bluuebunny/crossref_metadata_2025_split huggingface dataset:
N‐terminal Brain Natriuretic Peptide over the Menopause Transition and Cognitive Performance after Menopause: Study of Women’s Heath Across the Nation
Authors: Khoudary Samar R. El , Matuk James , Derby Carol A. , McConnell Daniel , Thurston Rebecca C 
Published: January 2025

AbstractBackgroundN‐terminal brain natriuretic peptide (NTproBNP) is a marker of cardiac health and a strong predictor of mortality, incident cardiovascular disease (CVD), and sudden cardiac death in community populations. A link between the menopause transition (MT), sex hormones, and NTproBNP has been suggested, though, no studies have formally examined how NTproBNP changes over the MT. In addition of being a marker of cardiac health, studies suggest NTproBNP to be related to cognitive performance, yet those studies have not considered the MT. We aim to 1) characterize NTproBNP changes over the MT, and 2) assess if the identified changes over the MT are associated with changes in cognitive performance post menopause.MethodMidlife women with a known date of the final menstrual period (FMP) for whom NTproBNP was measured for up to 5 time points across the MT and cognitive performance (processing speed measured using Symbol Digit Modalities test) was assessed repeatedly after FMP were included. Bayesian piecewise linear mixed‐effects models were used to estimate an inflection point and subject‐specific acceleration in NTproBNP relative to the FMP. Bayesian linear mixed‐effects models were used to relate subject specific acceleration in NTproBNP over the MT with cognitive performance changes in the post menopause.ResultThe study included 1218 women (age at first included cognitive performance measure 53.8(SD: 3.14) years; 43.8% White, 28.4% Black, 11.0% Chinese, 12.3% Japanese, 4.5% Hispanic). NTproBNP significantly accelerated 3.2 years post FMP (posterior 95% Credible interval: 1.4, 5.2 years); posterior mean (95% Credible Interval) of log NTproBNP acceleration 0.043(0.036, 0.051) (Illustration‐Figure). Increased log NTproBNP acceleration over the MT was associated with greater processing speed decline post menopause [posterior mean (95% Credible Interval): ‐0.001(‐0.002, ‐0.0004) in SD unit processing speed per one SD unit increase in log NTproBNP acceleration] in adjusted model (Illustration‐Table).ConclusionFindings suggest a link between cardiac health during the MT and cognitive performance after menopause. The MT is a sensitive period of women’s lives characterized by accelerated increase in NTproBNP that in turn associates with a greater decline in postmenopausal processing speed.
Adherence to the MIND dietary pattern and the association with cognitive outcomes in the UK Biobank
Authors: Smith Megan , Bauermeister Sarah 
Published: January 2025

AbstractBackgroundConsumption of the Mediterranean‐Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay (MIND) diet has been proposed to support advantageous cognitive outcomes. Intra Individual Variability (IIV) has been suggested as a useful outcome for predicting adverse cognitive outcomes. Executive function (EF) may be particularly susceptible to dietary influence. No studies have investigated the relationship between MIND adherence and IIV, nor MIND and EF in a large UK sample.MethodThis was an observational study including 84,520 (56.1% female) participants from the UK Biobank Study who completed at‐least two 24‐hr dietary recalls and cognitive tests either at baseline or imaging visits. MIND diet adherence scores were derived using food intakes from multiple 24‐hr dietary recalls. IIV was constructed using the variability of response times within the reaction time task during baseline assessments. Executive function composite was created using path analysis, included tests were digit symbol substitution, trail making task ratio, fluid intelligence score and IIV. Multiple linear regressions were used to explore whether adhering to the MIND diet was associated with IIV or EF.ResultThe mean (SD) MIND score was 6.8 (2.0) in the full sample. Adherence to the MIND diet was not associated with IIV. MIND dietary scores were significantly associated with worse performance in executive function tasks, albeit with a small beta value (β = ‐0.005, p = .003).ConclusionAdhering to the MIND diet was not associated with advantageous cognitive outcomes in our analysis. Here, MIND diet was inversely related to performance in EF tasks, but no association found with IIV. The association with worse cognitive performance should be interpreted in the context of a small beta value and the likely influence of residual confounding. Moreover, as analysis was cross‐sectional, reverse causality cannot be ruled out. Differences between this analysis and prior literature in terms of location, sample size, dietary and cognitive assessments may also be contributing to the contradictory results. Further evaluation is needed to determine if MIND diet is associated with positive cognitive outcomes.
A Comprehensive Neurological Study on the Relationship Between Smoking Cigarettes and Alzheimer’s Disease: Potential Effects of Transitioning to E‐Cigarettes
Authors: Ismail Youssef A. , El‐Satar Youssef M. Abd , Haitham Youssef , Mohamed Hazim , Walid Mohammad 
Published: January 2025

