公共卫生研究摘要 (2025-12-25)
共收录 54 篇研究文章
1. Age-Specific Associations Between eHealth Literacy and Sleep Quality Among Adults: Cross-Sectional Study.
期刊: Journal of medical Internet research 发表日期: 2025-Dec-24 链接: PubMed
摘要
Young and middle-aged adults are vulnerable to poor sleep quality. eHealth literacy, defined as the ability to effectively access and use digital health information, has been linked to improved health behaviors and may promote better sleep outcomes. However, its relationship with sleep quality remains unclear, especially across age groups. Age-related disparities in eHealth literacy may contribute to a digital health divide in sleep outcomes. This study aimed to examine the relationship between eHealth literacy and sleep quality among adults aged 18 to 59 years in Shanghai, China, as well as explore age-stratified effects. A cross-sectional study was conducted between October and December 2022 in 3 districts of Shanghai, with 7 community health service centers randomly selected. Participants were recruited through convenience sampling to complete an online survey. eHealth literacy was assessed using the eHealth Literacy Scale, and sleep quality was measured using the Pittsburgh Sleep Quality Index. Covariates included sociodemographic characteristics, health status, and health behaviors. Logistic regression models were applied to examine the relationship between eHealth literacy and sleep quality, with stratified analyses conducted by age (emerging adults [18-29 years], established adults [30-45 years], and middle-aged adults [46-59 years]). A total of 1810 participants completed the survey. The prevalence of poor sleep quality was 37.9% (686/1810). Participants with eHealth literacy scores in the 25th to 75th percentile range (odds ratio [OR] 1.594, 95% CI 1.216-2.089, P<.001) and below the 25th percentile (OR 1.584, 95% CI 1.149-2.182, P=.005) had a significantly higher likelihood of reporting poor sleep quality compared to those with scores above the 75th percentile. Age-stratified analysis indicated that this association was significant only among emerging adults (OR 2.491, 95% CI 1.133-5.479, P=.02 for scores between the 25th and 75th percentiles; OR 2.975, 95% CI 1.230-7.195, P=.02 for scores below the 25th percentile) and established adults (OR 1.439, 95% CI 1.001-2.067, P=.049 for scores between the 25th and 75th percentiles). This study found that eHealth literacy was associated with sleep quality among younger participants but not middle-aged ones, highlighting the digital divide in sleep health. These findings suggest that enhancing eHealth literacy may serve as an effective strategy for improving sleep outcomes. However, to ensure equitable health outcomes, interventions should be tailored to address the age-specific needs and varying levels of digital access across different groups.
2. Benchmarking Environmental Health Influences on Food Security in Very Remote Indigenous Communities in Australia: Protocol for a Mixed Methods Study.
期刊: JMIR research protocols 发表日期: 2025-Dec-24 链接: PubMed
摘要
Many factors including the impact of colonization and subsequent intergenerational trauma contribute to health inequalities for Aboriginal and Torres Strait Islander people, respectfully referred to as Indigenous Australians. The unacceptable health gap is higher for the Indigenous Australians living in very remote communities. Food insecurity-a lack of regular access to safe, nutritious, and affordable food-is influenced by both housing and retail environments. Ensuring that houses have functional and adequately maintained kitchens and access to affordable, healthy food are significant policy challenges for Australian governments; yet, little is known about these environmental health drivers in very remote areas. This study aims to benchmark environmental health food security risk factors impacting 19 very remote Indigenous communities in Western Australia. Specific objectives include using digital apps (1) to assess the appropriateness and suitability of kitchens in houses (internal environment), (2) to assess the affordability of food and sanitary goods (external environment) compared with the nearest town and capital city, and (3) to identify residents’ perceptions of appropriate kitchens. The mixed methods eHealth study includes 3 approaches. The internal environment is assessed via an in-house audit of facilities used to prepare, store, and cook food to maintain Healthy Living Principle 4 using a customized digital app and a 5-minute face-to-face yarn with tenants (n=130). This provides lived experience perspectives to inform housing and store pricing policy recommendations. The external environment assesses retail practices and food item (n=97) and sanitation product (n=28) prices in remote community stores, extending Healthy Diets ASAP (Australian Standardized Affordability and Price) to compare the mean price per product, the whole diet, and sanitation goods with the nearest town and capital city. Descriptive statistics and frequencies will be reported for the audits, and thematic analysis of the interviews will be undertaken. Tenant interviews and data collection for the in-house and retail audits across the 19 communities will be undertaken by mid-2026, and the analysis will be completed by the end of 2026. Findings will be collated and triangulated to provide benchmark data for environmental health determinants of food security in very remote Western Australian communities. Preliminary findings will be shared with each community to support their advocacy, policy, and practices for timely maintenance of homes, suitable kitchen design, and store retail practices. This is the first study in Australia to explore the environmental health drivers of food insecurity in very remote Indigenous communities using digital technology from the perspectives of the tenant, in-house facilities, and in-store retail practices. The food security environmental health benchmarking will provide evidence for advocacy to promote culturally appropriate and practical solutions to improve living conditions and health of families in these areas. PRR1-10.2196/71697.
3. The Epidemiology of Maternal Mortality in the United States: Trends, Structural Determinants, and Individual Risk Factors.
期刊: Annual review of public health 发表日期: 2025-Dec-24 链接: PubMed
摘要
Maternal mortality in the United States is an urgent public health concern. Despite advances in medical technology and obstetric care, maternal mortality remains elevated in the United States, with disparate burden across racial or ethnic, socioeconomic, and geographic communities. The reasons for these disparities are myriad and include a confluence of structural and social determinants, variation in medical care access and quality, and individual risk factors. This review explores the evolving patterns of maternal mortality in the United States by examining contributing causes, demographic disparities, and systemic challenges, with an emphasis on the limitations of current US maternal mortality surveillance infrastructure. We highlight the urgent need for data-driven policy interventions, equitable health care reforms, and research innovation to enhance maternal health and eliminate disparities.
4. Global status of HPV vaccination two decades in: effective, safe and preventing cancer.
期刊: Expert review of vaccines 发表日期: 2025-Dec-24 链接: PubMed
摘要
Prophylactic human papillomavirus vaccines have been in use in populations worldwide for nearly 20 years. Much has been learnt in relation to their effectiveness, safety and how best to effectively implement them in populations to prevent cancer and other HPV-related diseases. Global challenges such as limited supply and the mismatch between those who can afford them and those with the greatest disease burden from cervical cancer, have prevented optimal usage to date. Here we identified recent papers and focus upon the accumulated evidence regarding HPV vaccine i) effectiveness in preventing cancer and precancerous lesions ii) safety in population usage iii) trial evidence supporting registration of four newer vaccines iv) progress in country level introductions and coverage and v) lessons learned in effective implementation. Reasons for optimism are many, with vast cumulative knowledge on impact, safety and implementation and accelerating HPV vaccine introductions, simplification of delivery and reduced costs through single dose approaches and supply constraints easing. However considerable challenges remain in achieving and maintaining high and equitable global coverage, given the uncertainty in funding, risk to ongoing prioritization of health equity and to vaccine confidence in the current global public health environment.
