bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stakeholder engagement for successful practice change in long‐term care: Evaluating the Feasible and Sustainable Culture Change Initiative (FASCCI) model
Authors: Caspar Sienna 
Published: December 2020

AbstractBackground and ObjectivesInterventions aimed at increasing the provision of relational and person‐centred care in long‐term care (LTC) homes that do not address contextual and system issues most often fail. Promoting positive change in LTC homes requires a multilevel, systems approach. The objective of this study was to evaluate the feasibility and effectiveness of the Feasible and Sustainable Culture Change Initiative (FASCCI) model for change for improving the provision of person‐centred mealtime practices in a LTC home.MethodsA single‐group, time series design was used to assess the impact of the FASCCI model for change on outcome measures across four time periods (pre‐intervention, 2‐month, 4‐month and 6‐month follow‐up). Mealtime observations (n=38) using the Mealtime Scan (MTS+) were completed over the course of six‐months in a single dining room. Interviews (n=21) were also conducted to examine treatment fidelity and to ascertain the study participants’ perceptions of the process for making improvements using the FASCCI model.ResultsWe observed increases in care staffs’ capacity to consistently provide relational and person‐centred care during mealtimes. Mealtime environment scores started increasing immediately following the intervention, with statistically significant improvements noted in all mealtime environment scales by six‐months, including the: physical environment (z=‐3.43, p=0.004); social environment (z=‐4.17, p<0.001); relationship‐centred care (z= ‐4.121, p<0.001); and overall quality of dining environment (z= ‐4.08, p<0.001). Analysis of data from qualitative interviews demonstrated that use of the FASCCI model resulted in improved team leadership, communication, and collaborative decision‐making.ConclusionsThis study offers evidence that the FASCCI model provides a promising approach for improving the provision of relationship‐centred mealtime practices in LTC homes. Our findings reinforce the importance of cultivating and implementing workforce practices that increase staff empowerment and enable and encourage collaborative decision‐making. We found these practices to be essential to the outcomes associated with the improved relationship‐centred care practices that occurred during this study. This is consistent with the small but growing body of evidence demonstrating that staff empowerment has a significant effect on overall quality of resident care.
Measuring dose in a tailored lighting intervention to improve sleep and mood in Alzheimer's disease patients
Authors: Figueiro Mariana G , Page Erik , Rea Mark S 
Published: December 2020

AbstractBackgroundDaytime light helps consolidate sleep in persons with Alzheimer's disease and related dementia (ADRD), but light levels required are high and available lighting fixtures cannot deliver the light level and spectrum needed for the circadian system. Moreover, ambient light levels cannot be measured to determine treatment dose. The present study tested whether a tailored lighting intervention could improve sleep in eight ADRD patients living in long‐term care facilities and used a novel device to measure light dose (RAD).MethodIn a crossover, repeated‐measures design, we exposed ADRD participants (MMSE<24) to an active (circadian stimulus, CS=0.3) and inactive (CS=0.1) tailored lighting intervention for successive 4‐week periods, spaced by a 4‐week washout period. RAD devices, calibrated to measure circadian light, were placed in spaces where the intervention was administered. The lighting intervention was energized from wake time until 6:00 pm. Measures of sleep disturbances (Pittsburgh Sleep Quality Index, PSQI and actigraph) and mood (Cornell Scale for Depression in Dementia, CSDD) were collected at baseline and during the last weeks of each intervention periods.ResultCompared to their respective baseline conditions, the active lighting intervention significantly decreased wake percent and increased sleep percent. Compared to baseline and to the inactive intervention, PSQI scores reduced in the active intervention. Depression scores were significantly lower after the active than after the inactive intervention. The mean ± SEM PSQI scores was 10.9±1.1 and 7.3±0.7 at baseline and after active intervention and 10.0±1.0 and 10.3±1.6 at baseline and after the inactive intervention. The mean ± SEM CSDD scores was 9.0±1.7 and 8.0±1.3 at baseline and after active intervention and 12.0±1.6 and 12.0±2.1 at baseline and after the inactive intervention.ConclusionWhen carefully delivered to patients’ eyes and monitored with a calibrated instrument, daytime light can improve sleep and mood in nursing home residents with AD/ADRD. Additional data need to be collected to extend these preliminary results.
Non‐pharmacological management of Alzheimer's disease: A qualitative study in Mauritius
Authors: Dorkhy Geeta Devi , Goorah Smita 
Published: December 2020

