Dementia-related Diseases Research Articles

Ageing and dementia: age-period-cohort effects of policy intervention in England, 2006\u20132016

BackgroundDementia is one of the most critical challenges of our time. According to the Dementia Statistics Hub, only about 66 % of all UK residents with dementia were diagnosed in 2017–2018. Yet, there are reservations about the early diagnosis of dementia-related diseases. As a result, the UK National Screening Committee does not recommend systematic population screening of dementia, although case-finding strategies are still applied for high-risk groups.MethodsThis study added additional evidence of the effectiveness of the National Dementia Strategy and increased numbers of diagnosis of dementia on the younger cohorts of the older people, using the intrinsic estimator age-period-cohort (APC) models and the English Longitudinal Study of Ageing data.ResultsAge effects show that diagnosis increases in volume only among those aged 75 and above, suggesting that many of those aged below 75 might not be diagnosed in time. Period effects show that although there was an initial increase due to the new policy implementation, the trend stalled in later years, indicating that the increase might not have been even across the period when controlled for age and cohort. The study also shows that cohort effects indicate lower prevalence in younger cohorts controlled for age and period effects.ConclusionsAlthough more research in diverse contexts is warranted, this study cautions against the abandonment of timely diagnosis, increased screening and case-finding, and shows some effectiveness of prevention strategies on the national level.

Influence of Dental Prostheses on Cognitive Functioning in Elderly Population: A Systematic Review.

Aim:The aim of the systematic review was to assess the influence of dental prostheses on cognitive functioning in elderly population.Materials and Methods:This systematic review was conducted according to the PRISMA guidelines. The initial electronic search was conducted using the following search databases: MEDLINE (PubMed), Cochrane Library, Google Scholar, and EMBASE. The search was limited to English language using the search items/keywords: “dental prostheses and cognitive functioning,” “dental prostheses and brain function,” “Tooth loss and cognitive loss,” “mastication and prefrontal activity,” and “prostheses on mental state.” The search strategy was followed using the PICOS framework.Results:A total of 19 studies were selected according to the selection criteria. Out of 19 studies, 15 studies were included and 4 studies were excluded from the review.Conclusion:With the available evidence in the literature, it can be concluded that dental prostheses have a very significant role in preventing the cognitive impairment and act as a protective factor in enhancing the cognitive function in patients with dementia-related diseases and neurodegenerative diseases.

Fabrication of Electrochemical Biosensor for Detection of Full-Length Tau Protein through Biotin-Streptavidin on Gold Surface

Tau is a neuronal protein responsible for microtubule formation [1]. It is also the pathological protein active in the Alzheimer’s Disease (AD) pathway. When Tau begins to aggregate as a result of misfolding, the neuronal cells die due to the lack of microtubule formation and can take on prion-like properties [2]. Therefore, detection of aggregated Tau can serve as a powerful tool in the early diagnosis of AD and dementia related diseases. As has been previously demonstrated, Tau 441 can be detected with an electrochemical immunoassay based on the electrochemical impedance spectroscopy (EIS) by using gold electrode [3]. The EIS was also used to monitor interactions between Tau protein and Heparin [4]. Herein, we describe use of EIS to monitor and detect Tau and its aggregates by using gold electrode modified to include a biotinylated aptamer to tau and streptavidin-Au sensor through a series of surface modifications. Surface modifications were characterized using EIS and CV. After modifying the surface of the electrode, the detection of Tau was achieved using EIS. Aggregation of tau was also monitored as a function of Tau or Heparin concentrations, and incubation time and temperature. The control experiments included, Tau-free surface, Heparin-free solution, buffer solution in order to minimize aggregation. The charge transfer resistance, Rct, was determined by fitting the experimental data to the equivalent circuit. The Rct values for Tau-films on gold surface were compared prior and post aggregation. The Rct values were highly dependent on the experimental conditions. Data indicate that this electrochemical sensor holds great promise for detection of neurodegenerative biomarkers which undergo aggregation.

Protective Effects of Polydatin Against Dementia-Related Disorders.

