bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID‐19 on the quality of stroke care in people with dementia and stroke: a comparison with stroke‐only controls
Authors: Abzhandadze Tamar , Hoang Minh Tuan , Mostafaei Shayan , von Euler Mia , Xu Hong , Eriksdotter Maria , Garcia‐Ptacek Sara , Jurado Pol Grau 
Published: December 2023

AbstractBackgroundThe COVID‐19 pandemic has had a significant impact on healthcare systems worldwide, with many hospitals struggling to maintain the same level of care as before the pandemic. As a result, there is concern that the quality of stroke care for patients with dementia diagnoses may have worsened during the pandemic. Therefore, our aim was to study how the COVID‐19 pandemic has affected the quality of stroke care for patients with dementia versus without dementia after suffering a stroke.MethodsWe conducted a register‐based study, retrieving data from the Swedish Stroke Register and The Swedish registry for cognitive/dementia disorders. We included adult patients diagnosed with/without? dementia who had also suffered a stroke between 2017 and 2022. The pre‐pandemic period was defined as January 1, 2017, to February 28, 2020, while the pandemic period was defined as March 1, 2020, to September 19, 2022. The quality indicators of care were defined as care provided at specialized stroke units and assessment for rehabilitation.ResultsThe study included 3205 patients with dementia and 32666 dementia‐free controls, all of whom suffered a stroke. The mean age at onset of stroke was 83 (±6.8) years for those with dementia and 74 (±15.1) years for those without. In addition, the dementia‐stroke group and stroke‐only group had 55% and 48% females, respectively. Compared to the pre‐pandemic period, a lower proportion of patients with dementia were admitted to specialized stroke units and received rehabilitation assessments during the pandemic period, with 64% versus 36% and 65% versus 36%, respectively. Additionally, a lower proportion of patients with dementia compared to stroke‐only controls were admitted to specialized stroke units (36% versus 45%) and received rehabilitation assessments (35% versus 44%) during the pandemic period.ConclusionsOur study indicate that the COVID‐19 pandemic had a negative impact on the quality of stroke care for patients with dementia as compared to stroke‐only controls. This was evidenced by the lower proportion of patients with dementia who were admitted for care to specialized stroke units and assessed for rehabilitation during the pandemic period, compared to the pre‐pandemic period.
Brain Structure and Cognitive Dysfunction in Myotonic Dystrophy Type 2 (BraCE‐DM2)
Authors: Puwanant Araya , Flashman Laura A , Burgos‐Aguilar Carolina , Nopoulos Peggy , Craft Suzanne 
Published: December 2023

