bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau propagation is dependent on the genetic background in multiple mouse strains
Authors: Dujardin Simon , De Los Santos Mark , Fernandes Analiese R. , Bannon Riley N. , Kamath Tarun V. , Commins Caitlin , Hyman Bradley T. 
Published: December 2020

AbstractBackgroundThe hyperphosphorylation and deposition of tau proteins in insoluble aggregates inside neurons are a hallmark of around 20 pathologies called tauopathies including the well‐known Alzheimer’s disease (AD). In AD and other tauopathies, histopathological studies have shown that tau lesions appear progressively and hierarchically in the brain along anatomical connections. The mechanisms underlying such evolution had remained unexplained for many years, but recent evidence support the idea that the evolution across brain areas is the result of the active propagation of tau aggregation within the brain. We and others previously demonstrated in in vitro and in vivo models that tau assemblies are transferred from cell‐to‐cell and, by being taken up by a second cell, seed the aggregation of endogenous tau leading to the propagation of tau lesions in the brain. We hypothesized here that the genetic background of mice influences the propagation of tau across neural networks.MethodsWe used a model of tau propagation that we previously described consisting in the injection of adeno‐associated viral vectors (AAV) encoding the eGFP‐2A‐Tau construct into the entorhinal cortex of mice. The 2A peptide is a self‐cleaving peptide resulting in the equimolar independent expression of the eGFP and human tau. Using this model, we can therefore discriminate the neurons expressing the AAVs (GFP and tau positive) from the tau propagation recipient neurons (tau positive only). We injected mice from multiple strains (n = 5 males and 5 females per strain), with diverse genetic backgrounds, with this construct and subsequently quantified the number of neurons positive for tau propagation in each condition.ResultsIn a blinded analysis we found that the propagation of tau in vivo is highly dependent of the genetic background with strains (such as C57BL/6) that are mostly resilient to tau propagation when other (such as CD‐1 or A/J) show a high degree of tau propagation.Conclusionthese results provide an important insight to the idea that tau propagates from neuron‐to‐neuron in the human pathology. This could explain part of the human clinical heterogeneity and must be investigated further to understand the genetic factors responsible for such drastic differences.
Satisfaction with stroke care among dementia patients with stroke: A Swedish register study
Authors: Hoang Minh Tuan , Kåreholt Ingemar , von Euler Mia , von Koch Lena , Eriksdotter Maria , Garcia‐Ptacek Sara 
Published: December 2020

AbstractBackgroundPrevious studies showed that patient satisfaction with stroke care relates to age, care demands, functioning, mood, quality of life, and self‐rated health. Dementia and stroke are frequent comorbidities. It is still unknown how satisfied dementia patients are with stroke care compared to non‐dementia patients. Our study aimed to compare the satisfaction with stroke care between dementia and non‐dementia patients.MethodsIn this longitudinal observational registry study, 5,932 dementia patients (2007‐2017) who suffered a first stroke after dementia diagnosis were compared with 39,457 non‐dementia stroke patients (2007‐2017). Data on stroke was obtained through the Swedish Stroke Register (Riksstroke), linked to the Swedish Dementia Registry (SveDem), the Swedish National Patient Register and the Swedish Prescribed Drug Register. Questionnaires were completed by patients themselves, patients with the help of caregivers, patients’ family, or healthcare staffs on behalf of the patient three months after stroke. Outcomes comprised satisfaction with acute stroke care at hospital, inpatient rehabilitation, outpatient rehabilitation, healthcare staff’s attitude, communication with doctors and stroke information.ResultsCompared to non‐dementia patients, dementia patients who answered the questionnaire themselves reported lower odds of satisfaction with acute stroke care at hospital 0.72 (0.61 – 0.87), healthcare staff’s attitude 0.80 (0.67 – 0.97), communication with doctors 0.80 (0.68 – 0.95 ), and stroke information 0.63 (0.53 – 0.76); but not regarding inpatient rehabilitation 0.95 (0.77 – 1.19), or outpatient rehabilitation 0.96 (0.76 ‐1.23). When patients answered the questionnaire with the help of their caregivers, dementia patients reported significantly lower satisfaction for all items. Differences between dementia and non‐dementia patients disappeared in proxy‐reported satisfaction, except for family‐reported satisfaction with outpatient rehabilitation and stroke information, which was significantly lower in dementia group.ConclusionLower satisfaction in the dementia group is a sign of unfulfilled care needs among dementia patients. Further studies on the provision of stroke care for dementia patients and their care demands should be performed.
Single‐nuclei RNA‐seq of brains carriers of high‐risk variants and Mendelian mutations
Authors: Del‐Aguila Jorge L. , Brase Logan , Benitez Bruno A. , Karch Celeste M. , Cruchaga Carlos , Harari Oscar 
Published: December 2020

