bluuebunny/crossref_metadata_2025_split huggingface dataset:
A brief questionnaire of self‐reported cognitive decline predicts MMSE and study partner QDRS: findings from the Davis Memory and Aging Cohort at Mass General Brigham
Authors: Anzai Juliana A. U. , Christiano Caitlyn , Moreno Stephanie , Viera Andrea M Román , Kirn Dylan , Papp Kathryn V. , Chhatwal Jasmeer P. , Johnson Keith A. , Rentz Dorene M. , Selkoe Dennis J , Sperling Reisa A. , Amariglio Rebecca E. , Yang Hyun‐Sik 
Published: December 2023

AbstractBackgroundA brief self‐reported questionnaire to efficiently capture subjective cognitive decline, a stage considered to be between cognitively unimpaired and mild cognitive impairment, could enhance clinical research and practice. We hypothesized that a 3‐question measure of self‐reported cognitive decline is associated with worse cognitive performance and increased functional changes reported by a study partner (SP).MethodThe Davis Memory and Aging Cohort (MAC) at Mass General Brigham recruits individuals 45 years or older with a broad range of cognitive symptoms. Participants answered the following three questions adapted from the NIA‐AA research framework: Q1. “Have you experienced a change in your memory in the last 1‐3 years?” Q2. “Has this been a persistent change over the last 6 months?” Q3. “Are you concerned about this change?” scored on a Likert scale (0‐4), with high scores representing greater decline. Responses to Q2 and Q3 were set to 0 if Q1 = 0. Participants completed the Mini‐Mental State Examination (MMSE; cognitive performance), and SPs completed the Quick Dementia Rating System (QDRS; functional changes). We tested the association between the total BCSS score (Q1+Q2+Q3; predictor) and MMSE or QDRS total scores (outcome) using linear regression controlling for age, sex, and years of education. We then tested these associations in a subgroup without significant SP concern (QDRS<1.5).ResultThere were 399 MAC participants with complete data (mean age = 67.2±8.3, 64% female, Table 1). Based on QDRS cut‐offs, there were 248 cognitively unimpaired participants, 118 with mild cognitive impairment, and 33 with dementia. The total score was associated with lower MMSE (beta = ‐0.30, p<0.001) and higher QDRS (beta = 0.51, p<0.001). Q1 score by itself was associated with lower MMSE (beta = 0.98, p<0.001) and higher QDRS (beta = 1.2, p<0.001) (Figure 1). In a subset with QDRS<1.5 (n = 248), both the total score (beta = ‐0.22, p = 0.002) and Q1 score (beta = ‐0.62, p<0.001) were associated with lower MMSE.ConclusionSelf‐reported cognitive decline was associated with worse global cognition, even among those whose SPs reported no significant functional concerns. Our results suggest that the brief self‐reported questionnaire could be a useful screening tool in research and clinic that efficiently probes cognitive functioning.
Mediating effect of depressive symptoms on the relationship between digital literacy and cognitive function in older adults
Authors: Hong Jaewoo , Roh Hyun Woong 
Published: December 2023

AbstractBackgroundAlthough several studies have examined the individual relationships between digital literacy, cognitive function, and depressive symptoms, few have integrated all three factors into a single model. In this study, we aim to address this gap in the literature by investigating the mediating effect of depressive symptoms on the relationship between digital literacy and cognition. By doing so, we hope to contribute to a more comprehensive understanding of the complex interplay among these variables and their implications for mental health and well‐being.MethodParticipants were 7988 adults, 65 or older, who participated in Living Profiles of Older People Survey (LPOPS) 2020. The main exposure was digital literacy (communication literacy, information literacy, online transactions literacy, media literacy). The main outcome was depressive symptoms measured by Korean version of the 15‐item Geriatric Depression Scale (SGDS‐K), and cognitive function measured by a Mini‐Mental State Examination (MMSE) score. Multiple linear regression analyses and mediation analysis were performed.ResultAfter adjusting for covariates, our analysis found a significant association between digital literacy and both depressive symptoms and cognitive function (β of four types of digital literacy and depressive symptoms = ‐0.73, ‐0.152, ‐0.942, and ‐1.041 respectively, β of four types of digital literacy and cognitive function = 2.102, 2.217, 1.620, and 2.276 respectively). Moreover, our study suggests that depressive symptoms play a mediating role in the relationship between both online transactions and media literacy with cognitive function (95% CI of indirect effects = 0.1051 to 0.1928 and 0.1104 to 0.1864 respectively), implying an indirect pathway (digital literacy → depression → cognitive function).ConclusionThis study sheds light on the relationship between digital literacy, depressive symptoms, and cognitive function in older adults. We found that depressive symptoms mediate the association between specific aspects of digital literacy (online transactions and media literacy) and cognitive function. Our results indicate that community‐based digital literacy programs could be effective interventions for reducing depression and preserving or improving cognitive function in older adults.