AbstractBackgroundMyotonic dystrophy type 2 (DM2) is a pleiotropic multisystemic disease. Although progressive muscle weakness is the main symptom in DM2, almost two‐third of the patients report cognitive deficits as one of the most disabling symptoms. Emerging evidence has identified tau mis‐splicing and tangle pathology in DM2, which has prompted interest in elucidating the role of tau in DM2‐related cognitive impairment. Previous studies suggest that cerebral white matter (WM) is primarily affected in DM2. However, quantitative brain imaging studies incorporate with cognitive measures are extremely limited.Method3T brain MRIs were acquired in 10 adults with DM2 and 10 gender and age‐matched controls. Brain morphometry and WM integrity were assessed using T1‐MPRAGE and diffusion tensor imaging (DTI) sequences. DTI scalars, including fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and median diffusivity (MD) were compared between groups. A comprehensive battery of cognitive and behavioral measures was performed and correlated with MRI measures (Spearman’s Correlation).ResultOf 20 participants (60% female), mean age (62.2 vs. 62.6 years) and education (16.4 vs. 17.5 years) were similar between the two groups. Compared to controls, the DM2 group showed a significant reduction in global measures of cerebral gray matter (GM) volume in both cortex and deep gray structures (mean difference, ‐0.03; p<0.01), but not the WM volume. Widespread abnormalities in DTI measures (lower FA, higher RD) were among the most robust findings in DM2 (mean differences of FA, 0.04; p<0.01 and RD, 0.00004; p<0.01), indicating that the pathology is within WM microstructures. Overall, the DM2 group scored lower than controls in all cognitive domains, particularly executive function (mean difference, ‐12.5; p = 0.04). We found a strong correlation between cerebral FA and a test of executive function (rho = 0.71, p = 0.02). Cerebral FA also showed a moderate correlation with processing speed (rho = 0.50) and apathy evaluation scale (rho = ‐0.43).ConclusionOur pilot data demonstrate robust differences of brain structure, explicitly measures of WM integrity and cerebral GM volume between the DM2 group vs. controls. The strong correlation between cerebral FA and executive function also supports the notion that WM integrity plays an important role in cognitive dysfunction in DM2.
Targeting ceramides in 5XFAD mice reduces amyloid plaque deposition and gliosis
Authors: Wilkerson Joseph L , Chaix Amandine , Summers Scott A , Holland William L 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease and other neurodegenerative disorders have been linked to metabolic disorders associated with aberrant lipid deposition. Sphingolipids, such as ceramides, are among the most deleterious lipids that accumulate in the AD brain. Increased ceramides have been measured in post‐mortem AD brain samples and are abundant in Aβ‐plaques. As biomarkers, ceramides in the plasma and cerebrospinal fluid correlate with AD risk. The potential of ceramide‐lowering strategies to treat or prevent AD has been underexplored. We hypothesize that ceramides are causal contributors to AD pathologies and amenable to therapeutic targeting to improve AD outcomes.MethodTo address ceramides in AD, we have targeted serine palmitoyl‐transferase (SPT), the first enzyme and rate‐limiting step in ceramide de novo synthesis, with the drug myriocin in 5XFAD mice on a regular chow diet and an obesogenic high‐fat diet. We have also generated inducible genetic models to study loss‐of‐ceramides (overexpression of the ceramide‐degrading enzyme Asah1) or gain‐of‐ceramides (overexpression of the SPT complex), specifically in neurons in the 5XFAD model. We used immunocytochemistry to assess Aβ plaque numbers and size and both astrocyte and microglial activation and numbers. Cognitive behavior was measured using a Barnes maze.Result5XFAD mice treated with myriocin for 17 weeks had a reduction of hippocampal ceramides. As expected, control vehicle‐treated 5XFAD mice showed a significant memory deficit during behavioral testing. Myriocin‐treated mice had significantly improved memory of the Barnes maze. Treated mice had fewer and smaller Aβ plaques and had a reduction in both astrocyte numbers and arborization in the cortex and hippocampus. Microglia were reduced in the hippocampus of treated mice. In 5XFAD mice with neuron‐specific Asah1 overexpression, Aβ plaque size and number remained unchanged compared to a 5XFAD control. However, Gfap+ astrocytes and Iba1+ microglia/monocyte activation and migration were eliminated, resulting in plaques with no associated glia and glial morphology like non‐5XFAD mice.ConclusionDecreasing ceramide production by myriocin treatment in 5XFAD mice reduced Aβ plaque number and size and reduced gliosis in the cortex and hippocampus. Reducing ceramides in neurons results in the abrogation of gliosis throughout the brain of a 5XFAD mouse.
Investigating ApoE4‐mediated metabolic alteration of H4 neuroglioma cells of Alzheimer’s disease
Authors: Lu Li , Kotowska Anna , Kern Stefanie , Fang Min , Rudd Timothy R. , Alexander Morgan , Scurr David , Zhu Zheying 
Published: December 2023

