bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges when monitoring and providing care to loved ones,Perspectives of Dementia caregivers in Canada
Authors: Chowdhury Fariha , Dauphinee Dale , Luy Luis , Macaulay Susan , Masoud Sara , Mayo Nancy , Na Eunjung , Rhayel Ashwak , White Carole L , Kuspinar Ayse 
Published: December 2023

AbstractBackgroundFamily caregivers see firsthand the progression of their care recipient’s dementia and know every aspect of their lives and needs. They make important decisions on interventions and care. Currently, there are no measures that account for caregivers’ perspectives when evaluating the impact of dementia or interventions. The aim of this study was to explore the perspectives of caregivers’ of people living with dementia across Canada to generate domains for a new caregiver‐reported measure.MethodParticipants were recruited across Canada. Listening sessions were conducted virtually over three months, using open‐ended questions to encourage participants to share their perspectives. A semi‐structured interview guide was developed to facilitate the sessions. The interviewer asked questions to encourage caregivers to share their experiences on providing care, dementia monitoring, treatment impact and seeking alternative care. The data were coded and analyzed using NVivo. A thematic analysis approach was applied by two reviewers to analyze the data.ResultSeven listening sessions were conducted with 34 caregivers who were providing care to their loved ones with dementia. Seventy‐four percent of the participants were women and 59% had 6 or more years of caregiving experience. Each listening session included three to six caregivers and was approximately one hour long. Example of codes included gait limitations, distance walked, difficulties with memory, and changes in behaviour. Overall, data were organized into three broad themes (i) psychosocial impact of dementia, (ii) physical and emotional changes for dementia monitoring and treatment, (iii) symptomalogy changes for dementia monitoring and treatment.ConclusionThis study explored the perspective of caregivers across Canada, the activities and symptoms that are important to assess when evaluating dementia progression. It also questioned caregivers on how best to evaluate treatment effects. These findings may help identify strategies to better support caregivers and improve the quality of life of individuals living with dementia. Furthermore, the findings of this study can be a resource to help healthcare professionals, communities, and policymakers to provide better support for caregivers and the lives of individuals with dementia.
Detection of Brain‐derived Neurotrophic Factor Expression in Insulin‐Resistant SH‐SY5Y Neuroblastoma Cells
Authors: Nelson Mackayla 
Published: December 2023

AbstractBackgroundMore researchers are coining Alzheimer’s disease (AD) “type 3 diabetes” due to its significant comorbidity and shared pathology with type 2 diabetes mellitus (T2DM). A bi‐directional relationship between T2DM and AD exists, by which 50‐75% of individuals with T2DM have a greater risk of developing AD compared to non‐diabetes and that AD symptoms progress with impaired glucose utilization. Interestingly, brain‐derived neurotrophic factor (BDNF), a small protein that maintains neuron health and glucose homeostasis, has been implicated in both AD and IR. As such, this experiment investigates if insulin resistance (IR) alters BDNF expression in SH‐SY5Y neuroblastoma cells.MethodObjective 1: create a model of insulin resistance at 24, 48, 72 and 96 hours (hr) and determine expression of pAkt (S473), tAkt, insulin receptor b (INSRB) and pINSR (T1362) on Western blots. (n = 5)Objective 2: Detect mRNA and protein BDNF via Rt‐PCR and Western blotting. (n = 5)Objectives 3: Determine alterations to BDNF expression via Western blotting and qPCR. (n = 5)ResultLevels of pAkt expression were significantly decreased in insulin‐pretreated and activated samples at each timepoint of 24, 48, 72 and 96 hr; although, with each timepoint, pAkt does appear to steadily increase. pro‐BDNF and mature BDNF were detected at their respective sizes, 27kDa and 19kDa, on a Western blot and BDNF mRNA was detected on an agarose gel after PCR.ConclusionIt appears that insulin resistance is occurring at 24, 48, 72 and 96 hr solely based off Akt expression. This result will be further confirmed with the the completion of INSR‐B and p‐INSR blots. Ongoing experiments include western blots and qPCRs of BDNF to determine if there is any alteration to expression.
