bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial Transcriptomics Analysis of Vulnerable Cell Populations in Middle Temporal Gyrus
Authors: Long Brian 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is characterized by cognitive decline due to histopathological changes of neurodegeneration in a stereotypical neuroanatomical progression. Applying single‐nucleus ‘omics methods has extended our understanding of how AD impacts the brain and allowed the Seattle AD Brain Cell Atlas Center (SEA‐AD) to provide a detailed cellular‐molecular view of middle temporal gyrus (MTG) in AD. Previously, we identified transcriptomically‐defined cell types that are specifically affected by AD in MTG, however, cell types identified in ‘omics data lack spatial context. Identifying the location of these cell types in situ is necessary to pinpoint the location of affected cells and connect cellular‐molecular views of disease progression to histopathology. To accomplish this, spatial transcriptomics methods measure individual mRNA molecule locations with subcellular resolution and provide transcriptomic profiles of individual cells in situ.
MethodUsing a panel of genes designed to identify transcriptomic cell types, we performed spatial transcriptomics experiments using the Vizgen MERSCOPE platform across MTG tissue from 25 donors spanning AD pathology, yielding transcriptional profiles of over 1M cells across the cortical depth and white matter of 68 sections. These cells were assigned to transcriptomically‐defined cell types by integrating the spatial transcriptomics data with our existing single nucleus dataset. From the resulting maps of cell type locations, we measured cortical layer thickness, cell proportions, densities and cell type‐dependent pairwise distance distributions for each donor.ResultWe have successfully applied the MERSCOPE platform to generate cellular‐resolution spatial transcriptomic data in MTG across a wide range of AD disease progression. We applied novel deep generative models to assign cell type identity. These measurements revealed cell type‐specific spatial distributions and changes in cell type proportions due to disease, validating observations from single‐nucleus studies. Enhanced loss of Layer 2/3 excitatory neuron types and somatostatin‐expressing inhibitory neurons is calculating cell density within layers. Additional analyses uniquely available to spatial transcriptomics studies will be useful for quantitative description of cytoarchitectural changes in AD.ConclusionSpatial transcriptomics experiments across disease progression in MTG confirm cell type abundance changes measured in single‐nucleus RNASeq. The cellular spatial distributions provide detailed knowledge of the location of vulnerable cells within cortex.
Length of stay is related to inpatient antipsychotic use in Alzheimer type dementia at a large US based tertiary care hospital.
Authors: Cahan Joshua Gabriel , Bonakdarpour Borna 
Published: December 2023

AbstractBackgroundAntipsychotic(AP) medications carry a black box warning for increased risk of death in the elderly and should be used judiciously in a dementia population. Studies have shown that encounters with healthcare facilities increase the risk of AP exposure1. We wanted to know how admissions at our institution impacted antipsychotic use in patients with Alzheimer’s disease. Here we describe the results of a retrospective analysis of inpatient antipsychotic use in patients with Alzheimer’s disease at Northwestern Memorial Hospital(NMH), Chicago IL.MethodOur cohort was generated using NMH’s Enterprise Data Warehouse, including patients over 65 with a chart diagnosis of AD admitted to the hospital for over 48hrs between May 2005 and March 2018. We excluded patients with schizophrenia, schizotypal disorder, bipolar disorder, or psychotic illness due to primary psychiatric disease, enrollment in hospice, presence of tracheostomy or PEG‐tube and pervasive developmental disorder.Result1712 patients were admitted for a total of 4603 admissions amounting to 25,721 hospital days during the period of analysis. Demographic information is provided in Table 1. A higher proportion of admissions were four days or longer in encounters with an antipsychotic(Figure 1). Though longer LOS becomes progressively less common, this trend continued through a LOS of 20 days. When comparing LOS for encounters with an AP in the home medication list to encounters without, there was no impact on LOS. However, when comparing encounters with an AP prescribed while inpatient to encounters without, inpatient AP administration was associated with a longer length of stay (Table 2).ConclusionThese findings indicate that a longer LOS is associated with antipsychotic use. Because a longer length of stay was associated with new antipsychotic use but not the continuation of a home antipsychotic, our findings suggest that length of stay may contribute to behavioral and psychological symptoms of dementia requiring pharmacological treatment.1. Koponen M, Lavikainen P, Taipale H, et al. Accumulation of Hospital Days Among Antipsychotic Initiators With Alzheimer’s Disease. J Am Med Dir Assoc. 2019;20(12):1488‐1494.e3. https://doi.org/10.1016/j.jamda.2019.07.009
AD8 revisited: what’s the optimal cutoff value?
