bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal microbiota elicits IL‐17A production in neutrophil by regulating RORγt signaling and accelerated the pace of inflammageing in cerebral small vessel disease
Authors: Hu Mengyan , Cai Wei , Lu Zhengqi 
Published: December 2020

AbstractBackgroundIntestinal microbiota shapes the host immune system and influences the outcomes of various neurological disorders. Cerebral small vessels disease (CSVD) is highly prevalent among the elderly with its pathological mechanisms yet incompletely understood. The current study investigates the microbiota ecology in CSVD patients, particularly its impact on host’s immune system.MethodFresh fecal samples (∼500mg) were donated by recruited CSVD patients (n=55) or healthy controls (n=62) for high‐throughput 16S ribosomal RNA gene amplicon sequencing. Laboratory tests and standard magnetic resonance imaging (MRI) were performed in above 2 groups for cardiovascular risk factors screening and neuroimaging assessment respectively. The central immune organ of spleen from healthy wild type C57/Bl6 mouse and primary neutrophil cultures were used to explore the mechanisms of CSVD.ResultAltered composition of gut microflora was associated with undesirable disease outcomes and exacerbated inflammageing status. Neutrophils were activated by CSVD associated microflora and obtain increased capacity of IL‐17A production when were exposed to the fecal bacterial extracts from CSVD patients. Mechanistically, RORγt signaling in neutrophils was activated by CSVD associated gut bacterial extracts to upregulate IL‐17A production.ConclusionOur findings revealed a previously unrecognized implication of gut‐immune‐brain axis in CSVD pathophysiology, with therapeutic implications.
Comparing longitudinal changes in speech‐based digital measures in cognitively healthy, possible cognitive impairment, and MCI/AD individuals
Authors: Robin Jessica , Xu Mengdan , Kaufman Liam D , Simpson William 
Published: December 2020

AbstractBackgroundIn Alzheimer’s disease (AD), changes to speech and language differentiate individuals with AD from healthy controls and may be detectable years prior to clinical diagnosis. Speech‐based digital biomarkers are objective, naturalistic measures, which could detect early signs of mild cognitive impairment (MCI) and AD and track disease progression. The objective of this study was to compare speech‐based digital measures across older adults who were cognitively healthy, had possible cognitive impairment based on cognitive screening measures, or had diagnoses of MCI or AD.Method103 community‐dwelling older adults and 27 individuals with MCI or AD were recruited for this study in North America. Participants completed a tablet‐based speech assessment at Baseline and 6 month timepoints. Verbal responses were recorded, transcribed and analyzed to produce 8 composite measures pertaining to different aspects of speech and language. Participants were divided into a cognitively healthy group (>25 on the MoCA at baseline and at 6‐months), a possible cognitive impairment group (≤25 at both timepoints), and the MCI/AD group. Two‐way mixed ANOVAs were used to compare language scores across groups and assess change over time.ResultThere was a significant effect of group on five of the eight language composite scores: information units, local and global coherence, word finding difficulty and syntactic complexity, with the cognitively healthy group performing the best in all cases. There were significant overall declines in information units, global coherence and discourse mapping over the 6‐month period, but the interactions of time and group did not reach significance. Phonemic and semantic fluency scores also had significant main effects of group and significant declines over time. MoCA scores did not change over 6 months.ConclusionThis study demonstrates that speech‐based biomarkers are sensitive to detect differences in individuals based on cognitive status and MCI/AD diagnosis. A number of these measures declined over a 6 month period, unlike MoCA scores, but the rate of change did not differ significantly across groups. Ongoing work with larger samples and longer study periods will continue to examine which aspects of speech and language are most sensitive to cognitive status and disease progression and validate novel digital biomarkers.
CSF biomarkers within a Belgian allochthonous population
Authors: Lebrun Louisien , Hanseeuw Bernard , Ivanoiu Adrian 
Published: December 2020

