bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global challenges in cognitive assessment: How technology will drive neuropsychologists to the forefront
Authors: Au Rhoda , Christianson Kieffer , McManus Chelsea , Knight Arielle , Karjadi Cody 
Published: December 2020

AbstractBackgroundAge remains the strongest risk factor for Alzheimer’s disease (AD). With the number of people over 65 now outnumbering those under the age of 5, the global burden of AD is rapidly increasing. Cognitive decline is the hallmark behavioral symptom of AD. However, accurate cognitive assessment requires consideration of a myriad of factors, including education, language, and culture. In fact, in a majority of low‐to‐middle income countries, as well as many emerging economies, there is no formalized doctoral training in neuropsychology. These circumstances necessitate embracing novel data collection methods in order to preserve the voice of the neuropsychologist. Technological advances can provide the tools to address the global realities of AD and other related disorders.MethodWe have developed a brain health monitoring platform that leverages the relatively ubiquitous use of smartphones across virtually all countries and collects behavioral measures that are inextricably linked to cognitive skills. We are applying machine learning approaches to quantify digital indices into cognitive ones. Importantly, we have strategically selected mobile applications that measure behaviors that are 1) common regardless of age, education, language and culture and 2) can be flexibly customized to circumstances.ResultWe have begun deploying versions of this high tech‐driven platform in the U.S. Further, we are starting to have an impact internationally, particularly in Asia. The health and age demographics in China make its population particularly vulnerable to AD. We present findings that speak to this risk and how our platform, and others like it, will help fill the neuropsychological expertise gap that such countries are currently experiencing.ConclusionAD is a rising epidemic. Early and accurate detection is the first step to finding disease modifying interventions and providing the context necessary for maximized efficacy. The coupling of professional neuropsychology skills and digital technology will generate solutions that can sufficiently address the impending challenge of conducting cognitive assessments universally. This potentially includes resolving longstanding health disparities by extending neuropsychologists’ reach into regions with significant economic and/or geographical constraints.
Use‐cases and users' requirements for design of an individualized sensor‐based assistive system for people with dementia in nursing facilities: A user centered design approach using qualitative research
Authors: Köhler Stefanie , Goerss Doreen , Kowe Antonia , Kirste Thomas , Teipel Stefan J 
Published: December 2020

AbstractBackgroundChallenging behaviors often cause stress and burden for caregivers of persons with dementia (PwD). Individually tailored assistive devices have the potential to support the persons concerned and reduce caregivers‘ burden, if they are adapted to users’ needs. Therefore, it is an urgent need to focus on values and abilities of prospective users to design suitable technologies. Here, we introduce a user centered design approach in the development process of an assistive technology in institutionalized care for PwD.MethodWe identified three different groups of stakeholders and conducted 28 semi‐structured interviews (9 PwD, 10 relatives, 9 health professionals). Interview categories included daily life of PwD, difficulties in unfamiliar surroundings, presentation of challenging behaviors, previous experiences with technology and perceived use of assistive technologies to be developed. The interviews were transcribed and analyzed using qualitative content analysis according to Mayring.ResultResults show that the individual set of user values, the global cognitive status, previous experiences with available technology and general interest and curiosity in technology of PwD act as main contributors to the attitude toward using new assistive devices. During the conference we will present resources (i.e. user experience, personal benefit, routine in using technology and autonomous detection of needs) and obstacles/barriers (less support from others, missing time and interest, doubt about usability, complexity) for using technology as well as user values (autonomy, information, privacy). In parallel, we will list use‐cases extracted from the interviews: temporal (i.e. day time, appointments) and spatial disorientation (i.e. pacing, disability to find the right room), aggression and affective disorders, falls and information about (inter‐)national news service. Functional requirements like occupation and cognitive training, communication (caregiver‐relative, caregiver‐PwD), falls and sleep detection, memory function, playing music and spreading fragrance in case of aggression/agitation were named. Further, we will derive design requirements and suitable interventions offered by an assistive device adapted to the users' needs.ConclusionWe could show that user centered design is applicable even with cognitively impaired people. Qualitative research helps to identify personal key factors that may contribute to usage of assistive devices and should be integrated in future technologies to provide suitable interventions.
The relationship between sleep disturbance and cognitive impairment: A population‐based cross‐sectional study
Authors: Gao Fan , Gao Ling , Wei Shan , Dang Liangjun , Shang Suhang , Chen Chen , Wang Jin , Huo Kang , Deng Meiying , Wang Jingyi , Qu Qiumin 
Published: December 2020