Topological Network Analysis of Beta‐Amyloid and Tau in Alzheimer’s Disease Using PET Imaging Data
Authors: Wu Yuexuan , Ormsby Kyle , Shibata Dean , Chen Yen‐Chi , Biber Sarah , Kukull Walter A. , Chan Kwun Chuen Gary 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is characterized by the presence of beta‐amyloid (Aβ) and tau in the brain. Understanding the interplay between these proteins and their spatial distribution may provide insights into disease progression. This study aims to investigate the topological features of Aβ and tau networks in AD, mild cognitive impairment (MCI), and normal cognition (NC) groups using PET images from the ADNI dataset.MethodPartial correlation matrices between the standardized uptake value ratio of 68 regions of interest (ROI’s) were used to generate networks for the AD, MCI, and NC groups, with nodes representing ROI’s and edges representing correlation coefficients. Topological features, including H0 features (connected components), H1 features (loops), and landscape functions of H1 features, were calculated for each sample’s persistent homology. For each group, 100 bootstrapping samples were used to generate the 95% confidence intervals for landscape functions. The connected components were further studied by representing the samples as hierarchical tree structures. In the tree space, the first few generated connections, representing the most consistent pairs of regions positive for Aβ and tau, were compared across groups. Clustering performances were compared using Wasserstein distance of H0 features, Wasserstein distance of H1 features, landscape function distance, and geodesic distance in tree space respectively.ResultThe geodesic distance in tree space showed the best clustering accuracy in both Aβ and tau analyses. Compared with Aβ, H1 features and the corresponding landscape functions performed better for tau. Unique connections in AD and MCI groups were identified, with AD showing more unique connections than MCI compared to NC samples. Dominant unique connections in the AD group included left‐right isthmus cingulate and left fusiform‐left inferior temporal for Aβ, and left‐right paracentral and left cuneus‐left pericalcarine for tau. These connections indicate region pairs with related concentrations of Aβ and tau in AD.ConclusionTopological network analysis can reveal complex underlying structures in PET images and identify consistent patterns in ROI’s associated with Aβ and tau localization. Tau aggregation exhibits more complex behavior than Aβ and is more strongly associated with AD. The identified unique connections in the AD group may serve as potential biomarkers for disease progression.