5. Shaping future deprescribing priorities: outcomes of a World Café stakeholder workshop.
期刊: Expert review of clinical pharmacology 发表日期: 2025-Dec-24 链接: PubMed
摘要
Medicine-related harm associated with polypharmacy is a pertinent global health challenge. Deprescribing (reducing or stopping) medicines that cause more potential harm than benefit could mitigate the risk of medicine-related harm. However, the existing deprescribing research-to-practice gap threatens the long-term sustainability and scalability of deprescribing efforts. To address this, key stakeholders including healthcare practitioners, academics, policymakers and representatives of peak professional organizations, gathered at a World Café workshop to reflect on progress made in the deprescribing research and practice landscape while exploring the top future priorities for deprescribing. Thirty participants agreed on three top priorities: improving the clinical management of deprescribing; engaging consumers and gaining their perspectives; and raising awareness to enhance communication. Emerging themes and related barriers and catalysts were derived and mapped to a socio-ecological model offering a bird-eye’s view of these factors on an individual, interpersonal, organizational, and societal level. Our World Cafe’ highlights opportunities for future deprescribing research and practice. To promote the uptake of deprescribing in practice, catalysts could include leveraging new technology, promoting deprescribing via social media and optimizing workforce staff and knowledge. Ultimately, this knowledge may motivate deprescribing efforts and bridge the research-to-practice gap.
6. What do older adults seeking sexual health information want to know about? Findings from the Australian SHAPE2 survey.
期刊: Sexual health 发表日期: 2025-Dec-24 链接: PubMed
摘要
Older adults are not traditionally a priority group for sexual health (SH) promotion, however recent years have seen increasing interest in this population. Effective SH promotion requires an understanding of older adults’ interests, concerns and knowledge gaps. In 2021, we conducted the ‘SHAPE2’ online survey of Australians aged 60+ on SH information-seeking. Data are from two questions: i) SH topics participants wanted to know more about, and ii) last SH topic participants sought information on since turning 60. Quantitative data were collected as Topics organized into Categories. Free-text comments were classified into Categories using Content Analysis. Data were analysed using descriptive statistics and chi2 test. There were 1,470 respondents with a median age of 69 years and a balance between men and women. The Categories of most interest were ‘sexual anatomy and physiology’ (1,043/1,248, 83.6%; 95%CI: 81.4-85.6), ‘sex and ageing’ (942/1,175, 80.2%; 95%CI: 77.8-82.4), and ‘sexual difficulties’ (937/1,236, 75.8%; 95%CI:73.3-78.2). The specific Topics of most interest were ‘ageing and libido (sex drive)’ (771/1175, 65.6%; 95%CI: 62.8-68.3), ‘ageing and sexual pleasure’ (766/1175, 65.2%; 95%CI: 62.4-67.9), and ‘ageing and sexual performance’ (765/1175, 65.1%; 95%CI: 62.3-67.8). Men were more likely to have sought information (51.5% versus 30.6%, p<0.001) and indicated higher levels of interest, whereas women were interested in and/or had sought information on a wider range of issues. Differences were observed between SH issues of interest and those for which participants had sought information. Older adults seek information on, and are interested in, a variety of SH topics. To improve the sexual wellbeing of older people and address knowledge gaps, the priorities of older adults should be forefront when designing SH promotion strategies for this population.
7. Multi-site analysis of COVID-19 and new-onset diabetes reveals need for improved sensitivity of EHR-based COVID-19 phenotypes-a DiCAYA network analysis.
期刊: Journal of the American Medical Informatics Association : JAMIA 发表日期: 2025-Dec-24 链接: PubMed
摘要
We discuss implications of potential ascertainment biases for studies examining diabetes risk following SARS-CoV-2 infection using electronic health records (EHRs). We quantitatively explore sensitivity of results to misclassification of COVID-19 status using data from the U.S.-based Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network on children (≤17 years) and young adults (18-44 years). In our retrospective case study from the DiCAYA Network, SARS-CoV-2 was identified using labs and diagnoses from 6/1/2020-12/31/2021. Patients were followed through 12/31/2022 for new diabetes diagnoses. Sites examined incident diabetes by COVID-19 status using Cox proportional hazards models. Results were pooled in meta-analyses. A bias analysis examined potential impact of COVID-19 misclassification scenarios on results, guided by hypotheses that sensitivity would be < 50% and would be higher among those who developed diabetes. Prevalence of documented COVID-19 was low overall and variable across sites (children: 4.4%-7.7%, young adults: 6.2%-22.7%). Individuals with documented COVID-19 were at higher risk of incident diabetes compared to those with no documented infection, but results were heterogeneous across sites. Findings were highly sensitive to COVID-19 misclassification assumptions. Observed results could be biased away from the null under several differential misclassification scenarios. Although EHR-based documentation of COVID-19 was associated with incident diabetes, COVID-19 phenotypes likely had low sensitivity, with considerable variation across sites. Misclassification assumptions strongly impacted interpretation of results. Given the potential for low phenotype sensitivity and misclassification, caution is warranted when interpreting analyses of COVID-19 and incident diabetes using clinical or administrative databases.
8. Association between occupational stress responses and cardiovascular disease incidence in middle-aged Japanese: findings from the Aichi workers' cohort study.
期刊: International archives of occupational and environmental health 发表日期: 2025-Dec-24 链接: PubMed
摘要
9. Physical Activity and Sleep as Predictors of Well-Being in Young Adults.
期刊: American journal of health promotion : AJHP 发表日期: 2025-Dec-24 链接: PubMed
摘要
PurposeTo examine physical activity and sleep as predictors of well-being in young adults and explore differences by sex, age, and student status.Design & SettingA cross-sectional, online survey containing validated questionnaires was utilized to measure self-reported physical activity, sleep, and well-being.SampleParticipants were recruited through local and national recruitment efforts and social media. Of 329 survey respondents, 230 adults (69.9%) aged 18-25 years without current injury or physical activity limitations completed the survey between April 2020 and September 2020.MeasuresQuestionnaires utilized included the Godin Leisure Time Exercise Questionnaire for physical activity, the Pittsburgh Sleep Quality Index for sleep, and the Physical Summary Component and Mental Summary Component of the Modified Disablement in the Physically Active Scale for physical and mental well-being.AnalysisLinear regression models, Welch 2 Sample t-tests, Analysis of Variance, Tukey’s Honest Significant Difference tests, chi-square tests of independence, F-tests, and stepwise AIC techniques were utilized in data analyses.ResultsSleep quality was the strongest predictor of mental and physical well-being (Estimate = 0.500, P < .001). While no differences in sleep quality or well-being were identified by sex, age, or student status, physical activity was higher among males and younger participants.ConclusionYoung adulthood is a crucial time to establish healthy physical activity and sleep patterns to promote well-being. Collection of data during the COVID pandemic may limit generalizability of results.
