bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary performance of the Lumipulse G pTau 217 Plasma prototype assay on plasma samples
Authors: Vandijck Manu , Dekeyser Filip , Lambrechts Charlotte , Hasumi Yurina , Van Loo Maxime , Accou Flore , Sato Hideo , Inaoka Daigo , Nojima Hisashi , Degrieck Rosina , Bastard Nathalie Le , Vanbrabant Jeroen , Stoops Erik , Vandenbroucke Ina 
Published: December 2023

AbstractBackgroundMultiple publications demonstrated that plasma pTau species (e.g., 181, 217, and 231) have the potential to be a good predictor of amyloid status by either PET or cerebrospinal fluid (CSF). Such blood‐based biomarker testing could be used as a simple, accessible, and scalable approach to help support the diagnosis of Alzheimer’s disease (AD), avoiding the complexity of CSF sampling, and the high costs and limited availability of PET imaging. Multiple plasma pTau assays, established on different immunoassay platforms, are currently being evaluated in research settings with variable outcomes in terms of analytical and clinical performance. At Fujirebio, an assay for the measurement of plasma pTau217 was developed on the LUMIPULSE G platform to complement the commercially available plasma pTau181 RUO assay. The aim of this study was to determine the preliminary performance of the Lumipulse G pTau 217 Plasma prototype assay.MethodThe LUMIPULSE G System is a fully automated chemiluminescent enzyme immunoassay platform processing samples in ready‐to‐use immunoreaction cartridges in about 30 minutes. The assay uses an in‐house developed monoclonal antibody for capturing of pTau217. Analytical assay characteristics such as sensitivity, precision and dilutional linearity were determined. The analytical studies included a series of buffer and K2EDTA plasma samples, each tested in several replicates. Preliminary clinical performance was explored on a small set of patient and control samples.ResultAll analytical parameters tested were within the acceptance criteria. All clinical samples tested had a result above the limit of quantification (LoQ). The LoQ was obtained based on the evaluation of low concentrated plasma pTau217 samples. Imprecision was less than 15% CV on buffer‐based as well as plasma samples. Dilutional linearity on spiked samples was within ±20%. The Lumipulse G pTau 217 Plasma prototype assay outperformed the Lumipulse G pTau 181 Plasma RUO assay in a ROC curve analysis of clinically typed patients and controls.ConclusionThis preliminary performance evaluation of the Lumipulse G pTau 217 Plasma prototype assay indicated good results in terms of high sensitivity, low variability, dilutional linearity and clinical capability. More studies on well‐characterised and diverse cohorts are needed to confirm the assay’s clinical performance.
Baseline Frailty and Domain‐specific Cognitive Declines in Healthy and MCI Older Adults
Authors: Liu Albert C. , Chiang Grace Shu Hui , Carlson Michelle C , Xue Qian‐Li 
Published: December 2023