Disruptions in cell‐cell communication in the entorhinal cortex of patients with Alzheimer’s disease and the 5xFAD mouse model
Authors: Bartas Katrina , Macchia Desiree , Zhao Wei , Nie Qing , Beier Kevin T 
Published: December 2023

AbstractBackgroundSingle‐cell sequencing has been instrumental in understanding cell‐type specific changes in Alzheimer’s disease (AD). While sequencing provides information about changes in individual cells, how these changes impact the interaction between cells is not as well‐defined. Understanding how the transcriptional and epigenetic changes that emerge during disease impact cellular communication will be critical in understanding key pathological changes that contribute to AD.MethodWe performed single‐nucleus RNA and ATAC‐seq (10x Multiome) to investigate gene expression and epigenetic regulation of cells in the entorhinal cortex (ENT) of 2‐month and 8‐month‐old 5xFAD and WT mice (n = 2 for each age, condition), and used publicly available single‐nucleus RNA‐seq data from the ENT of patients with and without AD. We used CellChat and the new package NeuronChat to explore how intercellular communication networks change between healthy and AD humans and mice. Based on these results, we then explored relationships between chromatin accessibility and gene expression for genes of interest.ResultWe observed changes in cell‐cell communication between AD and healthy samples in both mice and humans, particularly in the later stages of disease. The most prominent change was increased signaling from astrocytes to glutamatergic neurons in AD (Figure 1). This relationship included upregulation of neuroligin and ephrin‐A‐mediated signaling in AD, both previously implicated in synaptic regulation. In inter‐neuronal communications, the pathways most significantly disrupted in both human and mouse neurons were related to glutamatergic signaling. Multiple types of glutamate receptors were upregulated in both AD patients and 5xFAD mice in glutamatergic neurons, while GABAergic signaling did not appear to change. This finding is consistent with the hypothesis that glutamatergic neurons are hyperactive in AD and extends these observations by providing a potential mechanistic explanation of this phenomenon.ConclusionOur results indicate that in patients with AD and 5xFAD mice, dysfunction of the glutamatergic system is a prominent feature of pathogenesis and includes both inter‐neuronal signaling and communication with astrocytes. These results provide a series of testable hypotheses to explore the consequences of the transcriptional and epigenetic changes on the circuit dysfunction observed in AD.
Older Adults’ Awareness and Perceptions of Blood Biomarker Testing for Alzheimer’s Disease: Results from the US National Poll on Healthy Aging (NPHA)
Authors: Roberts J. Scott , Cox Chelsea G. , Kirch Matthias , Malani Preeti N. , Singer Dianne C. , Solway Erica , Kullgren Jeffrey T. 
Published: December 2023

AbstractBackgroundBlood‐based biomarker testing (BBT) to detect amyloid‐beta and tau is becoming part of dementia care, with likely future use in asymptomatic populations. Little is known about older adults’ awareness of and experiences with BBT, or their perceptions of its potential benefits, risks, and limitations.MethodWe analyzed data from the March 2023 NPHA, a recurring nationally representative web and telephone survey of community‐dwelling US adults aged 50‐80. For this substudy, respondents aged 65‐80 were provided a brief definition of BBT for AD and asked about: 1) their familiarity and experiences with BBT, 2) perceptions of its pros and cons, and 3) their likely responses if they tested positive. For comparative purposes, a parallel set of questions was posed about cognitive screening. Chi‐square analyses assessed differences in responses to the two types of testing (BBT vs. cognitive screening), as well as demographic differences in responses to items regarding BBT (significance level p < .05).ResultOf 1,296 respondents, 19% said they were at least somewhat familiar with BBT, with 0.6% reporting having undergone BBT. Overall, respondents were more likely to endorse test pros than cons (e.g., 76% said BBT could be useful to inform medical care or advance planning). Women were more likely than men to say they’d respond to a positive BBT result with significant distress (21% vs. 10%) and engagement in brain health behaviors (67% vs. 56%), with men more likely to endorse concerns regarding privacy of test results (38% vs. 27%). Overall, BBT beliefs were similar to those about cognitive screening, although respondents were less likely to agree that BBT should be offered annually to all older adults (51% vs. 60%) and more likely to believe a positive test result would mean they’d be likely to develop AD (74% vs. 65%).ConclusionMost US older adults are not currently familiar with blood biomarker testing for AD but view it as potentially useful for informing medical care and health behaviors to reduce AD risk. Women may respond differently to BBT results than men, with future studies needed to examine the process and impact of disclosing test results.