AbstractBackgroundGrowing evidence suggest that sleep disturbance is a risk factor for Alzheimer’s disease, but the relationship between sleep disturbance and cognitive impairment is not clear.MethodThis was a population‐based cross‐sectional study. A total of 1649 participants from a village in the suburbs of Xi’an, China were enrolled from January 3 to March 26, 2017. Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Cognitive function was assessed with the mini‐mental state examination (MMSE). Univariate and multivariate analyses were used to analyze the relationships between sleep disturbance and cognitive impairment.ResultAmong 1649 subjects,110(6.7%) were diagnosed as cognitive impairment, and 960(58.2%) were diagnosed as sleep disturbance. In bivariate analysis, cognitive impairment was associated with insomnia)ρ=0.110; 95%CI=0.060‐0.154 ; P<0.01(, sleep efficiency)ρ=‐0.152; 95%CI=‐0.196‐ ‐0.105; P<0.01(, age)ρ=0.237; 95%CI=0.195‐0.279; P<0.01(and educational level )ρ=‐0.190; 95%CI=‐0.229‐ ‐0.149; P<0.01(. In the binary logistic regression, cognitive impairment was positively associated with the scales of PQSI (OR=1.072; 95%CI=1.016‐1.130; P=0.012). In the internal constitution of PQSI, cognitive impairment was positively associated with the sleep duration (OR=1.567; 95% CI=1.242‐1.979; P<0.01), step disturbances (OR=0.003; 95%CI=0.000‐0.023; P=0.017), and negatively associated with the habitual sleep efficiency (OR=1.068; 95%CI=1.012‐1.127; P<0.01). Cognitive impairment also was negatively associated with patients age (OR=0.130; 95%CI=0.069‐0.244; P<0.01).ConclusionSleep disturbances is associated with cognitive impairment. However, the causal relationships between sleep disturbances and cognitive impairment are not clear and need to be further studied.
Rapidly progressive dementia in Argentina: A multicentric study
Authors: Isa Santiago , Calandri Ismael Luis , Demey Ignacio , Dorman Guido , Couto Blas , Vigo Gabriela , Aleman Alberto , Mellinger Surai , Aldecoa Mayra , Genovese Osvaldo , Sanchez Maria Pilar , O'Neill Santiago , Vazquez Guido , Appiani Franco , Ollari Juan , Acosta Julian , Allegri Ricardo F , Gatto Emilia , Rojas Galeno 
Published: December 2020