10. Strategies to reduce malnutrition in children: what works in low-resource settings?
期刊: Current opinion in clinical nutrition and metabolic care 发表日期: 2025-Dec-24 链接: PubMed
摘要
Child malnutrition in low-and-middle-income countries remains persistently high, driven by converging biological, social, economic, environmental, and conflict-related factors. As progress slows and vulnerabilities intensify, this review synthesises emerging evidence from recent years to identify effective strategies and future directions for reducing undernutrition in resource-constrained settings. Recent literature demonstrates that nutrition-sensitive interventions, including women’s empowerment, social protection, WASH, immunisation, kitchen gardens, and biofortification, address key underlying drivers of child malnutrition and contribute to improved growth and dietary diversity. Building on these foundations, nutrition-specific strategies such as antenatal micronutrient supplementation, optimal infant and young child feeding practices, fortified complementary foods, and emerging approaches like microbiota-directed foods and fermentation have shown measurable gains in growth and nutritional status. Across the evidence base, integrated and multisectoral delivery models consistently outperform standalone programs, with particularly strong results when nutrition is combined with health services, social protection, community-based platforms, or climate- and conflict-responsive strategies. Current evidence underscores a shift toward integrated, layered, and context-responsive programming as the most effective path to reducing child malnutrition. Future research should prioritise implementation models that bridge nutrition-specific and nutrition-sensitive domains, strengthen health and community systems, and adapt to climate and humanitarian pressures.
11. Unique Coevolution of Organic Matter and Selenium Enrichment in Cold Region Mollisols.
期刊: Environmental science & technology 发表日期: 2025-Dec-24 链接: PubMed
摘要
Mollisols enriched with organic matter (OM) and selenium (Se) are a critical resource supporting global food security. Nonetheless, concerns arise as climate change and agricultural practices threaten Mollisol sustainability. Particularly, how the environmental conditions and biogeochemical processes constrain coevolution of OM and Se in Mollisols of cold regions is an unresolved issue. By combining pedogeochemical and multi-isotopic analyses with ultrahigh-resolution molecular and bioenergetic characterization of Mollisols in NE China, this research presents new evidence that unique cold region soil-forming environments are central to the coenrichment of OM and Se. While Mollisol OM originated from both C3 (e.g., meadow) and C4 (e.g., corn) plants, paleoclimate and redox shifts emerged as critical factors driving variations in the compositional and structural characteristics of OM, and substantial differences with the underlying parent material. The abundance of moderately energetic organic compounds (e.g., lipids and proteins) in Mollisols accounts for Se retention as organic-bound species. Under agricultural land use, the loss of OM and Se was accompanied by increasing proportions of microbial metabolites and fulvic acid-bound and hydrophilic Se species. By highlighting the dominant environmental drivers of changes in OM and Se chemistry in Mollisols, our research provides new knowledge that helps guide sustainable management of this valuable natural resource.
12. Extreme Weather Events and Their Health Impacts: International Variation.
期刊: Annual review of public health 发表日期: 2025-Dec-24 链接: PubMed
摘要
Climate change intensifies extreme weather events, and these events trigger cascading health impacts. Understanding the spatial variation of extreme weather events and their health impacts is critical for building tailored adaptation strategies. This review examines the trends in extreme weather events (including temperature extremes, floods, droughts, tropical cyclones, and wildfires), their linkages with climate change, the health impacts of these events, the global variations in the climate links and health impacts, and recommended adaptation policies. We found regional differences in observed trends and future projections in extreme weather events and discuss the associated uncertainty. Evidence on the global variations in health impacts is mixed and scarce, with differential hot spots identified by event type and by study. Adaptation policies should be designed and implemented in a holistic manner, including pre-event resilience building, during-event responses, and post-event recovery.
13. Exploring the Influence of a Novel App for Training and Evaluating Walking Aid Skills in Walking Aid Users: Protocol for a Pragmatic Single-Blind Randomized Controlled Trial.
期刊: JMIR research protocols 发表日期: 2025-Dec-24 链接: PubMed
摘要
More than 12% of the world’s population and more than 1 million Canadians use walking aids to support mobility. Unsafe use of walking aids due to a lack of training may lead to injuries and an increased risk of falls. A novel interactive video-based feedback mobile app to train walking aid fitting and safe use, called ICanWALK (Improving Canadians’ Walking Aid Skills, Learning, and Knowledge), was recently developed. The primary objective of this study is to explore the efficacy of the walking aid skills training app on the balance confidence of walking aid users. The secondary objective is to explore the influence of the mobile app on mobility and knowledge of walking aid users. A 2-site single-blind pragmatic randomized controlled trial is proposed. A total of 52 adults who use walking aids will be recruited through clinical and community organizations. Participants will complete measures of balance confidence (Activities-specific Balance Confidence scale; the primary outcome), mobility (6-Minute Walk Test and Timed Up and Go test), walking aid skills (Walking Aids Skills Test, WAST), and knowledge of and confidence in walking aid fit and use (self-reported questionnaire) at baseline (T1). Participants will then be randomly assigned to the experimental (ICanWALK app) or attention-matched control group (breathing activity app) and will complete two 20-minute sessions interacting with the assigned app. Participants will be reassessed 2 to 4 days after the intervention (T2) and again 4 weeks later (T3). Analysis of covariance will be performed for primary and secondary outcomes by using SPSS software. The study protocols were approved by the institutional review boards of both recruitment sites in 2023 and 2024. A feasibility study was conducted from 2023 to 2024 across the 2 sites. As of November 2025, participant recruitment is ongoing and expected to conclude in December 2026. To date, 26 individuals have been enrolled and have successfully completed all 3 assessment time points: T1, T2, and T3. Using a video-based feedback training approach, a novel app is hypothesized to improve balance confidence, mobility, and knowledge of and confidence in walking aid fitting and use. This structured educational program for fitting and training of walking aids may improve balance confidence. Better walking aid fitting and use may improve mobility, especially for older adults, thereby increasing independence and social participation. Establishing efficacy is an important first step before exploring how the ICanWALK app may be used by walking aid users and clinicians in clinical and community settings. ClinicalTrials.gov NCT05347875; https://clinicaltrials.gov/study/NCT05347875. DERR1-10.2196/71060.