Facebook interaction as a potential marker of cognitive decline
Authors: Qansuwa Esraa M 
Published: December 2023

AbstractBackgroundThe growth of social media and the continuous improvement of machine‐learning algorithms suggest that social media‐based screening methods for mental diseases will become increasingly feasible with high accuracy in the next few years. Additionally, artificial intelligence, particularly predictive machine learning (ML) Models, has been established as one of the more powerful approaches to building reliable models that might be useful as an early predictor for Mental disorders. Specifically, one of the current challenges in brain disorders is identifying patients with mild cognitive impairment (MCI) that might be converted to Alzheimer’s (AD) or other types of dementia. Cognitive decline in older adults is associated with decreased social interaction and changes in other features. We aim to use vast quantities of historical Facebook data from participants who conducted the MoCA test as a cognitive assessment test to examine if there are changes in their language mistakes and in a range of psychological features derived from natural language processing use and social engagement over time as a sign of MCI.MethodTo develop a Machine learning model to predict MCI using (n = 225), we should first consider how we can formulate Language mistakes and social interactions. Then, we aim to perform a longitudinal and cross‐sectional examination of the data to examine the changes in a range of features extracted from Facebook subjects’ data over time, using NLP algorithms, LIWC 2022, Go‐emotion dataset, and supervised Classification ML tools, such as support vector machine model (SVM).ResultWe are collecting identified Facebook data, de‐identifying it, translating the Arabic text into English, processing text augmentation and text preprocessing, defining language mistakes, social engagement over time features, and sentiments impeded in each syntax. Our classification model SVM shows significant prediction results, differentiating between patients (MCI& dementia) and normal subjects, using a sample of 225 subjects, resulting that the SVM prediction test score is 70%.ConclusionUsing our suggested pipeline, Our classification model SVM shows promising primary results in building a predictive model that has the ability for early detection of MCI.
Impact of the COVID‐19 Pandemic on Dementia Research Participants
Authors: Zhao Chen , Harvey Danielle J. , Whitmer Rachel A. , Meyer Oanh L. , Farias Sarah Tomaszewski , Decarli Charles 
Published: December 2023

AbstractBackgroundThe impact of COVID‐19 on Alzheimer’s disease and related dementias (ADRD) research participation is not fully known. Individual differences in stress and coping may impact research findings (Goldfarb, 2020). It is possible that participants with questionable cognitive impairment (QCI) may be more vulnerable to stress and loss to follow up. The objective of this study is to examine the differential impact of the COVID‐19 pandemic on dementia research participants among individuals with varying degrees of cognitive impairment.MethodThe COVID‐19 impact survey was mailed to participants of the UC Davis Alzheimer’s Disease Research Center (ADRC) in August 2020. The survey asked questions related to feelings about the pandemic and how it impacted willingness to participate in research. Fisher’s exact test was used to compare responses across diagnostic groups. All analyses were conducted using SAS software, version 9.4.ResultOf 115 participants (69.6% female, 52.2% non‐White), 38 had normal cognition, 38 had questionable cognitive impairment (QCI; defined as having one or more neuropsychological tests that was slightly low but did not rise to the threshold of impairment), 16 had mild cognitive impairment (MCI), and 22 had dementia (Table 1). Overall, 9% of the participants were very or extremely worried about getting COVID‐19, 19% felt very or extremely isolated, 36% felt the pandemic had been very or extremely disruptive. The pandemic changed willingness to participate in research at least a little for 50% and very much or extremely for 13%. Impaired participants (either MCI or dementia) were less concerned about getting COVID‐19 and felt less isolated than those with normal cognition or QCI (Table 2). A higher percentage of those with QCI (vs. normal cognition or impaired groups) felt that the pandemic was very or extremely disruptive. Although not statistically significant, a higher percentage of those with QCI also reported that the pandemic changed their willingness to participate in in‐person research very much or extremely.ConclusionThe COVID‐19 pandemic was more disruptive to participants with QCI than participants with normal or impaired cognition. More research is needed to evaluate the impact of the pandemic on dementia research participants.
