERN™, improved sensitivity of the CDP, and a reduction in the percentage of disease progression that is avoided with appropriate AD medication. A scenario analysis in which DISCERN™ reduces the utilization for patients of computed tomography from 21% in the base case to 16%, magnetic resonance imaging from 37% to 27% and cerebrospinal fluid biomarker testing, positive emission tomography, electroencephalograms, and polysomnography testing from 4%, 5%, 10%, and 8%, respectively, in the base case to 0%, results in an overall three-year net savings of $14.5M. DISCERN™ improves the rate of accurate, definitive diagnosis of AD earlier in the disease and may generate savings for Medicare Advantage plans.

Keywords: Alzheimer’s disease, budget, dementia, diagnosis.

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Faisal Almalki

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Pyran is a heterocyclic group containing oxygen that possesses a variety of pharmacological effects. Pyran is also one of the most prevalent structural subunits in natural products, such as xanthones, coumarins, flavonoids, benzopyrans, etc. Additionally demonstrating the neuroprotective properties of pyrans is the fact that this heterocycle has recently attracted the attention of scientists worldwide. Alzheimer's Disease (AD) treatment and diagnosis are two of the most critical research objectives worldwide. Increased amounts of extracellular senile plaques, intracellular neurofibrillary tangles, and a progressive shutdown of cholinergic basal forebrain neuron transmission are often related with cognitive impairment. This review highlights the various pyran scaffolds of natural and synthetic origin that are effective in the treatment of AD. For better understanding synthetic compounds are categorized as different types of pyran derivatives like chromene, flavone, xanthone, xanthene, etc. The discussion encompasses both the structure-activity correlations of these compounds as well as their activity against AD. Because of the intriguing actions that were uncovered by these pyran-based scaffolds, there is no question that they are at the forefront of the search for potential medication candidates that could treat Alzheimer's disease.

Keywords: alzheimer’s disease, pyran, coumarin, xanthone

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Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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Authors: Roshanim Koris, Norashidah Mohamed Nor, Sharifah Azizah Haron, Normaz Wana Ismail, Syed Mohamed Aljunid Syed Junid, Amrizal Muhammad Nur, Asrul Akmal Shafie, Suraya Yusuff, Namaitijiang Maimaiti

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An ageing population has huge implications for virtually every aspect of Malaysian societies. The elderly consume a greater volume of healthcare facilities not because they are older, but because of they are sick. The chronic comorbidities and deterioration of cognitive ability would lead the elderly’s health to become worst. This study aims to provide a comprehensive estimate of the direct and indirect costs of health care used in a nationally representative sample of community-dwelling elderly with dementia and as well as the determinants of healthcare cost. A survey using multi-stage random sampling techniques recruited a final sample of 2274 elderly people (60 years and above) in the state of Johor, Perak, Selangor and Kelantan. Mini Mental State Examination (MMSE) score was used to measure the cognitive capability among the elderly. Only the elderly with a score less than 19 marks were selected for further analysis and were classified as dementia. By using a two-part model findings also indicate household income and education level are variables that strongly significantly influence the healthcare cost among elderly with dementia. A number of visits and admission are also significantly affect healthcare expenditure. The comorbidity that highly influences healthcare cost is cancer and seeking the treatment in private facilities is also significantly affected the healthcare cost among the demented elderly. The level of dementia severity is not significant in determining the cost. This study is expected to attract the government's attention and act as a wake-up call for them to be more concerned about the elderly who are at high risk of having chronic comorbidities and cognitive problems by providing more appropriate health and social care facilities. The comorbidities are one of the factor that could cause dementia among elderly. It is hoped that this study will promote the issues of dementia as a priority in public health and social care in Malaysia.

Keywords: ageing population, dementia, elderly, healthcare cost, healthcare utiliztion

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Authors: Yishu Gong, Liangliang Yang, Jianyu Zhang, Zhengyu Chen, Sihong He, Xusheng Zhang, Wei Zhang

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide and is characterized by cognitive decline and behavioral changes. People living with Alzheimer’s disease often find it hard to complete routine tasks. However, there are limited objective assessments that aim to quantify the difficulty of certain tasks for AD patients compared to non-AD people. In this study, we propose to use speech emotion recognition (SER), especially the frustration level, as a potential biomarker for quantifying the difficulty patients experience when describing a picture. We build an SER model using data from the IEMOCAP dataset and apply the model to the DementiaBank data to detect the AD/non-AD group difference and perform longitudinal analysis to track the AD disease progression. Our results show that the frustration level detected from the SER model can possibly be used as a cost-effective tool for objective tracking of AD progression in addition to the Mini-Mental State Examination (MMSE) score.