Dementia is a collection of symptoms affecting a person’s cognition. Dementia is debilitating, and therefore, finding an effective treatment is of utmost importance. Resveratrol, which exhibits neuroprotective effects, has low bioavailability. However, its glucoside polydatin is more bioavailable. Here, the evidence that supports the protective role of polydatin against dementia-related diseases such as Alzheimer’s disease, vascular dementia, alcohol-related dementia, and Lewy body dementias is presented. The beneficial effects of polydatin from a mechanistic perspective are specifically emphasized in this review. Future directions in this area of research are also discussed.

Neuronal Tau Protein Film Stability on Gold Surface: Electrochemical Impedance Spectroscopy of Partial and Complete Surfaces

Tau is a neuronal protein responsible for microtubule formation [1]. It is also the pathological protein active in the Alzheimer’s Disease (AD) pathway. When Tau begins to aggregate as a result of misfolding, the neuronal cells die due to the lack of microtubule formation and can take on prion-like properties [2]. Therefore, detection of aggregated Tau can serve as a powerful tool in the early diagnosis of AD and dementia related diseases. As has been previously demonstrated, Tau 441 can be detected with an electrochemical immunoassay based on the electrochemical impedance spectroscopy (EIS) by using gold electrode [3]. The EIS was also used to monitor interactions between Tau protein and Heparin [4]. Due to the sensitive nature of protein molecules, buffers of physiological pH need to be employed to maintain native protein structure. However, not all buffer solutions are appropriately suited for surface studies. Herein, we describe use of EIS to monitor and detect surface stability of Tau protein films on gold electrode in two common buffers: MES buffer and Phosphate Buffer (PB). Additionally, the stability of partial and complete surfaces was also monitored. The partial surface was completed by backfilling with a solution of bovine serum albumin (BSA) and the complete surface was backfilled using 1-butylamine and hexanethiol. After modifying the surface of the electrode with activated lipoic acid and Tau, a series of further incubation steps were performed to test surface stability under various conditions. The EIS was measured as a function of Tau or Heparin concentrations, and incubation time and temperature. The control experiments included, Tau-free surface, Heparin-free solution, and buffer solutions in order to minimize non-specific interactions. The stability of the surfaces was measured as a signal change in EIS after incubations and it was discovered that certain buffered solutions and partial surfaces induced large changes in tau protein films on surfaces.

Mind the Gap

The “narrative turn” in biomedical discourses has dominated twenty-first-century medical humanities, pursuing the premise that narratives of illness, including patient and literary narratives, contribute toward our understanding of illness because they encourage us to reflect upon lived reality and even to imagine events and experiences with which we may be grossly unfamiliar (Charon et al.; Charon; Oyebode; Halpern; Altschuler). However, an emerging critical approach to the medical and health humanities challenges the assumption that narrative is incontestably and straightforwardly valuable for understanding illness. Following the work of Ahmed, Keen, Bishop, Jurecic, Whitehead and Woods, and Whitehead, the article suggests that narrative fiction may not cultivate empathy for another person, but may draw attention to the limitations of understanding another’s experience by encouraging us to look out for, and even to imagine, the multiple ways in which we experience the world differently to others. With a focus on the experience of dementia-related diseases—including Alzheimer’s disease—in B. S. Johnson’s House Mother Normal, the article shows that metafiction may not help us to empathize with others so much as it may problematize our ability to empathize in ways that are ethically valuable for an understanding of subjectivity, illness, and experience.