AbstractBackgroundAD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures. We sought to investigate the glial and neuronal pathways affected by AD at the cell specific resolution. To do so, we generated unsorted brain single‐nuclei RNA‐sequence from carrier of a Mendelian mutation and high‐risk variants associated with AD from the Knight‐ADRC and DIAN brain banks.MethodsWe sequenced 74 parietal lobe from carriers of APP, PSEN1 and PSEN2 mutations (N = 19), and high‐risk variants, including APOE e4 (N = 26) and TREM2 (N = 21), non‐carrier AD (N = 15) and neuropath‐free controls (N = 9). We employed the 10X Chromium 3’ chemistry V3, to sequence 10,000 nuclei and 40,000 reads per nuclei. In total. We generated data for more than 1,2 million nuclei. We applied stringent quality control and data cleaning procedures, including alternative methods to detect empty droplets and doublets, and used alternative clustering methods to a very large number of nuclei. We have assembled and curated a reference panel that we employ in different supervised and unsupervised methods to annotate the cell‐type of the different clusters.ResultsWe have identified the expression profile of Neurons, Oligodendrocytes, astrocytes, OPC and other cell‐types in the brain (Figure 1). Our dataset includes more than 17,500 nuclei from microglia cells (minimum 100 and mean 285 nuclei per donor) that present alternative transcriptional profiles that resemble that of the Disease Associated Microglia and Human Alzheimer Microglia.ConclusionSingle‐nuclei transcriptomic data from human brains provides a detailed molecular atlas to study the pathways dysregulated in AD. We have developed a unique resource to investigate amyloid‐beta protein clearance and degradation pathways, endolysosomal pathways, cholesterol metabolism and immune system contribution to AD etiology and pathogenesis.
Evaluating the Codesigning Dementia Diagnosis and Post‐Diagnostic Care (COGNISANCE) project
Authors: McAiney Carrie A , Vedel Isabelle , Doucet Shelley , Luke Alison , Jarrett Pamela , Team COGNISANCE 
Published: December 2020

AbstractBackgroundPersons with dementia and their family/friend care partners often report poor experiences at the time a dementia diagnosis was given and in the supports provided following the diagnosis. Such experiences often include a lack of information, a lack of support, and limited or no hope. While there are national guidelines that outline the steps required to make a dementia diagnosis, there is limited information about how best to engage persons with dementia and their care partners and communicate this information to them. There are also few resources to support individuals and care partners in navigating this challenging journey. The "Codesigning dementia diagnosis and post‐diagnostic care" (COGNISANCE) project aims to develop and evaluate toolkits and behaviour change campaigns for: 1) members of the at‐risk public and 2) health and social care providers to improve the dementia diagnosis experience and the supports provided following a diagnosis. The purpose of this poster is to describe the process of developing an evaluation plan, together with persons living with dementia and their care partners, that will be implemented in the five countries participating in COGNISANCE: Canada, Australia, Netherlands, United Kingdom, and Poland.MethodThe evaluation plan is being informed by social marketing theories and guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE‐AIM) framework. Working collaboratively with persons living with dementia and care partners, and a large international team, we are developing a comprehensive plan to evaluate the implementation and effectiveness of the behaviour change toolkits and campaigns.ResultWe will describe the process used to develop the evaluation plan. This includes our experiences working together with persons living with dementia and their care partners, as well as our international collaborators, to develop a plan that achieves our objectives and is feasible to implement across the participating countries.ConclusionFindings from the COGNISANCE evaluation will inform opportunities to spread the toolkits and campaigns within the participating countries, as well as the development of an implementation playbook, a resource aimed to support developing countries in creating and implementing their own toolkits and campaigns.
The role of education in resistance against development of vascular brain pathology
Authors: van Arendonk Joyce , Yilmaz Pinar , Steketee Rebecca , Zijlmans Jendé L , Lamballais Sander , Ikram M Arfan , Vernooij Meike W 
Published: December 2020