AbstractBackgroundRapidly progressive dementia (RPD) is a syndrome caused by different disease entities. Accurate diagnosis is crucial as numerous proportions of these diseases are highly treatable. There are few RPD series published in South America. Knowing regional data may be useful to establish specific diagnostic guidelines based on local information. The main study objectives are to describe the etiological diagnosis of patients with RPD in Argentina and to compare the clinical characteristics and data obtained from complementary studies among patients with Autoimmune Encephalitis (AE), Prion Diseases (PD), Neurodegenerative Diseases (ND) and Other Causes (OC).MethodA multicenter observational cross‐sectional study was performed with the information obtained from patients referred to the neurology department of the participant centers. Patients with RPD criteria (developing dementia in less than 24 months) were retrospectively included between Dec‐2001 and Jun‐2019. Based on International diagnostic criteria, patients were divided into: AE, PD, ND and OC. We compared baseline clinical data, complementary exams, MRI and serologic characteristics between groups. Parametric or non‐parametric statistic and multivariate analysis was used according to the sample distribution of the available data.ResultOn a sample of 328 patients with a diagnosis of RPD, 54.87% were men (n=180) with a mean age of 60.78±5.57 years at admission. The diagnosis time for dementia was 4.06 (0.83–23.6) months. The three most frequent causes were AE 23.17% (n=76), ND 22.86% (n=75) and PD 15.85% (n = 52). In 15.85% of the patients the diagnosis remained unknown. When comparing AE, ND, PD and OC, statistically significant differences were observed in age (younger age for AE, p=0.0001), higher mortality for PD (p=0.0001) and larger time of evolution in ND (p=0.0001). In the PD group more behavioral symptoms (p = 0.002) and pathological electroencephalogram (p=0.001) were found.ConclusionIn accordance with similar series, autoimmune etiology was the more frequent cause. This is the first South American RPD multicentric study. These results might supply valuable data for the healthcare system and future epidemiological investigations more focused diagnostic guidelines.
Participation in leisure activities and risk of dementia: Results from Whitehall II study with 18‐year follow‐up
Authors: Sommerlad Andrew , Sabia Séverine , Livingston Gill , Kivimaki Mika , Lewis Glyn , Singh‐Manoux Archana 
Published: December 2020

AbstractBackgroundSeveral studies have reported that participating more frequently in leisure activities protects against dementia, possibly by building cognitive reserve or through better vascular health. However, these studies have been highly susceptible to reverse causation bias due to short follow‐up duration.We therefore aimed to examine the association of leisure activity participation with incident dementia using data from a cohort study with very long follow‐up.MethodsWe used data from 8,280 participants of the Whitehall II prospective cohort study of London‐based civil servants. A 13‐item scale assessed leisure activities and we ascertained incident dementia status from three comprehensive linked national registers to 2017 (n cases=360). Cox regression models examined the association of leisure activity participation, measured on multiple occasions, and incident dementia, with multiple imputation to account for missing data. We also examined associations of individual activities and subsequent dementia, and examined the association of change in leisure activity participation during late‐middle age and dementia. All models were adjusted for potential confounders.ResultsParticipation in leisure activities at mean age 55.8, with 18.0‐year follow‐up, was not associated with dementia (hazard ratio [HR] 0.92, 95%CI 0.79‐1.06) but those with higher participation at mean age 65.7 were less likely to develop dementia with 8.3‐year follow‐up (HR 0.82 (0.69‐0.98)). No individual leisure activities were consistently associated with incident dementia. Decline in leisure activity participation between age of 56 and 66 years was associated with subsequent incident dementia (HR 1.35 (1.10, 1.66) per 1 SD larger activity decline.ConclusionsLeisure activity participation at 56 years was not associated with incidence of dementia over the subsequent 18 years. Associations were only evident when leisure activity was assessed at older ages, with less than 10 years between assessment of leisure activities and diagnosis of dementia. Decline in leisure activity participation over 10 years was associated with subsequent elevated risk of dementia. No consistent associations were found for participation in specific types of leisure activities. Taken together, these results do not support the hypothesis that leisure activity participation can lower dementia risk, but suggest instead that reduction in activity participation is an indication of possible prodromal dementia.
Stimulation of GLP‐1 signaling enhances protein clearance and reduces Aβ‐mediated toxicity in neuronal cells
Authors: Lin Chih‐Li , Huang Chien‐Ning , Li Hsin‐Hua , Chang Ching‐Chi , Ho Ying‐Jui , Chiu Pai‐Yi 
Published: December 2020