14. Exploring psychosocial experiences in clinically stable generalised Myasthenia Gravis: A thematic analysis.
期刊: Journal of neuromuscular diseases 发表日期: 2025-Dec-24 链接: PubMed
摘要
Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular condition that significantly impacts patients’ lives. Whilst psychosocial challenges are increasingly recognised as important in understanding the lived experience of patients, insight into these experiences during periods of clinical stability remains underexplored. This qualitative study explores the psychological and social aspects of living with MG through thematic analysis of semi-structured interviews with eight adults from a specialist MG care clinic in London, all considered clinically stable for at least three months. Data were derived from participants initially interviewed about their day-to-day experience of physical symptoms to inform development of a symptom monitoring tool. As psychosocial themes emerged strongly but remained unanalysed, this paper presents a secondary analysis focusing on psychosocial themes. Three overarching themes emerged: (1) coping with adaptation - including the burden of planning, struggles to accept diagnosis, therapeutic challenges and fear of the future; (2) social and identity disruption - involving changes in self-image, social withdrawal, and occupational challenges; and (3) emotional and psychological impact - highlighting negative emotions and cognitive fatigue. Uncertainty emerged as a meta-theme underpinning all other themes, reflecting, driving, and being created by MG’s fluctuating symptoms. Findings suggest that psychological and social challenges underscored by uncertainty persist independently of symptom stability, highlighting the importance of uncertainty-focused interventions and integrated psychosocial support in MG care.
15. An introduction to BASIC Guide: human biomonitoring and surveillance of chemical exposure in occupational settings.
期刊: Annals of work exposures and health 发表日期: 2025-Dec-24 链接: PubMed
摘要
Human biomonitoring (HBM) complements air and surface measurements by integrating exposure from all routes and sources, strengthening occupational exposure assessment and control. In occupational settings, HBM can quantify exposure during routine work and nonroutine activities, evaluate controls, investigate incidents (potential overexposures), and support medical surveillance. To use HBM to its full potential, occupational health and safety professionals (OHPs) should adopt harmonized biomonitoring approaches reflecting best practice. This short communication presents the BASIC Guide series (Human Biomonitoring and Surveillance of Chemical Exposure in Occupational Settings), initiated by the International Society of Exposure Science Human Biomonitoring working group (ISES Europe HBM WG) as an integral part of the HBM Global Network. These chemical-specific practical documents operationalize the OECD (Organisation for Economic Co-operation and Development) occupational biomonitoring guidance, supporting the consistent implementation of exposure biomonitoring programs. Each BASIC Guide provides clear instructions on biomarker selection, sample handling, analytical methods, quality assurance, and result interpretation and communication. By translating international frameworks into actionable protocols, the BASIC Guides improve reproducibility and regulatory alignment in occupational HBM and enable more defensible exposure assessments worldwide.
16. Investigation of radiation doses to the eyes of patients and medical staff during a videofluoroscopic swallowing study: a phantom study.
期刊: Radiological physics and technology 发表日期: 2025-Dec-24 链接: PubMed
摘要
The goal of this study was to assess radiation doses to the eyes of seated patients and medical staff during a videofluoroscopic swallowing study (VFSS), considering the effects of lead-equivalent glasses and the height of the medical staff. Entrance surface air kerma (ESAK) at eye level was measured using nanoDot dosimeters on anthropomorphic phantoms representing medical staff with heights of 150, 165, and 180 cm. ESAK measurements were performed with and without 0.5-0.6 mm lead-equivalent glasses. During a 10-minute fluoroscopy procedure, the mean ESAK at patient’s eyes without lead-equivalent glasses was higher in the anteroposterior (AP) position (36.5 mGy) than in the lateral position (14.5 mGy). The corresponding ESAK at medical staff’s eyes was notably higher in the 150-cm phantom (0.097 mGy), with an increase of 77.1% compared with that in the 165-cm phantom (0.043 mGy) and 87.4% compared with that in the 180-cm phantom (0.038 mGy). The radioprotective efficiency of lead-equivalent glasses in patients in the anteroposterior position was 92.0-93.4%, which was higher than that in the lateral position (15.8-83.2%). Radiation doses to the eyes were highest for shorter medical staff, highlighting the importance of protective measures, especially for those with shorter stature. The radioprotective efficiency of lead-equivalent glasses was found to be lower in the lateral position, underscoring the need for careful consideration of glasses design.
17. Health hazards of occupational exposure to benzene, toluene and xylene (BTX) and the role of Vanin-1: a populational-based study.
期刊: International archives of occupational and environmental health 发表日期: 2025-Dec-24 链接: PubMed
摘要
18. The next frontier in stormwater management and models: Multispectral and hyperspectral imaging of build-up and wash-off.
期刊: Journal of environmental management 发表日期: 2025-Dec-23 链接: PubMed
摘要
Stormwater pollution poses risks to ecosystems and public health, yet traditional monitoring is costly, labour-intensive, and spatially limited. These constraints impede reliable catchment-scale data collection for water quality modelling and management. This study demonstrates a non-contact method using multispectral and hyperspectral imaging to monitor pollutant build-up and wash-off on urban impervious surfaces. Experiments under controlled (5-500 g applied road dust) and natural dry-wet conditions showed that multispectral imaging effectively quantified build-up and wash-off with strong sensitivity to particulates. Pollutant build-up showed a strong relationship with a pre-defined Near Infrared-Long Wavelength Infrared spectral index (controlled conditions, R2 = 0.98; field conditions, R2 = 0.7), and the wash-off spectral index followed the same linear trend. In contrast, hyperspectral imaging (272 bands, 400-900 nm) detected particle-bound pollutants such as Fe3+ via distinct reflectance-absorption features, confirmed using hematite reference spectra from the U.S. Geological Survey Spectral Library. When integrated with unmanned aerial vehicles (UAVs), this approach can replace recurrent physical sampling, reduce monitoring costs, and improve data reliability and coverage. It establishes a novel pathway for catchment-scale stormwater monitoring and modelling, enabling more efficient, data-driven urban water management.
19. Drug Market in Brazil: An Analysis of Drug Discontinuation From 2018 to 2022.
期刊: Value in health regional issues 发表日期: 2025-Dec-23 链接: PubMed
摘要
Given the structural vulnerabilities and international dependency of the Brazilian pharmaceutical sector, exacerbated by the COVID-19 pandemic, this study aims to analyze drug market discontinuation patterns and their associated pricing trends in Brazil between 2018 and 2022. Using data from the Brazilian Health Surveillance Agency’s Notification Panel, we performed a descriptive analysis of drug discontinuations and public procurement pricing trends. The study cataloged 11 657 drug discontinuations; approximately 38% occurred during the COVID-19 health crisis. Most (76.37%) were transient, primarily attributed to commercial factors. Notably, cardiovascular drugs were significantly affected, accounting for approximately 22% of total discontinuations during the pandemic. Analysis of public procurement pricing revealed substantial fluctuations, with some medications seeing cumulative price surges exceeding 100% over the 5-year period. The steepest median price escalation occurred in 2020, coinciding with the pandemic’s onset. These findings underscore the urgent need to reform Brazil’s price regulation policies and increase investments in the national pharmaceutical industry. Such measures are essential to mitigate external dependency and ensure the consistent availability of essential medicines for the Brazilian population.
