bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiview analysis of clinical and MRI/PET imaging and socio‐demographic data in Alzheimer’s disease
Authors: Antelmi Luigi , Ayache Nicholas , Robert Philippe , Lorenzi Marco 
Published: December 2020

AbstractBackgroundThe joint analysis of heterogeneous data in Alzheimer’s Disease (AD) is important for better clinical diagnosis and to understand the relationship between biomarkers. Anamnestic questionnaires, imaging data, and psychological tests, for example, provide specific, complementary, and sometimes overlapping views on the patient’s latent state. A method providing an interpretable representation of the relationship between this heterogeneous information could be used for improving clinical assessment and for better understanding the complex dynamics of the pathology.MethodWe propose a novel approach for the multi‐modal analysis of heterogeneous data. The model assumes a latent factor across data observed through different modalities (e.g., clinical scores, structural imaging, functional imaging, …), and jointly estimates the parameters linking the latent factor to the observations.ResultWe applied our model to clinical, socio‐demographic, and MRI/PET imaging data from 504 subjects of the ADNI cohort. Our method allows to identify the joint effect of age and pathology (Figure 1) in describing clinical condition, and to unveil the joint relationship among the biomarkers through the generative sampling process (Figure 2). It allows to infer the subject state in the age‐pathology coordinates, to follow its evolution in time, and to predict imaging data if missing.ConclusionOur model allowed to link clinical and multi‐modal imaging data to identify a unique latent representation highly correlated with disease status and age. The estimated parameters also highlight clinically meaningful relationships across multi‐modal observations, such as the lowering of clinical and psychological performances with brain temporal atrophy, amyloid uptake, and impaired glucose metabolism. Our model can be used to develop optimal strategies for disease classification, quantification, and prediction. Acknowledgment: This work has been supported by (1) the French government, through the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR‐15‐IDEX‐01; (2) the grant AAP Santé 06 2017‐260 DGA‐DSH, and by the Inria Sophia Antipolis‐Méditerranée, “NEF” computation cluster.
Pattern of cortical thinning in patients with mild cognitive impairment associated with obstructive sleep apnea compared to patients with age‐associated mild cognitive impairment
Authors: Thanapornsangsuth Poosanu , Chokesuwattanaskul Anthipa , Phanthumchinda Kammant , Likitjaroen Yuttachai 
Published: December 2020

AbstractBackgroundObstructive sleep apnea (OSA) is a reversible cause of mild cognitive impairment (MCI). There are evidences that OSA associated with decline of brain cortex. The pattern of cortical thinning in OSA associated MCI has not been well characterized. This study sought to assess pattern of cortical thinning in MCI patients with OSA (MCI‐OSA).MethodWe analyzed magnetic resonance images (MRI) of MCI‐OSA and age associated (MCI‐AA) to determine difference in cortical atrophy pattern between two groups. Firstly, cortical surfaces were reconstructed from each patient’s MRI. Cortical thickness measurement was then processed on these surfaces. At last, thickness comparison between the two groups was performed using vertex‐by‐vertex general linear model (GLM) and standard t‐test.ResultSubjects were consecutively recruited including 22 MCI‐OSA patients and 20 MCI‐AA patients. Compared to MCI‐AA, MCI‐OSA patients has larger brain volume (p=0.002). Using GLM, we found 3 large clusters in the left anterior cingulate, the left and right lateral occipital cortices that were significantly thinner in MCI‐OSA (p<0.001, p=0.005, p=0.001, respectively). Using t‐test, we found 11 cortical regions with different thicknesses between the two groups. Only the left anterior cingulate cortex remained significantly thinner in the MCI‐OSA group using both methods.ConclusionWe demonstrated that MCI‐OSA patients had significant thinning of left anterior cingulate gyrus as compared to MCI‐AA despite having larger brain volume.
Evaluation of adaption skills in older adults using behavioural and EEG repeated measurements during a visual oddball object detection task
Authors: Delgado Laura M. Rueda , Nolan Hugh , Buick Alison R , Barbey Florentine , Dyer John , McGuinness Bernadette , Passmore Anthony Peter , Murphy Brian 
Published: December 2020