AbstractBackgroundBoth physical frailty and cognitive decline increase with age and each place adults at elevated risk for loss of independence. Inconsistent associations have been found between frailty and risk for cognitive declines across cognitive domains. However, most studies were cross‐sectional and did not include a comprehensive battery of neuropsychological tests. We hypothesized that frail older adults, whether with or without Mild Cognitive Impairment (MCI) at baseline, are at risk for accelerated domain‐specific cognitive declines.MethodThe Ginkgo Evaluation of Memory Study (GEMS) was a prospective study of 3069 dementia‐free older adults aged 72‐96 years, followed for up to 7.5 years or a diagnosis of dementia, 482 of whom were diagnosed with MCI at baseline. A modified physical frailty phenotype was constructed using GEMS baseline data. A Neuropsychological Battery consisted of 13 tests reflecting global cognition, memory, visual‐spatial construction, language, psychomotor speed/attention, and executive function were administered annually. Linear random effects models were used to compare differences in baseline and rate of change in domain scores among individuals with and without baseline frailty.ResultOverall, frail participants showed poorer baseline cognitive function in all domains, and greater declines in all cognitive domains. When stratified by baseline MCI, among non‐MCI participants, those with frailty revealed poorer baseline psychomotor speed/attention and executive function, and greater declines in all cognitive domains. Among MCI participants, those with frailty exhibited lower baseline visual‐spatial construction, and greater declines in all cognitive domains except for visual‐spatial construction and executive function. In all cognitive domains, the estimated effect of frailty on cognitive decline was greater in MCI participants than non‐MCI participants.ConclusionFrailty was predictive of accelerated cognitive declines across domains and more so in those with baseline MCI. The results from this study highlight the importance of assessing frailty as a risk factor for accelerated cognitive declines, particularly among those at elevated preclinical cognitive risk. These individuals may be at the greatest risk of transitioning to dementia.
Alzheimer’s disease biomarker profiling in a memory clinic cohort without common comorbidities
Authors: Daniilidou Makrina , Eroli Francesca , Alanko Vilma , Goikolea Julen , Leal Maria Latorre , Rodriguez Patricia Rodriguez , Griffiths William J , Wang Yuqin , Pacciarini Manuela , Brinkmalm Ann , Zetterberg Henrik , Blennow Kaj , Rosenberg Anna , Bogdanovic Nenad , Winblad Bengt , Kivipelto Miia , Ibghi Delphine , Minguez Angel Cedazo , Maioli Silvia , Matton Anna 
Published: December 2023

AbstractBackgroundComorbidities such as hypertension, hypercholesterolemia and diabetes are known contributors to Alzheimer disease (AD) progression. However, their mechanistic contribution to pathology and neurodegeneration has not been clarified. The aim of this study was to investigate cerebrospinal fluid (CSF) levels of markers reflecting brain changes in synaptic integrity, inflammation, oxidative stress, glucose homeostasis and cholesterol metabolism in memory clinic patients without known AD comorbidities.MethodCSF samples from 90 memory clinic patients without diagnosed hypertension, hypercholesterolemia, or diabetes nor other neurodegenerative disorder, were used to investigate 13 molecular markers representing key mechanisms underlying AD pathogenesis. Associations were analyzed by linear regression. Two‐step cluster analysis was used to determine patient clusters. Two key markers were analyzed by immunofluorescence staining in hippocampus from control and AD individuals.ResultCSF angiotensinogen, thioredoxin‐1, and interleukin‐15 had the most prominent associations with AD pathology, synaptic and axonal damage. SNAP‐25 and NFL were increased in MCI and AD cases. Grouping biomarkers by biological function, showed that inflammatory and survival components were associated with AD pathology, synaptic dysfunction and axonal damage. Moreover, a vascular/metabolic component was associated with synaptic dysfunction. In data‐driven analysis, two patient clusters were identified; cluster 1 had increased CSF markers of oxidative stress, vascular pathology and neuroinflammation and was characterized by elevated synaptic and axonal damage, compared to cluster 2. Clinical groups were evenly distributed between the clusters. Analysis of post‐mortem hippocampal tissue, showed that, compared to non‐demented controls, angiotensinogen staining was higher in AD and co‐localized with phosphorylated‐tau.ConclusionThe identification of biomarker‐driven endophenotypes of cognitive disorder patients, further highlights the biological heterogeneity of AD and the importance of tailored prevention and treatment strategies.
Tele‐Dementia in Africa: Setting roadmap for implementation
Authors: Farombi Temitope Hannah , Akinyemi Rufus O. , Ogunniyi Adesola , Consortium Africa Dementia 
Published: December 2023

