bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical validation of the Eli Lilly SPX P‐tau217 blood‐based immunoassay as a laboratory‐developed test (LDT)
Authors: Hodsdon Michael , Abel Adam , Chambers Antonio , Lu Ming , Morris Amanda , Pontecorvo Michael , Reiske Heinz , Collins Emily C. , Mintun Mark , Schade Andrew E. , Beck Rose C. 
Published: January 2025

AbstractBackgroundBlood‐based biomarkers have significant potential to aid in the diagnosis of Alzheimer’s disease (AD), providing a more accessible option than cerebrospinal fluid testing or positron emission tomography (PET). This study evaluated performance of a plasma P‐tau217 immunoassay for identifying AD pathology as detected by amyloid or tau PET.MethodPlasma samples from screened participants from the donanemab Phase 3 trial (NCT04437511) were analyzed using a chemiluminescent immunoassay for plasma P‐tau217 on the Quanterix SP‐X platform. A Receiver Operating Characteristic (ROC) curve explored the relationship between plasma P‐tau217 values and positive amyloid PET (Aβ+), defined as 24.1 Centiloid (CL). A two‐threshold approach was used to propose P‐tau217 cut‐points that result in sensitivity and specificity each ≥90%; <20% of cases falling between the two cut‐off values (classified as indeterminate). Similar evaluation was performed for P‐tau217 against tau PET in a subset of participants.ResultPlasma samples from 2071 participants (mean age 73.1 [SD = 6.4 years], Mini Mental State Examination mean 24.8 [SD = 2.5], 53.3% female, 50.7% APOE ε4 carriers, 65% Aβ+) were examined. The area under the curve (AUC) for the ROC of plasma P‐tau217 identifying Aβ+ participants was 0.915 (Figure 1). Stratification of P‐tau217 concentrations into three levels using two P‐tau217 cut‐points resulted in an upper‐level group with 95% positive predictive value (PPV) for Aβ+ and a low‐ level group with 84% negative predictive value (NPV) for Aβ‐, with a false positive rate of 7.5% and a false negative rate of 7.3% (Table 1). The remaining indeterminate group represented 18% of participant samples, of which 60% were Aβ+. Within this cohort, 359 participants had available tau PET results. Preliminary analysis revealed 93% ROC AUC for P‐tau217 against tau PET visual read (Figure 2).ConclusionThe presented plasma P‐tau217 assay has high concordance with amyloid PET for identification of amyloid pathology, indicating its potential utility in the diagnostic workup of AD. Preliminary analysis demonstrated a relationship between plasma P‐tau217 and tau PET; however, additional work is needed to establish the assay’s diagnostic performance for tau pathology.
The power of cognitive rehabilitation in Alzheimer’s disease ‐A Systematic review and meta analysis
Authors: Ahmad Logien Abuelgasim , Khalifa Mostafa A. , Hashad Mohammed Alaa 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is a challenging condition that forbids individuals of their memories and abilities to carry out their daily functioning. In the research for solutions, cognitive rehabilitation (CR) has emerged as a promising intervention to help individuals with Alzheimer’s disease improve their daily activities. Despite its potential benefits, the effectiveness of clinical trials (CT) remains a mystery, inconclusive further investigation. In this study, we aim to unravel the potential of CR in enhancing the lives of individuals with AD, with a focus on evaluating whether CR leads to meaningful enhancements in daily functioning as assessed by validated measures.MethodOur research is based on the PRISMA guidelines, and to identify relevant studies, a comprehensive search was conducted across multiple databases, including PubMed, Cochrane Library, Scopus, and Web of Science Keywords were used for searching, from inception to 2024. The research was limited to randomized controlled trials examining the effects of cognitive rehabilitation, including a total of 14 clinical trial articles, excluding studies focusing on cognitive stimulation, cognitive training, or cognitive intervention. Non‐English language articles and populations with diagnoses of other conditions are also excluded.ResultOur systematic reviews yielded a total of 1919 studies. After removing 287 duplicate records, we screened the title and abstract of 1877 papers, excluding 1835. Then, we proceeded to review the full text of 42 articles. 14 of them met the inclusion criteria. A pilot study of four papers is underway, and its results are expected to add to the existing evidence on the effectiveness of cognitive rehabilitation in AD. The meta‐analysis results for other domains of cognitive functions were not statistically complete yet. Further research is warranted to confirm these findings.ConclusionCognitive rehabilitation demonstrated significant positive effects on quality of life and occupational performance in patients with Alzheimer’s disease. Further, research is needed to investigate the efficiency of the intervention in specific domains to enhance understanding of Alzheimer’s disease management.