AbstractBackgroundAdaptation to new demands is a fundamental skill that relies on the neuroplasticity of the brain. The breadth of this adaptation (an aspect of cognitive function) is reduced with ageing and is further perturbed with amnesic mild cognitive impairment. Perturbed adaptation skills could be a potential marker of early cognitive deficits, which is key for early diagnosis. Here we aim to investigate behavioural and neurophysiological adaptation to a gamified tablet‐based version of the visual oddball paradigm in older adults across 12 weeks.Method89 neurotypical older adults (mean age: 58.7 years, SD: 8.89; mean MoCA score: 27.1, SD: 1.8; 77.5% female) were asked to perform a gamified 2‐stimulus visual oddball paradigm 5 times a week during a 3‐month period, while neurophysiology was recorded with a 16‐channel EEG headset designed for unsupervised use in the home. A session event‐related potential (ERP) was calculated per channel, which was then downsampled into 8‐ms bins. To assess the effect of session on the ERP signal and on the average reaction time (RT), we statistically tested two mixed effects models (per channel‐temporal bin): i) a reference model, with covariates and subject as a random effect; and ii) an across‐sessions model, with Session added as a fixed effect to the reference model.ResultBehaviourally, RTs to Target stimulus were significantly faster across sessions. RTs in the first session and the rate of improvement between the 1st and 2nd sessions were modulated by the MoCA score. In response to the Target stimulus, there were amplitude increases with session overlapping the P300 component on frontal channels (FCz, Fpz), and on parietal channels (CPz, Cz, P3, P4). In response to the Non Target stimulus, there was a higher amplitude with Session in FC3 between 209.9‐242 ms, and in Fpz between 482.6‐514.7 ms.ConclusionA gamified visual oddball task is sensitive to MoCA score categorization at baseline and early stages of adaptation in neurotypical subjects. Potential neurophysiological adaptation, accompanying the behavioural adaptation, is suggested by EEG P300 amplitudes that increase across sessions.
Alzheimer’s and related dementia (ADRD) episode payments and 30‐day readmission rate and timing comparing skilled nursing facility and home health discharge destinations in a statewide collaborative
Authors: Kamdar Neil , Syrjamaki John , Mahmoudi Elham 
Published: December 2020

AbstractBackgroundADRD patients are high resource utilizers for hospitals and health systems with higher levels of hospitalization than their non‐ADRD counterparts. Quantifying the cost and readmissions based on where patients are discharged can provide additional information on the resource expenditure for this patient population. This study examined medical and surgical hospitalizations in a statewide collaborative to estimate total 30‐day episode payments and all‐cause readmissions for ADRD patients in a matched cohort of those discharged to skilled nursing facilities (SNF) versus home health (HH).MethodWe performed a retrospective cross‐sectional analysis of adults with ADRD using the Michigan Value Collaborative (MVC), which is a Blue Cross Blue Shield funded clinical quality initiative. This dataset uses administrative claims representing Medicare and private insurance using 30 and 90‐day episode based price standardized payments. The study period covered 2012 to 2017.We conducted bivariate analyses of baseline demographic characteristics and comorbid conditions for medical and surgical episodes among ADRD patients with SNF versus HH post‐discharge payments. Controlling for selection bias, we performed propensity score matching for ADRD patients with SNF versus HH 1:1 at a caliper of 0.001 without replacement adjusting for age, sex, 79 hierarchical condition categories (HCC), 27 different medical/surgical hospitalization types, and insurance status (Blue Cross Blue Shield or Medicare). Post‐matched differences on risk adjusted, winsorized, price standardized 30‐day medical/surgical episode payments and all‐cause readmissions were compared.ResultAfter propensity matching, there were 6,024 SNF and HH ADRD matched pairs. Total 30‐day episode payments were significantly higher for SNF users ($41,719; 95% CI: $41,325, $42,112) compared to their HH counterparts ($24,132; 95% CI: $23,806, $24,458) with a difference of $17,587 (95% CI Diff: $17,075, $18,098). Furthermore, ADRD patients with SNF utilization had higher readmissions (29.1%; 95% CI: 27.9%, 30.2%) than those discharged for HH (21.4%; 95% CI: 20.4%, 22.4%; Rate Diff 7.7%; 95% CI Rate Diff: 6.2%, 9.3%). Substantially higher total post‐discharge episode payments were seen for SNF utilizers (Diff: $18,126; 95% CI Diff: $17,720, $18,531).ConclusionOur study demonstrates total 30‐day episode payments, readmissions, and post‐discharge payments are substantially higher for SNF ADRD patients compared to HH in a matched cohort.
The association between a parental family history of dementia and modifiable risk factors for dementia among middle‐aged individuals: A propensity score‐matched study
Authors: Vrijsen Joyce , Abu‐Hanna Ameen , De Rooij Sophia , Smidt Nynke 
Published: December 2020