Assessment of changes in place of death of older adults who died from dementia in the United States, 2000\u20132014: a time-series cross-sectional analysis

BackgroundAs the mortality attributable to dementia-related diseases in the United States escalates, providing quality and equitable end-of-life care for dementia patients across care settings has become a major public health challenge. Previous research suggests that place of death may be an indicator of quality of end-of-life care. This study aims to examine the geographical variations and temporal trends in place of death of dementia decedents in the US and the relationships between place of death of dementia decedents and broad structural determinants.MethodsUsing nationwide death certificates between 2000 and 2014, we described the changes in place of death of dementia decedents across states and over time. Chi-square test for trend in proportions was used to test significant linear trend in the proportion of dementia decedents at difference places. State fixed effects models were estimated to assess the relationships between the proportion of dementia decedents at difference places and state-level factors, particularly availability of care facility resources and public health insurance expenditures.ResultsDementia decedents were more likely to die at home and other places and less likely to die at institutional settings over the study period. There was wide inter-state and temporal variability in the proportions of deaths at different places. Among state-level factors, availability of nursing home beds was positively associated with rates of nursing home/long term care deaths and negatively associated with rates of home deaths. Medicaid expenditure on institutional long term supports and services was positively associated with rates of nursing home/long term care deaths and negatively associated with rates of home deaths. Medicaid expenditure on home and community based services, however, had a positive association with rates of home deaths.ConclusionsThere was a persistent shift in the place of death of dementia decedents from institutions to homes and communities. Increased investments in home and community based health services may help dementia patients to die at their homes. As home becomes an increasingly common place of death of dementia patients, it is critical to monitor the quality of end-of-life care at this setting.

Making Sense of Sensor Data: How Local Environmental Conditions Add Value to Social Science Research.

Recent advances in computing technologies have enabled the development of low-cost, compact weather and air quality monitors. The U.S. federally funded Array of Things (AoT) project has deployed more than 140 such sensor nodes throughout the City of Chicago. This paper combines a year's worth of AoT sensor data with household data collected from 450 elderly Chicagoans in order to explore the feasibility of using previously unavailable data on local environmental conditions to improve traditional neighborhood research. Specifically, we pilot the use of AoT sensor data to overcome limitations in research linking air pollution to poor physical and mental health and find support for recent findings that exposure to pollutants contributes to both respiratory and dementia-related diseases. We expect that this support will become even stronger as sensing technologies continue to improve and more AoT nodes come online, enabling additional applications to social science research where environmental context matters.

Neuronal Tau Protein Self-Assembly on Gold Surface: Electrochemical Impedance Spectroscopy and Cyclic Voltammetry Studies

Tau is a neuronal protein responsible for microtubule formation [1]. It is also the pathological protein active in the Alzheimer’s Disease (AD) pathway. When Tau begins to aggregate as a result of misfolding, the neuronal cells die due to the lack of microtubule formation and can take on prion-like properties [2]. Therefore, detection of aggregated Tau can serve as a powerful tool in the early diagnosis of AD and dementia related diseases. As has been previously demonstrated, Tau 441 can be detected with an electrochemical immunoassay based on the electrochemical impedance spectroscopy (EIS) by using gold electrode [3]. The EIS was also used to monitor interactions between Tau protein and Heparin [4]. Herein, we describe use of EIS and cyclic voltammetry (CV) to monitor and detect self-assembly of Tau protein on gold electrode. After modifying the surface of the electrode with Tau, the aggregation of Tau was performed using Heparin, as an aggregation inducer. The EIS and CV were measured as a function of Tau or Heparin concentrations, and incubation time and temperature. The control experiments included, Tau-free surface, Heparin-free solution, buffer solution in order to minimize aggregation. The charge transfer resistance, Rct, was determined by fitting the experimental data to the equivalent circuit. The Rct values for Tau-films on gold surface were compared prior and post aggregation. The Rct values were highly dependent on the experimental conditions used and that the electrochemical methods are promising sensing platforms for detection of neurodegenerative biomarkers which undergo self-assembly and aggregation.

Validation of Sleep EEG-based Brain Age Index for Dementia-related Diseases (4427)

Validation of Sleep EEG-based Brain Age Index for Dementia-related Diseases (4427)

Challenges of Integrative Disease Modeling in Alzheimer's Disease.