Authors: Hwang Tzung‐Jeng , Yang Cho‐Hsiang 
Published: December 2023

AbstractBackgroundThe 8‐item Informant Interview to Differentiate Aging and Dementia (AD8) was developed as a screening tool for dementia with a cutoff of 2 suggested by the initial study. However, various studies found different cutoff values, and many suggested a cutoff of 2 might result in a high false positive rate (up to > 80%). A higher false positive rate in Taiwan was repeatedly shown when AD8 was self‐administered in local government screening programs. This study aimed to examine the performance of AD8, determine its best cutoff value, and discuss factors that may affect the performance of AD8.MethodWe recruited 119 participant‐informant dyads from a psychiatric outpatient clinic of a university medical center. For each dyad, the AD8 was administered first, and then Mini‐Mental Status Examination (MMSE) and the Clinical Dementia Rating (CDR) to minimize contamination effect. Two geriatric psychiatrists made a consensus clinical diagnosis for each subject based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) using all available clinical information, including MMSE, CDR, clinical history, other past neuropsychological tests, and neuroimaging examinations (if available).ResultThere were 37 subjects with normal cognition, 44 with mild neurocognitive disorder (mild NCD), and 28 with major neurocognitive disorder (major NCD). When the cutoff value was 2 for the differentiation between major NCD and no‐dementia subjects (including normal cognition and mild NCD), the AD8 had an AUC of 0.756, a sensitivity of 0.929, and a specificity of 0.582. But the optimal cutoff value was 4 according to the Youden index, with an AUC of 0.888, a sensitivity of 0.786, and a specificity of 0.835.ConclusionAlthough many studies recommended 2 as the best cutoff value for screening dementia, our findings and those of others suggest a cutoff of 2 may result in a high false positive rate. Many factors could affect the performance of AD8, including sample characteristics (e.g. education level), region, conduct of the test, flow of the administration (whether AD8 is administered first or contaminated by other tests), etc. Details will be discussed during the AAIC meeting.
Population attributable fraction of potentially modifiable risk factors for dementia among United States Veterans: A retrospective cohort study 2000‐2020.
Authors: Schliep Karen Cecilia , Redd Andrew , Zhang Yue , Shaaban C. Elizabeth , Sorweid Michelle , Rupper Randall , Christine Cliatt Brown J 
Published: December 2023

AbstractBackgroundPrior international research has indicated that up to 40% of dementia risk may be amenable to prevention, before symptoms occur, by intervening on various factors. Whether modifiable factors vary between countries or within countries among different populations is beginning to be explored. Veterans are increasingly at elevated risk for dementia and cognitive decline due to health, lifestyle, and military‐related risk factors.MethodsData were collected from male and female United States (US) Veterans (≥45 years with no prevalent dementia by January 1, 2000) who had at least one inpatient or outpatient visit within Veterans Health Administration. 8,317,615 individuals were followed to January 1, 2020 to identify potential modifiable risk factors and subsequent dementia diagnoses. We calculated adjusted hazard ratios (aHR) and weighted population‐attributable fractions (PAF) for Alzheimer’s disease (AD) and Alzheimer’s disease related dementia (ADRD) for the following factors: hearing loss, smoking, obesity, depression, post‐traumatic stress disorder (PTSD), hypertension, diabetes, traumatic brain injury (TBI), and heavy alcohol use. Our models were adjusted for age at baseline, sex, race/ethnicity, and marital status and the PAFs accounted for communality among risk factors.ResultsOver the 20 year follow‐up period, 995,821 (12%) US Veterans developed AD/ADRD. The three highest risks for AD/ADRD were TBI (aHR: 3.11 [95% CI:3.08, 3.13]), depression (aHR: 3.06 [95% CI: 3.05, 3.07), and PTSD (aHR: 1.91 [95% CI: 1.90, 1.92]) (Table 1). A weighted estimate of 53.7% (95% CI, 53.2%, 54.1%) of Veteran dementia cases were attributable to the evaluated risk factors. The greatest attributable fraction of AD/ADRD cases was observed for depression (PAF, 19.3%; 95% CI 19.3%, 19.4%), hypertension (PAF, 14.4%; 95% CI: 14.3%, 14.5%), and diabetes (PAF, 6.4%; 95% CI: 6.3%, 6.4%).ConclusionThe PAF for modifiable risk factors for AD/ADRD is higher than in previous world reports, due to not only greater prevalence of cardiovascular risk factors among Veterans, but also due to higher prevalence of military‐related risk factors including PTSD and TBI. Targeted interventions to reduce key risk factors may decrease the projected rise in dementia cases among Veterans over the next several decades.