AbstractBackgroundCellular proteostasis failure is proposed to be the major cause of neurodegeneration. The deposition of both extracellular Aβ plaques and intracellular tau‐associated neurofibrillary tangles is central to Alzheimer's disease (AD) pathogenesis. Therefore, development of strategies targeting the removal of misfolded proteins may aid AD treatment. Glucagon‐like peptide‐1 (GLP‐1) is a potent incretin hormone primarily secreted by intestinal L‐cells. It can stimulate pancreatic β‐cells leading to insulin secretion and hence decreasing blood glucose. However, GLP‐1 can also be produced in the brain, and most neuronal cells including neurons and microglia express functional GLP‐1 receptors. Even though it is known for suppressing appetite in hypothalamus, the molecular mechanisms of GLP‐1 signaling are still poorly defined in the other brain regions.MethodIn the present study, we aimed at investigating the exact mechanisms underlying GLP‐1‐mediated neuroprotection, and exploring the potential molecular pathways against Aβ‐induced toxicity based on GLP‐1 signaling by using high‐content analysis (HCA) cellomics techniques.ResultWe found that GLP‐1 receptor agonist (GLP‐1 RA) liraglutide significantly displays anti‐Aβ neuroprotective effects. These effects were likely associated with an restoration of impaired neuronal insulin signaling. In addition, liraglutide also promoted abnormal protein clearance by upregulating autophagy through the AMP‐activated protein kinase (AMPK) pathway, which subsequently restored neuronal insulin signaling and led to upregulation of nuclear factor erythroid 2‐related factor 2 (NRF2)/heme oxygenase 1 (HO‐1) antioxidant signaling. Furthermore, the efficiency of microglial phagocytosis was also stimulated by liraglutide, and may have a beneficial effect on the clearance of extracellular Aβ.ConclusionOur results provided the basis for GLP‐1‐based regulatory mechanisms by diminishing Aβ‐related neurotoxicity of neuronal cells. Accordingly, enhanced protein clearance by targeting neuronal GLP‐1 signaling may lead to develop novel therapeutic strategies against AD.
Socioeconomic determinants of dementia in Caribbean Hispanics: An international comparison
Authors: Llibre‐Guerra Jorge J , Li Jing , Harrati Amal , Jiménez‐Velazquez Ivonne Z. , Acosta Daisy , Llibre Juan , Liu Mao‐Mei , Dow William H 
Published: December 2020

AbstractBackgroundHispanics populations in the U.S. are more likely to develop dementia than non‐Hispanic White populations; among Hispanics, those with Caribbean origin seem to carry the higher risk for developing dementia. However, little is known about how various social risk factors for dementia differentially affect non‐Hispanic Whites and Hispanics of Caribbean origin in the U.S., or between those living in the main Caribbean islands. The present study aimed to examine the associations of socioeconomic determinants(SES) with dementia across Puerto Rico, Cuba and the Dominican Republic and compared with similar populations living in U.S.MethodUsing a community‐dwelling population of Caribbean older adults ages 65+ from Puerto Rico, Dominican Republic, and Cuba, enrolled in the 10/66 study we determined dementia prevalence on the main Caribbean Islands using the 10/66 dementia algorithm. Associations between socioeconomic risk factors and prevalent dementia were estimated using linear probability models, stratified by gender and age. We then compared results from the main islands with Hispanic and non‐Hispanic populations living in US enrolled in the U.S. Health and Retirement Study, using the TICS dementia algorithm.ResultThe prevalence of dementia was high: 10.9% in Cuba and 11.7% in Puerto Rico and the Dominican Republic (95% CI, 9.8‐12.1). We found overall weaker associations between education and dementia in the three main Caribbean islands. By contrast, a stronger association between education and dementia was found in the US among non‐Hispanic whites, Mexican Hispanics, and non‐Mexican Hispanics; these persist after controlling for income and wealth(p<0.001). In both the US and in the Caribbean islands, working in a blue collar occupation as opposed to white collar occupation was associated with a higher risk of dementia(p=0.001), and higher income was negatively associated with dementia for both genders(p=0.001), although these associations were stronger in the U.S.ConclusionThe prevalence of dementia in the older Caribbean population is high, both in the main islands and in US compared to non‐Hispanic‐whites. There were differential associations between SES risk factors, particularly education, and dementia probability between Caribbean islands and the U.S., which may be attributed to differences across societies in risk factors correlated with education.
In‐silico and in‐vitro evaluation of imidazolone fused quinazolinone derivatives as anti‐amyloidal agents in Alzheimer’s
Authors: Sharma Lalit , Kumar Deepak , Bisht Gopal Singh 
Published: December 2020