AbstractBackgroundIndividuals with a positive parental family history (PFH) of dementia have an increased risk to develop dementia in the future. It is unclear whether this risk is caused by genetic factors or by modifiable‐risk‐factors for dementia, as parents and their children often share their psychosocial behavior. The aim of this study is to investigate the association between a positive PFH of late‐onset‐dementia and modifiable‐risk‐factors for dementia among middle‐aged individuals.MethodA subsample of Lifelines (n=89,869; 35‐65years), a population‐based cohort study in The Netherlands, was used. Multiple‐imputation‐using‐Chained‐Equations (MICE) was used to replace missing values. We assessed in each imputed dataset, the association between modifiable‐risk‐factors (hypertension, cardiovascular diseases, obesity, diabetes, physical inactivity, smoking, depression, high cholesterol, unhealthy diet, excessive alcohol use, stress, social inactivity, renal dysfunction and the Lifestyle‐for‐Brain‐Health(LIBRA) score) and a PFH‐of‐dementia in two steps. First, each individual with a PFH‐of‐dementia was matched based on age, gender, education, and depending on the risk‐factor also on other potential confounders, to an individual without a PFH‐of‐dementia (ratio 1:1), using propensity‐score‐matching (PSM). Second, we used logistic, linear and multinomial regression analyses on the matched dataset to obtain the effect estimate. Effect estimates in the imputed datasets were then pooled using Rubin’s rules.ResultsAfter PMS, the study population consisted of 26,604 individuals with a positive PFH‐of‐dementia (mean age=46.1years(7.6); 63% female; 3% low education) and 26,604 participants without a PFH‐of‐dementia (mean age=45.1(5.1); 59% female; 1% low education). Individuals with a PFH‐of‐dementia had more often hypertension (OR=1.20;95%‐CI:1.14,1.25), high cholesterol (OR=1.35;95%‐CI:1.25,1.45), diabetes (OR=1.29;95%‐CI:1.14,1.47), cardiovascular diseases (OR=1.54;95%‐CI:1.28,1.84), depressive symptoms (OR=1.25;95%‐CI:1.09,1.42), and obesity (OR=1.15;95%‐CI:1.08,1.22) compared to individuals without a PFH‐of‐dementia. Although individuals with a PFH‐of‐dementia were more often physically active (OR=1.07;95%‐CI:1.03,1.10), they were more often current‐smokers (OR=1.12;95%‐CI:1.07,1.18).ConclusionMiddle‐aged individuals with a PFH of late‐onset‐dementia have more often modifiable‐risk‐factors for dementia compared to their peers without a PFH of late‐onset dementia. Middle‐aged individuals with a PFH of late‐onset‐dementia is a group at risk for dementia. Further research should explore whether this group is willing to assess their dementia risk and subsequently change their health behavior in order to prevent or postpone dementia and increase healthy ageing.
The significance of reticulon4A as a potential indicator of neurodegeneration
Authors: Kulczynska‐Przybik Agnieszka , Kułakowska Alina , Tarasiuk Joanna , Dulewicz Maciej , Kurzyna Piotr , Borawska Renata , Kochanowicz Jan , Mroczko Barbara 
Published: December 2020

