bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surrogate Decision‐Making Regarding Life‐Sustaining Treatments for Older Adults with Dementia Admitted to Long‐Term Care Hospitals
Authors: Kim Hyejin , Cho Jeonghyun , Park Jongsun , Kim Sang Suk 
Published: January 2025

AbstractBackgroundLong‐term care hospitals are the main healthcare setting for the growing population with dementia in South Korea. Despite various deficiencies (e.g., insufficient resources, impractical policies and regulations) in providing quality end‐of‐life care in this care setting, few studies have explored decision‐making practices in the context of dementia and end‐of‐life care planning. Thus, this study aimed to explore how decisions concerning life‐sustaining treatments were made for patients with dementia admitted to long‐term care hospitals, identify facilitators and challenges in the process, and suggest directions to improve the current decision‐making practices.MethodThis qualitative descriptive study included 24 healthcare providers—physicians, registered nurses, social workers, or oriental medicine doctors involved in dementia care for at least six months in their current long‐term care hospitals—and 7 surrogates—family members involved in medical decision‐making. We conducted individual, semi‐structured interviews with the participants regarding decision‐making approaches, facilitators and challenges to decision‐making, and suggestions to improve decision‐making practices. Data were analyzed using a directed content analytic technique.ResultThe analysis yielded 2 main categories, 7 categories, and 19 subcategories: How decisions about life‐sustaining treatments were made for patients with dementia?; and How to support decision‐making about life‐sustaining treatments for this patient population? Physicians, nurses, and surrogates were the key personnel in decision‐making about life‐sustaining treatments in long‐term care hospitals and played different but complementary roles. Although their primary goal of care was to maintain patients’ current functional status as long as possible while securing comfort, they showed three different views toward life‐sustaining treatments. When making decisions, they considered patients’ autonomy and best interests, surrogates’ interests, and other ethical factors. Various patient/surrogate/staff‐related factors facilitated or challenged decision‐making about life‐sustaining treatments. Individual/institution/policy/regulation‐level efforts were suggested to support such decision‐making.ConclusionThe findings highlight the importance of open communication between healthcare providers and surrogates regarding end‐of‐life care for patients with dementia. Multi‐faceted strategies (e.g., the promotion of advance care planning, education to enhance healthcare providers’ competency in end‐of‐life care discussions, development of policies and regulations supporting life‐sustaining treatment‐related practices in long‐term care hospitals) are necessary to effectively assist surrogates in treatment decision‐making in this care setting.
Improving diagnostic accuracy: development of an artificial intelligence model to aid in the diagnosis of Alzheimer’s disease dementia
Authors: Espinosa Valeria Guerra , Maestre Juan Carlos Arbelaez , Zabaleta Daniela , Espinosa Mateo Ruiz , Lopera Francisco , Aguillon David Fernando , Espinosa Sofia Guerra 
Published: January 2025

AbstractBackgroundCurrently, the diagnosis of Alzheimer’s disease dementia (ADD) is determined based on clinical criteria, as well as specific imaging and cerebrospinal fluid (CSF) biomarker profiles. However, healthcare professionals face a variety of challenges that hinder their application, such as the interpretation and integration or large amounts of data derived from neuropsychological assessment, the importance attributed to each source of information and the impact of unknown variables, among others. Therefore, this research focuses on the development of a computerized diagnostic tool based on Artificial Intelligence (AI), to strengthen the capacity of healthcare professionals in the identification and diagnosis of ADD.MethodDuring this research, all phases of the Cross‐Industry Standard Process for Data Mining (CRISP‐DM) methodology were applied. Specifically, seven types of machine learning (ML) classifier algorithms were trained with data derived from the medical and neuropsychological evaluation of 870 people with and without ADD. Additionally, genetic algorithms (GAs) were used to choose the hyperparameters of six of the models and the best performing model was deployed through a graphical user interface.ResultA total of 147 ML models were trained to differentiate or classify between people with and without ADD. Using a random forest (RF) algorithm and 31 predictor variables we achieved a sensitivity of 98%, a specificity of 100% and an area under the curve (AUC) of 0,988.ConclusionWe trained and evaluated a variety of ML models, highlighting the accuracy of a RF algorithm together with the use of GAs, to distinguish people with and without ADD. Additionally, we deployed the model with the best performance metrics through a graphical user interface in order to promote its future use in clinical settings.Although these results are promising, the ongoing need to evaluate and re‐train the model, as well as the ethical considerations of its implementation, are well acknowledged.
Local disruptions in non‐rapid eye movement sleep expression are associated with cerebrovascular pathology and worse memory performance in older adults
Authors: Berisha Destiny E , Rizvi Batool , Chappel‐Farley Miranda G. , Dave Abhishek , Meza Novelle J , Sattari Negin , Lui Kitty K. , Chen Ivy Y. , Tustison Nicholas J. , Neikrug Ariel , Benca Ruth M , Yassa Michael A. , Mander Bryce A 
Published: January 2025