AbstractBackgroundUndergoing intense research and investigation, smoking has garnered attention due to its extensive implications for public health, particularly focusing on cardiovascular and pulmonary issues. however In comparison, the neurological effects of nicotine have not yet been thoroughly investigated. Our objective is to investigate the relationship between smoking cigarettes and Alzheimer disease (AD) and possible effects of switching to E‐cigarettes.MethodsWe reviewed database searches through October 2023 in MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials; and additional searches for ongoing trials through ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and Current Controlled Trials (ISRCTN Register).ResultsNicotine has been observed to yield cognitive benefits and alleviate cognitive deficits associated with neurological diseases, such as Alzheimer’s disease (AD), in certain studies. Conversely, a notable increase in the risk of AD has been linked to active smoking in other studies, while another investigation suggests no discernible distinction between smokers and non‐smokers in this context. Although e‐cigarettes generally entail fewer adverse health effects, the neurological impact persists, attributed primarily to nicotine. As of July 2023, approximately 1.3 billion individuals, constituting approximately 16.2% of the global population, are smokers according to the World Health Organization (WHO). In the United States, 17.2% of adults are active smokers, with 11.1% employing traditional smoking methods. Notably, there is an observable decline in cigarette smoking, decreasing from 14.4% in 2019 to 11.1% in 2023, while the use of E‐cigarettes among US adults has risen from 4.4% to 6.1%. This trend is even more pronounced among youth, with around 14.1% of high school students and 3.3% of middle school students reporting e‐cigarette usage.ConclusionThe divergent findings regarding the impact of nicotine on cognition suggest the existence of an overlooked co‐factor associated with the effects of nicotine on the brain, warranting further investigation. Nevertheless, our analysis indicates that the shift to e‐cigarettes potentially elevates the risk from a neurological standpoint, as evidenced by documented cases of nicotinic overdosing, a phenomenon not possible with traditional cigarettes.
Molecular biomarkers for Alzheimer’s disease and related dementias – improved methods to facilitate global studies
Authors: Zetterberg Henrik 
Published: January 2025

AbstractBackgroundRecent advancements in sample collection and storage methods, as well as biomarker measurement technologies, have made it possible to determine highly accurate biomarkers for Alzheimer’s disease (AD) in regular plasma samples collected by venipuncture or as dried plasma spots.MethodsA novel ultrasensitive biomarker measurement method called NUcleic acid Linked Immuno‐Sandwich Assay (NULISA), which improves the sensitivity of traditional proximity ligation assays to attomolar level, by suppressing assay background via a dual capture and release mechanism, was evaluated against Single molecule array (Simoa) technology for AD biomarker measurement. Dried plasma spots were evaluated in relation to regularly collected EDTA plasma samples.ResultsProteins from dried plasma spots, stored at room temperature over weeks, can be eluted and AD‐related biomarkers, including P‐tau217, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), can be accurately quantified with r values above 0.80 (p<0.00001) compared with validated Simoa‐based measurements. Absolute concentrations of biomarkers in dried plasma spots are lower than in regularly collected venous samples. NULISA was at least 10‐fold as sensitive to measure AD‐related biomarkers compared with Simoa; a multiplexed NULISA method allows for the measurement of P‐tau217, NfL and GFAP concentrations in a single blood drop. Data from under‐represented populations will be presented.ConclusionThe measurement of biomarkers in dried plasma spots using novel ultrasensitive measurement technologies is feasible for biomarker assessment in remote populations with limited access to healthcare resources. Dried plasma spot‐specific reference limits are needed. Combining this with digital assessment tools for cognitive function should facilitate studies of the global epidemiology of dementia.
Inclusive Approaches To Promote Participation of Diverse Demographic Groups in Preclinical AD Clinical Trials Through Centralized Recruitment
Authors: Molina‐Henry Doris P. 
Published: January 2025