AbstractBackgroundVascular brain pathology due to cerebral small vessel disease is one of the leading causes of cognitive decline and dementia in the elderly. The concept of brain resistance postulates that individuals with the same amount of risk factors show different levels of neuropathology than expected based on their risk profile. In this study, we investigate the role of education, as proxy for resistance, on the development of brain pathology due to vascular risk factors.Method4440 participants without stroke or dementia were included from the population‐based Rotterdam study (mean age, 62.9±10,7 years). Structural MRI was measured on a 1.5T MRI scanner and comprehensive psychometric data was obtained. Educational attainment was assessed during the baseline interview and classified in three categories. Hypertension and the Framingham Stroke Risk Profile were used as the primary vascular risk factors of interest. Vascular brain pathology as outcome was assessed by white matter hyperintensities (WMH), microbleeds and lacunar infarcts. We used multiple linear regression models to determine the relation between vascular risk factors and brain pathology, stratified by educational level.ResultSignificant interaction effects between education and hypertension were found on their association with WMH, hippocampal volume and microbleeds. The association of hypertension with hippocampal volume differed significantly across strata of education: β=0.02, 95%CI ‐0.07‐0.11 for high education compared to β=‐0.12 95%CI ‐0.21‐ ‐0.03 for low education. Moreover, the association of hypertension with WMH differed significantly between the intermediate and low education strata, and differed borderline significantly between the high and low education strata: β=0.15, 95%CI 0.08‐0.22 for high education, β=0.20, 95%CI 0.11‐0.29 for intermediate education and β=0.28, 95%CI 0.18‐0.38 for low education. Lastly, the association of hypertension with microbleeds also differed significantly across strata of education: β= 0.00, 95%CI ‐0.04‐0.03 for intermediate education compared to β=0.05, 95%CI ‐0.01‐0.10 for low education.ConclusionA similar vascular risk profile leads to fewer WMH, microbleeds and less hippocampal atrophy in participants with a higher education level compared to persons with lower education. This suggests that people with a higher education level are more resistant against vascular brain pathology and hippocampal atrophy due to vascular risk factors.
Development of a digital system to assess and manage unmet needs of family dementia caregivers in clinical practice
Authors: Klein Olga A , Thyrian Jochen René , Boekholt Melanie , Teipel Stefan J , Hoffmann Wolfgang , Kilimann Ingo 
Published: December 2020