The relevance of tract‐specific white matter hyperintensity burden to clinical impairment in groups at risk of Alzheimer’s disease
Authors: Heyman Cameron C , Morgan Catherine A , Stones Richard , Dell'Acqua Flavio , Manson Tabitha , Roberts Reece P , Kirk Ian J , Melzer Tracy R , Heron Campbell J Le , Dalrymple‐Alford John C , Anderson Tim J , Cutfield Nick J , Tippett Lynette J ,   the NZ‐DPRC
Published: December 2023

AbstractBackgroundWhite matter hyperintensities (WMHs) are common in normally functioning older adults. While greater WMH volume may be associated with an increased risk of cognitive dysfunction and dementia, the impact of the location of WMHs is less well understood. We investigated whether WMH burden in specific white matter (WM) tracts is associated with clinical classification and global cognitive scores in at‐risk groups for Alzheimer’s disease (AD).MethodParticipants from Dementia Prevention Research Clinics, New Zealand, were classified as control, subjective cognitive decline, single‐domain amnestic mild cognitive impairment (MCI), multiple‐domain amnestic MCI, or early AD by a multidisciplinary team (Table 1). Several tract‐WMH “overlap scores” (the percentage of total tract voxels containing WMHs) were calculated for each participant’s binarised WMH map (Lesion Segmentation Toolbox, SPM) using seven tract probability templates from a 140‐subject tract atlas (www.megatrackatlas.org). Tract templates were of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), inferior fronto‐occipital fasciculus (IFOF), uncinate fasciculus (UF), cingulum (CB), fornix, and corpus callosum (CC). Between‐group differences in overlap scores were tested with ANOVAs. Pearson’s correlations examined associations between tract‐WMH overlap and global cognitive scores.ResultFigure 1 shows WMH overlap with one tract, the IFOF, in a representative participant. Considering the whole sample, the highest tract‐WMH overlap scores can be seen in the IFOF and CC. Significant between‐group differences were found for the SLF, ILF, IFOF, UF, and CC (p < .05), but not the CB or fornix (Fig. 2), with significant linear trends describing the relationship between overlap scores and clinical classification. Post‐hoc tests confirmed significant pairwise comparisons for overlap scores in all aforementioned tracts except the SLF (Fig. 2). We found Addenbrooke’s Cognitive Examination‐III scores negatively correlated with overlap scores in the ILF (r = ‐0.19), IFOF(r = ‐0.22), UF(r = ‐0.22), and CC(r = ‐0.19) (all p < .01), but not the SLF, CB, or fornix (p > .05).ConclusionOur findings highlight that WMH burden within specific WM tracts is associated with degree of clinical impairment in groups at‐risk of AD. Future research will investigate relationships between overlap scores in specific WM tracts and executive functioning, episodic memory, and processing speed performance.
“By Any Means Necessary”: Understanding the willingness of African‐American and American Indian/Alaska Native communities to engage in genetic and biomarker research: The UBIGR Study
Authors: Gooding Diane C. , Umucu Emre , Van Hulle Carol A. , Zuelsdorff Megan , Carter Fabu P. , Lewis Jordan P. , Bouges Shenikqua , James Taryn T. , Salazar Hector , Floyd Lytonia , Bester James , Gleason Carey E. 