Keywords: Alzheimer’s disease, speech emotion recognition, longitudinal biomarker, machine learning

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Authors: Berit Johannessen

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Introduction: Depression and dementia are the two most common psychiatric disorders of older people. The use of antidepressants does not always have the desired effect and serious side effects are common. Aroma therapists claim that the essential oil of Bergamot has an antidepressant effect. Aromatherapy is defined as holistic or complementary medicine and is rarely used in the Norwegian public health service, but in recent years, there has been an increasing interest in, and use of complementary and alternative therapies (CAM) in the Norwegian population, and aromatherapy is one of the most widely used. Focus for this study: How do nurses experience the use of Bergamot essential oil for patients suffering from dementia and depression? Method: Action research study including 12 patients and 8 nurses. The patients were strategically selected by the nurses and were given Bergamot in a fan diffuser every day for 12 weeks. The patients' mood and behavior patterns were reported daily and the nurse`s experiences were reported weekly. Individual interviews with the nurses were conducted at the end of the project. Results: The nurses reported that bergamot had positive impact on patients mood and wellbeing, and was considered as an effective method for six patients, four had uncertain effect and two had no effect. They also reported less use of medication and that the fan diffusers were easy and pleasant to administer. They found the use of natural remedies as Bergamot inspiring and wanted to learn more about aromatherapy and its use in nursing. Some were disturbed by the smell and some had to deal with critical and negative colleagues. Conclusion: Nurses experienced aromatherapy using bergamot oil in fan diffusers as a simple and useful procedure for patients suffering from dementia and depression. The effects were varying. Further research is needed.

Keywords: aromatherapy, bergamot, dementia, depression

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Authors: Fatih Sonmez

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

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Authors: Hediyeh Talebi, Shokoofeh Ghiam, Changiz Eslahchi

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Traditionally, Alzheimer’s disease research has focused on genes with significant fold changes, potentially neglecting subtle but biologically important alterations. Our study introduces an integrative approach that highlights genes crucial to underlying biological processes, regardless of their fold change magnitude. Alzheimer's Single-cell RNA-seq data related to the peripheral blood mononuclear cells (PBMC) was extracted from the Gene Expression Omnibus (GEO). After quality control, normalization, scaling, batch effect correction, and clustering, differentially expressed genes (DEGs) were identified with adjusted p-values less than 0.05. These DEGs were categorized based on cell-type, resulting in four datasets, each corresponding to a distinct cell type. To distinguish between cells from healthy individuals and those with Alzheimer's, an adversarial autoencoder with a classifier was employed. This allowed for the separation of healthy and diseased samples. To identify the most influential genes in this classification, the weight matrices in the network, which includes the encoder and classifier components, were multiplied, and focused on the top 20 genes. The analysis revealed that while some of these genes exhibit a high fold change, others do not. These genes, which may be overlooked by previous methods due to their low fold change, were shown to be significant in our study. The findings highlight the critical role of genes with subtle alterations in diagnosing Alzheimer's disease, a facet frequently overlooked by conventional methods. These genes demonstrate remarkable discriminatory power, underscoring the need to integrate biological relevance with statistical measures in gene prioritization. This integrative approach enhances our understanding of the molecular mechanisms in Alzheimer’s disease and provides a promising direction for identifying potential therapeutic targets.

Keywords: alzheimer's disease, single-cell RNA-seq, neural networks, blood biomarkers

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Authors: J. Fox, J. Randhawa, M. Chan, L. Campbell, A. Weakely, D. J. Harvey, S. Tomaszewski Farias