AbstractBackgroundNeuropsychological testing is difficult in allochthonous older individuals due to language, sociocultural, and educational differences with autochthones. Using biomarkers could help making early diagnosis of neurodegeneration in this population, but so far very few studies have investigated biomarker differences between allochthones and autochthones. We aimed to characterize the Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers (protein TAU, amyloid β42, tau/amyloid β42 ratio and pTau) in autochthonous and allochthonous patients. Besides ethnic origin, we matched our groups for sex and age.MethodBetween 2010 and 2014, patients had CSF sampling in Belgium, either at the Saint‐Luc Memory Clinic, Brussels (n=309) or at other hospitals (n=2096) which sent their CSF samples to the Saint‐Luc Neurochemistry lab. We conducted three linear regressions each predicting one CSF biomarker with demographic variables: age, sex and presumed ethnic origin. For this last variable, we categorized the patients according to their names and surnames in: autochthones and allochthones. Secondary analyses in a subset (n =346) adjusted for age and sex.ResultsAllochthones (65,9 +/‐ 9,0) attended the Memory clinic at a younger age than autochthones (70,5 +/‐ 9,3) (mean +/‐ SD). The Mann‐Whitney test we conducted has shown a significant difference for age (p<0,0001). The multiple regressions have pointed out the age to have a significant effect on all the biomarkers (p=0,0001), the sex a significant effect on TAU (p<0,05) and the ethnic origin on both TAU and tau/amyloid ratio (p<0,02). Adjusting for age and sex [median (interquartiles)] TAU 263 (165,5 – 508,3) for Italians, 277 (174,5 – 447,5) for Maghrebis, 207 (128,5 – 298,5) pg/ml for autochthonous), pTAU 44,5 (32 – 71) for Italians, 44 (31 – 58,5) for Maghrebis , 32 (23 – 44) pg/ml for autochthonous and the TAU/amyloid ratio 0,62 (0,31 – 1,34) for Italians, 0,54 (0,28 – 1,37) for Maghrebis, 0,32 (0,21 – 0,74) for autochthonous) were significantly higher in the allochthones than in the autochthones after conducting a Mann‐Whitney test.ConclusionAllochthones have higher TAU and pTau pathology than autochthones even after adjusting for age and sex. Different genetic background or sociocultural aspects that were not captured here might explain the observed differences.
Healthcare providers’ perceptions of the efficacy of antipsychotics in dementia‐related psychosis
Authors: Chen Jeanny , Bell Stephen , Brain Cecilia 
Published: December 2020

AbstractBackgroundAntipsychotics are commonly used to treat dementia‐related psychosis, i.e. hallucinations and delusions in dementia due to the lack of approved pharmacological options. The treatment need is large as rates of hallucinations and delusions have been approximated to affect about 2.4 million people in the U.S. alone.1‐15 This vulnerable population should however be carefully monitored in regard to the risk‐benefit of receiving dopamine D2 blocking APs.16
Methods249 U.S. healthcare providers (HCPs), including physicians, nurse practitioners, and physician assistants, completed an online survey. For those of their patients with dementia who were treated with APs for hallucinations and delusions, the HCPs were asked to estimate the percentages for whom the symptoms were (1) completely stopped; (2) stabilized (not stopped) and without relapses; (3) stabilized but with relapses; and, (4) not stabilized. In the survey, “relapse” was defined as “a symptom becoming worse after a period of stability.” Respondents were also asked to estimate the percentages of their AP‐treated patients who were on their first, second, third, or fourth (or higher) AP agent. In the data analysis, mean percentages were computed.ResultsThe HCPs estimated that: (1) Of patients treated with APs for hallucinations, efficacy outcomes were: 39%, symptom completely stopped; 23%, stabilized without relapses; 34%, stabilized but with relapses; and, 25%, not stabilized. (2) For delusions, corresponding percentages were 16%, 23%, 34%, and 27%. (3) Of their patients currently being treated with APs, 39% are on their first AP agent, 28% are on their second, 15% their third, and 8% are on their fourth agent (or higher).ConclusionsU.S. HCPs estimated that for about 60% of their patients with dementia treated with APs for dementia‐related‐psychosis, the patients' hallucinations and delusions were poorly controlled—either never stabilized at all, or stabilized but with relapses. The high proportion of AP‐treated patients (51%) who require two or more lines of AP therapy also attests to the difficulty U.S. HCPs have in controlling hallucinations and delusions with APs.
Two‐point dynamic observation of Alzheimer’s disease cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus
Authors: Jingami Naoto , Uemura Kengo , Asada Megumi , Kuzuya Akira , Takahashi Ryosuke , Kinoshita Ayae 
Published: December 2020