AbstractBackgroundRecruitment of demographically diverse participants into Alzheimer’s disease (AD) clinical trials, encompassing both screening and randomization, remains a consistent and persistent challenge contributing to underrepresentation of certain groups. Despite the exciting prospects of identifying therapeutic interventions for biomarker‐eligible, cognitively unimpaired individuals, these studies grapple with the inherent complexities of AD trials coupled with intricate and time‐consuming screening processes. Addressing this the issue of underrepresentation necessitates concerted and intentional efforts that prioritize inclusivity and equitable access to enroll adults meeting study criteria, reflecting the demographic and social diversity of North America. This presentation delves into the strategic approach undertaken by the Recruitment, Engagement, and Retention Unit (the Unit) within the National Institute on Aging‐funded Alzheimer’s Clinical Trials Consortium (ACTC).MethodsThe Unit defines and monitors populations of emphasis across dimensions of diversity such as race, ethnicity, sexual and gender minorities (LGBTQ+), and socially minoritized and underserved groups to underscore inclusivity. Guided by principles of research access, media outreach, site engagement, and community partnerships, the Unit implements a dynamic multi‐pronged strategy across clinical trials that span several stages of the disease.ResultResearch access involves evaluating and adapting messaging in digital and print formats, ensuring linguistically compatible communication, and providing informational resources tailored to these specific groups. Media efforts include earned and print media interviews across a variety of outlets focused on engaging communities of emphasis. ACTC’s Coordinating Center’s central activities are a supplement and in complement to local site endeavors via continued and robust community and site engagement. Thus far, these strategies have resulted in increased engagement and screening in preclinical AD trials across diverse communities.ConclusionAs we actively implement and expand these strategies, discussions evolve around early successes, lessons learned, and new and persisting challenges. We discuss centrally coordinated community screening pilot studies that are currently under evaluation and will help identify eligible individuals based on biomarker assessments before site referral. Additionally, we explore opportunities to further improve inclusivity by expanding into other dimensions of diversity through the study of social determinants of health that may influence cognitive health in groups that are disproportionately biomarker‐ineligible for AD trials.
New anti‐tau VHH: from biophysical characterization to proof‐of‐concept in experimental models
Authors: Danis Clément , Caillierez Raphaelle , Mortelecque Justine , Bégard Séverine , Zejneli Orgeta , Rain Jean‐Christophe , Colin Morvane , Dupre Elian , Landrieu Isabelle , Buee Luc 
Published: January 2025

AbstractBackgroundTau proteins aggregate in a number of neurodegenerative disorders known as tauopathies. Various studies have highlighted the role of microtubule‐binding domains in the intracellular aggregation of Tau protein.MethodUsing a library of synthetic VHHs humanized in collaboration with Hybrigenics, we have developed a number of anti‐tau VHHs. We use a combination of biophysical and biochemical methods, cell‐based assays, viral vectors and tau transgenic mice to explore the ability of these VHHs to target intracellular tau protein.ResultA dozen anti‐tau VHHs were obtained near and in microtubule‐binding regions. After screening and optimization, three of them (F8‐2, H3‐2 and Z70) were selected for further studies and AAV vector delivery to tau transgenic mice. Biochemical characterization of F8‐2 has already been published [1]. VHH Z70 targeting the PHF6 epitope has already demonstrated its ability to reduce tau seeding in cellular FRET assays and by lentiviral vectorization in animals [2]. Here, using AAV vectors, we demonstrate its safety in wild‐type mice and its efficacy in tau transgenic mice. VHH H3‐2 has a unique mode of action which will be discussed.ConclusionIn our tau pipeline, we have developed innovative new therapeutic tools, which are at various stages of development for preclinical validation.References[1] Danis C, et al. (2022) Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment. Mol Ther, 30(4):1484‐1499[2] Dupré E, et al. (2019) Single chain antibody fragments as new tools for studying the neuronal Tau protein physiopathology. ACS Chemical Neurosci, 10(9):3997‐4006
Understanding the Prescription Drug Costs among People with ADRD and Comorbidities: Evidence from Nationally Representative Datasets 2003‐2021
Authors: Jang Seyeon , McCoy Rozalina G. , Chen Jie 
Published: January 2025