Exploring the impact of a co‐created dementia awareness session on dementia knowledge and attitudes in culturally diverse carers: a cross‐sectional analysis
Authors: Manimaran Manjari , Caballero Gabriela E , Shatnawi Eman , Tsouros Emy , Tran Mai , Jasim Nibras , Nguyen An , Cope Emily , Chan Sonia , Siette Joyce , Dadich Ann , DiGiacomo Michelle , Steiner‐Lim Genevieve Z , Karamacoska Diana 
Published: January 2025

AbstractBackgroundMany carers of people living with dementia display misperceptions and negative attitudes about dementia due to limited education. This stigma can impact care and the accessibility of appropriate support services. Culturally diverse people living with dementia and their carers remain underserviced and lack culturally inclusive resources despite having specialised dementia needs. Our study aimed to explore the impact of a co‐created dementia awareness‐raising session on the dementia knowledge and attitudes of culturally and linguistically diverse carers.MethodA quasi‐experimental cross‐sectional study was conducted in South‐Western Sydney, Australia, targeting English, Arabic, Vietnamese, Cantonese, Mandarin, and Greek‐speaking carers. A survey comprising 10 items from the dementia knowledge assessment scale (DKAS) and 15 items from the dementia attitudes scale (DAS) was administered to carers who attended a two‐hour awareness‐raising session co‐created with community stakeholders (intervention group) and online to carers who self‐reported having no previous dementia education (comparison group). The surveys and information sessions were translated and conducted in‐language by bilingual educators. Mann‐Whitney U tests were used to compare the mean rank differences between the two groups on each scale item.ResultsFor 8 of 10 DKAS items that assessed knowledge of the risk factors, presentation, and management of dementia, the intervention group (n = 42) had a higher proportion of correct answers relative to the comparison group (n = 74) (all p ≤.041). For 3 of 15 DAS items, regarding self‐perceived knowledge and awareness of local services, the intervention group (n = 188) displayed more positive attitudes relative to the comparison group (n = 427) (all p <.001).ConclusionOur co‐created multilingual dementia education initiative was effective in supporting dementia knowledge and awareness of local services among carers. However, the single session was likely insufficient to modify attitudes towards people living with dementia. The observational design used limits our understanding of baseline levels of knowledge and attitudes and thus the impact of this initiative. Future pre/post‐test experimental research should examine the improvement of dementia knowledge and attitudes with longer‐term carer‐specific education.
Transcriptomic similarities in the brain of Alzheimer’s disease and COVID‐19 patients
Authors: de Mello Guilherme Bastos , Carello‐Collar Giovanna , de Souza Débora Guerini , de Bastiani Marco Antônio , Zimmer Eduardo R. 
Published: January 2025

AbstractBackgroundNeurological symptoms, such as the lack of concentration, memory impairment and cognitive dysfunction are among the main complaints of COVID‐19 patients and seem to overlap with some of the Alzheimer’s disease (AD) symptoms. However, whether COVID‐19 and AD share a molecular signature is yet unclear. Thus, we aimed to explore transcriptomic similarities in the brains of COVID‐19 and AD individuals.MethodWe obtained frontal cortex transcriptomics datasets of COVID‐19 and AD from the Gene Expression Omnibus. Demographic characteristics of included individuals are reported in Table 1. Differentially expressed genes (DEGs) of COVID‐19 or AD versus controls were identified using the R statistical environment (FDR‐adjusted p‐value <0.05). Functional enrichment analyses (FEA) were accomplished to identify similar signatures considering the overlapped DEGs found between these two conditions.ResultWe identified 6,533 DEGs in COVID‐19 brains and 5,592 in AD brains. We found a striking overlap of 2,789 DEGs between these pathologies (Figure 1). Considering the DEGs in common, cluster observation suggests that COVID‐19 and AD share similar enriched processes, such as “central nervous system differentiation and development”, “signal release from synapse and neurotransmitter secretion” and “cognition, behavior, learning and memory” (Table 2).ConclusionOur results highlight core molecular programs shared by COVID‐19 and AD in the frontal cortex. These similarities may contribute to understanding the pathogenesis and the clinical course of COVID‐19 neurologic manifestations. These findings highlight the need for a careful evaluation of COVID‐19 survivors still presenting with neurological symptoms, which could be at high risk of developing AD.