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Early identification of individuals at risk for conversion to dementia provides an opportunity for preventative treatment. Many older adults (30-60%) report specific subjective cognitive decline (SCD); however, previous research is inconsistent in terms of what types of complaints predict future cognitive decline. The purpose of this study is to identify which specific complaints from the Everyday Cognition Scales (ECog) scales, a measure of self-reported concerns for everyday abilities across six cognitive domains, are associated with: 1) conversion from a clinical diagnosis of normal to either MCI or dementia (categorical variable) and 2) progressive cognitive decline in memory and executive function (continuous variables). 415 cognitively normal older adults were monitored annually for an average of 5 years. Cox proportional hazards models were used to assess associations between self-reported ECog items and progression to impairment (MCI or dementia). A total of 114 individuals progressed to impairment; the mean time to progression was 4.9 years (SD=3.4 years, range=0.8-13.8). Follow-up models were run controlling for depression. A subset of individuals (n=352) underwent repeat cognitive assessments for an average of 5.3 years. For those individuals, mixed effects models with random intercepts and slopes were used to assess associations between ECog items and change in neuropsychological measures of episodic memory or executive function. Prior to controlling for depression, subjective concerns on five of the eight Everyday Memory items, three of the nine Everyday Language items, one of the seven Everyday Visuospatial items, two of the five Everyday Planning items, and one of the six Everyday Organization items were associated with subsequent diagnostic conversion (HR=1.25 to 1.59, p=0.003 to 0.03). However, after controlling for depression, only two specific complaints of remembering appointments, meetings, and engagements and understanding spoken directions and instructions were associated with subsequent diagnostic conversion. Episodic memory in individuals reporting no concern on ECog items did not significantly change over time (p>0.4). More complaints on seven of the eight Everyday Memory items, three of the nine Everyday Language items, and three of the seven Everyday Visuospatial items were associated with a decline in episodic memory (Interaction estimate=-0.055 to 0.001, p=0.003 to 0.04). Executive function in those reporting no concern on ECog items declined slightly (p <0.001 to 0.06). More complaints on three of the eight Everyday Memory items and three of the nine Everyday Language items were associated with a decline in executive function (Interaction estimate=-0.021 to -0.012, p=0.002 to 0.04). These findings suggest that specific complaints across several cognitive domains are associated with diagnostic conversion. Specific complaints in the domains of Everyday Memory and Language are associated with a decline in both episodic memory and executive function. Increased monitoring and treatment of individuals with these specific SCD may be warranted.

Keywords: alzheimer’s disease, dementia, memory complaints, mild cognitive impairment, risk factors, subjective cognitive decline

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Authors: Mounia El Jaouhari, Mira Goral, Samir Diouny

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Introduction: Previous research has indicated that language impairments are recognized as a feature of many neurodegenerative disorders, including non-language-led dementia subtypes such as Alzheimer´s disease (AD). In this preliminary study, the focal aim is to quantify the semantic content of naming and connected speech samples of Moroccan patients diagnosed with AD using two tasks taken from the culturally adapted and validated Moroccan version of the Boston Diagnostic Aphasia Examination. Methods: Five individuals with AD and five neurologically healthy individuals matched for age, gender, and education will participate in the study. Participants with AD will be diagnosed on the basis of the Moroccan version of the Diagnostic and Statistial Manual of Mental Disorders (DSM-4) screening test, the Moroccan version of the Mini Mental State Examination (MMSE) test scores, and neuroimaging analyses. The participants will engage in two tasks taken from the MDAE-SF: 1) Picture description and 2) Naming. Expected findings: Consistent with previous studies conducted on English speaking AD patients, we expect to find significant word production and retrieval impairments in AD patients in all measures. Moreover, we expect to find category fluency impairments that further endorse semantic breakdown accounts. In sum, not only will the findings of the current study shed more light on the locus of word retrieval impairments noted in AD, but also reflect the nature of Arabic morphology. In addition, the error patterns are expected to be similar to those found in previous AD studies in other languages.

Keywords: alzheimer's disease, anomia, connected speech, semantic impairments, moroccan arabic

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Authors: Ryuji Yamazaki, Masahiro Kochi, Weiran Zhu, Hiroko Kase

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In care for older adults, behavioral and psychological symptoms of dementia (BPSD) like agitation and aggression are distressing for patients and their caretakers, often resulting in premature institutionalization with increased costs of care. To improve mood and mitigate symptoms, as a non-pharmaceutical approach, emotion-oriented therapy like reminiscence work is adopted in face-to-face communication. Telecommunication support is expected to be provided by robotic media as a bridge for digital divide for those with dementia and facilitate social interaction both verbally and nonverbally. The purpose of this case study is to explore the conditions in which robotic media can effectively attract attention from older adults with dementia and promote their well-being. As a pilot study, we introduced the pillow-phone Hugvie^®, a huggable humanly shaped communication medium to five residents with dementia at a care facility, to investigate how the following conditions work for the elderly when they use the medium; 1) no sound, 2) radio, non-interactive, 3) daily conversation, and 4) reminiscence work. As a result, under condition 4, reminiscence work, the five participants kept concentration in interacting with the medium for a longer duration than other conditions. In condition 4, they also showed larger amount of utterances than under other conditions. These results indicate that providing topics related to personal histories through robotic media could affect communication positively and should, therefore, be further investigated. In addition, the issue of ethical implications by using persuasive technology that affects emotions and behaviors of older adults is also discussed.