AbstractBackgroundCaregiver burden is a risk factor for negative health outcomes in carers and randomized realization in people with dementia. With the rising prevalence of dementia, it is essential to identify unmet needs of family caregivers to promote wellbeing and randomize caregiver related burden. However, validated instruments to identify unmet needs of family caregivers are scarce and it is unclear whether and to what extent existing instruments are used in clinical practice.AimTo develop a digital system to identify and manage unmet needs of family dementia caregivers in clinical practice.MethodThis study is part of a large, cluster randomized controlled trial (cRCT) examining the clinical use and cost‐effectiveness of a computer‐based care management programme for family caregivers. We conducted a literature search identifying existing instruments assessing medical, psychological, and social unmet needs. With the help of 25 caregivers and experts including neurologists, psychologists, psychiatrists and nurses, an initial selection of questions and existing instruments was generated and piloted. Items and response options were judged for content, clarity, interpretability, and length. The instrument was adapted and a computer‐based version was created. Questions were paired with care management recommendations which will be automatically triggered by the system if an item is identified as unmet need. Further expert interviews will examine the usability in clinical practice. This study is supported by the German Federal Joint Committee (G‐BA).ResultThe preliminary selection comprised 63 questions. Caregivers and experts commented on the content, wording and order of questions, the response options provided, the length of the instrument, and the layout of each section. Questions and response options were re‐worded to avoid ambiguity. The order and layout of questions was changed based on respondents’ comments. On average, it took 37 minutes (range 15‐90, SD=24.23) to complete the instrument. Some respondents stated that they lost focus towards the end of the assessment. As a result, the instrument was simplified.ConclusionThe development of the digital system is currently ongoing. Results will be presented.
Deficits in emotion recognition monitoring in dementia patients
Authors: Cordero Indira Ruth Garcia , Migeot Joaquín , Aquino Alexia , Fittipaldi Sol , Rivera Mariano Díaz , Sedeño Lucas , Garcia Adolfo M. , Ibanez Agustin 
Published: December 2020

AbstractBackgroundThe capacity to ascertain other people’s emotional states is crucial for establishing and maintaining social interactions. In particular, accurate recognition of facial expressions and beliefs about whether we trust what a face transmits are fundamental for guiding and adjusting this social behavior. Yet, although emotion recognition impairments are well documented in neurodegenerative diseases, the role of monitoring skills in this domain remains poorly understood in the field of dementia.MethodWe recruited patients with behavioral variant frontotemporal dementia (bvFTD, n = 18), Alzheimer’s disease (AD, n = 27), and demographically‐matched controls (n = 38). Participants performed a classic test of facial expression recognition and, after each trial, they provided a confidence judgment about their performance. A monitoring index was calculated considering both performance on each emotion type and associated confidence ratings (with higher values of the index indicating worse monitoring). Then, whole‐brain grey matter volume was analyzed via voxel‐based morphometry (VBM) to track possible associations with the monitoring index.ResultsCompared to controls, both groups of patients exhibited difficulties in monitoring negative emotions. Monitoring of disgust was specifically impaired in bvFTD, and monitoring of sadness and neutral faces, in AD. VBM results showed that, in bvFTD, reduced grey matter volume in areas belonging to the limbic system and subcortical regions was associated with emotion recognition deficits. Monitoring impairments were also related with different subcortical and cortical areas, including the prefrontal lobe, insula and the cingulate cortex. On the other hand, in AD, temporal and parietal areas were associated with emotion recognition and parietal and frontal regions, with monitoring.ConclusionThese results indicate that dementia patients present emotion recognition monitoring impairments and that these deficits are associated with damage of cortical and subcortical regions as well as limbic circuits. In both groups, recognition and monitoring of emotions shared several structural substrates. The monitoring impairments presented in bvFTD and AD could be related with the changes in social cognition and behavior that these patients presented in daily life. Therefore, these preliminary findings could contribute to a better understanding of emotion monitoring processes.
A multisite analysis of the concordance between visual image interpretation and quantitative analysis of [18F]flutemetamol PET images
Authors: Farrar Gill , Nordberg Agneta K , Sur Cyrille , Scott David , Lhommel Renaud , Collij Lyduine , Molinuevo Jose Luis , Hansson Oskar , Gunn Roger N , Rowe Christopher C , Dore Vincent , Buckley Chris J 
Published: December 2020