The assessment of synaptic dysfunction in neurodegenerative disorders by a novel single molecular array for Neuronal pentraxin 2
Authors: Sauer Mathias , Gomes Bárbara Fernandes , Zetterberg Henrik , Blennow Kaj , Brinkmalm Ann , Belbin Olivia , Alcolea Daniel , Fortea Juan , Hansson Oskar , Nilsson Johanna , Ashton Nicholas J. 
Published: January 2025

AbstractBackgroundSynaptic dysfunction is a prominent feature in neurodegenerative disorders, associating with cognition. In contrast to most synaptic proteins assessed in cerebrospinal fluid (CSF), Neuronal pentraxin 2 (NPTX2), essential for synaptic plasticity, exhibits downregulation neurodegenerative disorders through mass spectrometry (MS) methods. While MS‐based assays hold promise, their constraints hinder widespread clinical adoption. Thus, our study aimed to develop a novel single molecular array (Simoa) for quantifying NPTX2 levels in CSF.MethodHomebrew NPTX2 was validated for the Simoa platform using commercial antibodies (EPR15618, ERP24020‐38; Abcam) in 2uL of CSF. After validation, we performed a study in Alzheimer’s disease (AD) and healthy controls (HC) from the BioFINDER pilot cohort (n = 99 participants; 48.5%AD; mean age 76.2 years [7.0 SD]). As a further validation, we quantified NPTX2 in the Sant Pau Initiative on Neurodegeneration (SPIN) cohort with 199 patients (58 AD, 51 HC, 60 Lewy body dementia (LBD) and 41 behavioral variant of frontotemporal dementia (bvFTD)). The mean age was 69.5 (11.4 SD) and both cohorts had an even distribution of sex. We examined group differences by the Wilcoxon rank sum test (corrected with Dunn‐test) and associations between the biomarkers and MRI, Tau PET, amyloid‐β (Aβ) PET and MMSE were determined by linear regression, adjusting for age and sex.ResultIn BioFINDER, Fold change (FC) in NPTX2 was significantly decreased in AD (median [95%CI], 0.85[0.65‐1.00]; p = 0.005) as compared to HC. NPTX2 showed a significant association in the full cohort with MMSE (β = 5.46, p<0.001), cortical thickness (β = 0.18, p<0.001) and Tau PET (β = ‐0.46, p = 0.002), but not with Aβ PET. In the SPIN cohort, the FC for neurodegenerative groups were significantly decreased as compared to HC (AD, 0.58[0.52‐0.79]; p<0.001; LBD, 0.66[0.56‐0.81]; p<0.001; and bvFTD, 0.50[0.33‐0.61]; p<0.001), with AUCs of 0.77(AD, 95%CI = 0.68‐0.86), 0.73(LBD, 0.63‐0.83) and 0.86(bvFTD, 0.78‐0.94). NPTX2 showed a significant association with MMSE (β = 2.10, p = 0.01) in the full cohort. Further results will explore NPTX2 in blood.ConclusionThis novel ultra‐sensitive immunoassay confirms the decrease of CSF NPTX2 in neurodegenerative diseases and a significant relationship to cognitive decline. This approach could streamline and increase the assessment of synaptic dysfunction in neurodegenerative diseases, providing valuable insights for disease management and treatment strategies.