AbstractBackgroundExtensive research into cerebrospinal fluid (CSF) biomarkers was performed in patients with idiopathic normal pressure hydrocephalus (iNPH). Most prior research into CSF biomarkers has been one‐point observation.ObjectiveTo investigate dynamic changes in CSF biomarkers during routine tap test in iNPH patients.MethodsWe analyzed CSF concentrations of tau, amyloid‐β (Aβ) 42 and 40, and leucine rich α‐2‐glycoprotein (LRG) in 88 consecutive potential iNPH patients who received a tap test. We collected two‐point lumbar CSF separately at the first 1 ml (First Drip (FD)) and at the last 1 ml (Last Drip (LD)) during the tap test and 9 patients who went on to receive ventriculo‐peritoneal shunt surgery each provided 1 ml of ventricular CSF (VCSF).ResultsTau concentrations were significantly elevated in LD and VCSF compared to FD (LD/FD = 1.22, p = 0.003, VCSF/FD = 2.76, p = 0.02). Conversely, Aβ42 (LD/FD = 0.80, p < 0.001, VCSF/FD = 0.38, p = 0.03) and LRG (LD/FD = 0.74, p < 0.001, VCSF/FD = 0.09, p = 0.002) concentrations were significantly reduced in LD and VCSF compared to FD. Gait responses to the tap test and changes in cognitive function in response to shunt were closely associated with LD concentrations of tau (p = 0.02) and LRG (p = 0.04), respectively.ConclusionsDynamic changes were different among the measured CSF biomarkers, suggesting that LD of CSF as sampled during the tap test reflects an aspect of VCSF contributing to the pathophysiology of iNPH. CSF circulation is disturbed in iNPH and old style one‐point CSF biomarker observation can be misestimated. This study detected dynamic changes of CSF biomarkers in iNPH during routine tap test and revealed the linkage between 1ml Last Drip of lumbar CSF and ventricular CSF.
Developing non‐invasive, objective assessment tools for social apathy in neurocognitive disorders: The role of action kinematics
Authors: Manera Valeria , Galperti Guenda , Rovini Erika , Zeghari Radia , Mancioppi Gianmaria , Fiorini Laura , Plonka Alexandra , Mouton Aurelie , Zory Raphael , Corveleyn Xavier , Robert Philippe , Cavallo Filippo , Gros Auriane 
Published: December 2020

AbstractBackgroundApathy, a reduction in goal‐directed activities in the domains of behavior, cognition, emotion and social interaction, is one of the most common behavioral symptoms in Neurocognitive Disorders (NCD)[1]. Current apathy assessment strongly relies on self‐reports or clinical scales, which are subjective and dependent on the information provided by patients and caregivers. For this reason, growing attention is devoted to defining more objective, measurable and non‐invasive apathy proxies. In the present study we investigated the interest of recording action kinematics in a short reach and grasp protocol[2] for the assessment of apathy social component, characterized by a reduction of the willingness to interact with others.Methods19 subjects with Mild NCD (6M, age=75,7±6,3y, MMSE=26,0±3,0) were recruited at the Nice Memory Center. Based on the Apathy Motivation Index (social motivation subscale[3]), subjects were classified as socially apathetic (N=9) vs non‐apathetic (N=10). SensRing, a novel ring‐shaped wearable sensor[4], was placed on their dominant hand’s index finger. Subjects were asked to reach and grasp a can to place it into a cup (individual condition) and pass it to a partner (social condition). Several parameters were extracted, including movement velocity, acceleration, jerk (representing the smoothness of the movement) and execution time.ResultsNon‐apathetic participants showed a significantly lower peak velocity (p=0,009) and a lower jerk (p=0,038) in the social vs individual condition when moving the can to the final position, suggesting a more careful approach in placing the object in the partner’s hand vs a cup. Non‐apathetic participants showed no significant differences between conditions in any of the extracted parameters.ConclusionPrevious studies showed the interest of recording patients’ level of weekly motor activity for apathy assessment. Here, for the first time, we showed that a 5‐minutes reach and grasp protocol may be able to show differences between socially apathetic and non‐apathetic subjects with Mild NCD, thus providing a tool easily usable in the clinical practice. Future studies with a bigger sample are needed to better characterize these findings. [1] Manera et al., 2019, doi.org/10.1002/gps.5125. [2] Becchio et al., 2008, doi.org/10.1016/j.concog.2007.03.003. [3] Ang et al., 2017, doi:10.1371/journal.pone.0169938. [4] Rovini et al., 2020, EMBC‐2020.
“Hero Behind the Curtain”: Multicultural workers in culturally diverse dementia care
Authors: Antoniades Josefine , Croy Samantha , Kent Mike , Ellis Katie , Brijnath Bianca 
Published: December 2020