AbstractBackgroundMetabolites and proteins in ApoE4‐carried H4 neuroglioma cells were analyzed to investigate the potential mechanism of the risk gene ApoE4 involved in Alzheimer’s disease (AD).MethodMetabolomics of ApoE4‐carried and wild‐type H4 cells was performed by applying a novel workflow composed of Orbital trapping secondary ion mass spectrometry (OrbiSIMS) as a screening tool, followed by LC‐MS/MS targeted metabolomics for further confirming polar molecules. Proteins affected by ApoE4 were identified by performing LC‐MS‐based proteomics, followed by investigating the protein network and functional enrichment analysis using the STRING database.ResultThe initial OrbiSIMS approach has shown the advantages of detecting large numbers of metabolites with minimal sample preparation, small sample size and a relatively rapid analysis time, allowing 192 putatively annotated metabolites detected in our study. We found glycerophospholipid metabolism, aspartate, glutamate and alanine are the most affected pathways by ApoE4. Polar‐targeted metabolomics of LC‐MS/MS further revealed that the metabolism of taurine and hypotaurine is also affected by ApoE4. Besides, proteomics results suggest an overall metabolic process, RNA splicing process, and translation associated with ApoE4‐related AD development.ConclusionOur results have elucidated the metabolic alteration of H4 neuroglioma cells in the presence of ApoE4, supporting the hypothesis of the low ability of ApoE4 in transporting lipids and discovering two new potential pathways that may be involved in AD. In addition, proteomics analysis by LC‐MS further proved the ApoE4‐mediated dysfunction of nitrogen compound metabolism and RNA splicing process.
Social network typologies of Korean older adults and digital literacy differences: A latent class analysis
Authors: Park Kang‐Hyun , Park Hae Yean , Lee Hamin , Kim Mi Kyeong 
Published: December 2023

AbstractBackgroundThis study aimed to categorize older Korean adults’ social networks and analyze the characteristics and digital literacy differences among older adults according to each type.MethodThe data of 9,377 older Korean adults were analyzed using the 2020 national survey of older Koreans. Latent class analysis (LCA) was performed using the data, χ2 and variance analyses were performed to understand the characteristics of each social network type, and Scheffe post‐hoc test was performed to determine the significant differences between groups.ResultThree social network types were derived using LCA and classified as ‘child‐centered type,’ ‘child‐friend type,’ and 'friend‐centered type.’ Results showed a statistically significant difference in digital literacy levels according to the social network types.ConclusionThis study findings can be used to propose intervention programs and services associated with older adults’ social networks by examining the social network types of older adults and corresponding differences in digital literacy.
A Preliminary Feasibility Study on Screening Cognitive Impairment based on Multi‐Modal Biomarkers and Stacking Ensemble AI Approach
Authors: Kim Whani , Kim Jin Sung , Ko Hyun Jeong , Yun Byung Hun , Kim Yo Young , Kim Dong Han , Kwon Ui Jun , Lim Sang Kwon , Kim Bo Ri , Lee Jee Hang , Kim Geon Ha , Kim Jin Woo 
Published: December 2023

AbstractBackgroundEarly screening of cognitive impairment is crucial for patients demanding timely treatment. The need for cost‐effective, easily accessible, and accurate tools to detect cognitive decline rapidly progressed with the breakout of the COVID‐19 pandemic. In this work, we proposed a mobile‐app based cognitive assessment tool, “Alzguard‐D”, equipped with two digital biomarkers along with a cognitive task. Next, we investigated the efficacy of “Alzguard‐D” in early screening of cognitive impairment using a machine learning approach.MethodNine “Alzguard‐D” tasks were designed based on three biomarkers: Keystroke, speech and eye movement (Table 1; Figure 1). Total of 289 participants were recruited from the national institute of dementia, welfare center, and nursing homes. The participants first completed the Korean Mini‐Mental State Examination (K‐MMSE; 2nd Edition), then performed all tasks in “Alzguard‐D”. “Alzguard‐D” took approximately 20 to 30 minutes. The participants were then categorized to healthy control (HC; n = 241) and cognitively impaired (CI; n = 48), defined as when the scores of K‐MMSE were one standard deviation below the age, education and gender‐matched norm. Given the data, we investigated the extent in which the combination of digital biomarkers and cognitive tasks improves the screening accuracy. We used a stacking ensemble model where the first stack analyzed speech and eye movement, and the second performed the classification.ResultThe screening result confirmed that the addition of digital biomarkers collected by “Alzguard‐D” significantly improved the classification performance (p < 0.0001; sample paired t‐test). CatBoost algorithm statistically outperformed all other candidate algorithms (Bagging, Logistic Regression, LGBM, Naïve Bayes, XGBoost, Random Forest, SVM, Gradient Boosting). We then conducted an ablation study with three classifiers trained with (i) Cog+Bio, (ii) Bio and (iii) Cog. Cog+Bio achieved the highest AUC score, 0.876 (max: 0.942), followed by Bio with 0.783 (max: 0.845), then Cog with 0.677 (max: 0.726) (Figure 2).ConclusionA combination of cognitive and digital biomarkers significantly increased the screening performance of cognitive impairment, and employing an intermediate feature‐level ensemble approach to effectively analyze the collected multi‐modal data increased the AUC levels.
Brain pathological mechanism of weight loss preceding incident mild cognitive impairment
Authors: Chen Yaojing , Dang Mingxi , Zhang Zhanjun 
Published: December 2023

