bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attitudes towards people with dementia: Questionnaire validation and comparison between Germany and China
Authors: Zhu Lin , Schall Arthur , Tesky Valentina Antonia , Paulitsch Michael , Pantel Johannes 
Published: December 2020

AbstractBackgroundIn both professional and family settings, attitudes towards dementia influence the way this group of patients is treated. It is therefore of great importance to conduct research into intercultural differences in attitudes towards dementia and then to adapt concepts of care to better suit the target population. This project examines the question whether differences exist in attitudes towards persons with dementia between Germany and China.MethodThe Dementia Attitudes Scale (DAS) has been validated for different European languages (English, German, French, Italian). For this study the DAS was professionally translated and validated for the Chinese language (Mandarin). Samples were recruited of the general population and of professional hospital nurses in both countries (total N of recruits: 195).ResultInternal consistency was very good for both the Chinese and German versions of the DAS (Cronbach’s alpha > 0.8). The two groups differed in terms of experience with persons with dementia: Respondents in the German group had significantly more experience of interacting with persons with dementia. With regard to attitudes towards persons with dementia, the Chinese group had a more negative attitude than the German group. A comparison of the two sub‐groups “qualified personnel” with “general population” showed that professional knowledge has a positive influence.ConclusionThis pilot study revealed differences in attitudes toward people with dementia between Germany and China. The reason for this (e.g. knowledge/education, cultural differences, personal experience) should be addressed in future studies. Ultimately this may help to increase the well‐being and quality of life of persons with dementia over the long term and in a culturally sensitive manner
A new biological assay of Aβ clearance: The Aβ mid‐domain immunoassay
Authors: Torsetnes Silje Bøen , Wettergreen Marianne , Nordengen Kaja , Gisladottir Berglind , Sharma Kulbhushan , Christensen Erik , Fladby Tormod 
Published: December 2020

AbstractBackgroundDecreased Aβ clearance is thought to precede the clinical AD symptoms by a decade or more. Clearance of Aβ include phagocytosis and degradation are two important components. Innate immune‐linked genetic risk factors contribute to AD, and innate immune cells – microglia in the brain and monocytes/macrophages in the peripheral blood – phagocytize and degrade Aβ. Based on this, we hypothesize that intra‐ and extracellular Aβ fragments, specifically mid‐domain Aβ, reflect phagocytic activity or Aβ degradation efficiency. Our objective was thus to develop an assay measuring intra‐ and extracellular Aβ mid‐domain peptides in relevant biological specimens.MethodFirstly, a panel of sheep monoclonal antibodies (mAbs by Bioventix Ltd, UK) was raised against the Aβ20‐34 peptide. Secondly, an anticomplex antibody (HuCal, BioRad, CA, USA) was screened for, needing to be selective for only Aβ20‐34 bound to the most sensitive sheep mAb. Throughout these processes, immunoprecipitation and reversed phase liquid chromatography mass spectrometry (IP LCMS) were used to map the affinity and selectivity of the best performing antibodies pair (sheep mAb 2A9 and HuCal H3). Thirdly and finally, an immunoassay on the Quanterix Single Molecule Array (Simoa, Quanterix, MA, USA) platform was developed, resulting in our final product.ResultIP LCMS experiments showed that sheep mAb 2A9 bound to a mid‐domain peptide is needed for complex formation with HuCal H3. In selectivity mapping, where endogenous Aβ was screened for in CSF using these antibodies in a sandwich, a preferential binding of AβX‐34>>AβX‐40 was demonstrated. The two antibodies applied in a new immunoassay on the Simoa platform, gave a sensitive immunoassay detecting Aβ mid‐domain peptides with a LOD<0.5 pg/ml. Thus detecting endogenous levels both in CSF and in blood derived samples such as serum, plasma and monocyte lysates. Various samples from healthy subjects, study participants in AD intervention studies, and other clinical samples are currently being analyzed.ConclusionHere, we present the first immunoassay able to detect endogenous catabolic Aβ peptides in a range of biological tissue fluids. This functional assay thus paves the way for novel studies on Aβ clearance and catabolism and may serve as a tool for peripheral blood measurement in both disease progression‐ and intervention studies.
Management of sleep disturbances in people with dementia living in care homes: The SIESTA qualitative study
Authors: Webster Lucy A , Powell Kingsley , Gonzales Sergi Costafreda , Livingston Gill 
Published: December 2020