Genetic diversity differentially regulates molecular mechanisms of brain aging under normal and pathological conditions
Authors: Uyar Asli , Onos Kristen D , Keezer Kelly J , Carter Gregory W , Sasner Michael , Howell Gareth R 
Published: December 2023

AbstractBackgroundGenetically diverse mouse strains have varying life‐spans and varying brain‐aging hallmarks under normal conditions. Studies show that AD mouse models on diverse genomic backgrounds better recapitulate AD‐relevant neuropathological and molecular phenotypes. Mouse models carrying mutant APP and PS1 alleles (APPswe,PS1de9) were generated on eight diverse mouse strains, and significant strain‐specific differences were observed in amyloid deposition, vascular phenotypes, neurodegeneration and transcriptomic signatures. Among those, wild‐derived strains WSB/Eij‐(WSB) and PWK/Phj‐(PWK) gained further attention in AD research. Compared to the APP/PS1 model on standard C57BL/6J‐(B6) mice, WSB.APP/PS1 was associated with elevated neuronal and vascular impairments, whereas, PWK.APP/PS1 was shown to be resilient.MethodWild‐derived strains were originally generated via a backcross strategy, and all PWK.APP/PS1 and WSB.APP/PS1 used in this study were congenic. Cohorts of male and female PWK.APP/PS1 and WSB.APP/PS1 mice and wild‐type controls were aged to 4‐ and 14‐months, and brain hemispheres were processed for RNA‐Seq transcriptomics and neuropathological assessment. In both strains, 14‐months‐old wild‐type mice were compared to 4‐months‐old wild‐type controls to assess brain aging under normal conditions, and 14‐months‐old APP/PS1 mice were compared to 4‐months‐old wild‐type group to assess aging in presence of amyloid pathology (n = 12). Differentially expressed genes were identified and gene set enrichment analysis were performed to determine gene modules and biological pathways associated with brain aging in health and disease.ResultWild‐type aging signatures were mainly strain‐specific with a strong up‐regulation of immune response in WSB, and up‐regulation of metabolic and signaling pathways in PWK. Varying levels of amyloid plaques deposition was observed in the brain of both WSB.APP/PS1 and PWK.APP/PS1 mice. In presence of amyloid, consistent up‐regulation of microglia genes and an elevated immune response was observed. Down‐regulated genes were enriched in synaptic function in WSB, and in pathways of neurodegeneration in PWK.ConclusionThis study suggests that molecular mechanisms of brain aging under normal conditions is modulated by genetic background, and is associated with the response to amyloid pathogenesis. Our findings suggest a potential link between aging‐associated inflammatory state in wild‐type WSB mice and elevated neuronal damage in amyloid pathogenesis, and between preservation of cellular communication in the brain of aged PWK mice and neuronal resilience.