AbstractBackgroundWeight loss in late life is associated with a higher risk of dementia and higher mortality. However, the temporal and etiological associations between weight loss and mild cognitive impairment (MCI) remain unclear.MethodWe examined 709 Alzheimer’s Disease Neuroimaging Initiative participants to investigate body mass index (BMI) trajectories preceding the progression from normal cognition to MCI (N‐t‐M progression), and to explore the association between brain pathology and BMI trajectories preceding incident MCI.ResultDuring N‐t‐M progression, participants developed multiple brain pathologies, and amyloid β (Aβ) accumulation in the frontotemporal region at baseline was associated with decreased BMI (Figure 1, false discovery rate‐corrected p<0.05). For pathological changes, participants had increased accumulation of Aβ and tau, accelerated hypometabolism, and decreased gray matter volume in the brain during N‐t‐M progression. More importantly, accelerated hypometabolism (p<0.001) and gray matter atrophy (p = 0.011) were associated with a rapid decline in BMI during N‐t‐M progression.ConclusionThese findings highlight the importance of regular monitoring of weight changes in older adults as faster BMI decline and lower BMI may be the result of brain pathology and associated with rapid progression of pathology, and provide a theoretical basis for strategies to minimize weight loss to prevent or delay MCI onset.
Detection and management of suspected infections in people with dementia: A scoping review of current practices
Authors: Ivosevic Mihaela , Waldemar Gunhild , Janbek Janet 
Published: December 2023

AbstractBackgroundPeople with dementia are at increased risk for hospitalization, readmission and mortality due to infections. Timely infection detection and management is essential and is often challenged by the presence of atypical infection signs in people with dementia, difficulties in communicating their symptoms, and inadequate external support. Thus, understanding what takes place in the decision‐making processes and interventions of suspected infections is crucial to provide clarity over the best way to deliver the needed interventions.ObjectiveTo explore the decision‐making processes and interventions for detecting and managing suspected infections in people with dementia and involved actors and determinants. The goal was to identify existing practices and knowledge gaps to inform targeted interventions.MethodsA scoping review was conducted through comprehensive searches of Embase and PubMed 2010‐2023, guided by research questions and predetermined inclusion (original qualitative and quantitative articles focusing on people with dementia) and exclusion criteria (palliative and end‐of‐life care). Two authors independently screened and extracted data and synthesized findings through mapping and narrative analysis.ResultsThe search identified 13 933 records and 11 full‐text studies were included in the analysis. We additionally included snippets from 10 studies where parts of the findings were related to dementia. Research was mostly based on populations in the United States, followed by Sweden and the United Kingdom. Majority of research was on practices within nursing homes, and mainly concentrating on urinary and respiratory infections.Decision‐making processes were presented in almost two thirds of the studies, with the rest being Interventions targeting healthcare staff and one targeting proxies. Interventions included decision‐support tools (computer algorithms, posters), early warning/detection systems or pathways (based on observing behavioral and physical changes in patients), a communication technique, and training/education interventions (seminars, courses, booklets).Actors involved were dementia patients, nurses, proxies, physicians, physician assistants, and nursing and care assistants.ConclusionsOverall, we found little attention in research towards infection detection in people with dementia, particularly outside of the nursing homes. Our findings and the highlighted knowledge gaps both inform and encourage further research which will ultimately translate into targeted interventions improving infection detection practices.
Age‐Related Enhanced BMP Signaling Elicits APOE‐Isoform Dependent Effects in IPSC Model of Alzheimer’s Disease
Authors: Linden Anne K , Affaneh Amira , Kessler John A , Peng Chian‐Yu 
Published: December 2023