Keywords: BPSD, reminiscence, tactile telecommunication, utterances

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Authors: Carlos Roncero-Parra, Alfonso Parreño-Torres, Jorge Mateo Sotos, Alejandro L. Borja

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In this research, different methods based on machine/deep learning algorithms are presented for the classification and diagnosis of patients with mental disorders such as alzheimer. For this purpose, the signals obtained from 32 unipolar electrodes identified by non-invasive EEG were examined, and their basic properties were obtained. More specifically, different well-known machine learning based classifiers have been used, i.e., support vector machine (SVM), Bayesian linear discriminant analysis (BLDA), decision tree (DT), Gaussian Naïve Bayes (GNB), K-nearest neighbor (KNN) and Convolutional Neural Network (CNN). A total of 668 patients from five different hospitals have been studied in the period from 2011 to 2021. The best accuracy is obtained was around 93 % in both ADM and ADA classifications. It can be concluded that such a classification will enable the training of algorithms that can be used to identify and classify different mental disorders with high accuracy.

Keywords: alzheimer, machine learning, deep learning, EEG

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Authors: Ramazan Bakir, Gizem Kayar

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It is known that Alzheimer and Dementia are the two most common types of Neurodegenerative diseases and their visibility is getting accelerated for the last couple of years. As the population sees older ages all over the world, researchers expect to see the rate of this acceleration much higher. However, unfortunately, there is no known pharmacological cure for both, although some help to reduce the rate of cognitive decline speed. This is why we encounter with non-pharmacological treatment and tracking methods more for the last five years. Many researchers, including well-known associations and hospitals, lean towards using non-pharmacological methods to support cognitive function and improve the patient’s life quality. As the dementia symptoms related to mind, learning, memory, speaking, problem-solving, social abilities and daily activities gradually worsen over the years, many researchers know that cognitive support should start from the very beginning of the symptoms in order to slow down the decline. At this point, life of a patient and caregiver can be improved with some daily activities and applications. These activities include but not limited to basic word puzzles, daily cleaning activities, taking notes. Later, these activities and their results should be observed carefully and it is only possible during patient/caregiver and M.D. in-person meetings in hospitals. These meetings can be quite time-consuming, exhausting and financially ineffective for hospitals, medical doctors, caregivers and especially for patients. On the other hand, digital support systems are showing positive results for all stakeholders of healthcare systems. This can be observed in countries that started Telemedicine systems. The biggest potential of our system is setting the inter-user communication up in the best possible way. In our project, we propose Machine Learning based digitalization of validated traditional cognitive tests (e.g. MOCA, Afazi, left-right hemisphere), their analyses for high-quality follow-up and communication systems for all stakeholders. R. Bakir and G. Kayar are with Gefeasoft, Inc, R&D – Software Development and Health Technologies company. Emails: ramazan, gizem @ gefeasoft.com This platform has a high potential not only for patient tracking but also for making all stakeholders feel safe through all stages. As the registered hospitals assign corresponding medical doctors to the system, these MDs are able to register their own patients and assign special tasks for each patient. With our integrated machine learning support, MDs are able to track the failure and success rates of each patient and also see general averages among similarly progressed patients. In addition, our platform also supports multi-player technology which helps patients play with their caregivers so that they feel much safer at any point they are uncomfortable. By also gamifying the daily household activities, the patients will be able to repeat their social tasks and we will provide non-pharmacological reminiscence therapy (RT – life review therapy). All collected data will be mined by our data scientists and analyzed meaningfully. In addition, we will also add gamification modules for caregivers based on Naomi Feil’s Validation Therapy. Both are behaving positively to the patient and keeping yourself mentally healthy is important for caregivers. We aim to provide a therapy system based on gamification for them, too. When this project accomplishes all the above-written tasks, patients will have the chance to do many tasks at home remotely and MDs will be able to follow them up very effectively. We propose a complete platform and the whole project is both time and cost-effective for supporting all stakeholders.