Clinical and epidemiological baseline characterization of Dementia cases in a specialized center in Recife, Brazil
Authors: Santana Ana Rosa , Chagas Victor de Moraes , Costa Bruno Henrique Carneiro , Macedo Luísa Couceiro de Albuquerque , Shirahigue Livia , de Santana Joao Pedro Matos , da Silva Rodrigo Cavalcanti Machado , Brandao Simone Cristina Soares , Barbosa Breno José Alencar Pires 
Published: December 2023

AbstractBackgroundPopulation aging has been considered the main risk factor for the development of dementia globally. In low‐ and middle‐income countries such as Brazil, the projections are for expressive numbers due to poor socio‐economic conditions. However, the epidemiological profile of dementias in Brazil is still little known due to the scarcity of studies, especially in the northeast of the country, where poverty and illiteracy are severe.MethodRetrospective and descriptive study of data obtained from the comprehensive review of medical records after approval by the Ethics Committee. Records of cases treated between 2018 and 2021 were examined, cases that did not have information in the medical record were excluded from the study.Result128 medical records were analyzed, 109 of which met inclusion criteria. 57.8% of patients were male with a mean age of 65.3 years. 38.4% of the sample had less than 8 years of formal education and 15.1% were illiterate. Unskilled manual labor was the occupation type in 50% of the sample. The mean baseline Mini‐Mental State Examination (MMSE) score was 16.88. Alzheimer’s disease was the most frequent diagnosis (37%) mostly in a moderate (22%) to advanced stage (20%) of dementia. 32% of all cases met criteria for mixed forms of Dementia. Frontotemporal Dementia (14%), Lewy Body’s Disease (6%) and Pure Vascular Dementia (6%) were also reported. 69.7% of our sample underwent magnetic resonance imaging and 24% also had access to molecular imaging methods.ConclusionThe low level of education possibly reflects socioeconomic inequalities in Brazil, since we had a lower level of education compared to epidemiological studies of Dementia in the south‐southeast region. The degree of dementia of the examined cases caught our attention, most of them in a moderate or advanced stage, probably related to the time patients wait for care at a specialized center. Such bias may also explain the high frequency of non‐AD pathologies in the sample, in contrast to data from the general population. With the limitation of its descriptive and retrospective design, the present study represents an important initiative in the sense of characterizing data on Dementia in northeastern Brazil.
Item‐based scoring and serial position of words generated during the Category Fluency Test: differences between controls and MCI subtypes
Authors: De Marco Matteo , Venneri Annalena 
Published: December 2023

AbstractBackgroundThe order in which words are recalled during the 1‐minute Category Fluency Test (CFT) can be informative about the integrity of the underlying semantic memory (SM) system. Typically, the first entries tend to be easier exemplars and, as the category is explored in more depth during the course of the minute, words generated tend to become more difficult. We hypothesised that an item‐based scoring method that quantifies this increase in difficulty will help identify the semantic feature(s) most sensitive to the loss of SM integrity observed in people with a form of mild cognitive impairment (MCI).MethodTwo‐hundred participants (age: 58.68 ± 12.08 years) were sub‐divided into four clinical diagnostic groups: 50 healthy controls, 50 individuals with amnestic MCI, 50 individuals with non‐amnestic MCI and 50 individuals with subjective cognitive complaints but no objective deficits. No differences in age, years of education or gender existed across the four groups. All participants were administered a 1‐minute CFT (two categories: animals and fruits). Individual performance was scored word‐by‐word according to nine semantic features: age of acquisition, frequency, prevalence, recognition time, valence, arousal, dominance, sensorimotor interaction and concreteness. Correlation coefficients (Spearman’s rho) were calculated between each feature and the serial position of each word within the list. Correlations were then converted to z‐scores and analysed across the four groups with Kruskal‐Wallis one‐way analyses of variance.ResultThe z‐converted correlation between serial position and dominance was the only one differing across groups (at a p = 0.009). Bonferroni‐corrected post‐hoc tests showed a difference between healthy controls and individuals with amnestic MCI (p = 0.008). The decline in word dominance was significantly steeper in the group of amnestic MCI (z = ‐0.322) than in controls (z = ‐0.199).ConclusionThe study of SM is relevant to characterising the clinical mechanisms of normal and abnormal ageing. A procedure that focuses on CFT words difficulty and order of recall can complement classic methods that are typically used to detect loss of SM integrity. This pilot study indicates that ‘dominance’ is a semantic feature that might help characterise loss of SM integrity in individuals with amnestic MCI.