AbstractBackgroundAging is associated with disruptions in non‐rapid eye movement (NREM) sleep and memory decline. Cerebral small vessel disease (CSVD) increases with age and is associated with clinical sleep disturbance, but little is known about its relationship with local expression of NREM sleep. Here, we explore associations between CSVD burden, memory, and local electroencephalography (EEG) measures during NREM sleep in older adults.MethodsFifteen cognitively intact older adults (mean age 71.8±6.3 years, 10 female, Apnea Hypopnea Index (AHI)=7.82±7.95) underwent T2‐weighted fluid‐attenuated inversion recovery magnetic resonance imaging, an in‐lab overnight polysomnography with 128‐channel EEG, and a sleep‐dependent mnemonic discrimination task was administered. Lobar white matter hyperintensity (WMH) volumes were calculated using a validated semi‐automated toolbox. Topographical correlations were run with 5000‐permutation threshold free cluster enhancement.ResultsOlder age was associated with lower absolute posterior total (all p<0.016, r>‐0.61) and slow sigma power (all p<0.018, r>‐0.60) and slow wave activity (SWA) (all p<0.017, r>‐0.61) over centro‐posterior EEG derivations. Age was also positively associated with frontal (τ=0.51, p<0.01) and parietal (τ=0.49, p<0.01) but not occiptal (τ=0.33, p=0.092) or temporal (τ=0.36, p=0.064) WMH burden. Occipital WMH burden was also not associated with AHI (τ=0.038, p=0.843). Occipital WMH burden was associated with global reductions in alpha activity (all p<0.043, τ>‐0.78), centro‐posterior reductions in SWA (all p<0.043, τ>‐0.63) and Delta (all p<0.009, τ>‐0.63), frontal reductions in total (all p<0.043, τ>‐0.71) and fast sigma power (all p<0.004, τ>‐0.57), global reductions in slow sigma power (all p<0.043, τ>‐0.71), and central reductions in theta activity (all p<0.042, τ>‐0.57). Better lure discrimination for low similarity lures was significantly positively associated with higher relative slow oscillation expression over fronto‐parietal regions, though this did not survive TFCE correction (all p<0.033, r>0.55).ConclusionsCollectively, these findings indicate that WMH burden in older adults is associated with local disruptions in NREM sleep expression in multiple frequency bands, of which lower frequencies were particularly vulnerable. This in turn may explain weakened memory performance. Future studies should examine the role of NREM sleep expression in cognitive decline associated with CSVD burden.
Life‐course food insecurity is associated with cognition in later life: Evidence from the National Longitudinal Youth Survey 1979 Cohort
Authors: Esaryk Erin E , Vable Anusha M , Hebert Jillian , Pacca Lucia , Gaye S. Amina , Khadka Aayush , Singh Sonali , Wells Whitney M , Hill‐Jarrett Tanisha G , Martinez Suzanna 
Published: January 2025