Published: December 2023

AbstractBackgroundResearch investigating underrepresented groups’ willingness to engage in research has largely relied on qualitative research and/or specialized samples (e.g., patients’ first‐degree relatives). Moreover, extant quantitative studies include disproportionately small numbers of these participants. This investigation is from an ongoing project whose overall goal is to understand biomarker and genetic Alzheimer’s disease (AD) and schizophrenia research participation in underrepresented groups (UBIGR Study), to facilitate greater diversity in future biomarker research and clinical trials. We extended knowledge by including community‐based participants, more racialized participants, and utilizing quantitative methods.MethodWe administered an online questionnaire to 1444 adults. Focusing exclusively on data pertaining to AD detection, we assessed demographic characteristics as well as participants’ views on dementia, research, and genetic and biomarker testing. We tested our conceptual model (Figure 1) with structural equation modeling (SEM; SPSS AMOS). Our model consisted of demographic covariates (gender, education, family history of AD dementia), racial‐ethnic identity group, knowledge about AD, stigma, willingness to undergo any type of AD biomarker testing (outcome variable). Not implying white to be the standard, we created a BIPOC variable (Black, Indigenous, Person of Color) to examine differences based on Black/African American and American Indian/Alaska Native vs. White identity. A stigma score was derived from 5 questions. The knowledge score was based on 2 questions. The specific survey item used as the outcome measure asked for agreement with the statement: “I would be willing to undergo any type of testing necessary if it was the only way to find out if I was at risk for AD before there were any symptoms,” answered on a Likert scale (1 = strongly disagree – 7 = strongly agree)ResultParticipants were mostly male and middle‐aged (Table 1). Path analysis revealed an excellent model fit, χ2(6, N = 1444) = 14.203. See Figure 2 for paths and factor loadings.Conclusion1. BIPOC participants in our nonpatient, non‐research sample were less willing to undergo testing than White participants. 2. Stigma and knowledge regarding AD are influential and modifiable factors underlying research willingness. Findings indicate need for outreach and engagement programs to occur before attempting research recruitment, particularly with BIPOC populations.
Could differential under‐reporting of loneliness between men and women bias the gender‐specific association between loneliness and memory aging? A quantitative probabilistic bias analysis
Authors: Yu Xuexin , Zahodne Laura B. , Gross Alden L. , Needham Belinda L , Langa Kenneth M , Cho Tsai‐Chin , Kobayashi Lindsay C 
Published: December 2023

AbstractBackgroundLoneliness is associated with later‐life dementia risk, with conflicting findings on gender as an effect modifier. The causality of this effect modification is difficult to assess, as men may have a lower propensity than women to admit loneliness potentially due to self‐perceived “masculinity”, leading to distorted gender‐specific estimates. We aimed to estimate the potential magnitude of information bias due to differential loneliness under‐reporting by gender in the gender‐specific associations between loneliness duration and memory aging.MethodData were from respondents aged ≥50 in the US Health and Retirement Study from 1996‐2016 (N = 9,032). We conducted quantitative probabilistic bias analyses to simulate various bias‐parameter selections and reclassify loneliness status (yes; no) at the record level as measured biennially from 1996‐2004. We used sensitivity values of loneliness self‐reports of 0.20‐0.45 among men and 0.30‐0.55 among women, and specificity values of 0.90‐1.00, as informed by a validation analysis. We ran mixed‐effects linear regression models on the corrected data with a three‐way interaction between loneliness duration (0, 1, 2, or ≥3 time points), years of follow‐up (0‐12), and gender (men; women) to test gender differences in the association between loneliness duration and memory decline (100 replications).ResultCompared to the uncorrected estimate (‐0.008), mean estimates of the three‐way interaction attenuated in magnitude, ranging from ‐0.006 (sensitivity 0.40‐0.45 for men and 0.50‐0.55 for women) to ‐0.001 (sensitivity 0.20‐0.25 for men and 0.30‐0.35 for women; see Figure 1). Approximately 64%, 84%, 96%, and 100% of simulation estimates remained negative while holding sensitivity distribution at 0.20‐0.25, 0.25‐0.30, 0.30‐0.35, and >0.35 among men, respectively.ConclusionThe likelihood of observing gender‐specific loneliness‐memory relationship reduces as sensitivity values of loneliness self‐reports declines.