Continuous Picture Naming Performance in Older Adults
Authors: Chok Jas M. , Herron Timothy J , Lwi Sandy J. , Curran Brian , Schendel Krista , Geraci Kristin , Blank Michael , Williams Garrett , Hall Kathleen , Woods David L. , Baldo Juliana 
Published: December 2023

AbstractBackgroundTasks using speech and language have proven to be useful in assessing for neurodegenerative diseases and cognitive decline. Specifically, deficits in naming have been associated with various degrees of cognitive impairment in those with dementia.MethodThe Continuous Picture Naming (CPN) task was administered as part of a new computerized cognitive assessment tool, the California Cognitive Assessment Battery (CCAB), to 309 aging older adults (aged 56‐89, 40.6% female) with a six‐month and one‐year follow‐up to assess for cognitive changes due to aging. The CPN task measures how fast and accurately a subject can verbally produce the names of a series of items pictured onscreen. The battery scores tasks automatically and utilizes an online speech‐to‐text transcription, consensus automated speech recognition (CASR), to transcribe responses on verbal tasks.ResultResponse times and accuracy were on CPN collected and analyzed to observe for effects on age and education. The analysis showed that age and education were significantly associated with the task’s performance. Overall, CPN performance demonstrated good test‐retest reliability at the six‐month (r = .76, p<.001) and one‐year (r = .74, p<.001) follow‐ups. Moreover, a significant relationship was observed between the total time spent and the total errors on the task.ConclusionOverall, the CPN demonstrates good reliability in tracking changes in cognition. Ongoing evaluation of the CCAB will aid in assessing cognitive impairments in aging populations.
Utility of Cognitive Abilities Screening Instrument (CASI) subscores in detecting early impairment in autosomal dominant Alzheimer’s disease (ADAD)
Authors: Tureson Kayla N , Beam Christopher R. , Medina Luis Daniel , D'Orazio Lina M , Ringman John M 
Published: December 2023

AbstractBackgroundPrior research among patients with autosomal dominant Alzheimer’s Disease (ADAD) has identified early cognitive changes 10‐20 years before formal dementia diagnosis. ADAD provides a model of Alzheimer’s disease (AD) with a relatively predictable onset and with fewer age‐related comorbidities, and as such, may aid in identifying presymptomatic stages of cognitive change for early AD detection. The CASI is a comprehensive screening tool for dementia with multilingual adaptations and may be useful in identifying early cognitive changes among those with or at risk of ADAD.MethodWe examined whether subscales of the Cognitive Abilities Screening Instrument (CASI) could identify early cognitive changes in ADAD as well as the effects of test language (English or Spanish), education, and acculturation on CASI subscales. 141 persons (96 mutation carriers [MC], 45 noncarriers [NC]) with or at risk for inheriting PSEN1/2 or APP mutations completed the CASI. Linear mixed‐effect models were used to examine the effects of adjusted age, mutation status, mutation type (APP or PSEN), test language, education, and acculturation on the 9 CASI subscales.ResultMCs performed significantly worse on CASI subscales than NCs (ps<.001). Adjusted age (βs = ‐.29— ‐.09), mutation status (βs = ‐2.62—‐0.09), and adjusted age x mutation status (βs = ‐.29— ‐0.09) significantly predicted Attention (R2 = 0.36), Concentration (R2 = 0.40), Orientation (R2 = 0.53), Short‐Term Memory (R2 = 0.61), Long‐Term Memory (R2 = 0.27), Language (R2 = 0.39), Visuoconstruction (R2 = 0.53), Fluency (R2 = 0.34), and Abstraction/Judgment (R2 = 0.37), all ps <.001. Acculturation significantly predicted Long‐Term Memory (β = .34, p = .03). The effects of acculturation, test language, and education were not significant for any other CASI subscales.ConclusionAdjusted age, mutation status, and an interactive effect between adjusted age and mutation status appear to be important predictors in CASI performance, such that MCs closer to their familial age of dementia diagnosis are more likely to perform worse on the CASI. No subtest emerged as the best predictor of early cognitive changes in MCs. Attention to potential cultural influences on the Long‐Term Memory subtest warrants further research.