AbstractBackgroundThe major form of dementia is Alzheimer’s disease (AD). In Mauritius it was estimated in year 2015 that around 12,000 persons had Alzheimer’s disease (Alzheimer disease International). Many of the pharmacological therapies provide only modest results in AD. Therefore, apart from pharmacological therapies, non‐pharmacological treatment (NPT) which can influence cognitive performance such as cognitive training, occupational therapy, reminiscence therapy, are being highly investigated. The only NGO in Mauritius is “Alzheimer’s Association”, from where the persons with AD were recruited.MethodNon‐interventional methods of qualitative study was carried out with in‐depth semi‐structured, one‐to‐one interviews lasting 30‐45 minutes. This was audio recorded. An informed consent from the carer or patient‐relative prior to starting was ensured. Open‐ended questions were used, relating to NPT, to yield in‐depth responses about people’s experiences, perceptions, opinions, feelings, and knowledge. Data analysis of qualitative research data proceeded with coding and decoding.ResultQualitative study (n=20) emerged with 7 main themes. Among these, dependency on family was identified as an important theme. Responses of the person with AD was mainly related to their experiences, perceptions, opinions, feelings, and various levels of dependency.ConclusionNon‐pharmacological interventions has an important role to prolong the active age of older individuals, as well as to maintain quality of life. There is still a greater demand on the market for non‐pharmacological interventions and Mauritius should plan and devise national guidelines to deal with the unmet proportion of elderly so as to curb for future health equality and stability.
Modulation of histone deacetylase 2 (HDAC2) drives neuronal gene expression, mitochondrial dynamics and AD pathophysiology in human stem cell derived neurons
Authors: Frankowski Harald , Berry Bonnie J. , Yeboah Fred , Evitts Kira , Kinoshita Chizuru , Kinoshita Yoshito , Morrison Richard S. , Young Jessica E. 
Published: December 2020

AbstractBackgroundHistone deacetylase 2 (HDAC2) is a major HDAC protein in the adult brain and has been shown to regulate many neuronal genes. Aberrant expression of HDAC2 and subsequent dysregulation of neuronal gene expression has been implicated in Alzheimer’s disease (AD) and brain aging. In vitro models of AD and other neurodegenerative disorders using human induced pluripotent stem cells (hiPSCs) are being increasingly utilized and have provided novel insights into disease mechanisms. However, the role of HDAC2 in living, human neurons and how its manipulation in an AD model may affect disease phenotypes has not been investigated.MethodWe used human induced pluripotent stem cells and lentiviral‐mediated manipulation of HDAC2 in hiPSC‐derived neurons to study the effects of increasing or decreasing HDAC2 expression on neuronal mitochondrial gene expression, morphology, and AD phenotypes.ResultIn this study, we show that levels of HDAC2 naturally decrease as hiPSCs are differentiated towards a neuronal lineage and that this suppression of HDAC2 inversely corresponds to an increase in neuronal‐specific isoforms of Endophilin‐B1, a multifunctional protein involved in mitochondrial dynamics. Manipulation of HDAC2 and Endophilin‐B1 using lentiviral approaches shows that knock‐down of HDAC2 or overexpression of Endophilin‐B1 promote mitochondrial elongation in hiPSC‐derived neurons, but HDAC2 knock‐down specifically influences genes regulating neuronal mitochondrial dynamics. We also observe that the endogenous decrease in HDAC2 levels upon neuronal differentiation also correlates with natural increases in neuronal activity and knock‐down of HDAC2 in differentiated neurons increases expression of genes related to neuronal synapses and further increases neuronal firing. Finally, we demonstrate that knock‐down of HDAC2 reduces amyloid beta peptides and the phospho/total Tau ratio in iPSC‐derived neurons.ConclusionCollectively, our study demonstrates that HDAC2 regulates key neuronal functional and bioenergetic pathways in hiPSC‐derived neurons and suggests that HDAC2 may represent a novel therapeutic target for AD.
Pathological significance of neuron‐derived EVs in Alzheimer's disease and their potential as biomarkers
Authors: Kudo Takashi , Akamine Shoshin , Yanagida Kanta , Marutani Noriko , Kanayama Daisuke , Tokuda Takahiko , Ishikawa Mitsuru , Morimoto Satoru , Maeda Sumihiro , Okano Hideyuki 
Published: December 2020