AbstractBackgroundThe number of culturally and linguistically diverse (CALD) people with dementia in Australia is projected to rise. CALD groups are diagnosed later and access care services less than other Australians. Accessing services is fraught with barriers for CALD communities and service providers face challenges in meeting the needs of CALD clients. We explore the experiences of multicultural service providers working with members of their own communities, focusing on strategies employed to facilitate access and provide care to CALD people with dementia and their families.MethodsWe conducted 25 in‐depth video‐recorded interviews with multicultural service providers working with CALD clients in Victoria, New South Wales and Western Australia. Interviews were conducted both in language and in English, and were translated and transcribed verbatim. The data were analysed thematically.ResultsParticipants identified cultural expectations around family caring and stigma associated with extrafamilial care as significant challenges, leading to reluctance to engage with services. Drawing on understandings of different communities’ approaches to dementia and norms around care for older people, participants were able to address concerns and enable access to much needed services in culturally acceptable ways. In residential aged care, participants described strategies to make aged care more palatable, emphasising the family’s continued role in care as they allowed providers to ‘take over the dirty jobs’. Familiarity and a sense of belonging were fostered for clients with dementia through attention to culturally‐specific needs, whilst building relationships with families to address deep‐seated guilt at placing their loved ones in residential care.ConclusionsThe perspectives of multicultural workers in CALD dementia care provide insight into opportunities for provision of culturally‐appropriate care. The study highlights the significant contributions of multiethnic workers in providing care that is flexible, person‐centred and attentive to cultural needs of CALD clients with dementia and their families.
Validation of a telemedicine tool for patient monitoring in clinical dementia trials
Authors: König Alexandra , Zeghari Radia , Guerchouche Rachid , Linz Nicklas , Ramakers Inez HGB , Lemoine Pascale , Bultingaire Vincent , Robert Philippe 
Published: December 2020

AbstractBackgroundWith the current pandemic crisis, now even more than ever, remote solutions such as telephone or telemedicine platforms are of great importance to provide isolated elderly people with timely access to health care. This study aims to determine feasibility and reliability of an automated tool utilizing artificial intelligence (AI) to facilitate large‐scale population‐based neurocognitive pre‐screening and monitoring of potential clinical trial participants.Method21 participants (out of 120 still to include) over age 55 with and without cognitive impairment were administered in two conditions, once by telemedicine and once by face‐to‐face, a neuropsychological assessment consisting of 8 neurocognitive tests. The administration procedure was randomized. Each participant was asked to complete an acceptability questionnaire regarding the experience of being evaluated through a telemedicine tool.ResultsSimilar results were obtained on the several cognitive test measures when comparing the remote to the face‐to‐face administration method. Word recall (r=0,928) and picture naming task (r=0,939) showed the strongest correlation. Acceptability of the tool was relatively high with preference even in the remote method for more convenience.ConclusionResults support the feasibility and reliability of remote cognitive testing through administration via a telemedicine tool. These systems can be used for remote disease monitoring, enabling patients to be assessed in their own homes and improve utilization of expert assessors allowing them to conduct neurocognitive testing remotely.
Studying ABI3 variant immune contributions to Alzheimer’s disease in a transgenic mouse model
Authors: Liang Xinyan 
Published: December 2020