AbstractBackgroundSleep disturbances, including difficulty falling asleep, night time awakening, and excessive daytime sleepiness, effect nearly 40% of people with dementia living in care homes. Though hypnotic medications are commonly used, they are not recommended as they have been linked to increased risk of falls and mortality, and have little efficacy. There are currently no evidence‐based treatments. Through the SIESTA qualitative study (Sleep problems In dEmentia: interviews with care home STAff), we aimed to explore the alternative ways that sleep disturbances in residents with dementia are managed by care home staff.MethodWe interviewed 18 nurses and care assistants working both day and night shifts at four care homes in the UK providing residential and nursing care. We used a topic guide to explore staff experience of sleep disturbance in residents with dementia. The interviews were audio‐recorded, transcribed, and analyzed thematically by two researchers independently.ResultAll staff described a range of strategies they used to manage sleep disturbance in residents with dementia. Often this began with preventative techniques in the daytime, with staff ensuring where possible residents stayed active, ate well, and took part in activities to avoid napping. In the evening time staff settled residents into a dark, noise free, comfortable bedroom environment. When residents woke during the night‐time they were often given caffeinated tea or food, particularly if they had not eaten or drank much in the day due to napping. Tea and comfort were often used together, with staff sitting with the resident providing company and reassurance. If someone was agitated staff would think about pain and discomfort, and would use telecare to monitor residents who often left their bed at night and were a safety risk. As the last resort, sleep medications were used, but staff described how they only worked sometimes, as well as the side effects.ConclusionStaff used a range of techniques and described how these often worked in reducing, maintaining or preventing sleep disturbance, however, some of the strategies reported by staff to deal with sleep disturbances such as feeding or providing caffeinated tea at night might be counter‐productive.
Enhancing family quality‐of‐life outcomes: The NEUROQUALYFAM project
Authors: Ortega Eva González ,   NEUROQUALYFAM group
Published: December 2020

AbstractBackgroundNeurodegenerative diseases (ND) have a great impact on both patients and their relatives, since the latter play an essential role in the care process. Consequently, the families require support to perform this function with higher levels of wellbeing. The objective of the NEUROQUALYFAM project (Interreg V‐A Spain‐Portugal, POCTEP) is to analyze the quality of life of families of people with ND, to identify their needs and to plan family‐centered support resources in order to offer high‐quality social health services for people with ND and their families.MethodThe study sample will consist of 300 families from the Spanish‐Portuguese cross‐border area. The Family Quality of Life Survey ‐ Dementia (FQoLS) will be translated, adapted and validated (DiZazzo‐Miller & Samuel, 2011) to assess their quality of life. Focus groups with families and professionals from health, social services and the third sector will be conducted to identify needs and support resources. The “section 2‐Support and Services” of the validated Spanish version of the Beach Center Family Quality of Life Scale (Verdugo, Rodríguez and Sainz, 2012) will be adapted for families of people with ND to identify the types of support needed and to what extent they are provided. A confirmatory factor analysis will be conducted to examine the validity of the construct FQoLS‐ ND. A top‐down content analysis will be undertaken for qualitative data.ResultThe project will provide: (a) a procedure to evaluate the quality of life of families of people with ND; (b) the identification and mapping of unmet support needs regarding the health and social system; (c) the planning of a family‐centered support system for the improvement of health and wellbeing outcomes, and (d) the design of a comprehensive ICT platform of support resources that enhances training, information exchange and collaborative networks between and among families and professionals.ConclusionThe project NEUROQUALYFAM provides a research and intervention model that might be applied in other regions and countries. It strengthens cooperation between the institutions (health and social services, third sector) to improve the quality of family life and optimize support resources for family caregivers.
Reliability of wrist‐worn accelerometry devices and algorithms for sleep detection
Authors: Peraza Luis R , Joules Richard , Dauvilliers Yves , Wolz Robin 
Published: December 2020