Dementia-related diseases like Alzheimer's Disease (AD) have a tremendous social and economic cost. A deeper understanding of its underlying pathophysiologies may provide an opportunity for earlier detection and therapeutic intervention. Previous approaches for characterizing AD were targeted at single aspects of the disease. Yet, due to the complex nature of AD, the success of these approaches was limited. However, in recent years, advancements in integrative disease modeling, built on a wide range of AD biomarkers, have taken a global view on the disease, facilitating more comprehensive analysis and interpretation. Integrative AD models can be sorted in two primary types, namely hypothetical models and data-driven models. The latter group split into two subgroups: (i) Models that use traditional statistical methods such as linear models, (ii) Models that take advantage of more advanced artificial intelligence approaches such as machine learning. While many integrative AD models have been published over the last decade, their impact on clinical practice is limited. There exist major challenges in the course of integrative AD modeling, namely data missingness and censoring, imprecise human-involved priori knowledge, model reproducibility, dataset interoperability, dataset integration, and model interpretability. In this review, we highlight recent advancements and future possibilities of integrative modeling in the field of AD research, showcase and discuss the limitations and challenges involved, and finally, propose avenues to address several of these challenges.

27 Decision-Making Capacity Assessment: Occupational Therapy’s Contribution within a Multidisciplinary Approach

Abstract Background Increasing age and life expectancy, alongside the growing incidence of chronic conditions and dementia-related diseases, indicate more older individuals are likely to experience challenges regarding decision-making capacity. In Ireland, the Assisted Decision Making (Capacity) Act 2015 provides a statuary framework for adults who are experiencing difficulties with decision-making. This legislation has significant implications for all who work in health and social care, especially those working with older adults. An online survey was conducted to explore occupational therapy practices regarding decision-making capacity assessment and factors impacting on engagement in this area. Methods Occupational therapists in Ireland were invited to participate in a cross-sectional online questionnaire. Results One hundred and seventy-two occupational therapists responded. Most occupational therapists (65.77%, n=98) reported involvement in decision-making capacity assessments, particularly those working with older adults. Occupational therapists were more frequently requested to contribute to assessments of capacity regarding independent living (79.19%, n=118), driving (45.89%, n=67), and financial management (44.44%, n=64). Occupational therapists reported using a combination of approaches to inform decision-making capacity assessment, including interviews, observations and assessments of cognition and functional performance, and emphasised a strength-based approach. Many participants reported decision-making capacity assessment is more difficult than other aspects of practice and that they are not satisfied with decision-making capacity assessment procedures in their workplace. A large majority (91.86%, n=113) reported occupational therapists would benefit from additional training and practice resources for decision-making capacity assessment. Conclusion The study confirms that occupational therapists have a role to play in assessment of decision-making capacity assessment, particularly regarding independent living. However, the recommended approach to assessment should include all appropriate multidisciplinary team members. There is need for further education, resources and guidelines for occupational therapists and other healthcare professionals to better guide decision-making capacity assessment.

Overview of the Assisted Decision-Making (Capacity) Act (2015)

PurposeIn Ireland, the Assisted Decision Making (Capacity) Act 2015 provides a statutory framework to adults who are experiencing difficulties with decision-making. This legislation has significant implications for all who work in health and social care. Increasing age and life expectancy, alongside the rising incidence of chronic health conditions and dementia-related diseases, indicates that more individuals are likely to experience challenges regarding decision-making capacity. Therefore, the need for more consistent, best-practice processes to assess decision-making capacity is likely to increase. To ensure occupational therapists are responsible in their contributions, and to ensure those with disabilities are supported, clinicians must be well-informed of the principles underscoring the Act. The purpose of this paper is to provide an overview of this multidisciplinary issue, including recent legislation, and consider how occupational therapy can contribute.Design/methodology/approachThe authors reviewed current literature and considered occupational therapy’s role in decision-making capacity assessment.FindingsOccupational therapists have potential to play a key role in multi-disciplinary assessments of decision-making capacity for clients. Further research is required to explore professional issues, identify clinical best practices and determine training and resource needs.Originality/valueThis paper seeks to provoke consideration of how occupational therapists can contribute to capacity assessment from a client-centred, occupation-based perspective that is mindful of ethical and legislative considerations.

Extending XNAT Platform with an Incremental Semantic Framework.