AbstractBackgroundAlzheimer’s disease and dementia related disorder incidence and prevalence continue to increase in Africa due to changing ageing demographics. Despite this rise, overall quality and quantity of available evidence to inform best practices in recruitment, retention and inclusion of underrepresented population in ADRD research is very low. Africa needs creative innovations to bridge the dementia care gap and telemedicine offers a unique opportunity for prompt diagnosis, follow up and care supportMethodThis was an observational study of remote video assessment of persons living with Dementia and their caregivers. Mobile phone and web‐based applications for virtual consultation and health information management system were built to engage patients with various clinical conditions across multiple specialties. The assessment and follow up were done between September 2020 and December 2022.Cognitive assessment tools were administered via telemedicine platform for screening and post diagnostic management due to the COVID‐19 lock downResultA total of 50 patients with Dementia and their caregivers attending Neurology clinic at the Geriatric centre UCH were engaged on the platform for clinical follow up. Mean(+SD) age of was 74.0(+7.2) year and 56% were females, 82.8% had some form of formal education, 67.2% married and 97.9 lived with other persons. Over 31.9% participants had at least one comorbidity. 93% of the participants expressed satisfaction with video conferencing platform. 87% retention rate on follow up on the platform,13% of drop out rate due to technical fault and poor internet connectionConclusionwe believe implementation of telemedicine will improve recruitment and retention of persons living with dementia and it offers a promising dementia management strategy for Africa
Including drawings in future dementia research: identification and modification of negative stereotyping
Authors: Bormans Kasper , Zwakhalen Sandra , Pate Melannie 
Published: December 2023

AbstractBackgroundMost countries in Western civilization are segregated societies with little or no contact between generations. Elementary schools and nursing homes are separated worlds in proximity. Children alienate further from the elderly and rely on indirect experiences with old age and dementia. The elderly can embody negative stereotypes from media and society leading to disparities in health care, social isolation and loss of functional ability.MethodIn this study we collected 796 drawings from 98 children in 4 elementary schools in Belgium and The Netherlands. The 10‐y‐old pupils made portraits of grandparents and the elderly in neutral, happy and unhappy conditions. The standardized drawing assignments were repeated after a psychosocial intervention program of 16 weeks to connect generations. The effects of non‐pharmacological interventions in Alzheimer’s research are mostly studied with classical questionnaires. These tools are insufficient to detect unconscious motives and subtle mental representations of old age and dementia. Before and after drawings are an added value to the field of research. The implicit measurements circumvent social desirability, go beyond the level of awareness and give a clearer picture of negative stereotypes of old age and dementia.ResultThe content analysis of the drawings demonstrated that children represent ‘happy elderly people’ as: outdoors, active, and surrounded by others, while ‘unhappy elderly people’ are generally portrayed indoors, sedentary and lonely.ConclusionChildren’s drawings as implicit measurement are an added value for non‐pharmacological interventions. The act of drawing is pleasant, easy and effective for the identification and modification negative stereotyping of old age and dementia.
Medical‐assistance in Dying (MAiD) for Dementia Patients in Canada and Netherlands: A Literature Review
Authors: Shrestha Lucy , Shrestha Hom Lal 
Published: December 2023

AbstractBackgroundDementia is the seventh leading cause of death worldwide. The notion of Medical‐assistance in Dying (MAiD) among dementia and Alzheimer’s patients has been legalized in Canada and Netherlands. However, there has been little research dedicated to clinical intervention and clinical ethics in MAiD as well as policy, legal, ethical barriers and challenges, and research gaps for physicians, dementia care specialists, healthcare providers, and carers. In Canada, MAiD accounts for 2.5% of all deaths, including dementia.MethodA comprehensive search in Google Scholar, PubMed, and the National Library of Medicine was conducted to discover evidence‐based MAiD practice, legislation, and ethical protocols among dementia and Alzheimer’s patients worldwide through peer‐reviewed research articles published between 2012 and 2022 that focused on quantitative, qualitative, and mixed methods. This includes MAiD education, clinical practices, legislation, attitudes and experiences of physicians, geriatricians, dementia care specialists and health care providers and barriers in MAiD in dementia for patients and their decision‐making capacity in the early or late stages of dementia.ResultThree Canadian studies demonstrate knowledge and experiences of dementia care specialists for advanced requests for MAiD in British Columbia; capture physicians' characteristics and attitudes toward MAiD for non‐competent dementia patients in Quebec; and reflect insight into the current practises of MAiD among dementia patients focused on their autonomy and mental capacity of consent in Canada. Studies in the Netherlands reveal physicians' experiences and workload, pressure and expectations of relatives and societies to access end‐of‐life options and care for MAiD; and argue on early vs. late stages in Dutch practices and decision‐making and consent among incompetent dementia patients.ConclusionThe roles of Alzheimer’s societies, stakeholders, MAiD assessors and providers, and social support systems are critical in educating, advocating for, and empowering dementia patients and carers to MAiD in the early and late stages. More research is needed to inform policymakers and legislators in developing a roadmap for educational interventions to MAiD assessors and providers, health care providers, medico‐legal practitioners, stakeholders, and family carers on ethical, cultural, spiritual, and legal issues, as well as legislative process related to MAiD any changes to the law in societies.
Transcriptomics similarities between Alzheimer’s Disease and Cardiovascular Disease
Authors: Da Ros Lucas Uglione , Bastiani Marco Antônio De , Lobato Lara Willers , Zimmer Eduardo R. 
Published: December 2023