AbstractBackgroundNeurodegeneration characterizes by dysfunction, progressive atrophy and loss of neurons, which is presented in both neurodegenerative as well as demyelinating disorders. Both groups of diseases share common pathological hallmarks: neuroinflammation and gradual loss of neurons and axons, which lead to the central nervous system (CNS) damage and the development of these disorders. Mounting evidence has supported the reticulon4A (RTN4A) role in the pathogenesis of some neurodegenerative and demyelinating disorders, including MS. RTN4A also known as Nogo‐A protein, contributes to neuroinflammation and demyelination. Moreover, this protein acts as a relevant inhibitor of neurite outgrowth and axonal regeneration. Therefore, the objectives of the present study were evaluation of Nogo‐A and Tau levels in the cerebrospinal fluid (CSF) of MS patients and subjects from the control group, as well as the assessment of a relationships between concentrations of immunoglobulins, albumin, immunoglobulins and albumin quotients, as well as oligoclonal bands.MethodThe concentrations of Nogo‐A and Tau proteins were measured in the CSF of 15 MS patients and 16 subjects from control group by means of quantitative technique ELISA. CSF and serum concentrations of albumin and immunoglobulins were measured by using nephelometer. To evaluate the integrity of the blood‐CSF barrier and intrathecal immunoglobulins production, albumin and immunoglobulins quotients were calculated. Furthermore, the oligioclonal bands were assessed by using isoelectofocusing method.ResultThe CSF concentrations of Nogo‐A was significantly higher in MS group in comparison with controls. The increased CSF level of the protein was observed significantly correlate with the concentration of Tau protein in MS patients. Furthermore, we revealed associations between Nogo‐A protein and CSF levels of albumin, Tau and QIgG in the whole study group.ConclusionOur preliminary results indicate a potential role of Nogo‐A protein in the neurodegenerative pathology of MS. Moreover, it seems that reticuon4A is a promising candidate biomarker for demyelinating disorders, including MS, but these investigations need to be further clarified using a larger study group. The study was conducted with the use of equipment purchased by Medical University of Białystok as part of the RPOWP 2007‐2013 funding, Priority I, Axis 1.1, contract No. UDA‐RPPD.01.01.00‐20‐001/15‐00 dated 26.06.2015.
Recurrent vascular insult leads to memory impairment and synaptic dysfunction detected as F‐actin loss
Authors: Diwakar Latha , Maurya Shashank Kumar , Ravindranath Vijayalakshmi 
Published: December 2020

AbstractBackgroundVascular dementia may begin as mild cognitive changes due to blockade of blood vessels that worsen gradually as a result of multiple minor strokes. Such vascular insults occurring in the aging human brain can induce various types of cerebral tissue lesions like hemorrhage, infarction, hippocampal sclerosis and white matter lesions leading to cognitive decline. Studies have shown that multi‐infarct dementia is accounted for most cases of vascular dementia. We wanted to develop an animal model to study the vascular pathology affecting synaptic function during such multiple vascular insult to pave way for better understanding of vascular dementia.MethodVasoconstriction was induced by ET‐1, a 21 amino acid peptide. C57/BL6J mice aged 4‐5 months was implanted with cannula on left side of the hemisphere. ET‐1 2ug/2ul was injected through guide cannula into the intracerebroventricular space of lateral ventricle. The animals were injected with 3 doses of ET‐1 at interval of three weeks for each dose for a period of 9 weeks, at the end of dosing mice were subjected behavioral task. Animals were sacrificed, different brain regions like cortex and hippocampus were dissected out to process for biochemical analysis.ResultAnimals were injected for a period of three weeks to make sure that animal completely recovers from first vascular insult. There was significant difference in novel object task, contextual fear conditioning test and Morris water maze in ET‐1 injected mice indicating memory deficits. Gait analysis demonstrated discrepancies in stride and stance length in chronic ET‐1 injected mice compared to vehicle control. Actin treadmilling plays important role in maintaining F/G‐actin equilibrium for optimal synaptic function. Hence, we wanted to know whether chronic vascular insult affects F/G‐actin equilibrium and our results demonstrated that synaptic dysfunction seen as F‐actin disassembly might be contributing to behavioral dysfunction.ConclusionRepeated vascular insult resulted in irreversible learning and memory deficits in ET‐1 injected mice compared to controls leading to vascular dementia. Gait analysis indicated changes in stride and stance length after three injections of ET‐1. We observed loss of F‐actin in synaptosomes prepared from cortex of mice with chronic dose of ET‐1.
Syk inhibitor reduces oligomeric tau associated with GSK3β inactivation and autophagy activation
Authors: Yamaguchi Tomohisa , Hamano Tadanori , Sada Kiyonao , Kanaan Nicholas M. , Sasaki Hirohito , Yen Shu‐Hui , Asano Rei , Enomoto Soichi , Shirafuji Norimichi , Ueno Asako , Ikawa Masamichi , Yamamura Osamu , Nakamoto Yasunari 
Published: December 2020