Chaperone interventional therapy restores proteostasis, improves cognition and increases ADAM10 in young and aged APP knockin mice
Authors: Hafycz Jennifer , Strus Ewa , Naidoo Nirinjini 
Published: December 2023

AbstractBackgroundTwo distinct phenotypes of Alzheimer’s disease are deficits in cognition and proteostasis, including chronic activation of the unfolded protein response (UPR) and aberrant Aβ production. The UPR is a signal transduction pathway activated in the endoplasmic reticulum (ER) at the onset of proteostatic stress. With age the UPR is less efficient and the expression of the key regulator, the chaperone BiP / Hspa5, also declines. It is unknown if restoring proteostasis by reducing chronic and aberrant UPR activation in AD can improve pathology and cognition. Here, we present data using an APP knock‐in mouse model of AD and several small molecule chaperone supplementation paradigms, including an early and late‐stage intervention.MethodTransgenic APP knock‐in mice were used as a model for AD. Two groups of mice and their wildtype littermates, (treatment starting early at 1‐2 mos old and late at 12 mos old) were administered the chemical chaperone 4‐phenyl butyrate (PBA) by weekly I.P. for 10 weeks. Controls were given I.P. injections of sterile saline. After 10 weeks of PBA or saline treatment, mice were subjected to the Spatial Object Recognition (SOR) cognitive tasks. A third group of APP knock‐in mice and wildtype littermates were given stereotaxic local hippocampal AAV‐BiP overexpression or AAV‐mCherry control injections. Following recovery and viral expression, mice were subjected to the SOR test. All mice were perfused, and tissue was collected for both immunohistochemistry and biochemical analyses.ResultPBA treatment improved performance in the SOR test both with early and late‐stage PBA interventions. AAV‐BiP overexpression recapitulated those results. Histological data indicates that chaperone treatment, both with PBA injections and AAV‐BiP overexpression, reduced hippocampal ER stress and was correlated with increased pCREB. Chronic PERK activation which leads to inhibition of protein translation was reduced, while XBP1s levels were increased with chaperone treatment. This was coupled with increased ADAM10, which is associated with non‐amyloidogenic cleavage of APPConclusionReducing proteostatic stress even at a late age improves cognition in a mouse model of Alzheimer’s disease. The implications of these results could have an impact on the development of therapies to inform the development of potential treatments for Alzheimer’s disease.
Therapeutic Modulation of WASH Complex‐Retromer Interactions is a Novel Target for Alzheimer’s Disease (AD)
Authors: Yilmaz Gokhan Nathan 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Although production and accumulation of amyloid beta (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of AD, monoclonal antibodies targeted against the Aβ oligomers have failed to modify the disease progression clinically despite confirmed target engagement. Here we present, characterization of 3xTg‐AD mouse model treated with an engineered recombinant tandem protein consisting of a WASH complex member FAM21 linked with Retromer complex member VSP35 in order to stabilize these intrinsically disordered proteins. In addition, we present complete rescue of autophagic flux deficiencies and lipid accumulation phenotypes seen in iPSCs (from non‐familial AD patients)‐derived neurons and microglia with this therapeutic tandem protein. We will discuss our findings as a novel disease modifying treatment for Alzheimer’s Disease.MethodBy using proteomics, biochemical analysis and iPSCs‐derived neurons and microglia, we have characterized a recombinantly produced fusion protein’s (FAM21/VPS35) utility in reduction of the accumulation of soluble amyloid β oligomers; resolution of autophagic flux deficiencies and misfolded protein burden and neural degeneration in vitro and 3xTg‐AD in vivo model of AD.ResultTreatment of 3xTg‐AD mice and iPSCs‐derived neurons and glial cells with a novel recombinant therapeutic protein resulted in a statistically significant reduction of accumulation of soluble amyloid Aβ oligomers and neural degeneration; reversal of autophagic flux and lipid deregulation.ConclusionTherapeutic modulation of WASH Complex‐Retromer interactions merits further analysis especially in early AD & mild cognitive impairment for its potential neuroprotective and disease modifying effects.