AbstractBackgroundIt has recently been reported that pathological molecules of Alzheimer’s disease (AD), such as tau, are transmitted through extracellular vesicles (EVs). We hypothesized that AD‐related proteins are detectable in neuron‐derived EVs (NDE) present in peripheral blood, since the pathological proteins will be protected by the lipid bilayer of EVs from degradation. The objective of the study is to assess the novel NDE isolation method for the quantification of AD‐related proteins using ultra‐sensitive digital ELISA method.MethodBlood‐derived EVs were first isolated from control and AD patients, and the degradation efficiency of AD‐related proteins in the blood and EVs was assessed by protease treatment in vitro. The remaining AD‐related molecules were quantified by Simoa HD‐1 Analyzer. The amount of protease‐resistant AD‐related proteins in the blood‐derived EVs was compared between healthy control subjects and AD patients. Next, NDE was affinity‐purified from peripheral blood‐derived EVs and conditioned medium of iPS‐derived neurons/astrocyte using novel antibodies specific to neuron‐specific membrane protein X (MPX). The purification efficiency was assessed by quantification of neuronal markers present in the isolated NDE.ResultProtease treatment of human plasma degraded more than 99% of Aβ40 and Aβ42 present in the blood. On the other hand, around 5% of tau in the blood was protease‐resistant implied that the 5% of tau in blood might be protected from proteases by the EV structure. Actually, in blood‐derived EV fraction, more than 50% of tau was protease resistant, although Aβ40 and Aβ42 were hardly detectable after protease treatment, indicated that 50% of EV‐associated tau was compartmentalized inside of the EV. Furthermore, we succeeded in efficient separation of NDE from blood‐derived EV fraction using anti‐MPX antibody.ConclusionThe present study revealed the difference in the amount of protease‐resistant Aβ40, Aβ42 and tau in the blood, which are more enriched in blood‐derived EVs. This phenomenon may be strongly involved in the transmission of AD pathological proteins through EVs. In addition, the novel NDE isolation method may be highly beneficial for the future development of NDE biomarkers.
CSF Aβ42, P‐tau and noradrenaline metabolite MHPG levels are synergistically related to cortical thickness in a memory clinic population
Authors: van Hooren Roy W.E. , Verhey Frans R.J. , Ramakers Inez H.G.B. , Jansen Willemijn J. , Jacobs Heidi I.L. 
Published: December 2020

AbstractBackgroundThe earliest signs of tau pathology have been traced back to the locus coeruleus (LC). The LC is the primary site for the synthesis of noradrenaline in the brain and there is evidence for LC volume loss as early as preclinical Braak stage 1 of Alzheimer's disease (AD). Increased levels of a noradrenaline metabolite called 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) have been found in advanced AD, while there is also a correlation between MHPG levels and cognitive performance. Additionally, MHPG may be an upstream driver of amyloid and tau pathology in AD, while both of these hallmark pathologies are linked to cortical thickness. Therefore, this study investigates the association between the noradrenergic system and AD pathology in relation to cortical thickness as a measure of structural brain morphology.MethodThe study sample included a total of 77 patients from the memory clinic with a mean age of 63 years, of whom 49 (64%) were male. Of this sample, 36 patients had subjective memory complaints (cognitively unimpaired) and 41 patients were cognitively impaired (mild cognitive impairment or AD). All patients had complete cerebrospinal fluid (CSF) measures of MHPG, Aß42 and p‐tau. Vertex‐based cortical thickness analyses were performed using FreeSurfer V6.0 while correcting for age, sex, education and MMSE score. Critical p‐values were adjusted for multiple comparisons using cluster‐based correction.ResultResults showed interaction effects between MHPG levels and AD pathology to predict cortical thickness. As MHPG levels increased, both lower levels of CSF Aß42 and higher levels of CSF p‐tau were incrementally associated with lower cortical thickness. Moreover, higher AD signature p‐tau/Aß42 ratio was similarly associated with lower cortical thickness as MHPG increased. Results remained significant after the addition of apolipoprotein E4 information.ConclusionOur results suggest that synergistic relationships exist between MHPG, levels of AD pathology and cortical thickness. These findings provide support for an influential role of the noradrenergic system in AD, in tandem with established AD pathologies. These results suggest that in addition to clinical trials focusing on amyloid and tau pathologies, noradrenergic targets for pharmaceutical interventions may also be a promising focus.
Early diagnosis for Alzheimer’s disease: Clinical criteria and use of biomarkers
Authors: De Souza da Silva Raquel Carolina , da Cunha Ludmila Souza , de Almeida Fonseca Marcilene Maria 
Published: December 2020