Development of a neuroimaging biomarker of the pro‐coagulant state in Alzheimer’s disease: The BioClotAD Project
Authors: Casquero‐Veiga Marta , Cerón Carlos , Herreros‐Pérez Desiré , Fernandez‐Nueda Irene , Kossatz Susanne , Sehlin Dag , Desco Manuel , Salinas Beatriz , Cortes‐Canteli Marta 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common form of dementia1. Its multifactorial profile includes a strong vascular factor, partially driven by an early haemostatic dysregulation. Accordingly, fibrin, the main protein component of blood clots, is significantly increased in AD‐patients’ brains2. Furthermore, amyloid‐β contributes to this process by interacting with fibrin and producing degradation‐resistant clots3. Consequently, this pro‐thrombotic milieu intensifies hypoperfusion, neurodegeneration and blood‐brain barrier (BBB) disruption4, but it does not affect all patients. Therefore, early detection of these phenomena would be invaluable to identify patients likely to benefit from anticoagulant therapies5. Therefore, the BioClotAD Project aims to develop an imaging biomarker based on a fibrin binding probe (FBP)6 to non‐invasively identify AD’s pro‐coagulant state.MethodBioClotAD involves four partners in three European countries with complementary expertise. To optimize and test FBP we use extensive in vitro, ex vivo and in vivo assays, including AD animal models and human AD samples. Our project is comprised of three blocks: 1) Testing the FBP to in vivo detect the cerebral occlusions by nuclear imaging. 2) Detecting fibrin deposits inside the brain parenchyma with FBP coupled to a transferrin receptor antibody (FBP‐TfR) to facilitate BBB crossing7. FBP‐TfR will be labelled for optical and nuclear imaging. 3) Validating the most promising FBP probes in frozen brain samples of AD patients by autoradiography or fluorescence microscopy.ResultBioClotAD provides feasible neuroimaging strategies to in vivo detect the fibrin cerebral accumulation of AD models and identify the specific regional distribution in the brain. Our project will set the basis for future clinical trials on neuroimaging of the cerebral fibrin accumulation in AD.ConclusionBioClotAD neuroimaging biomarkers will allow the early detection of the pro‐thrombotic state in AD, opening a window of opportunity to delay the disease progression by personalized anticoagulant therapies.
Funding: EU Joint Programme – Neurodegenerative Disease Research (JPND)References1. Alzheimer’s Association. 2021. https://www.alz.org/media/documents/alzheimers‐facts‐and‐figures.pdf.2. Cortes‐Canteli, et al. 2015. https://doi.org/10.1016/j.neurobiolaging.2014.10.0303. Petersen, et al. 2018. https://doi.org/10.1038/nrn.2018.134. Cortes‐Canteli, et al. 2012. https://doi.org/10.3233/JAD‐2012‐1208205. Cortes‐Canteli, et al. 2019. https://doi.org/10.1016/j.jacc.2019.07.0816. Oliveira, Caravan. 2017. https://doi.org/10.1039/c7dt02634j7. Sehlin, et al. 2019. https://doi.org/10.1007/s00259‐019‐04426‐0
What causes relative difficulties with technology and non‐technology based activities of daily living in those with ADRD?
Authors: Benge Jared , Ali Arsh , Gonzalez David A. , Kiselica Andrew M , Scullin Michael K , Hilsabeck Robin C. 
Published: December 2023

AbstractBackgroundDigital skills are critical to performing a host of instrumental activities of daily living (iADLs) in the 21st century. For example, financial management activities increasingly rely on managing accounts online, social interactions are frequently mediated by technologies like text messaging and social media, and critical health and commerce activities occur via tech enabled platforms. Despite the ever increasing importance of technology related iADLs to real world functioning, there are concerns that the digital divide may disproportionately impact those with ADRD making the modern technological environment more difficult to navigate. The current study explored two broad questions: 1) how do relative difficulties with tech iADLs relate to demographic factors and diagnostic staging?, and 2) what cognitive difficulties predict relative difficulties technology versus traditional iADL performance?MethodCare‐partners of 135 older adults (mean age 75.3 years (sd = 7.9); 10.5% with no cognitive disorder diagnosis, 37.0% with mild cognitive impairment; 51.1% with dementia) referred to a comprehensive interprofessional memory clinic for neuropsychological evaluations completed both the Functional Activities Questionnaire (as a measure of traditional ADL performance) as well as a series of 11 technology based iADL items (i.e. remembering passwords, managing online accounts, etc). In addition, clinic patients completed a battery of neuropsychological measures.ResultWhile decreasing performance in both traditional and technology iADLs were noted with the transition from MCI to dementia, diagnostic stage (Figure 1), age, and verbal memory performance did not predict disproportionately greater difficulties with tech iADLs relative to overall iADL performance. However, lower education (B = ‐1.77; p = .003; Figure 2), and more difficulties with cognitive set shifting (B = 1.03; p = .0116; Figure 3) predicted greater relative difficulties with tech iADLs.ConclusionIn our current sample, relative difficulties with technology related iADLs was associated with greater executive dysfunction and less educational attainment. These factors may identify individuals with ADRD at particular risk for having difficulties navigating an ever more technologically enriched environment. Implications for helping those with ADRD cross the digital divide, clinical assessment, and technology based interventions for ADRD are discussed.