AbstractBackgroundEscalating drug costs are likely to disproportionately burden individuals with Alzheimer’s disease and related dementias (ADRD) as they often have multiple chronic conditions (MCC). This study aimed to estimate the incremental total and out‐of‐pocket (OOP) drug costs associated with ADRD and MCC across the drug cost distributions.MethodThe study used a nationally representative cross‐sectional dataset from 2003 to 2021 Medical Expenditure Panel Survey. The study sample comprised of 83,667 elderly community dwelling individuals aged 65 and above, among which 3,046 individuals had ADRD diagnosis and 2,710 had both ADRD and MCC. To address the skewed distribution of the drug costs, quantile regression models were used to examine the associations between prescription drug costs and having ADRD/MCC across the drug cost distributions at 25th, 50th, 75th, and 90th percentiles, after adjustment for other sociodemographic factors. MCC was defined as having two or more chronic conditions. Survey weights were applied to all estimates.ResultADRD patients and those with ADRD and MCC had significantly higher incremental costs at the upper end of the total and OOP drug cost distributions than at the lower end of the distributions, compared to those who had no ADRD diagnosis. The incremental OOP drug costs of ADRD at the 90th percentile were over 14 times higher than that at the 25th percentile ($624.43, p<0.001, 90th percentile; $42.66, p<0.001, 25th percentile), while the incremental total drug costs of ADRD at the 90th percentile was about 9 times higher than that of ADRD at the 25th percentile ($3,372.27, p<0.001, 90th percentile; $381.31, p<0.001, 25th percentile). Similarly, the incremental OOP drug costs among individuals with ADRD and MCC at the 90th percentile were 11 times more than that at the 25th percentile ($756.91 vs. $68.55, respectively), while the incremental cost difference for the total drug costs was 7 times higher among individuals with ADRD and MCC at the 90th percentile than those at the 25th percentile ($3,940.53 vs. $548.80, respectively).ConclusionThe results of the study highlighted that ADRD patients with and without MCC who are heavy prescription drug users face a disproportionately greater burden in OOP payments.
The mapping of active sites of amyloid‐targeting compounds through the utilization of immobilized fragments of amyloid hexamers
Authors: Cho Illhwan , Yoon Soljee , Kim Hye Yun , Kim YoungSoo 
Published: January 2025