AbstractBackgroundNeurofibrillary tangle (NFT), composed of highly phosphorylated tau is one of the pathological hallmarks of Alzheimer’s disease (AD). Spleen tyrosine kinase (Syk) is non receptor type tyrosine kinase, and has various physiological functions, including histamine release in mast cells, phagocytosis in macrophage, and B cell differentiation. The possibility of Syk inhibitor for clinical application was proposed in allergic rhinitis, rheumatoid arthritis, and immunologic thrombocytopenia. The possible relationship between Syk and AD has been reported recently. We have examined the effects of Syk specific inhibitor BAY61‐3606 on phosphorylation levels of tau protein and oligomeric tau by using cell culture model of tauopathy, M1C cells.MethodsWe utilized human neuroblastoma cell line M1C cells, which expresses wild type tau protein (4R0N) via tetracycline off induction (Tet Off induction). Reduction of phosphorylated tau protein and oligomeric tau protein by Syk inhibitor was examined by using various phospho‐tau antibodies, and tau oligomer specific antibody. Influences of activity of autophagy by Syk inhibitor was also examined by western blot analysis.ResultsIn this cell line, 72kDa of Syk protein was identified by Western blot analysis. Phosphorylated tau detected by various phospho‐tau antibodies, including PHF‐1, CP13, and AT270 was decreased by 1, 10 μM of Syk inhibitor. One of the patholoigical form of tau, caspase cleaved tau detected by TauC3 was also decreased by Syk inhibitor. Oligomeric tau, which detected by tau oligomer specific antibody, TOC1 was also decreased by Syk inhibitor. Syk inhibitor also inactivated glycogen synthase kinase 3β (GSK3β). Syk inhibitor upregulated autophagy detected by increase of LC3‐II, and reduction of P62. In summary, Syk inhibitor decreased phosphorylated tau as well as total tau by upregulating autophagy, and inactivating tau kinases, including GSK3β. Finally, oligomeric tau was reduced by Syk inhibitor.ConclusionSyk inhibitor may have promising for the treatment of tauopathy, including AD.
Cross‐cultural validation of the motivation to change lifestyle and health behaviours for dementia risk reduction scale in the Dutch general population
Authors: Joxhorst Tessa , Vrijsen Joyce , Niebuur Jacobien , Smidt Nynke 
Published: December 2020

AbstractBackgroundSince treatment options for curing dementia are unavailable to date, prevention of dementia is the key in decreasing the burden of dementia for patients, their families, and caregivers, as well as societies as a whole. Around one third of all dementia cases worldwide is estimated to be attributable to nine modifiable risk factors (Livingston et al., 2017). Although behavioural change is crucial for dementia risk reduction, changing health behaviour is complex. Currently, no valid scale exists to measure attitudes and beliefs towards lifestyle change for dementia risk reduction in the Netherlands. This study aims to validate the Motivation to Change Lifestyle and Health Behaviors for Dementia Risk Reduction (MCLHB‐DRR) scale (Kim et al., 2014) in the Dutch general population.MethodTranslation and back‐translation of the MCLHB‐DRR scale (7 factors, 27 items) was performed to establish a well‐translated Dutch version of the questionnaire. Data were collected by an online survey ‘Lifestyle and dementia’ among a random sample of 4500 residents of the municipality of Groningen (the Netherlands) aged between 30 and 80 years. Exploratory and Confirmatory Factor Analyses (EFA and CFA) were conducted to assess construct validity. Cronbach’s alpha was calculated to assess internal consistency.ResultResults of the EFA (N = 618) pointed towards a seven‐factor solution with a nearly perfectly clean factor structure. Deletion of four problematic items resulted in a clean factor structure. Fit indices from CFA after deleting these four items indicated an excellent model fit (RMSEA = 0.043, CFI = 0.960, TLI = 0.951, χ²/df = 2.130). Cronbach’s alphas ranged from 0.69 to 0.93, indicating good internal consistency.ConclusionThe Dutch version of the MCLHB‐DRR scale (7 factors, 23 items) is a valid instrument to assess the attitudes and beliefs towards lifestyle and health behavioural changes for dementia risk reduction in the Dutch general population aged between 30 and 80 years old. Before the MCLHB‐DRR scale can be used in intervention studies aimed at dementia risk reduction in the Netherlands, insight in the reproducibility and responsiveness is needed.