20. Mapping the discourse of environmental sustainability in intensive care nursing: a lexicometric exploration of professional meaning-making.
期刊: Intensive & critical care nursing 发表日期: 2025-Dec-23 链接: PubMed
摘要
Intensive Care Units (ICUs) are among the most resource-intensive hospital environments, contributing substantially to healthcare’s environmental footprint. While sustainable practices are increasingly recognized as essential, little is known about how critical care nurses linguistically frame and make sense of sustainability within their professional culture and daily work. To explore how critical care nurses construct and articulate meanings of environmental sustainability in their professional discourse. Semi-structured interviews were conducted with 29 critical care nurses across diverse hospital settings. Narratives were analyzed using Automatic Analysis of Textual Data (IRaMuTeQ) with similarity analysis to map term relationships and uncover semantic clusters. Statistical associations (χ2 ≥ 3.84; p < 0.05) guided identification of lexical hubs and thematic subnetworks. Computational findings were integrated with qualitative interpretation to ensure contextual depth and rigor. The central lexical hub, sustainability, connected clusters reflecting reflective engagement, collaborative responsibility, organizational structures, and systemic gaps. Secondary hubs included environment (ecological impact and cost considerations), practice (behavioral integration), patient (embedded in bedside care), and waste (material handling, energy use, lifecycle awareness). Nurses framed sustainability as both a professional duty and systemic challenge, mediated by organizational support, personal commitment, and environmental constraints. ICU nurses’ discourse reveals sustainability as a multidimensional construct bridging ethics, operational practice, and systemic limitations. Lexicometric mapping provides a structured view of how sustainability is embedded in professional narratives, offering insights to inform targeted educational and organizational strategies. Integrating sustainability into professional identity enhances patient care and environmental responsibility. These findings deepen understanding of which dimensions of environmental sustainability can be meaningfully enacted through professional culture and organizational alignment, rather than through the direct imposition of fixed behavioural routines.
21. From adaptive networks to expanding state spaces: Comment on "Beyond networks: Toward adaptive models of biological complexity" by Pessoa.
期刊: Physics of life reviews 发表日期: 2025-Dec-19 链接: PubMed
摘要
22. Ablation of mitochondrial calcium uniporter alleviates cardiac dysfunction in type 1 diabetes.
期刊: Cell calcium 发表日期: 2025-Dec-17 链接: PubMed
摘要
Calcium (Ca2+) enters the mitochondria primarily through the mitochondria calcium uniporter (MCU). Conflicting results have been reported regarding the role of MCU in metabolic heart disease. Therefore, we employed a cardiomyocyte-specific MCU knockout (KO) model to assess its impact on the development of diabetic cardiomyopathy (DCM). Type 1 diabetes was induced in mice through streptozotocin (STZ) injection. The study included four groups: a wild-type (WT) control, two STZ-injected groups, designated as WT-STZ and MCUKO-STZ, and a MCUKO control. WT-STZ mice developed DCM, exhibiting contractile dysfunction (assessed by echocardiography) and ventricular arrhythmias (identified via electrocardiogram). Fluorescent imaging of isolated WT-STZ myocytes revealed impaired Ca2+ homeostasis and increased reactive oxygen species (ROS) production. Histological staining of WT-STZ cardiac tissue showed cellular hypertrophy and increased apoptosis. Mitochondrial energetics was also compromised in the WT-STZ model. MCU ablation significantly improved cardiac function in MCUKO-STZ mice, which maintained normal contractile function. Both cellular and in vivo arrhythmias were ameliorated in MCUKO-STZ. MCUKO-STZ myocytes exhibited improved Ca2+ handling and lower ROS emission. Hypertrophy and apoptosis were also alleviated in this group. Additionally, mitochondrial energetics, while not reversed, exhibited a slight trend toward improvement. Our study suggests that MCU ablation attenuates DCM progression. Inhibiting MCU-dependent Ca2+ entry may serve as a potential therapeutic strategy for type 1 diabetic cardiomyopathy by preventing arrhythmogenesis and pathological remodeling.
23. Prevalence, infestation, and morphological characterization of the fish parasitic isopod Alitropus typus.
期刊: Veterinary parasitology 发表日期: 2025-Dec-15 链接: PubMed
摘要
The infestation of crustacean parasites affects the freshwater and marine fishes, causing retarded growth rate, reduced production, low reproduction, and mass mortality. Fish parasites from the isopod family Aegidae, in recent years, have received increased global attention due to their serious socio-economic, ecological, and welfare consequences in finfish aquaculture. This is particularly true for the buccal-inhabiting genus Alitropus typus, which has emerged as a major parasitic threat to freshwater and brackishwater fish populations across tropical and subtropical regions, adversely affecting the health of both farmed and wild-caught fish. As research on this group increases, so does our understanding of their prevalence, infestation, and morphological characterization. The present review focuses on the infestation, intensity, prevalence, and diversity of A. typus in different fish communities. The biochemical composition of crustaceans and various control strategies, including the use of chemicals, vaccination, and biological treatments, are briefly described and explained. The risk of parasite transmission from the aquaculture enterprises to wild fish populations underscores the urgent need for the initiation of control programmes to safeguard the original endemic fish stocks. The review aims to highlight the advantages of using bacteria as an alternative treatment to eradicate parasites in aquaculture and to show the possible negative environmental impacts of chemical treatments used in fish farming systems. Finally, we also highlight the potential of the bacterial consortium to control parasites in fish farming as it assures health health-promising effect to the fish community due to parasiticidal activity without any side effects.
24. Spatial Analysis of Drug-Resistant Tuberculosis in Colombia (2020-2023): Departmental Rates, Clusters, and Associated Factors.
期刊: Tropical medicine and infectious disease 发表日期: 2025-Dec-15 链接: PubMed
摘要
Drug-resistant tuberculosis (DR-TB) constitutes a serious threat to global public health due to the increase in strains resistant to multiple drugs, especially isoniazid and rifampicin. This resistance increases mortality, estimated at 25.6% globally, and complicates treatments due to its high toxicity and cost. A quantitative ecological study was carried out with data on drug-resistant tuberculosis reported in Sivigila in the years (2020-2023) SIVIGILA database. 1694 cases were analyzed, considering sociodemographic variables such as age, sex, nationality and prioritized population groups. Departmental rates per 100,000 inhabitants were calculated with DANE projection, from these choropleth maps were developed. Applying a Kulldorff spatial scan under a Poisson model using the SMERC package of R (version 4.5.1), with windows centered on each department and Monte Carlo simulation contrast to identify high-risk clusters (RR > 1). (DR-TB) Predominantly in men aged 30-44 years, with a progressive increase until 2023 (IRR = 2.11). Three high-risk clusters were detected in the southwest and center of the country. Drug-resistant tuberculosis in Colombia showed a sustained increase in the years of study, with a cumulative increase of 110% compared to 2020, associated with economically active people more exposed due to occupational and social factors. The greatest burden was observed in the general population. Cases also increased in groups with social and health vulnerability conditions. The departments of Risaralda, Meta, and Valle del Cauca presented the highest drug resistance rates in Colombia.