AbstractBackgroundAs amyloid‐β (Aβ) aggregates are considered as the biomarkers and key factors in the pathology of Alzheimer’s disease, there has been extensive investigation into Aβ‐targeting compounds for the development of diagnostics and drug discovery related to the disorder. However, the polymorphic and heterogenous nature of Aβ aggregates impedes the structural understanding of their structure. Consequently it is a major challenge to develop new diagnostic and therapeutic development of AD and to study the mechanism of Aβ‐targeting compounds.MethodUtilization of solid‐phase peptide synthesis, 37 Aβ hexameric Aβ fragments were synthesized. These fragments were immobilized on the 96‐well microplane to develop a mapping plate for investigating the active sites of Aβ‐targeting compounds. To confirm the mapping potential of our plate, previously reported fluorescent Aβ‐imaging agents (CRANAD‐28, bis‐ANS), Aβ aggregation inhibitors (curcumin, scyllo‐inositol), and Aβ aggregate dissociators (necrostatin‐1, sunitinib) were treated.ResultUsing the mapping plate, we confirmed that CRANAD‐28 interacted with three domains of Aβ HHQKLVFF (Aβ13‐20), IIGLMV (Aβ31‐36), and GGVVIA (Aβ37‐42), and bis‐ANS were bound to the predominant parts of Aβ sequences except N‐terminal regions. We further determined that curcumin inhibited three distinct fragmental regions of Aβ (Aβ14‐21, Aβ29‐35, and Aβ37‐42) and scyllo‐inositol targeted VHHQKLVFF (Aβ12‐20), VGSNKGAIIGL (Aβ24‐39), and GGVVIA (Aβ37‐42) sites. Lastly, we confirmed that both necrostatin‐1 and sunitinib strongly dissociated GLMVGGVVIA (Aβ33‐42), the C‐terminal hydrophobic residue.ConclusionThis mapping plate can be employed to understand the active sites of Aβ‐targeting compounds, even in the lack of a comprehensive structural understanding of Aβ aggregates. Moreover, the insights gained from identifying targeting sites using this mapping plate can contribute to the rational approach in the development of diagnostic and therapeutic strategies for Alzheimer’s disease (AD).
PENSA study, results of a 12‐month personalized intensive multimodal lifestyle intervention complemented with epigallocatechin gallate (EGCG) to prevent cognitive decline in APOE‐ ɛ4 carriers with Subjective Cognitive Decline: a randomized, double‐blinded clinical trial
Authors: Forcano Laura , Soldevila‐Domenech Natalia , Boronat Anna , Lorenzo Thais , Cuenca‐Royo Aida , Pizarro Nieves , Puig‐Pijoan Albert , Piera Iris , Gomis Maria , Diaz‐Pellicer Patricia , Aldea Ana , Grau‐Rivera Oriol , Sánchez‐Benavides Gonzalo , Fauria Karine , Minguillon Carolina , Gispert Juan Domingo , Molinuevo Jose Luis , de la Torre Rafael 
Published: January 2025

AbstractBackgroundLifestyle interventions targeting multiple Alzheimer’s disease (AD) risk factors are effective strategies to prevent cognitive decline. Emerging evidence suggests synergistic effects between various intervention components, including lifestyle modifications, supplements, and pharmacological approaches. The PENSA study, part of the World‐Wide FINGERs network, is a randomized, double‐blind clinical trial following the Finger 2.0 Model. This work aims to show the results of the effectiveness of this 12‐month intensive personalized multimodal lifestyle intervention (MI) encompassing diet, physical activity, cognitive/social stimulation combined with epigallocatechin gallate (EGCG), in mitigating cognitive decline in individuals with Subjective Cognitive Decline (SCD) carriers of the APOE‐e4 allele. Aspects related to the nature and intensity of the intervention that might influence cognitive improvements will be discussed.Method129 individuals aged 60‐80 years, APOE‐ε4 carriers meeting SCD, were enrolled and randomized into MI+EGCG (N = 52) or MI+placebo (N = 52), or allocated to a control group (CG) (receiving healthy lifestyle recommendations) (N = 25). The primary efficacy outcome was cognitive performance measured with the modified PACC‐exe battery. eHealth and mHealth tools/devices were used for the continuous monitoring of MI.ResultAlthough specific numerical results are not reported due to the upcoming submission for peer‐reviewed publication, we can anticipate that the results reflect promising results in cognitive performance, among participants undergoing MI + EGCG and a reduction in the risk of dementia as measured by the LIBRA index. Adherence to intervention components was very high (90.3% nutrition, 62.1% gymnasium, 72.6% cognitive training, 79.0% psychoeducation sessions, 89.0% daily ecological momentary assessments). Global findings will be shared in their integrity during the meeting.ConclusionThe PENSA Study is the first clinical trial exploring the effectiveness of integrating an intensive personalized MI with a pro‐cognitive complement, EGCG, in slowing cognitive decline in APOE‐ɛ4 carriers with SCD. Our findings emphasize the feasibility and effectiveness of a personalized MI for cognitively healthy individuals at higher risk of AD, applying an intense approach and incorporating new technologies. In the upcoming discussion, we will delve into the results and their broader implications.