Sentiment Analysis on Household Audio Conversation with Automated Chatbot for Hospital Visits Prediction
Authors: Su Ting , Jouaiti Melanie , Vaidyanathan Ravi 
Published: December 2023

AbstractBackgroundPeople living with dementia (PLwD) often experience difficulties describing their physical conditions and seeking medical attention timely, resulting in hospital visits that may cause frustration and exhaustion. Therefore, we aim to develop a machine learning model that helps identify potential hospital visit needs to provide early medical attention for PLwD.MethodPortable smart chatbots are deployed to PLwD households. We collected audio clips between households and chatbots and the hospitalisation records of PLwD. We manually labelled the sentiment scores of each audio clip based on its content and tone to between ‐3 and 3, where ‐3 indicates very negative, 0 indicates neutral, and 3 indicates very positive. We use 10 days of sentiment scores on a minute basis (0 when there’s no interaction) to predict the need for hospital visits in the following days. The positive outputs indicate that hospital visits happened within the 5 following days, while the negative outputs indicate no hospital visits occurred. A gradient boosting model (GBM) is trained to predict if hospital visits will happen in the following 5 days. We evaluated the trained model using the cross‐validation (cv = 5) method and reported Accuracy, Sensitivity, Specificity and macro F1 score.ResultBetween May 13th, 2021, to June 5th 2022, we collected 14 PLwDs’ hospital visit records and 12,278 audio clips between their households and their chatbots. Among all the participating households, we constructed a total of 3065 days as training and testing data (albeit no activities some days), with 37 hospital visit occurrences. This results in 139 days where hospital visits occurred in the following 5 days. The GBM model classified the need for hospital visits in the following 5 days with 0.682 Accuracy while obtaining 0.890 in Sensitivity, 0.669 in Specificity, and 0.522 in F1 score.ConclusionSentiment scores obtained by analysing audio clips between households of PLwD and their chatbots can be used to predict hospital visits in the following 5 days, with 0.890 in Sensitivity. This can help health professionals to provide more timely care to PLwD without frequent home visits. However, further research is needed to improve the Specificity and F1 of the predicting model.
Interaction between Hippo Pathway Elements and the E3‐ligase CHIP regulate a potential marker of Alzheimer`s disease
Authors: Suluova Melek , Nita Erisa , Ball Kathryn 
Published: December 2023

AbstractBackgroundThe transcriptional coactivator YAP‐1, a known CHIP substrate that has a role in the regulation of adaptation to cellular stress, cell size and metabolism, was investigated as a potential link between CHIP and VGF.MethodPreviously, CRISPR‐Cas9 method was used to create CHIP KO neuroblastoma cell line. Then, SWATH‐MS experiment was applied to get proteomic data of CHIP KO and WT neuroblastoma cells. Validation of data analysis done by immunoblot and IF. Following gene manipulations were applied by transfection of RNAi and following assessments done by immunoblot and IF.ResultAccording to our proteomic analysis, CHIP KO neuroblastoma cells have 10X more VGF protein than isogenic WT cells. YAP1 was expressed at high levels in the nucleus of CHIP KO neuroblastoma cells and manipulation of YAP1 impacted on the expression of VGF.ConclusionAs VGF is an Alzheimer’s disease biomarker, discovering mechanisms of VGF regulation could support efforts to find new targets for the development of disease modifying drugs.