AbstractBackgroundLife‐course food insecurity may influence cognition through pathways of stress and poor health. Yet, few longitudinal studies examine whether life‐course food insecurity is associated with cognition among U.S. adults.MethodsWe performed a secondary data analysis using National Longitudinal Youth Survey 1979 data from 1979‐2016 (N = 7,320). Annual food security status was estimated between the ages of 22‐45 using 2008 Supplemental Nutrition Assistance Program eligibility requirements for household income and assets as a proxy. Sequence and cluster analyses were used to identify prototypical food security status trajectories. We identified seven trajectory groups ranging from persistently food secure to persistently food insecure. Trajectory groups varied by order, timing and duration of food security status. Cognition (ages 45‐59) was measured using five assessments, which were summarized into z‐scores (attention, memory, overall cognitive) and Langa‐Weir cognition score. We used linear regression to model associations between food security trajectory groups and cognition, while controlling for covariates.ResultsMost respondents were in the persistently food secure group (65%), with a Langa‐Weir cognition score of 15.84 (SD = 4.57, scale = 0‐27), and z‐scores as follows: memory, 0.00 (SD = 0.00); attention, 0.01 (SD = 0.76), overall cognitive, 0.00 (SD = 0.00). Compared to the persistently food secure group, the following groups were negatively associated with cognition after adjustment: persistently food insecure (β Langa‐Weir cognition: ‐2.08, 95% CI [‐2.64,‐1.52]), food insecure with bouts of food security in emerging and early adulthood (β Langa‐Weir cognition: ‐1.51,[‐2.19, ‐0.83]), food secure through middle adulthood and food insecure in later adulthood, (β Langa‐Weir cognition: ‐1.19, [‐1.73, ‐0.65]), and food insecure through middle adulthood and food secure in later adulthood (β Langa‐Weir cognition: ‐0.66, [‐1.17, ‐0.14]) Coefficients were consistent for z‐score outcomes.ConclusionsWe observed a dose‐response trend, such that cognitive ability decreased among groups with prolonged food insecurity exposure. Food insecurity is modifiable; therefore, strengthening policies to improve food access among Americans is imperative.
Gabapentin initiation and neurocognitive changes in older adults with cognitive impairment
Authors: Oh GYeon , Moga Daniela C , Fardo David W. , Harp Jordan P. , Abner Erin L. 
Published: January 2025

AbstractBackgroundGabapentin has been increasingly prescribed to older adults for off‐label indications, and accumulating evidence suggests potential for gabapentin misuse and related adverse events. However, the relation between gabapentin initiation and longer‐term neurocognitive changes is not well understood.MethodA retrospective cohort study was conducted using the National Alzheimer’s Coordinating Center Uniform Data Set (2005‐March 2023). Participants with cognitive impairment at the visit of gabapentin initiation (i.e., index visit) were included. Using the incidence density sampling method, up to 9 non‐users were randomly selected for each initiator. Cognitive decline over one year was defined as any increase in Clinical Dementia Rating global score (CDR®GLOB) or a 1‐point increase in CDR® sum of boxes (CDR®SB). Functional status decline over one year was defined as at least a 3‐point increase in the Functional Activities Questionnaire (FAQ) sum or a 0.3‐point increase of mean of FAQ. Motoric decline over one year was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, joint stabilized inverse probability of treatment weights and censoring weights were used. Generalized estimating equations with an exchangeable working correlation structure were used to fit logistic regression models and account for the weighting, The confounders were selected using directed acyclic graphs. All analyses were conducted comparing index to index+1 and index+2 visits.ResultFor the study of cognitive and functional status decline, we included 505 initiators (mean age [SD]: 78.8 [7.4]; male = 45%) and 4,545 non‐users (79.2 [7.6]; 50.1%). For the study of motor decline, we included 353 initiators (78.3 [7.2]; 42.8%) and 3,177 non‐users (78.5 [7.4]; 48.1%). Gabapentin initiation was not statistically associated with decline on CDR®GLOB, CDR®SB, FAQ sum, or mean FAQ at the index+1 or index+2 visits. However, gabapentin initiation was significantly associated with increased odds of new falls at the index+2 visit (odds ratio [95% confidence interval]: 2.1 [1.1, 3.9]) (Figure 1).ConclusionOver 1 or 2 years of follow‐up, gabapentin initiation was not associated with decline in cognitive or functional status but was associated with increased odds of falling among research participants with cognitive impairment.
Comparing Research Attitudes in Down Syndrome and Non‐Down Syndrome Research Decision‐makers
Authors: Lu Thuy V , Campos Paola , Leader Sean , Lee Xavier , Xu Helena , Doran Eric , Gillen Daniel L , Grill Joshua D , Lott Ira T. 
Published: January 2025

AbstractBackgroundRecruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision‐makers for individuals with and without DS.MethodWe compared scores on the Research Attitudes Questionnaire (RAQ) of individuals enrolled in two recruitment registries: the UCI Consent to Contact [C2C (N = 4818)] and DS‐Connect (N = 976). We compared total RAQ scores using linear regression. We assessed item‐level RAQ differences using proportional odds regression.ResultMean total RAQ scores were not statistically different between DS (DS‐Connect) and non‐DS (C2C) decision‐makers, adjusting for age, sex, race and ethnicity, education, and COVID‐19‐time frame (Est. Diff = 0.11, 95% CI: ‐0.22, 0.43; p = 0.531) (see Table 1). In prespecified item‐level comparisons we did, however, find evidence of differential attitudes on item‐level RAQ scores (see Figure 1). Specifically, DS participants had an increased odds of a more favorable response to the question of responsibility to help others (DS vs non‐DS: OR = 1.26, 95% CI: 1.08, 1.48) and a decreased odds of a more favorable response to the question regarding belief that medical research would find cures for major diseases during their lifetime (DS vs non‐DS: OR = 0.77, 95% CI: 0.66, 0.90).ConclusionOur findings provide a framework for researchers to develop precise strategies for recruiting DS and non‐DS individuals into clinical research. The apparent differences in particular research attitudes across these two populations warrant further investigation to instruct these strategies.
PROGRESS‐AD: a phase 2 study to evaluate efficacy and safety of GSK4527226 (AL101), an anti‐sortilin monoclonal antibody, in patients with early Alzheimer’s disease
Authors: Machlitt‐Northen Sandra , Abdelkarim Azza , Bailey Christine , Budda Balasubrahmanyam , Bombois Stéphanie , Brew Bruce , Brintziki Dimitra , Burgess Brady , Cohen Sharon , Ganji Gopinath , Germani Massimiliano , Inman Dave , Jayabalan Tharaka , Mummery Catherine J. , Park Lovingly , Parker Christine , Romano Gary , Sadowski Martin , Salvadore Giacomo , Lai Robert Y. K. 
Published: January 2025

AbstractBackgroundProgranulin (PGRN), a glycoprotein secreted by microglia and neurons, regulates lysosomal function, neuroinflammation, and has neurotrophic effects. Variants in the granulin gene (GRN) that cause a reduction of PGRN in plasma and cerebrospinal fluid (CSF) are associated with an increased risk of Alzheimer’s disease (AD). The sortilin receptor (SORT1) on neurons and microglia regulates PGRN degradation. GSK4527226 (AL101) is a human monoclonal immunoglobulin G1 antibody that inhibits SORT1 and increases extracellular PGRN levels in plasma and CSF. In Phase I studies, GSK4527226 was well tolerated with an acceptable safety profile in healthy volunteers, and showed dose‐dependent PGRN elevation in plasma and CSF (Ward et al. CTAD 2021; Germani et al. ACCP 2023).MethodPROGRESS‐AD is a phase 2, parallel group, randomized, double‐blind, global study which aims to evaluate the efficacy and safety of GSK4527226 versus placebo in patients with early AD (N = 282) (EU CT: 2023‐505083‐11‐00; NCT06079190). Eligible patients are in the Alzheimer’s continuum, with amyloid positivity and clinical severity consistent with mild cognitive impairment or mild dementia, as defined by the 2018 National Institute on Aging and Alzheimer’s Association Research Framework (Figure). Patients (aged 50‐85 years) will be randomized to receive intravenous GSK4527226 (dose 1), GSK4527226 (dose 2), or placebo for 76 weeks, followed by a 12‐week safety follow‐up period (Figure). Randomization will be stratified by APOE4 status, AD stage and participation in the CSF sub‐study. The primary endpoint is change from baseline (CFB) in the Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) score across Weeks 52, 64, and 76. Key secondary endpoints include CFB in the iADRS, ADAS‐Cog14, ADCS‐iADL component of ADCS‐ADL‐MCI, and ADCOMS. Safety endpoints include incidence of treatment‐emergent adverse events. Key exploratory endpoints include effect of GSK4527226 on pharmacodynamic and disease biomarkers, and pharmacokinetics of GSK4527226. The primary analysis will use a proportional MMRM (Wang, 2022) under a Bayesian framework with a non‐informative prior distributions. Three sub‐studies will be conducted to assess the effects of GSK4527226 on amyloid PET, tau PET, and CSF biomarkers.ResultN/A.ConclusionThis study of the anti‐sortilin antibody, GSK4527226, will comprehensively evaluate its efficacy, safety and effects on pathogenesis in early AD.
Investigating the effects of semaglutide in early Alzheimer’s disease using single‐cell transcriptomics and proteomics – rationale and design
Authors: Johannsen Peter , Bentsen Marie , Attfield Kate , Frederiksen Kristian Steen , Frisoni Giovanni B , Jeppesen Rose , Malik Ibrahim J , Knudsen Lotte Bjerre 
Published: January 2025