AbstractBackgroundCardiovascular disease, such as coronary artery disease (CAD), is considered a risk factor for the development of dementia, especially due to Alzheimer’s Disease (AD). The mechanisms through which these two entities interact are not totally elucidated, even with some evidence indicating a role of microinfarcts and white matter lesions. CAD is a severe form of cardiovascular disease, in which the arteries that irrigate the heart are compromised. Here, we aimed to assess altered biological processes that are shared between CAD and AD using blood transcriptomics.MethodWe used the GEO repository to search for available transcriptomics studies of whole peripheral blood for CAD and AD; for CAD we selected GSE20680, GSE20681, GSE98583, GSE42148 and GSE12288, and for AD GSE63063 and GSE85426, together with the ADNI database. All CAD patients had angiographic confirmation of coronary stenosis. The data was downloaded using the GEOquery package and the differentially expressed genes (DEG) were defined as having p‐value < 0.05 and logFC > 0.27. We then proceeded to determine the intersection of DEGs present both in CAD and AD and these DEGs were submitted to Gene Ontology (GO) enrichment analysis using the clusterProfiler package (v3.16.1) and enrichGO function. GO terms were clustered using semantic similarity with the package GOSemSim. All analyses were performed in R.ResultWe found a total of 3561 DEGs for AD and 1873 for CAD, with an intersection of 352 of those. After the functional enrichment analysis, these were translated into 32 GO terms enriched in both diseases. These terms were clustered based on semantic similarity into 9 groups: myeloid cell differentiation; homeostasis of number of cells; positive regulation of I kappa B kinase/NF‐κB signaling; regulation of immune effector process; positive regulation of cell adhesion; positive regulation of proteolysis; positive regulation of cytokine production; phospholipid biosynthesis process; miscellaneous biological processes.ConclusionHere we provide evidence that shared systemic pathological changes, including inflammatory processes, may also contribute to the development of both cardiovascular disease and dementia.
APOEε4 potentiates the effects of Aβ pathology on the deposition of neurofibrillary tangles via tau phosphorylation
Authors: Ferrari‐Souza João Pedro , Bellaver Bruna , Ferreira Pamela C.L. , Benedet Andrea Lessa , Povala Guilherme , Lussier Firoza Z , Leffa Douglas Teixeira , Therriault Joseph , Tissot Cécile , Soares Carolina , Wang Yi‐Ting , Chamoun Mira , Servaes Stijn , Macedo Arthur C. , Vermeiren Marie , Bezgin Gleb , Kang Min Su , Stevenson Jenna , Rahmouni Nesrine , Pallen Vanessa , Poltronetti Nina Margherita , Cohen Annie , Lopez Oscar L. , Klunk William E , Soucy Jean‐Paul , Gauthier Serge , Souza Diogo O. , Triana‐Baltzer Gallen , Saad Ziad S. , Kolb Hartmuth C. , Karikari Thomas K , Villemagne Victor L , Tudorascu Dana , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Zimmer Eduardo R , Rosa‐Neto Pedro , Pascoal Tharick A. 
Published: December 2023