AbstractBackgroundAlzheimer’s Disease (AD) is a progressive disorder populating in a world‐wide range, which causes dementia with accumulation of amyloid‐beta (Aβ) and hyperphosphorylated tau. AD destroys memory and disrupts cognition, as well as impairs thinking, behaving and person’s ability to function independently. Numbers of genes now have been confirmed through large scale genetic studies as significant AD risk genes, including ABI3. Abelson interactor (ABI) family is an adaptor protein family commonly participating in regulation of actin cytoskeleton in cell. As a member of ABI family, ABI3 can modulate cell motility process like inhibiting tumor metastasis and migration. Genetic variants of ABI3 have been found to be strongly associated with late onset AD (LOAD) in various human populations, but the molecular mechanisms of how they influence AD pathogenesis remain unknown.MethodIn order to further study the pathological mechanisms of ABI3 in AD in vivo, we created an Abi3 transgenic mouse model on C57BL/6 background carrying a human ABI3 mutation (S209F) by CRISPER/Cas‐mediated genome engineering. ABI3 S209F mutation is encoded by a very rare variant rs616338 (MAF=0.008, OR = 1.43 for AD with P = 4.56 × 10−10). In this transgenic model, a corresponding mouse S212F mutation was introduced into Exon 5 on Chromosome 11 by homology‐directed repair, and homozygous Abi3F/F mice were generated by crossing the F1 heterozygotes. In addition, we also crossed Abi3F/F with the 5xFAD model of AD to determine the influence of this ABI3 mutation on AD pathology and cognitive functions in vivo.ResultWe hypotheses 5xFAD mice who carrying the ABI3 mutation may exhibit exacerbated AD pathologies compared with 5xFAD with wildtype ABI3, including accelerate Aβ aggregation and neuroinflammation. As ABI3 is exclusively expressed in immune cells in the brain and peripheral, this new Abi3F/F model will be an effective method for us to understand the immune contribution in AD pathogenesis and perhaps the crosstalk between peripheral and central in the disease as well.ConclusionWe believe that studying AD with ABI3 Tg mouse models can allow us to have better understanding on the immune contribution to AD pathogenesis and provide valuable strategies on clinical therapy.
Molecular profiling of serotonergic neurons from nonhuman primate embryonic stem cell R366.1
Authors: Reddy Arubala P , Bunquin Lloyd S , Sawant Neha , Reddy Hemachandra 
Published: December 2020

AbstractBackgroundIn the past decade, knowledge of Alzheimer’s disease advanced exponentially. Many in vitro and in vivo models emerged to conduct the mechanistic target‐oriented study. Midbrain pathogenesis is comparatively newer and unexplored in NDDs Research. We have developed a rhesus embryonic stem cell differentiated from NHP cells . Learning the neurodegenerative study in humans is impossible in human, hence cell model are essential to understand.Objective: This study is to investigate the blueprint of Rhesus stem cell Rh 366.4 in the differentiation of5HT of midbrain Isodendritc core. Newborn neurons are expressing 5HT character further analyzed using TAC and IPA analysis software, and all serotonin‐related mRNA using Human low‐density array.MethodRhesus monkey embryonic stem cells R366.4 (XY) differentiated to serotonin enriched neurons. RNA extracted from ESC colony, Embryoid body, stage N1, proliferation stage N2, and differentiated 5HT neurons. RNA isolated from the previously conducted study hybridized to Affymetrix chip Clariom D Human chip as it has entire RNA species expressing more than 135000 probe set. The more comprehensive and dynamic range of the newer chip. Data analyzed using TAC 4.0 and Ingenuity Pathway Analysis (IPA). In the previous study shows the 366.4 GATA3 driven, FGFR2 dominate, and Sonic hedgehog (Shh) and FEV1 enriched neural cells have many characteristics of serotonin neurons of the dorsoventral axial plate.ResultN3 cells 5HT neurons compare to ESC R366.1: Canonical pathway altered are: axonal guidance, integrin signaling, synaptogenesis signaling. network: Cellular movement development, growth, cell proliferation, and survival. Top5 network: cell death and survival, nervous system development. Results: ESC366.4 cells compare to N3 cells (5HT Neurons): Canonical pathways altered are Oxidative phosphorylation, EIF2 signaling, mitochondrial dysfunction, protein ubiquitination. Upstream regulator: function: RNA/DNA damage repair, cell death, and survival, post‐translational modification, nervous system development. Top5 network function: related to disease mechanism of metabolism, development disorder, metabolic disease Analysis active Detail bioinformatic analysis will be presented in the poster.ConclusionR366.1 cell differentiated in early serotonergic neurons, and many pathways and miRNA will be reported 1st time. The ESC R366.1 is a potential cell line close to human homology essential to study in neural grafting, molecular targets, and cellular metabolism.