Keywords: alzheimer’s, dementia, cognitive functionality, cognitive tests, serious games, machine learning, artificial intelligence, digitalization, non-pharmacological, data analysis, telemedicine, e-health, health-tech, gamification

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Authors: Ammar Alobaidy, Lamees Alsawafi, Malak Almawali, Balqees Alabri, Hajer Alhamrashdi

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Background: There is scarce data in the literature concerning the use of Arabic version neuron psychological cognitive tests in the geriatric age group of the Omani population. Objectives: Our aim is to obtain norms for normal elderly Omanis assessed by The Consortium to Establish a Registry for Alzheimer's disease (CERAD) neuro psychological battery and to compare these norms with other studies in the literature. Methods: 84 attendants and visitors of in-patients at Sultan Qaboos University Hospital, elder than 55 years, were interviewed. All participants were assessed by Dementia Rating Scale & Geriatric Depression Scale to ensure the integrity of their activities of daily living and the absence of depression, respectively. The performance of all participants in the CERAD battery was rated by a single rater to optimize the inter-rater reliability. Results: The cut-point for average performance in CERAD battery is dependent on the age, sex, and level of education and cannot be set as a single cut-point for all elderly Omanis. Conclusion: This study has shown the effect of age, sex, and level of education on the cognitive performance of normal elderly Omanis. The normative data obtained from this study can be utilized to differentiate between the cognitive decline of normal aging and the cognitive impairment due to various neuro cognitive disorders in the elderly Omanis, and probably culturally similar Arabic speaking communities.

Keywords: CERAD, neuropsychological battery, normal aging, elderly Omanis

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Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

Abstract:

Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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Authors: Mohammad Aladwan

Abstract:

Alzheimer’s disease (AD) is a widespread dementing illness with a complex and poorly understood etiology. An important role in improving our understanding of the AD process is the modeling of disease-associated changes in tau protein phosphorylation, a protein known to mediate events essential to the onset and progression of AD. A main feature of AD is the abnormal phosphorylation of tau protein and the presence of neurofibrillary tangles. In order to evaluate the respective roles of the microtubule-binding region (MTBR) and alternatively spliced exons in the N-terminal projection domains in AD, we have constructed SHSY-5Y cell lines that stably overexpress four different species of tau protein (4R2N, 4R0N, N(E-2), N(E+2)). Since the toxicity and spreading of tau lesions in AD depends on the interactions of tau with other proteins, we have performed a proteomic analysis of exosome-fraction interactomes for cell lysates and media samples that were isolated from SHSY-5Y cell lines. Functional analysis of tau interactomes based on gene ontology (GO) terms was performed using the String 10.5 database program. The highest number of exosomes proteomes and tau associated proteins were found with 4R2N isoform (2771 and 159) in cell lysate and they have a high strength of connectivity (78%) between proteins, while N(E-2) isoform in the media proteomes has the highest number of proteins and tau associated protein (1829 and 205). Moreover, known AD markers were significantly enriched in secreted interactomes relative to lysate interactomes in the SHSY-5Y cells of tau isoforms lacking exons 2 and 3 in the N-terminal. The lack of exon 2 (E-2) from tau protein can be mediated by tau secretion and spreading to different cells. Enriched functions in the secreted E-2 interactome include signaling and developmental pathways that have been linked to a) tau misprocessing and lesion development and b) tau secretion and which, therefore, could play novel roles in AD pathogenesis.

Keywords: Alzheimer's disease, dementia, tau protein, neurodegenration disease

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Authors: Hanan F. Aly, Fateheya M. Metwally, Hanaa H. Ahmed

Abstract:

The current study is undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer’s disease in experimental rat model. Alzheimer’s disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl3 (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also, brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer’s disease.