AbstractBackgroundWearable devices have shown great potential for obtaining measures of real world evidence in clinical trials, but standardization and variability between different devices remain one of the barriers for systematic deployment. In this investigation, we present a neural network algorithm for sleep detection, Deep Learning Sleep (DLS), and compare its reliability across different datasets and two widely used sleep algorithms.MethodA publically available dataset TUD (Borazio; ICHI 2014, N=45) and the CONTEXT dataset collected in Montpellier, IXI (Wolz; Alzheimer’s & Dementia 2017, N=45) were used to compare algorithm performance. Each dataset provided one‐night accelerometry data alongside polysomnography (PSG) per participant. DLS performance was compared against two other algorithms for sleep segment detection; Cole‐Kripke, CK (Cole; Sleep 1992), and estimation of stationary segments or ESS (Borazio; ICHI 2014). Then, cross‐validations were implemented with the datasets; e.g. training with dataset TUD and testing on dataset IXI, and vice versa.ResultThe cross‐validations experiments showed no significant differences in performance (sleep detection: 85‐89% sensitivity, 43‐45% specificity and 72‐74% accuracy) for the DLS algorithm. On the contrary, CK and ESS showed significant differences in their performances across experiments, and CK showed the highest difference for specificity (mean specificity = 27‐52%), demonstrating that CK and ESS algorithms are susceptible to different devices and/or data sources (Figure 1).ConclusionThe CK and ESS algorithms showed susceptibility to different devices or data sources (e.g. clinical groups) and this raises questions about their reliability. In conclusion, we presented a deep learning based algorithm (DLS) that showed high robustness against different data sources as well as high accuracy when compared against the gold standard PSG.
Transcript analysis using long‐read sequencing reveals the complex splicing profile of AD‐associated gene ABCA7
Authors: Duchateau Lena , Küçükali Fahri , Van Dongen Jasper , Bossaerts Liene , Hens Elisabeth , De Roeck Arne , Mateiu Ligia , Van Broeckhoven Christine , Sleegers Kristel 
Published: December 2020

AbstractBackgroundThe ATP‐Binding Cassette Subfamily A member 7 (ABCA7) gene is one of most alluring risk genes for Alzheimer’s disease (AD). Of special interest are alternative splice events that are a) able to rescue the effect of premature termination codon (PTC) mutations, possibly explaining the wide range in phenotype and onset age of PTC mutation carriers, and b) associated with an elongated intronic variable number of tandem repeat (VNTR). However, our knowledge of alternative splice events in ABCA7 is limited. Here, we analyze the ABCA7 transcript using long‐read sequencing in a unique population of ABCA7 PTC carriers. Moreover, we look for possible association between rescue splicing and AD onset age.MethodsWe characterized the ABCA7 transcript of 28 AD patients (24 PTC carriers), 17 controls (11 PTC carriers) and 5 mild cognitive impairment patients using targeted long‐read cDNA sequencing on an Oxford Nanopore MinION platform. RNA was extracted from 47 lymphoblastoid cell lines, as well as 4 hippocampi and 2 prefrontal cortices. Alternative splice events and rescue events were quantified using the full‐length alternative isoform analysis of RNA (FLAIR) pipeline and an in‐house R script.ResultAll PTC mutation carriers displayed nonsense‐mediated mRNA degradation escape (mutant reads <5%‐67% of total reads). Rescue events were found in 17 carriers. While most carriers displayed a rescue/canonical splicing ratio <0.02, this ratio went up to 3.21. Rescue however did not have a strong association with onset age (p = 0.2) or phenotype (p = 0.8). We identified 199 previously undescribed splice events with an alternative/canonical ratio of at least 0.05. This is an almost 4‐fold increase compared to the 53 known junctions. Moreover, 15 of these alternative splice events occur more frequently than the corresponding canonical event (ratio>1). This seems to occur more frequently in AD patients (n = 20) than controls (n = 8) (OR = 2.74), to higher extent in brain tissue and more frequently outside the transmembrane domains, nucleotide‐binding domains or extracellular loops.ConclusionOur results highlight a complexity of the ABCA7 transcript that has not been described before. Moreover, splicing seems to occur more frequently in AD patients. These results suggest that ABCA7 splicing might be an important mechanism in AD.
Validation of the Spanish version of the Mini‐Linguistic State Examination for the diagnosis of primary progressive aphasia
Authors: Matias‐Guiu Jordi A. , Pytel Vanesa , Patel Nikil , Delgado‐Álvarez Alfonso , Matias‐Guiu Jorge , Garrard Peter , Cuetos Fernando 
Published: December 2020