AbstractBackground[18F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual interpretation of scans as either negative (equating to none or sparse amyloid plaques in pathology SoT), or amyloid positive (equating to moderate or frequent plaques). Quantitation is however fundamental to the practice of Nuclear Medicine and hence can be used to supplement amyloid reading methodology especially in unclear cases. Data was collected from multiple sources to assess comparability of the two methods of image interpretation.Method9 separate studies where visual reading of [18F]flutemetamol and quantitative analysis of images was available were combined to form a single cohort to measure the percentage agreement between the two methods of image interpretation. Scans covered a wide range of cases (eg from cognitively unimpaired subjects to patients attending the memory clinics see table). Methods of quantifying amyloid ranged from using CE marked/510K cleared software (eg Cortex ID), to other research tools (eg PMOD, CapAIBL) as well as newer methods such as AmyloidIQ. Concordance between visual and quantiative imaging used thresholds robustly established using pathology as the standard of truthResultA total of 2,566 [18F] flutemetamol images were collected from 9 clinical studies, visually interpreted by readers using the approved reading methodology and compared to quantitative measures using thresholds which had a binary delineation of amyloid. The mean concordance between visual read and quantitation was 95.01% (SD 3.00%), the median was 95.0%, and the range of the 9 studies was from 89.7% to 99.0%. A total of 379 images were compared using CE marked/510k cleared amyloid quantitation software and the percent agreement in these studies was 98.8% to 99.0%.ConclusionGiven the high concordance of visual and quantitation from over 2500 scans, users are able apply quantitative amyloid PET software methods to supplement visual inspection. The decision to use these methods as an adjunct to visual reading is left to the choice of the physician as both methods of image interpretation are comparable. The European Medicines Agency (EMA) have agreed to update the prescribing instructions for [18F]flutemetamol (Vizamyl) based upon this analysis.
Improved repeatability of amyloid quantitation using FSL: Implications on ability to detect small longitudinal changes
Authors: Msayib Yunus , Buckley Christopher , Battle Mark R , Pillay Lovena Chedumbarum 
Published: December 2020

AbstractBackgroundMonitoring changes in amyloid load requires repeatable image quantification methods. Several different brain‐image analysis pipelines are used, including SPM8, PMOD, and FSL [1]. Test‐retest (TRT) repeatability is an important parameter for assessing how useful a given pipeline is for longitudinal within‐subject studies, providing a measure of the pipeline’s likely variability and helping to determine the optimal approach to quantitation [1]. We report the results of a test‐retest study that compared pipelines from relevant software packagesMethodSix pipelines were evaluated: our previously‐published FSL pipeline (FSL1) [1] and a revised version (FSL2), SPM8, PMOD, and two PET‐only pipelines (CortexID** Windows, PMODPET). FSL2 differs from FSL1 by additional heuristic checks that help identify failed registrations, which are then automatically re‐attempted using adjusted registration parameters. The heuristic checks in FSL2 were manually tuned through qualitative evaluation on a large and heterogenous PET‐MR database comprising 812 Alzheimer’s (AD) and non‐AD subjects, for which FSL2 had a final successful registration rate of 98%.For the TRT analyses, 10 subjects [1] with confirmed AD were evaluated. Each subject received an initial (test) [18F]flutemetamol scan, followed by a retest scan within 2 weeks. For each pipeline, TRT variability was calculated for individual subjects and reported as a group mean and standard deviation (SD) (thereby equally weighting each observation): TRT variability of cortical uptake (%) = |retest – test|/0.5*(retest + test). Results were reported on three different scales: SUVRcereb, SUVRcereb‐1, and centiloids (CL).ResultFigure 1 shows TRT variability for each pipeline. Using CL measures for example, FSL2 exhibited the lowest TRT variability (mean ± SD) (2.6 ± 1.9%), followed by FSL1 (3.0 ± 2.7%), SPM8 (3.1 ± 2.7%), PMOD (3.3 ± 1.6%), and the PET‐only pipelines (CortexID: 5.8 ± 4.7%, PMODPET: 6.8 ± 6.4%). Note that FSL2 and PMOD had relatively low dispersion of TRT variability, whereas the other pipelines exhibited a spread that was at least at least 1.4 times larger.ConclusionOur FSL‐based pipeline exhibited higher repeatability than other platforms, thus it may be better‐suited for quantifying small longitudinal changes in cortical amyloid load. [1] Battle et al. EJNMMI Res. 2018;8. **CortexID and its PET‐only adaptive template was used as the core for AmyPype, which outputs centiloid quantification.