25. Impact of a Universal Nirsevimab Prevention Program Against Respiratory Syncytial Virus Bronchiolitis in Infants in Sicily (Italy) During the 2024-2025 Epidemic Season: A Retrospective Cohort Study.
期刊: Vaccines 发表日期: 2025-Dec-02 链接: PubMed
摘要
Objectives: The introduction of universal prophylaxis with Nirsevimab represents a major innovation in preventing respiratory syncytial virus (RSV) infections in newborns. In Sicily, Nirsevimab administration began on 1 November 2024, for all newborns under one year and at-risk infants during the 2024-2025 season. This study assessed the real-world impact of this strategy in reducing RSV-related hospitalizations. Methods: This retrospective cohort study examined newborns residing in Sicily from 2015 to May 2025, evaluating hospitalization incidence rates attributable to RSV during the first year of life. RSV hospitalizations were identified using ICD-9 codes (079.6, 466.11, 480.1) in any diagnostic position. Incidence rates in the 2024-2025 season (intervention period) were compared with preceding seasons. Results: During the study period, 4431 RSV hospitalization cases occurred (19.84 cases per 1000 person-years), peaking in 2023-2024 (53.47 cases per 1000 person-years). A statistically significant 40% reduction in RSV hospitalizations was observed during the 2024-2025 season (October-April) compared with the preceding season, with a relative reduction ranging between 33.4% and 54.8% across sensitivity models. Conclusions: These results confirm the significant impact of the universal prophylaxis program in real-world practice, consistent with other European programs. These findings support universal RSV prevention strategies and provide insights for optimizing regional and national health policies.
26. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Alzheimer’s disease (AD) poses a significant public health burden. Despite extensive research, current therapeutic options offer limited efficacy in halting disease progression. Understanding the systemic physiological changes influencing AD development is crucial for developing innovative strategies for effective treatment. Leveraging genetic variants as instrumental variables, Mendelian randomization and proteome-wide association study have identified numerous protein biomarkers associated with AD risk, yet potential nonlinear associations have largely been overlooked. In this study, we applied a nonlinear modeling approach, combining two-stage sliced inverse regression (2SIR) with nonlinear transformations via adjusted inverse regression (AIR), to investigate associations between genetically predicted protein concentrations and AD risk by integrating data from the INTERVAL study, which contains both blood proteome and genome data, and the summary statistics of large genome-wide association study of AD. We identified 131 proteins associated with AD after stringent Bonferroni correction. Of these, 46 had been previously reported using linear modeling methods, highlighting the complementarity of the currently used nonlinear approach. Notably, many of the identified proteins have established biological relevance to AD, including APOE, ADAM11, LRP1B and TREML2, indicating that these critical AD-associated proteins could only be identified in instrumental variable analysis by allowing for nonlinear associations. Our study underscores the importance of accounting for nonlinear relationships in uncovering important gene products associated with AD. Our method could improve the understanding of AD pathogenesis and inform future therapeutic and preventive strategies to reduce AD burden.
27. Positive demography: changing the perspective on population aging from the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
The focus on the negative-at times depicted as catastrophic-consequences of population aging have overshadowed more optimistic stances. In this position article, we advance the notion of “positive demography,” which-while acknowledging existing challenges-contends that since a new demographic phase is inevitable, high-income countries should focus on making the most of it. We discuss this view with reference to Italy, one of the fastest-aging countries in the world, drawing lessons from Spoke 1 (The Demography of Aging) of the Age-It Research Program. We integrate different perspectives from social research on aging, informed by the most up-to-date literature in demography. This approach allows for a comprehensive understanding of demographic changes, highlighting their benefits while proposing forward-looking policy solutions. Longer life expectancy and improved health outcomes create opportunities for extended workforce participation and intergenerational contributions. Bridging the gap between desired and actual fertility is feasible through structural policies. Migration, at least in the short term, offers a means to mitigate aging-related challenges and accelerate demographic renewal. A positive demography agenda extends beyond addressing aging-related needs; it requires investments in younger generations to help them prepare for long and fulfilling lives. Achieving this vision necessitates interdisciplinary collaboration, innovation in data collection, and a methodological shift from forecasting to backcasting-identifying present actions necessary to shape a desirable demographic future.
28. An index of intergenerational justice: main concepts and preliminary evidence from the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
Aging reshapes the balance between younger and older generations within the population. These demographic shifts have significant implications for economic and environmental resource allocations and the transformation of social and political status and individual rights. To explore these dynamics, we present findings from Spoke 7 (Cultural and Political Dimensions of Ageing Societies) of the Age-It Research Program, which has developed a novel Index of Intergenerational Justice. The Index of Intergenerational Justice, applied to a broad sample of European countries, captures three key dimensions of justice: distributive fairness, social (status and relational) equality, and political equality. We focus on differences across age groups, rather than across cohorts, due to well-documented challenges in direct cohort comparisons. The distributive fairness dimension covers economics (relative poverty, unemployment, permanent contracts, wages), health (unmet medical needs), and the environment (environmental risk exposure). The social equality dimension captures social isolation (measured through leisure activities, internet access, social contacts, and close relationships), discrimination, and mental well-being. Finally, the political equality dimension considers political perceptions, political engagement, and political representation. Preliminary findings reveal substantial differences across age groups in the distributive fairness dimension. A cluster of countries appears to favor older adults, while another favors younger adults. By contrast, in the social equality dimension, nearly all countries tend to favor young adults. The Intergenerational Justice Index provides a valuable tool for assessing fairness across age groups. By highlighting disparities, it can inform and support public policies aimed at fostering more equitable relationships between generations.