AbstractBackgroundPrimary progressive aphasia (PPA) is a clinical syndrome of neurodegenerative origin with three main clinical variants (nonfluent, semantic, and logopenic). Clinical diagnosis and accurate classification into the three clinical variants is challenging and often time‐consuming. The Mini‐Linguistic State Examination (MLSE) has been recently developed as a short language test specifically designed for language assessment in neurodegenerative disorders. Our aim was to adapt and validate the Spanish version of MLSE for PPA diagnosis.MethodCross‐sectional study involving 70 patients with PPA and 42 healthy controls were evaluated with the MLSE. Patients were independently diagnosed and classified according to a comprehensive cognitive and advanced neuroimaging.ResultInternal consistency was 0.702. Influence of age and education was very low. The area under the curve for discriminating PPA patients and healthy controls was 0.989. Effect sizes were moderate‐large for the discrimination between PPA and healthy controls. In addition, motor speech, phonology and semantics subscores discriminated between the three clinical variants.ConclusionOur study provides a useful and brief language test for the diagnosis of PPA with excellent properties for both clinical routine assessment and research purposes.
The difference in cortical thickness between posterior cortical atrophy patients and age‐associated memory impairment subjects
Authors: Likitjaroen Yuttachai , Phanthumchinda Kammant 
Published: December 2020

AbstractBackgroundPosterior Cortical Atrophy (PCA) is a variant of Alzheimer’s disease. The Perceptual‐motor function deficits are the presentations. Here, we used the imaging technique to demonstrate the pattern of cortical thinning in PCA patients compared to age‐associated memory impairment (AAMI) subjectsMethodFourteen PCA patients and 20 AAMI subjects were recruited from Neurocognitive Clinic, King Chulalongkorn Memorial Hospital, Thailand. All PCA patients met the criteria and structural brain magnetic resonance imaging revealed predominantly atrophy of the parieto‐occipital area. 11 PCA patients had FDG‐PET confirmed. Cortical surfaces of all participants were reconstructed using freesurfer software. The cortical thickness were compared between the two groups.ResultEight of PCA and 17 of AAMI were female. The mean age of PCA group and AAMI group were 63.87 and 75.88 respectively (P<0.001). Brain segmented volume was not different (P=0.081). Cortical volume was significantly lower on the right hemisphere in PCA group (P=0.047). The white matter volume in PCA group was lower on both hemispheres (right p=0.017, left P=0.027). The whole brain analysis revealed PCA had significantly thinner cortical areas on the left hemisphere including superiorparietal, supramarginal, transversetemporal, superiortemporal, lateraloccipital, isthmuscingulate, entorhinal as well as the right hemisphere including superiorparietal, supramarginal, superiortemporal, insula, lateraloccipital, temporalpole, entorhinal and lingual. We also found the area where PCA group are significantly thicker than AAMI group in the frontal lobe and primary visual area on both hemisphere.ConclusionWe demonstrated a diffused cortical thinning pattern in PCA compared to age‐matched AAMI group. The significant cortical thinning in PCA were profound on parietal, occipital and posterior temporal on both hemisphere. Furthermore, we found the predominant decline of white matter volume in PCA. Frontal areas and primary visual cortex were spared which may be due to younger age or the nature of the disease.
The genetic association between ACE1 and Alzheimer’s disease
Authors: Guzel Ozge , Tayler Hannah Mary , Skrobot Olivia Anna , Miners Scott , Kehoe Patrick Gavin 
Published: December 2020