The impact of a smartphone‐assisted real‐world wayfinding training on spatial memory performance as measured in VR in older adults
Authors: Marquardt Jonas , Kuehn Esther , Schreiber Stefanie , Maass Anne , Diersch Nadine 
Published: January 2025

AbstractBackgroundNon‐pharmacological interventions that improve cognitive functioning in patients with Alzheimer’s disease will play a crucial role in the coming years to support their independence in daily living. Here, we investigated the potential of a novel smartphone‐assisted real‐world wayfinding training, tailored for older adults, to improve their spatial memory as one of the first cognitive functions affected by the disease. Spatial memory performance was assessed using a VR‐based navigation task and the Gardony map drawing analyzer.MethodTo date, eight cognitively healthy older adults (65‐73 years) completed the wayfinding training on the medical campus area in Magdeburg, Germany, using our smartphone application “Explore” (Figure 1). In two egocentric sessions, participants had to walk repeatedly from a fixed start location to a target location and back. In four allocentric sessions, participants had to walk to several target locations consecutively by planning a route (four routes per session). All target locations were shown on a map in the app at the beginning of a track, which disappeared during walking but could be re‐opened. The app recorded GPS data and the number of map views. Potential changes in spatial memory were assessed by means of a pointing task in a virtual campus version before and after the training and by comparing the accuracy in the computerized map drawing after each session.ResultA linear mixed‐effect model analysis confirmed a significant training effect on pointing errors, while controlling for pre‐training familiarity, p < .001 (Figure 2). Map drawing accuracy improved over the course of the training, p < .001 (Figure 3a), while the number of map views during walking in allocentric sessions decreased, p = .021 (Figure 3b).ConclusionWe provide first evidence that a remotely administered real‐world wayfinding training might be able to improve spatial memory in older adults. As a next step, data will be collected in more participants with some of them assigned to a walking‐only control group. (f)MRI data, measured during the virtual pointing task, and biomarker status will be analyzed to investigate the mechanisms of the training effects and to determine the applicability as dementia intervention.
Associations between sleep apnea and tau in cognitively unimpaired older adults
Authors: Tennant Victoria R , Tsiknia Amaryllis A , Peltz Carrie B. , Lee Noelle , Hand Maxwell W , Leng Yue , Stone Katie L , Redline Susan , O'Bryant Sid E. , Braskie Meredith N , Yaffe Kristine 
Published: January 2025

AbstractBackgroundOlder age is associated with sleep disruptions and the aggregation of pathological tau in the medial temporal lobe (MTL). Associations between sleep disruptions and the progression of Alzheimer’s disease (AD) have been widely demonstrated. However, data addressing the association of objectively measured sleep apnea to tau deposition beyond the MTL in cognitively unimpaired older adults are limited.MethodWe included 357 cognitively unimpaired participants from the DORMIR sleep study, an ancillary study of HABS‐HD, with available information on the apnea‐hypopnea index (AHI; number of respiratory events with ≥3% desaturation divided by the estimated all‐night sleep time) derived from a home sleep apnea test (WatchPat, Itamar, Medical), Aβ (florbetaben), and tau (PI‐2620) PET scans. We calculated Aβ and tau standardized uptake value ratio (SUVR) using FreeSurfer (v5.3.0) derived regions, with whole cerebellum and posterior gray matter of the cerebellum as the reference regions, respectively. Between‐group differences for high AHI (AHI≥15) and low AHI (AHI<15) were assessed using t‐tests for continuous variables and χ2 tests for categorical variables. We evaluated the independent effect of log‐transformed AHI on continuous global Aβ and tau in separate linear regression models, adjusting for age, sex, education, ethnoracial group, and APOE4 carrier status. When predicting tau, we also included continuous global Aβ as a covariate.ResultMedian lateral parietal tau SUVR was significantly higher in the high AHI group (p = 0.04). Higher AHI was associated with higher median lateral parietal tau SUVR (p = 0.02, std.β = 0.11) and higher posterior cingulate tau SUVR (trend; p = 0.07, std.β = 0.10), but not with MTL tau SUVR (p = 0.71, std.β = ‐0.02) (Figure 1). AHI was not associated with global Aβ SUVR (p = 0.24, std.β = 0.06).ConclusionPast work has linked sleep apnea to impaired Aβ clearance. Intriguingly, our findings link higher AHI to more tau in the lateral parietal and posterior cingulate cortex, independent of Aβ burden, suggesting a separate pathway by which sleep apnea may exert effects on the aging brain. If replicated in longitudinal studies, this may have important implications for the development of sleep health guidelines and AD prevention strategies.