AbstractBackgroundThe mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences Alzheimer’s disease (AD) pathophysiological progression are poorly understood. Here, we tested the association of APOEε4 carriership and amyloid‐β (Aβ) burden with longitudinal tau pathology progression.MethodWe studied 104 individuals across the aging and AD clinical spectrum from the McGill TRIAD cohort. Study participants underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([18F]AZD4694) and tau ([18F]MK6240) at baseline, as well as an additional follow‐up tau‐PET scan (mean follow‐up, 2.4 years). We further assessed longitudinal changes in tau phosphorylation (plasma phosphorylated tau at threonine 217 [p‐tau217+]), brain atrophy (gray matter density), and clinical function (clinical dementia rating scale sum of boxes).ResultWe found that APOEε4 carriership potentiates Aβ effects on longitudinal tau tangle accumulation over two years (Figure 1). Interestingly, the APOEε4‐potentiated Aβ effects on tangles were mediated by longitudinal plasma p‐tau217+ increase (Figure 2). In addition, this longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline during the follow‐up period (Figure 3).ConclusionOur results support a model in which the APOEε4 allele plays a key role in Aβ downstream effects on the aggregation of phosphorylated tau in the form of neurofibrillary tangles in the living human brain, which is a key factor in the development of dementia. These observations have important implications for the design of future trials by suggesting that the combination of therapies targeting both ApoeE4 and Aβ pathology might have the potential to synergistically halt tau progression in AD.
Association of human brain‐age with genetically predicted plasma levels of brain rejuvenating and aging factors identified in mice
Authors: Anastasi Federica , Genius Patricia , Escalante Armand González , Rodríguez‐Fernández Blanca , Cumplido‐Mayoral Irene , Falcon Carles , Minguillon Carolina , del Campo Marta , Esteller Manel , Navarro Arcadi , Gispert Juan Domingo , Suárez‐Calvet Marc , Vilor‐Tejedor Natalia 
Published: December 2023

AbstractBackgroundAging is the primary risk factor for Alzheimer’s disease. Experiments in mice have identified circulating proteins with an “aging/rejuvenating” effect on the brain. However, whether these proteins have an effect on the human brain remains unknown. Here, we leverage genetic data to study links between the predicted plasma levels of these proteins and human brain age.MethodsThis study includes 1,394 cognitively unimpaired individuals of the ALFA study. Plasma proteins with an effect on mice brain aging were identified through a systematic review [Figure 1]. Summary statistics data of protein quantitative trait loci (pQTLs) associated to these proteins in human (inclusion threshold<5×10−5) were acquired from a previous study (Pietzner et al.,2021), and used for computing protein genetic scores (pPRS). For each ALFA cohort participant, DeltaAge scores was calculated by subtracting chronological age from MRI‐based estimation of brain age (Cumplido et al.,2022). Positive values are interpreted as brain age older than chronological age, and viceversa. The associations between brain DeltaAge measurements and pPRSs were assessed through general linear regression models stratified by sex, amyloid‐β (Aβ) status (CSF‐Aβ42/40<0.071 [Milà‐Alomà et al.,2020]) and APOE‐ε4 carriership. Results were reported for nominal and group‐correction (two experimental aging groups) level of significance (p<0.05, p<0.025, respectively). All pQTLs included in the significant pPRS were functionally annotated and an enrichment analysis was performed.ResultsGenetically predicted plasma levels of CSF2, VCAM1, HP, GHRH and BGLAP were associated with negative values of brain DeltaAge, while KLOTHO with positive values. Results for GHRH (Aβ+ and APOE‐ε4 non‐carriers) and BGLAP (APOE‐ε4 carriers) remained significant after p‐value correction, with an effect in agreement with their brain rejuvenation role as found in mice [Figure 2]. Enrichment analysis found immune response and complement activation processes associated with negative values of DeltaAge [Figure 3].ConclusionsThese results show that plasma levels of the brain aging/rejuvenating proteins discovered in mice may also influence human brain aging. In particular, genetically predicted levels of two rejuvenating factors in mice (BGLAP and GHRH) were associated with a younger brain age than chronological age. Follow‐up analyses will include protein level measurements to unravel the molecular complexity of brain aging.