AbstractBackgroundAlzheimer's disease (AD) is by definition a functional cognitive decline that causes gradual memory loss, compromising areas of the brain responsible for cognition, function and behavior. AD is responsible for 60‐70% of dementias, affecting about 25 million people worldwide. Therefore, the early diagnosis allows therapeutic intervention with reduction of treatment costs, prolongation of autonomy and delay in the onset of the dementia process.MethodThe bibliographic research was performed in digital platforms, using articles published in the last 11 years in Spanish, English and Portuguese. Its aspects of early clinical diagnosis were analyzed and compared with the results observed in clinical and imaging examinations.ResultIn DSM‐5, AD was separated into three stages: preclinical, mild cognitive impairment (MCI) and dementia. Studies indicate that subtle changes can be detected years / decades before the first clinical symptoms that characterize MCI through biomarkers. Today, there is no obligation for memory loss to precede other symptoms, sensory and motor changes may be present 5‐15 years earlier in the early stages. Clinically, the patient needs to have cognitive and behavioral symptoms that affect daily activities, showing a reduction in their performance that cannot be attributed to other neurocognitive disorders, evidenced in anamnesis taken from the patient and a family member who is aware of the condition and conducting neuropsychological tests or cognitive assessment such as the Mini‐Mental. It is important to remember that tests such as computed tomography or magnetic resonance imaging of the skull should be performed to rule out differential diagnoses, since CSF examination may help to identify infectious dementia of the central nervous system.ConclusionThe percentage of clinically identified cases decreases as the stages of AD are earlier. However, tests with biomarkers are at the same time more sensitive and specific to the diagnosis of AD and may expose the disease even before the onset of symptoms due to the marking of the dementia triggering gene.
Associations of truncal body composition with cognitive status in patients with dementia
Authors: Kim Seonah , Kim Jin Ok , Kwon Kyoung JA , Kim Dong Wook , Han Seol‐Heui , Moon Yeonsil 
Published: December 2020

AbstractBackgroundCognitive impairment is one of the most common age‐related diseases, and there are many modifiable risk factors, such as obesity and sarcopenia, which are extensively researched these days. Although many studies examined the relationship between obesity and cognitive impairment, the common methods to measure obesity have a limitation that they do not accurately measure truncal fat. Moreover, as truncal muscles are an indispensable component for movement for activity, it could be expected that the many truncal muscles are related to better cognitive functions. The objective of this study is to investigate the relationship between truncal body composition (fat and muscle) and cognitive impairment in patients with dementia in Korea.MethodFemale over 60 years of age with probable Alzheimer’s Disease were recruited between November 2014 and September 2015. The Mini‐Mental state examination, Global deterioration scale and Clinical dementia rating scale were used to assess the cognitive functions. Both truncal fat and muscle mass were measured using body dual energy X‐ray absorptiometry, and used as a percentage of body weight (TMM% and TFM%). Correlations between truncal composition and cognitive status were assessed by simple correlation analysis, which was followed by partial correlation analysis with age, educational years.ResultTFM% was not related to cognitive impairment. In contrast, TMM% had a significantly negative correlation with all three cognitive assessment scores. After further adjusting for age and educational years, there was still a relationship between TMM% and cognitive functionsConclusionWhile truncal fat mass showed no relevance with cognitive functions, the truncal muscle mass was negatively correlated with cognitive status. The truncal muscle mass is thought to affect cognitive status in dementia patients somehow.
Design, synthesis and pharmacological evaluation of some 1,4‐benzoquinone‐piperazine hybrids for the management of cognitive dysfunction in Alzheimer’s disease
Authors: Silakari Pragati , Piplani Poonam 
Published: December 2020