29. Multidimensional determinants of active and healthy aging trajectories: a position paper from the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
This position paper presents perspectives from Spoke 4 (Trajectories for Active and Healthy Aging) of the Age-It Research Program, which adopts a One Health perspective to examine the interplay of cognitive, behavioral, nutritional, social, and environmental determinants of aging. Addressing these multidimensional factors is crucial to promoting health, independence, and well-being across the life course. We reviewed evidence on lifelong determinants of aging, including physical activity, nutrition, mental engagement, and social participation, alongside emerging digital health solutions. The One Health framework guided our analysis, emphasizing the interconnectedness of individual, societal, and environmental influences. Spoke 4 integrates multidisciplinary expertise to translate scientific knowledge into practical tools for communities, healthcare providers, and policymakers. Evidence shows that sustained engagement in physical activity, cognitively stimulating activities, and strong social networks supports resilience, reduces frailty, and preserves independence. Tailored nutritional strategies further enhance functional capacity. Digital technologies-such as mobile apps, wearable devices, and online platforms-demonstrate potential to improve disease prevention and health monitoring. However, disparities in digital literacy and access remain significant barriers, particularly for older adults. Spoke 4 of Age-It highlights the need for multidimensional, One Health-based strategies that integrate traditional health determinants with digital innovations. By combining evidence-based interventions with user-centered e-health platforms, scalable and inclusive solutions can be developed to support healthy aging. These efforts provide policymakers and healthcare systems with tools to foster resilience, mitigate frailty, and enhance quality of life in aging populations.
30. Clarifying healthy aging: building a common language for policy innovation within the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
This study aimed to map and classify the definitions of “healthy ageing” (HA) employed in randomized controlled trials (RCTs) over the past decade, and to identify conceptual and methodological trends, with the goal of informing future research and policy efforts toward harmonization. A systematic review of HA definitions was conducted according to the PRISMA guidelines. A search strategy was designed, refined, and executed using Medline (Ovid) up to July 19, 2024. The primary search term was “healthy aging,” with results filtered specifically for RCTs. Of 38,219 records initially retrieved, 1,588 were screened, and 48 met the inclusion criteria. No unified definition of HA was identified. Instead, three main types emerged: (a) multidimensional definitions with qualitative assessments (29.2%), (b) multidimensional definitions with quantitative assessments (27.0%), and (c) condition- or disease-specific definitions (43.8%). The most common intervention targets were active aging (29.2%), nutritional supplementation (14.6%), cognitive decline (12.5%), and physical activity (12.5%). Considerable heterogeneity was observed in the domains (e.g., physical, cognitive, psychological, and social) and the tools used to assess HA. The findings highlight substantial conceptual variability in how HA is defined and measured in RCTs. This diversity reflects the multidimensional and context-dependent nature of HA but poses challenges for synthesis and comparison across studies. A shared framework for defining HA in interventional research is needed to support evidence-based aging policies. By mapping the range of operational definitions used in RCTs, this review provides a foundation for standardizing future HA research.
31. Education and learning for active aging: promising practices and findings from the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
This study maps “promising practices” across a range of organizations that support older adults’ participation and learning to develop an evidence base for relevant policies and programs. It presents findings from the Learning, Education, and Active Aging Board of the Age-It Research Program. This mixed-methods study, following a sequential explanatory design, gathered quantitative data via a questionnaire, completed by public and private organizations active in offering programs/activities to older adults. The questionnaire collected information about the organization profile, the target population, and the educational activity. For qualitative data, semi-structured interviews were conducted with staff coordinators and managers. Forty-three organizations, mostly Italian non-governmental organizations (NGOs), reported on 50 “promising practices” with a wide range of aims, consistent with the definition of lifelong and lifewide learning: social inclusion, health promotion, caregivers support, social work and volunteering, digital literacy, and intergenerational activities. Lack of coordination, low exchange between organizations, funding, and sustainability were the main weaknesses. From the analysis of qualitative data, three main topics emerged: prevention of frailty, empowerment through innovation, and participation. This exploratory study outlines the richness of the mapped activities, as well as limited exchange and collaboration among the involved actors, the absence of a shared framework to assess the quality of practices addressed to older adults’ learning and participation, and the need for research and evaluation. Furthermore, national policies for active and healthy aging should allocate specific resources for learning and education to support older adults in terms of skills, social participation, meaning, and recognition.
32. Clinical and environmental factors, functional status, and multimorbidity-stratifying progression and prognosis of multimorbidity, frailty, and disability: the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
This paper describes the methodology and activities of the third thematic challenge (Spoke 3) of the Age-It program. Spoke 3 aims to address the clinical complexity and heterogeneity of older subjects’ phenotypes through an interdisciplinary biomedical approach. Spoke 3 will investigate biomarkers related to multimorbidity and frailty, develop prognostic algorithms using novel methodological approaches, including artificial intelligence (AI) techniques to combine biological and clinical data, and identify management strategies for complex older subjects with multimorbidity and frailty. These activities will be realized by launching new prospective longitudinal studies and through new analyses of existing longitudinal cohorts. Spoke 3 is expected to generate original evidence concerning older subjects with multimorbidity and/or frailty, to support a more precise diagnostic evaluation, to improve the ability to predict the functional and cognitive trajectories, with the final aim of better managing this complex population. Spoke 3 also aims to evaluate the impact of climate change and pollution on the health status of older subjects by combining health and environmental data. Overcoming the traditional medical approach, focused on the diagnosis and treatment of single diseases, Spoke 3 should provide important original evidence to improve the management of older subjects with multimorbidity and frailty.
33. Basic Science and Pathogenesis.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Alzheimer disease (AD) genetic research increasingly recognizes the importance of ancestral diversity in understanding the genetic mechanism of AD. The “Recruitment and Retention for Alzheimer’s Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP)” initiative addresses this need by building a resource to study AD genetics across diverse populations in the United States and Africa. This global collaboration, spanning four U.S. sites and ten African countries through the Africa Dementia Consortium, aims to examine and understand genetic and non-genetic factors involved in AD risk and progression. READD-ADSP employs genomic and epidemiological methods to investigate AD across diverse populations in the United States and Africa. This international collaboration integrates whole-genome sequencing and blood biomarker data, along with social determinants of health (SDOH) and clinical measures, to examine the interplay among genetic, ancestral, and SDOH factors. Ancestral analyses define population structure, assess risk-gene effect heterogeneity (e.g., APOE), and explore locus-specific variation (e.g., ABCA7). Through comprehensive association analyses, the study aims to evaluate the generalizability of known AD risk loci to African ancestry populations and identify novel genetic risk or protective factors. Preliminary analyses reveal substantial ancestral variation within African populations, particularly when comparing West and East African populations. Previous AD genetic studies showed heterogeneity in risk effect size such as the APOE4allele and risk marker heterogeneity at the same risk locus across ancestries such as ABCA7 gene, but these differences remain understudied in African continental populations. Our findings highlight the potential of diverse genomic backgrounds to uncover protective genetic factors, such as the African-specific protective PSG2 locus, found to confer a protective effect among APOE4 carriers. By incorporating underrepresented groups, this research can broaden our understanding of AD and inform interventions that benefit globally. The study of genetic variations within African and African American populations opens new avenues for identifying novel risk and protective AD loci and refining our understanding of AD etiology. Future work will benefit from continued cross-continental collaboration integrating genetic data with SDOH factors. The READD-ADSP initiative will enhance our understanding of AD, informing precision therapies that are globally tailored to the unique genetic profiles of all populations.