Keywords: Alzheimer’s disease, oxidative stress, apoptosis, dehydroepiandrosterone

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

Abstract:

Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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Authors: Ghazal Mortazavi, S. M. J. Mortazavi

Abstract:

Electricians, power line engineers and power station workers, welders, aluminum reduction workers, MRI operators and railway workers are occupationally exposed to different levels of electromagnetic fields. Mercury is among the most toxic metals. Dental amalgam fillings cause significant exposure to elemental mercury vapour in the general population. Today, substantial evidence indicates that mercury even at low doses may lead to toxicity. Increased release of mercury from dental amalgam fillings after exposure to MRI or microwave radiation emitted by mobile phones has been previously shown by our team. Moreover, our recent studies on the effects of stronger magnetic fields entirely confirmed our previous findings. From the other point of view, we have also shown that papers which reported no increased release of mercury after MRI, may have some methodological flaws. Over the past several years, our lab has focused on the health effects of exposure of laboratory animals and humans to different sources of electromagnetic fields such as mobile phones and their base stations, mobile phone jammers, laptop computers, radars, dentistry cavitrons, and MRI. As a strong association between exposure to electromagnetic fields and mercury level has been found in our studies, our findings lead us to this conclusion that occupational exposure to electromagnetic fields in workers with dental amalgam fillings can lead to elevated levels of mercury. Studies which reported that exposure to mercury can be a risk factor of Alzheimer’s disease (AD) due to the accumulation of amyloid beta protein (Aβ) in the brain and those reported that long-term occupational exposure to high levels of electromagnetic fields can increase the risk of Alzheimer's disease and dementia in male workers support our concept and confirm the significant role of the occupational exposure to electromagnetic fields in increasing the mercury level in workers with amalgam fillings.

Keywords: occupational exposure, electromagnetic fields, workers, mercury release, dental amalgam, restorative dentistry

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Authors: Murat Emre, Zeynep Tufekcioglu

Abstract:

Objective: We describe a patient with late onset phenylketonuria which presented with rapidly progressive dementia and parkinsonism that were reversible after management. Background: Phenylketonuria is an autosomal recessive disorder due to mutations in the phenylalanine hydroxlase gene. It normally presents in childhood, in rare cases, however, it may have its onset in adulthood and may mimic other neurological disorders. Case description: A previously normal functioning, 59 year old man was admitted for blurred vision, cognitive impairment and gait difficulty which emerged over the past eight months. In neurological examination he had brisk reflexes, slow gait and left-dominant parkinsonism. Mini-mental state examination score was 25/30, neuropsychological testing revealed a dysexecutive syndrome with constructional apraxia and simultanagnosia. In cranial MRI there were bilateral diffuse hyper-intense lesions in parietal and occipital white matter with no significant atrophy. Electroencephalography showed diffuse slowing with predominance of teta waves. In cerebrospinal fluid examination protein level was slightly elevated (61mg/dL), oligoclonal bands were negative. Electromyography was normal. Routine laboratory examinations for rapidly progressive dementia and parkinsonism were also normal. Serum amino acid levels were determined to explore metabolic leukodystrophies and phenylalanine level was found to be highly elevated (1075 µmol/L) with normal tyrosine (61,20 µmol/L). His cognitive impairment and parkinsonian symptoms improved following three months of phenylalanine restricted diet. Conclusions: Late onset phenylketonuria is a rare, potentially reversible cause of rapidly progressive parkinsonism with dementia. It should be considered in the differential diagnosis of patients with suspicious features.

Keywords: dementia, neurology, Phenylketonuria, rapidly progressive parkinsonism

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Authors: Jonathan Turner, Julie Doyle, Laura O’Philbin, Dympna O’Sullivan

Abstract:

People living with dementia should be at the centre of decision-making regarding goals for daily living. These goals include basic activities (dressing, hygiene, and mobility), advanced activities (finances, transportation, and shopping), and meaningful activities that promote well-being (pastimes and intellectual pursuits). However, there is limited involvement of people living with dementia in the design of technology to support their goals. A project is described that is co-designing intelligent computer-based support for, and with, people affected by dementia and their carers. The technology will support self-management, empower participation in shared decision-making with carers and help people living with dementia remain healthy and independent in their homes for longer. It includes information from the patient’s care plan, which documents medications, contacts, and the patient's wishes on end-of-life care. Importantly for this work, the plan can outline activities that should be maintained or worked towards, such as exercise or social contact. The authors discuss how to integrate care goal information from such a care plan with data collected from passive sensors in the patient’s home in order to deliver individualized planning and interventions for persons with dementia. A number of scientific challenges are addressed: First, to co-design with dementia patients and their carers computerized support for shared decision-making about their care while allowing the patient to share the care plan. Second, to develop a new and open monitoring framework with which to configure sensor technologies to collect data about whether goals and actions specified for a person in their care plan are being achieved. This is developed top-down by associating care quality types and metrics elicited from the co-design activities with types of data that can be collected within the home, from passive and active sensors, and from the patient’s feedback collected through a simple co-designed interface. These activities and data will be mapped to appropriate sensors and technological infrastructure with which to collect the data. Third, the application of machine learning models to analyze data collected via the sensing devices in order to investigate whether and to what extent activities outlined via the care plan are being achieved. The models will capture longitudinal data to track disease progression over time; as the disease progresses and captured data show that activities outlined in the care plan are not being achieved, the care plan may recommend alternative activities. Disease progression may also require care changes, and a data-driven approach can capture changes in a condition more quickly and allow care plans to evolve and be updated.