AbstractBackgroundCognitive dysfunction is one of the testimonial indications of neurological disorder like Alzheimer’s disease. Based on the causative factors four main hypotheses have facilitated to draw sketch of real situation of AD, i.e. cholinergic misbalance, neurofibrillary tangles, senile plaques, and oxidative stress. The inhibition of acetylcholinesterase (AChE) has been a promising target for the management of AD which is mainly associated with the decreased level of acetylcholine (ACh). Currently, only four AChE inhibitors (tacrine, rivastigmine, donepezil and galanthamine) have been approved by the FDA for the symptomatic treatment of AD. However, these acetylcholinesterase inhibitors are not devoid of side effects and have lesser CNS permeability. A series of 1,4‐benzoquinone‐piperazine hybrid molecules were designed and synthesized based on the best pharmacophoric features against the target AChE and evaluated for their AChE inhibitory activity for the development of novel potent molecules for the management of cognitive decline in AD.MethodAtom based 3D QSSR study of 1,4‐benzoquinone hybrids as acetylcholinesterase inhibitors for its selective binding with AChE was performed. Molecules were designed on the basis of the best model features and were docked with 3D crystal structure of AChE with the target. These designed hybrid molecules of 1,4‐benzoquinone and piperazine moiety were synthesized and evaluated as acetylcholinesterase inhibitors.ResultThe best 3D‐QSSR model displayed acceptable values of statistical parameters. The designed molecules showed good binding interactions with the important amino acids of the target protein. These molecules were synthesized and evaluated for their cognition improvements abilities. Out of all the synthesized compounds, few were selected for passive avoidance memory elevator test based on their in vitro AChE inhibitory activity. These molecules showed comparable improvement in the memory with that of the standard drug donepezil.ConclusionThe statistical measures of the best model clearly indicate that the generated model has satisfactory prediction power for new molecules. Out of all the synthesized molecules, some compounds showed significant in vitro AChE activity along with improved memory function during step down passive avoidance studies. Hence the present study facilitates the process of designing, synthesis and development of new potent and selective AChE inhibitors.
Epilepsy in early onset Alzheimer’s disease
Authors: Haoudy Sarah , Jonveaux Therese , Aron Olivier , Puisieux Salomé , Hopes Lucie , Tyvaert Louise 
Published: December 2020

AbstractBackgroundEpilepsy seems to be an important comorbidity in patients with Alzheimer’s disease (AD), especially in young onset AD (<65 years old). At this time epileptic seizures are still underestimated in this population. However, seizures may interact with AD evolution with possible acceleration of cognitive decline and early institutionalization. Seizures may also be a marker of a more aggressive subtype of AD.This study aims to determine the prevalence of the epileptic comorbidity in patients with early onset AD. Secondly, it will investigate the temporal relationship between AD and epilepsy and extract specific characteristics of AD patients at higher risk of epilepsy.MethodAll patients diagnosed as early‐onset Alzheimer disease between 2013 and 2019, with abnormal CSF biomarkers for Alzheimer disease, and followed at the University Hospital of Nancy (AD regional center) were selected. Patients with cortical focal lesion or old history of epilepsy were excluded. The usual clinical follow‐up was extended with a prolonged EEG and a specific consultation with an epilepsy expert. Based on this dedicated interrogation and EEG results, patients were then classified as epileptic or non‐epileptic. We collected demographic data and information on epilepsy and AD disorders.ResultAmong the 22 included patients, 10 were classified as epileptic with a prevalence of 45%. Considering seizure types, patients presented generalized seizures (n=4), typical temporal seizures (n=4), myoclonus (n=1) and extratemporal seizures (n=1). EEG recordings were not useful in our population. Epileptic patients presented a more severe cognitive decline than patients without seizures (MMSE 8.4+/‐6.9 versus MMSE non epileptic 20.9 +/‐ 5.45). 100% of patients with a MMSE <10 had epileptic comorbidity. In our population, epilepsy never occurred before AD diagnosis.ConclusionEpilepsy appears to be a frequent comorbidity in early onset AD patients, with a prevalence of 45% in our study. This comorbidity seems to be a marker for severe AD. The role of the epileptic disorder in the acceleration of cognitive decline as the positive impact of antiepileptic drugs still need to be determined.