Informatics increases the yield from neuroscience due to improved data. Data sharing and accessibility enable joint efforts between different research groups, as well as replication studies, pivotal for progress in the field. Research data archiving solutions are evolving rapidly to address these necessities, however, distributed data integration is still difficult because of the need of explicit agreements for disparate data models. To address these problems, ontologies are widely used in biomedical research to obtain common vocabularies and logical descriptions, but its application may suffer from scalability issues, domain bias, and loss of low-level data access. With the aim of improving the application of semantic models in biobanking systems, an incremental semantic framework that takes advantage of the latest advances in biomedical ontologies and the XNAT platform is designed and implemented. We follow a layered architecture that allows the alignment of multi-domain biomedical ontologies to manage data at different levels of abstraction. To illustrate this approach, the development is integrated in the JPND (EU Joint Program for Neurodegenerative Disease) APGeM project, focused on finding early biomarkers for Alzheimer's and other dementia related diseases.

Genetic Rescue of Mitochondrial Calcium Efflux in Alzheimer's Disease Preserves Mitochondrial Function and Protects against Neuronal Cell Death

Background. Alzheimer's disease (AD) is characterized by neurodegeneration, specifically the progressive loss of neuronal populations in the frontal cortex and hippocampus. Numerous studies have shown that neuronal cell death and metabolic dysregulation are fundamental cellular mechanisms driving the progression of AD and other dementia-related diseases. Previous studies have suggested numerous mechanisms whereby intracellular Ca2+ load is increased in AD and thereby likely significantly impacts mCa2+ signaling. Methods. To discern if mCa2+ signaling is causative in the progression of AD, human AD brain samples, an AD mutant mouse model (3xTg) and an AD-mutant cell line (N2a/APPswe) were examined for mitochondrial alterations in: Ca2+ handling, ROS generation, membrane potential (ΔΨ), permeability transition pore activation, OxPhos, APP metabolism and cell death. Results. 3xTg-AD mice and human AD brain samples displayed significant alterations in the expression of key mCa2+ exchange genes, most notably a reduction in the expression of the mitochondrial Na+/Ca2+ exchanger (mNCX, SLC8B1), the major efflux pathway in excitable cells. We discovered that mCa2+ efflux and mCa2+ retention capacity was severely impaired in N2a/APPswe cells. Rescue of mCa2+ extrusion, via adenoviral expression of mNCX, enhanced the clearance of pathogenic mCa2+, recovered (ΔΨ), enhanced OxPhos, reduced extracellular Aβ1-40 levels and protected from ionomycin-, glutamate- and ROS-induced cell death. Conclusions. Our data suggest that impaired mCa2+ exchange is a central contributor to neuronal cell death in AD and that mNCX represents a new therapeutic target to inhibit or reverse AD progression.

A molecular dynamics study of the binary complexes of APP, JIP1, and the cargo binding domain of KLC.

Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level. We used molecular dynamics and free energy estimations to gauge the affinity for the binary complexes of KLC1, APP, and JIP1. We find that all binary complexes (KLC1:APP, KLC1:JIP1, and APP:JIP1) contain conformations with favorable binding free energies. For KLC1:APP the inclusion of approximate entropies reduces the favorability. This is likely due to the flexibility of the 42-residue APP protein. In all cases we analyze atomistic/residue driving forces for favorable interactions. Proteins 2017; 85:221-234. © 2016 Wiley Periodicals, Inc.

Phytosterols and Dementia.

As the aging of the world's population is becoming increasingly serious, dementia-related diseases have become a hot topic in public health research. In recent years, human epidemiological studies have focused on lipid metabolism disorders and dementia. The efficacy of phytosterol intake as a cholesterol-lowering agent has been demonstrated. Phytosterols directly serve as ligands of the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), activating Sirtuin 1 (SIRT-1), which areinvolved in the regulation of lipid metabolism and the pathogenesis of dementia. Moreover, phytosterols mediate cell and membrane cholesterol efflux or beta amyloid (Aβ) metabolism, which have preventative and therapeutic effects on dementia. Additionally, incorporation of plant sterols in lipid rafts can effectively reduce dietary fat and alter the dietary composition of fiber, fat and cholesterol to regulate appetite and calories. Overall, the objectives of this review are to explore whether phytosterols are a potentially effective target for the prevention of dementia and to discuss a possible molecular mechanism by which phytosterols play a role in the pathogenesis of dementia via the PPARs-SIRT-1 pathway.