AbstractBackground
ACE1 is a reported risk gene for Alzheimer’s disease (AD), highlighted by several meta‐analysis and recent GWAS studies (Marioni et al., 2018; Kunkle et al., 2019) . ACE1 encodes angiotensin II converting enzyme‐1 (ACE‐1), a rate‐limiting enzyme in the classical renin‐angiotensin system (cRAS) and is overactivated in AD (Miners et al., 2008, Miners et al., 2009). ACE‐1 generates Ang‐II, itself elevated in AD, and is increased in relation to parenchymal Aβ load. We investigated the relationship between the ACE1 variant (rs4343) (Abdollahi et al., 2008) (a proxy marker for the more commonly studied indel polymorphism) and Aβ plaque and tau tangle load (assessed by IHC) and levels of Aβ40 and Aβ42 (soluble and insoluble) and Ang‐II level, measured by ELISA.MethodWe studied a total cohort of 318 dementia cases (AD, Mixed AD and vascular dementia) and 116 controls from the South West Dementia Brain Bank, University of Bristol, UK. The ACE1 indel proxy polymorphism, rs4343, was genotyped using PCR based method. The A and G alleles for rs4343 are equivalent to the insertion and deletion variation in ACE1, respectively. Parenchymal Aβ plaque and tau tangle load was quantified by computer‐assisted field fraction analysis in the frontal and parietal cortex for 134 AD and Mixed dementia cases. Aβ40 and Aβ42, and Ang‐II level, was also measured by ELISA in 254 dementia cases and controls. We performed logistic regression to determine the association between ACE1 genotype and AD and non‐parametric Mann‐Whitney U test to determine the association between ACE1 genotype and Aβ and tau pathology.ResultG/G homozygotes were associated with reduced risk of AD and Mixed dementia (p = 0.037). AD and Mixed dementia cases with the G/G genotype also had significantly lower (p = 0.0109) parenchymal Aβ load in the frontal cortex compared with A/A and A/G genotypes, but this was not evident in the parietal cortex. We will further explore the relationship between rs4343 variants and levels of Aβ (soluble and insoluble) and Ang‐II and examine the potential interaction with tau pathology.ConclusionOur initial findings indicate that the ACE1 rs4343 polymorphism may associate with both AD risk and AD‐related Aβ pathology.
Correlation of Aβ‐pE(3) and ptau in human and mouse brain
Authors: Temmel Magdalena , Neddens Joerg , Flunkert Stefanie , Walker Lauren , Attems Johannes , Hutter‐Paier Birgit 
Published: December 2020

AbstractBackgroundSenile plaques frequently contain pyroglutamate amyloid β (Aβ‐pE(3)), a N‐terminally truncated Aβ species that is more closely linked to Alzheimer’s Disease (AD) compared to other Aβ species. Tau protein is highly phosphorylated at several residues in AD, specifically tau protein phosphorylated (ptau) at Ser202/Thr205 is known to be increased in AD. First studies suggest that the two pathologies of plaques and tau phosphorylation might be linked to each other.MethodTo evaluate if Aβ‐pE(3) and ptau Ser202/Thr205 levels correlate in human and transgenic AD mouse models we analyzed human cortical and hippocampal brain tissue of different Braak stages as well as murine brain tissue of two transgenic mouse models for levels of Aβ‐pE(3) and ptau Ser202/Thr205 and correlated the data.ResultOur results show that Aβ‐pE(3) formation increases already at early Braak stages while ptau Ser202/Thr205 mostly increases at later stages. Further analyses revealed strong correlations between the two pathologies in the temporal, frontal, cingulate and occipital cortex. However, correlation in the hippocampus was weaker. Evaluation of murine transgenic brain tissue demonstrated a slow but steady increase of Aβ‐pE(3) from 6 to 12 months of age in the cortex and hippocampus of APPSL mice and a very early and strong Aβ‐pE(3) increase in 5xFAD mice. ptau Ser202/Thr205 levels increased at the age of 9 months in APPSL mice and already at 6 months in 5xFAD mice.ConclusionOur results show that Aβ‐pE(3) and ptau Ser202/Thr205 levels strongly correlate in human as well as murine brain tissues, suggesting that tau phosphorylation might be amplified by Aβ‐pE(3).