Keywords: care goals, decision-making, dementia, self-care, sensors

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Authors: Ali Bayram, Burak Uz, Remzi Yiğiter

Abstract:

The impairment of lipid metabolism in the central nervous system has been suggested as a critical factor of Alzheimer’s disease (AD) pathogenesis. Homo sapiens acyl-coenyme A synthetase short-chain family member 2 (ACSS2) gene encodes the enzyme acetyl-Coenzyme A synthetase (AMP forming; AceCS) providing acetyl-coenzyme A (Ac-CoA) for various physiological processes, such as cholesterol and fatty acid synthesis, as well as the citric acid cycle. We investigated ACSS2, transcript variant 1 (ACSS2*1), mRNA levels in the peripheral blood mononuclear cells (PBMC) of patients with AD and compared them with the controls. The study group comprised 50 patients with the diagnosis of AD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 49 healthy individuals without any neurodegenerative disease are included as controls. ACSS2 mRNA expression in PBMC of AD/control patients was 0.495 (95% confidence interval: 0.410-0.598), p= .000000001902). Further studies are needed to better clarify this association.

Keywords: Alzheimer’s disease, ACSS2 Genes, mRNA expression, RT-PCR

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Authors: Choi Younshick, Lee Wonseok, Lee Jaemeun, Park Sun-Hyun, Kim Sunwoung, Park Sua, Kim Eun Ho, Kim Jong-Ki

Abstract:

Iron accumulation in the brain accelerates Alzheimer’s disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ-fibril structure or the Aβ plaque in a mouse model of Alzheimer’s disease (AD). A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe₃O₄) to measure the field-sensitized electro-Fenton effect and resultant reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7–1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer’s disease (AD) mouse model revealed the removal of intraplaque ferrous magnetite iron deposit and Aβ-plaque burden together at the same time compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Western blot assay found some disease-modifying biological responses, including down-regulating ferroptosis, neuroinflammation and reactive astrocytes that eventually made cognitive improvement feasible. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

Keywords: electroceutical, intraplaque magnetite, alzheimer’s disease, transcranial electric field, electro-fenton effect

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Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

Abstract:

Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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Authors: Holly D. Shan, Monique L. Bautista Neughebauer

Abstract:

Sunscreen usage is emphasized in public health strategy as it reduces the risk of sunburns and skin cancers. This study aims to explore factors that influence sun protective behavior and outcomes. Data was received from the National Health Interview Survey (NHIS) 2020. Adults were asked how often they wore sunscreen when outside on a sunny day. Consistent use (“always”) of sunscreen, the incidence of sunburn within a year, and ever having a diagnosis of skin melanoma were compared by gender, race, and the diagnosis of anxiety, depression, and dementia. Individuals identifying as a mixed race were excluded. Statistical analysis was adjusted for large-scale surveys using STATA VSN 7.0, and a two-sided p<0.05 was considered significant. Of the 37,352 participants (53.18% females, 75.01% white, 10.49% black, 0.76% Indian Americans,5.60% Asian), 13.11% had a diagnosis of anxiety, 14.78% depression, and 0.84% dementia. Females wore sunscreen more often than males (24.72% vs. 10.91%, p<0.001). White individuals wore sunscreen most frequently; black individuals the least (17.37% vs. 6.49%, p<0.001). White individuals had the highest rate of sunburn (25.61%, p<0.001) and a history of skin melanoma (3.38%, p<0.001). Participants with anxiety, depression, and dementia all had statistically significantly decreased sunscreen use and increased frequency of sunburn compared to the general population. Only those with dementia had an increased incidence of skin melanoma (2.85% vs. 1.22%, p=0.009). Dermatologists and public health professionals should consider gender, race, and psychiatric comorbidities when counseling patients on sun protection.

Keywords: sun protective behavior, psychiatric disorder, melanoma, sunburn

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