Dance for Individuals With Dementia.

The movement and music associated with dance plays an important role in many individuals' lives and can become imprinted upon the body and mind. Dance is thus closely associated with memory because of these deep connections. Without conscious thought, dance has the potential to be initiated as individuals age. In the current article, the authors share narrative reflections about their experiences with, and the potential of, dance as an intervention for aging populations diagnosed with dementia-related diseases. They draw upon their experiences in working with the aging population and a dance program currently being developed by Canada's National Ballet School and Baycrest Health Sciences for individuals with dementia-related diseases in long-term care. The current article is structured as dialogue between the authors because it mimics dance as a dialogical encounter between movement and music, and/or between individuals.

Characterizing Apolipoprotein E ε4 Carriers and Noncarriers With the Clinical Diagnosis of Mild to Moderate Alzheimer Dementia and Minimal β-Amyloid Peptide Plaques.

β-Amyloid peptide (Aβ) plaques are a cardinal neuropathologic feature of Alzheimer disease (AD), yet more than one-third of apolipoprotein E ε4 (APOE4) noncarriers with the clinical diagnosis of mild to moderate Alzheimer dementia may not meet positron emission tomographic criteria for significant cerebral amyloidosis. To clarify the percentage of APOE4 carriers and noncarriers with the primary clinical diagnosis of mild to moderate Alzheimer dementia near the end of life and minimal Aβ plaques noted at autopsy and the extent to which these cases are associated with appreciable neurofibrillary degeneration or a primary neuropathologic diagnosis other than AD. Data on participants included in this study were obtained from the National Alzheimer Coordinating Center's Uniform Data Set, which comprises longitudinal clinical assessments performed at the AD centers funded by the National Institute on Aging. Neuropathology data are available for the subset of participants who died. A total of 100 APOE4 noncarriers and 100 APOE4 carriers had the primary clinical diagnosis of mild to moderate Alzheimer dementia at their last visit, known APOE4 genotype, died within the ensuing 24 months, and underwent neuropathologic evaluation on autopsy. The study was conducted from September 1, 2005, to September 1, 2012; analysis was performed from October 9, 2012, to March 20, 2015. Standardized histopathologic assessments of AD neuropathologic changes were the primary measures of interest in this study, specifically Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque density score, diffuse plaque density score, and Braak stage for neurofibrillary degeneration. The distributions of scores for these measures were the primary outcomes. Of the 37 APOE4 noncarriers with minimal neuritic plaques, 16 individuals (43.2%) had Braak stages III to VI ratings, and 15 of the others (75.0%) met neuropathologic criteria for other dementia-related diseases. Of the 13 APOE4 carriers with minimal neuritic plaques, 6 individuals (46.2%) had Braak stages III to VI ratings and met neuropathologic criteria for other dementia-related diseases. Similarly, of the 7 APOE4 carriers with minimal neuritic plaques and Braak stages 0 to II, 4 participants (57.1%) were thought to have pathologic changes and alterations resulting from non-AD neuropathologic features. In this study, more than one-third of APOE4 noncarriers with the primary clinical diagnosis of mild to moderate Alzheimer dementia had minimal Aβ plaque accumulation in the cerebral cortex and, thus, may show limited or no benefit from otherwise effective anti-Aβ treatment. Almost half of the participants with a primary clinical diagnosis of mild to moderate Alzheimer dementia and minimal Aβ plaque accumulation had an extensive topographic distribution of neurofibrillary degeneration. Additional studies are needed to better understand and provide treatment for patients with this unexpectedly common cliniconeuropathologic condition.

Contribution of neuropathology in the diagnosis and treatment of dementia related diseases

Contribution of neuropathology in the diagnosis and treatment of dementia related diseases