AbstractBackgroundAlzheimer’s disease with a long preclinical period of ∼20 years is a chronic, insidious, and progressive neurodegenerative disease of old age. Neuropathologically AD is characterized by the presence of accumulated Amyloid‐beta in plaques (in extracellular spaces, and walls of blood vessels) and aggregated tau protein in neurofibrillary tangles. Quinazolinone derivatives exhibit inhibition to β‐secretase as well as its core quinazoline moiety prevents the cholinergic system from pathological activities of Aβ by possessing significant amount of inhibition.MethodIn‐silico evaluation was based over computational approaches counting receptor and ligand preparation, grid formation, docking simulation, and its analysis followed by in‐vitro investigation via Thioflavin T‐amyloid binding assay and Protease (Trypsin) digestion assay.ResultThe computational approach provides us with two molecules A and B with higher estimated free energy of binding whereas for the justification of in‐vitro test results one molecule J with lower estimated free energy of binding from top ten docked scored molecules was selected. In‐vitro investigation of these three compounds reveals that compound A cause significant (p<0.005) reduction in fluorescence intensity of ThT as well as Aβ1‐42 peptides resistance to tryptic digestion, when compared with control. Compound B possess lesser amount of reduction (p<0.005) in both the assays as compared to compound A whereas, activity of Compound J was found to be almost negligible.ConclusionFrom the present study we found that our test compound A has shown significant results in modulating the Aβ aggregates i.e. Aβ fibrils. This study strongly suggests the further evaluation of this imidazolone fused quinazolinone derivative.
Flow cytometry detection of inflammatory markers in glial cells and synaptosomes derived from AD cortex
Authors: Melnik Mikhail , Bilousova Tina , Huang Calvin , Cole Emma , Head Elizabeth , Gylys Karen H. 
Published: December 2020

AbstractBackgroundPrevious research has indicated the involvement of nearly all cell types of the brain (i.e. neurons, microglia, etc.) in progression of Alzheimer Disease (AD). In the case of microglia, increased production of neuroinflammatory markers accompanies AD and has been implicated in the loss of synapses and neurons. In mouse models of AD, gene expression of many inflammatory markers is increased in microglial cells, including genetic risk factors LPL and TREM2, while homeostatic markers are diminished. Intact cells from post‐mortem AD tissue were isolated and used to better explore the relationship of inflammatory markers and AD‐specific pathological species. Further, microglial elements have been found to be associated with synaptosomes (resealed axon terminals) and were further explored to determine if specific inflammatory signals vary with amyloid and tau pathology.MethodPost‐mortem AD tissue (PMI<6 hours) from late AD patients (Braak V‐VI) and age‐matched controls was enzymatically dissociated, processed and labeled using fluorophore‐conjugated antibodies. The labeled cells were subsequently analyzed by an LSRII flow cytometer using FCS Express v5 software. Synaptosomes were prepared from the same AD patients by homogenizing brain tissue in 0.32 M sucrose with a cocktail of enzyme inhibitors. This preparation, known as P2, then underwent probing using western blotting (10‐20% Tris‐Glycine gel with PVDF membrane) and flow cytometry using the same instrument and software.ResultPreliminary results show a significant increase in the number of P2ry12+ (homeostatic) microglia in AD patients relative to controls. Further labeling of microglia with CD11b (myeloid marker) and TGFbeta1 (homeostatic marker) showed no significant difference between AD and controls, suggesting a more complex picture of microglial changes compared to mouse models. Preliminary results showed an increase in inflammatory markers TLR4 and IL‐6 in AD P2 samples relative to controls. Further, TLR4 was increased in individuals with at least one APOE4 allele.ConclusionMicroglial activation in AD mouse models differs from human AD. Human AD microglia demonstrate an increased expression of one homeostatic marker (P2ry12) but not another (TGFB1) while mice show a more uniform decrease of these markers. Further, microglial signals associated with synaptosomes suggests they contribute to neurotoxicity and synaptic loss, a parameter highly correlated with dementia.