AbstractBackgroundAging is the strongest risk factor for developing Alzheimer’s Disease (AD), and APOE is the largest genetic risk factor for developing AD. Bone morphogenic protein 4 (BMP4) expression and subsequent signaling increases 10‐fold with age and is increased in AD patients compared to age‐matched controls. Enhanced BMP signaling in aged and AD brains suggest a potential molecular cascade involved in AD pathogenesis. A potential interaction exists between increased BMP signaling across lifespan APOE expression that contribute to risk of AD.MethodAD patient derived iPSC’s (APOE3/E4 genotype) and isogenic controls (APOE3/E3 genotype) were differentiated into astrocytes and neurons. Cells were grown for 35 days before treatment with BMP4 or vehicle for 3 days prior to fixation, protein/media collection, or preparation for single cell RNA sequencing (scRNAseq). For coculture studies, neurons and astrocytes of the same patient background were differentiated separately prior to combined plating and BMP treatment. Cocultures were in matched (APOE3/E4 neurons with APOE3/E4 astrocytes) or mismatched (APOE3/E3 neurons with APOE3/E4 astrocytes) conditions to understand the non‐cell autonomous effects of APOE genotype.ResultUpon BMP treatment, APOE3/E4 compared to APOE3/E3 astrocytes exhibit accumulation of lipid droplets with changes in lipid composition. Increased free cholesterol levels as well as triglyceride accumulation is observed in APOE3/E4 astrocytes and is further exacerbated with BMP treatment. RNA‐sequencing analysis reveals marked decreased expression in genes related to oxidative phosphorylation and increased cholesterol synthesis and metabolism in APOE3/E4 astrocytes that is modulated by BMP treatment. In a non‐cell autonomous fashion, APOE3/E3 neurons, when paired with APOE3/E4 astrocytes, express exacerbated pTau levels and aberrant metabolic processes in a BMP‐dependent manner.ConclusionOur results indicate an interaction between genetic and aging factors in cellular processes relevant to AD. Enhanced BMP signaling confers aberrant lipid composition and metabolic processing in APOE3/E4 astrocytes when compared to APOE3/E3. Subsequent BMP‐dependent non‐cell autonomous effects in APOE3/E3 neurons are observed when cocultured with APOE3/E4 astrocytes. This data suggests age‐associated increase in BMP signaling may modulate APOE isoform‐dependent metabolic processes and increase risk for APOE‐mediated pathological cascades.
Falls and Cognition in Adults Aging with Down Syndrome
Authors: Washington Selena E , Bollinger Rebecca M. , Ances Beau , Stark Susan L. 
Published: December 2023

AbstractBackgroundAdults with Down syndrome (DS), who are at risk, will show the neuropathological changes of Alzheimer’s Disease (AD) within their 40s, partially due to an overexpression of beta‐amyloid, which accumulates in the brain across their lifespan. The risk of developing AD in adults aging with DS increases with age and is marked by increased confusion, short‐term memory problems, and/or a loss of the ability to complete daily activities. There is limited evidence on the functional changes that happen to adults aging with DS prior to any marked AD symptoms. Growing evidence suggests that functional mobility abnormalities and an increase in falls may precede cognitive impairment and marked AD symptoms. The relationship between falls and cognition in adults with DS has not been thoroughly investigated; and could potentially serve as a less invasive method of assessment.MethodThe purpose of this study is to assess patterns of falls and functional mobility impairments that occur within an adult population aging with DS and their relationship with cognition. The participant receives an initial home visit, conducted by the PI, who completes and collects data on functional performance, fall risk(s), and the environment. The participant agrees to document any fall incidents using a calendar journal, and completes the monthly check‐in calls and/or emails initiated by the study team.ResultWe conducted a correlation analysis with the preliminary data from this cohort of 17 participants, 9 male and 8 female, with a mean age of 38.5 years (SD = 8.81). Increased falls were significantly related (p < .05) to impaired gait speed (r = .528) and balance (r = ‐.624), while cognition (r = .474, p >.05) was not associated with falls. Increased fear of falling assessment scores were correlated with impaired gait speed (r = .687), lower extremity (r = ‐.502) and mean grip strength (r = ‐.492), and balance (r = ‐.596).ConclusionWe demonstrated that (1) participants were willing to enroll; (2) the assessment and monitoring plan were well tolerated; and (3) fear of falling scores and decreased functional mobility were similar in aging adult with DS populations to older adult (≥ 65 years of age) populations.