Word Young Leaders of Dementia Roadmap 2024‐2029: Approaches and Global Goals for Dementia Challenges
Authors: Clarens Maria Florencia , Arruabarrena Micaela Maria , Suemoto Claudia Kimie , Llibre‐Guerra Jorge J. , Crivelli Lucía , Sexton Claire , Ismail Ozama 
Published: January 2025

AbstractBackgroundThe 2021 WHO report highlights the importance of global planning for dementia. Initiatives that unite and support young leaders and stakeholders from diverse backgrounds in dementia care & research are crucial. The G8 Summit on Dementia in 2013 led to the creation of the World Dementia Council and the World Young Leaders in Dementia (WYLD) network, which connects professionals to work together on finding solutions to dementia challenges. With the emergence of new leadership and structure in January 2024 we aim to present our 2024‐2029 roadmap.MethodWe conducted a systematic review of the WYLD’s membership database to map out the geographical and sociodemographic landscape of our members and to further improve our recruitment of young leaders. Approaches and Goals for WYLD 2024‐2029 have been established with the advisory council and global partners, ensuring that the roadmap’s objectives are informed by a wide spectrum of insights and expert contributions.ResultOur review of current membership has revealed a diverse member network in 21 countries‐Fig. 1‐ with a majority of female professionals (67.78%)‐Fig. 2‐.Our mission, empowering emerging leaders through innovation, collaboration, and creative problem‐solving in dementia care strategies guided us in our roadmap, influencing our strategic proposal and aims.WYLD Structure: We are creating an advisory council and global partnerships by fostering strategic partnerships with leading organizations in the field. Appointments of Regional Leads in Africa, Asia, Australia/New Zealand, Europe, North America, and South America demonstrate our commitment to diversity.Leadership Development Activities: WYLD will offer leadership development through diverse mentorship training programs, curated webinars for young members in dementia care & research, and grant opportunities for rising Young LeadersOutreach: Regular and extensive distribution of young dementia leader’s work to inspire and facilitate worldwide progress in the field.ConclusionThe WYLD 2024‐2029 roadmap is a strategic blueprint that guides our mission to empower young leaders and innovate dementia care globally. Our growing, diverse membership, and collaborative initiatives set the stage for impactful change, ensuring that the vital work of these leaders is recognized and disseminated worldwide.
Funding Opportunity in Functional Target Validation for ADRD
Authors: Laeng Pascal , Cywin Charles 
Published: January 2025

AbstractBackgroundAlthough the success rate of novel treatments for CNS diseases is low, this has not limited the enthusiasm of academic and industry neuroscientists to undertake novel drug discovery approaches for the treatment of Alzheimer’s Disease‐Related Dementias (ADRD) due to the significant unmet need. A first major obstacle in the development of promising treatments for ADRD and other CNS disorders is the need for well‐validated targets linked to the disease process. Partial and incomplete knowledge about the biology of the selected molecular target(s) often limit their chance to translate into successful drug discovery projects. Translating these discoveries to the clinic will depend on the quality of the target validation process and the confidence in a causative link between the modulation of a target(s) and its functional physiological consequence(s) associated with treating or preventing a disease state. Recent technological innovations provide new opportunities in developing new converging approaches to validate the molecular and physiological functions of novel target candidates and their causality in disease progression.MethodNINDS, in partnership with NIA, is supporting new funding opportunity in functional target validation for ADRD to increase confidence in the efficacy and safety of novel emerging target(s) to trigger the development of customized therapeutic strategies. This will be implemented by a NOFO to fund the development of customized technologies, models, and protocols to modulate the expression (or activity) of ADRD target candidate(s) and monitor their functional biological consequences in in vitro and in vivo disease models. To inform future therapeutic efforts, positive as well as the negative functional impacts of the target modulation need to be tested in different modalities and across collaborating laboratories.ResultNINDS invites applications to propose the comprehensive functional validation of newly identified therapeutic target candidates for ADRD. This poster will outline in more detail, the eligibility requirements for the target candidate, potential druggability and knowledge gaps as well as the budget and the research objectives and scope.ConclusionThis funding opportunity will provide the translational research community with increased confidence in the efficacy and safety of the novel emerging target(s).