AbstractBackgroundEvidence suggests glucagon‐like peptide 1 receptor agonists (GLP‐1RAs) may have therapeutic potential in Alzheimer’s disease (AD). Cumulative evidence has indicated a potential reduction in cognitive decline in people with AD, while real‐world evidence has shown decreased dementia risk in patients with type 2 diabetes. Non‐clinical data reveal that GLP‐1RAs impact neuroinflammation and other biological processes believed to be involved in AD pathophysiology, including effects on central and peripheral immune cells. The safety and efficacy of the GLP‐1RA semaglutide in early AD (Clinical Dementia Rating global score 0.5–1) is being investigated in two phase 3 trials (evoke [NCT04777396] and evoke+ [NCT04777409]). The aim of this exploratory study is to investigate the effect of semaglutide on central (cerebrospinal fluid [CSF]) and peripheral (blood) inflammation in a similar population using single cell transcriptomics (i.e., assessment of gene expression in individual cells) to complement and expand on the molecular understanding of semaglutide and AD.MethodAn interventional, randomized, parallel‐group, double‐blind, placebo‐controlled, multicenter, multinational study is designed to evaluate the effects of semaglutide versus placebo on central and peripheral inflammation in participants with early AD (NCT05891496; Figure). The 24 participants will be aged 55‐75 years and have established amyloid positivity. Central and peripheral inflammation will be investigated using single‐cell RNA sequencing, T‐cell receptor sequencing, and proteomics; AD‐related biomarkers (including glial fibrillary acidic protein and phosphorylated tau 217) will link cellular changes to AD pathology proxies. Cellular, protein, and biomarker changes will be assessed after 12 weeks of treatment.ResultThe study is expected to read out at the end of 2024.ConclusionInvestigation of CSF and peripheral blood mononuclear cells at the single‐cell level in combination with protein and biomarker changes in the same individuals with early AD is an unprecedented opportunity to understand both the effects of semaglutide and the role of immune processes in early AD.
Characteristics of brain topological networks in posterior cortical atrophy: a hybrid FDG PET/MRI study
Authors: Wu Liyong , Chu Min , Nie Binbin , Liu Li 
Published: January 2025

AbstractBackgroundGraph theory is an advanced method for analyzing the balance of brain networks. However, the changes in white matter (WM) and metabolic networks and their correlation with clinical features in patients with posterior cortical atrophy (PCA) require further investigation. This study aims to clarify the structural, metabolic, WM, and metabolic topological network in PCA, and explore their correlation with clinical features.MethodThirty‐four PCA patients and 34 healthy controls (HC) participated in the study and underwent hybrid FDG‐PET/MRI scans and neuropsychological evaluations. Voxel‐based morphometric analysis and Tract‐Based Spatial Statistics was used to assess gray matter volume and white matter integrity and standard uptake value ratio (SUVR) was calculated to evaluate the gray matter metabolism. Then, the topological network connectivity of 90 brain regions was computed using graph theory analysis.ResultPCA patients exhibited gray matter atrophy and metabolic decline in the posterior regions (including the occipital, temporal, and parietal lobes), while white matter damage was more widespread, affecting the parietal, temporal and frontal to occipital tract. In both WM and metabolic topological network analyses, PCA patients displayed significant damage to global and local topological network properties. Particularly in local properties, including nodal centrality, degree centrality, nodal clustering coefficient, nodal efficiency, and nodal shortest path, the changes in the metabolic network were more significant than those in the white matter network. Not only were the posterior brain regions affected, but the frontal node was significantly impacted. PCA patients' WM and metabolic topological networks exhibited different centrality distribution patterns. Several network metrics were correlated with the clinical severity of PCA and the degree of visual impairment, notably the close association between the occipito‐frontal network and visual functional impairment.ConclusionThe study revealed complex alterations in the topological brain networks in PCA patients, not only confined to the posterior brain but also involving the frontal nodes. In addition, the brain topological network characteristics can serve as important markers for assessing the severity of PCA, with potential value for earlier diagnosis and therapeutic intervention.