34. Basic Science and Pathogenesis.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Despite evidence that Alzheimer’s Disease (AD) is a highly heritable disease, there remains substantial “missing” heritability, likely due to the clinical and neuropathologic heterogeneity inherent in the disease. Here, we leverage sensitive longitudinal cognitive measures as endophenotypes in a rare variant analysis to identify novel genetic drivers of cognitive decline in aging and disease. We leveraged 8 cohorts of cognitive aging with whole genome sequencing data from the AD Sequencing Project to conduct rare variant analyses of multiple domains of cognition (N = 8,481; mean age=73; 56% female; 52% cognitively unimpaired). Harmonized scores for memory, executive function, and language were derived using confirmatory factor analysis models. Longitudinal scores were generated for each domain using linear mixed model regressions. Participants of European ancestry inferred using SNPweights and 1000G reference panel were included. Variants included had a minor allele frequency < 0.01 and were annotated as a high or moderate impact SNP using VEP. We performed SKAT-O testing for genes with at least two variants contributing and with a minimum aggregate minor allele count >10. All tests were adjusted for sex, baseline age at cognitive assessment, sequencing center and platform, and the first 5 principal components of genetic ancestry. Correction for multiple comparisons was completed using the false discovery rate (FDR) procedure. We identified 9 genes associated with our cognitive domains. Two genes (APOE, PSEN1) were associated with baseline memory (both pFDR=0.07), one (PEDS1-UBE2V1) with baseline language (pFDR=0.01), and six (HPN, HPN-AS1, GAB1, CXCL3, SIGIRR, PLA2G4A) with executive function decline (pFDR range=0.01-0.08). SIGIRR, PLA2G4A, and HPN all had high impact variants contributing to the gene score that were significantly associated with executive function decline. These results highlight novel rare variants associated with cognition. GAB1 is an AGORA nominated gene target for potential AD treatment. Decreased expression was found in cholinergic neurons in AD patients and decreased learning and memory in a mouse model of AD. PLA2G4A has increased expression in AD patients that is evident in early stages but is decreased in healthy aging brains. Future work will incorporate other ancestries.
35. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Speech features derived from verbal responses to cognitive tests have been shown to indicate mild cognitive impairment and later risk of Alzheimer’s Disease (AD). However, research in validating speech features using established AD biomarkers remains limited. This study aims to validate linguistic features from digital audio recording against AD biomarkers. We analyzed data from participants of the Framingham Heart Study who were cognitively intact and had (1) Tau PET and amyloid PET scans conducted on the same date or within a 3-month interval; (2) a logical memory delayed recall (LMd) test within one year of the Tau PET scan; and (3) manually transcribed response from the LMd test. Using natural language processing methods and spaCy Python library, we extracted 52 linguistic features from transcribed LMd responses, which included measures of lexical density, syntactic complexity, and speech fluency. We validated these features against AD biomarkers: (1) beta-amyloid status (+/-) derived through Gaussian mixture modeling and (2) Tau PET signals in five brain regions: amygdala, entorhinal, inferior parietal (IP), inferior temporal (IT), and precuneus. First, we used multiple linear regression to assess the association between each feature (dependent variable) and the biomarker status (independent variable), adjusting for age, sex, and education. Features associated with an AD biomarker (p <0.05) were further analyzed using Lasso regression. Data from 238 participants (age: 54.9±8.3, 51.3% females, 7.1% were amyloid positive) were analyzed. While the standardized LMd test score showed no association with AD biomarkers, several linguistic features demonstrated significant associations with these biomarkers (Table 1, Figure 1). Decreased content complexity (i.e., lower ideaDensity) was associated with amyloid positivity (Beta: -0.542, p = 0.03) and higher Tau burden in entorhinal (Beta:-0.148, p = 0.03), IT (Beta:-0.143, p = 0.04), and Amygdala (Beta:-0.139, p = 0.04). Reduced syntactic complexity (i.e., lower Yngve_avg scores) were associated with higher Tau burden in IP (Beta:-0.168, p = 0.02), and IT (Beta:-0.145, p = 0.04). Longer between-utterance pause duration was positively associated with higher Tau burden in IP (Beta:0.322, p <0.001) and IT (Beta:0.196, p = 0.01). Linguistic-based speech features are associated with amyloid positivity and tau accumulation and can potentially serve as digital biomarkers for preclinical AD but need further validation.
36. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Alzheimer’s disease (AD) manifests differently across racial and ethnic groups, influenced by genetic and environmental factors. Blood-based biomarker testing has the potential to enable early detection of AD, facilitating timely intervention and effective management. However, biomarkers validated only in homogenous populations may not accurately reflect disease presence, progression, or response to treatment in diverse groups. In this review, we assess the performance of blood-based biomarker concentrations and AD clinical outcomes within studies conducted across different ethnoracial populations. A comprehensive search of original scientific studies was conducted across Ovid MEDLINE, Embase, Web of Science, Scopus, and PubMed for articles published from 2000. Studies are included if they report blood-based biomarkers (i.e., Aβ, p-tau, t-tau, NfL and GFAP) and their associations with AD clinical outcomes - including cognitive performance, diagnostic accuracy, and disease progression - and an ethnic or racial breakdown of the population sample. Data extraction focussed on study design, population demographics, biomarkers assessed, diagnostic metrics and statistical methods. Heterogeneity was evaluated using I2 statistics, and subgroup analyses were performed based on ethnoracial diversity and biomarker types. A total of 3472 titles were imported, of which 109 articles were eligible for full-text screening. Overall, we found a paucity of studies evaluating blood-based biomarkers for AD across ethnically diverse populations. Individual studies focusing on the diagnostic performance of peripheral biomarkers as well as their variability across ethnoracial groups suggested that there are likely to be important variations in both biomarker levels and diagnostic performance across ethnoracial categories. However, the heterogeneity in measures and outcomes across the small number of relevant studies meant that high quality pooled evidence to guide clinical practice could not yet be derived. Blood-based biomarkers for AD are likely to vary in their absolute concentrations and diagnostic performance across ethnoracial groups. High quality studies with harmonised exposures and outcomes are required to provide evidence about how this issue should influence clinical implementation and interpretation of blood-based biomarkers in diverse real-world settings.
37. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
The logical memory delayed (LMd) recall test has been widely used in screening tools for Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The test performance was evaluated by trained professionals based on the number of predefined key terms the participant accurately recalled from a previously narrated standard story. This process is subjective and labor-intensive. We aim to develop novel, automated digital markers for MCI using large language models (LLMs) and transcriptions of recorded verbal responses from the LMd test. We analyzed data from participants of the Framingham Heart Study who (1) had at least one audio transcription from the LMd test and (2) completed all the neuropsychological (NP) tests (in the same visit as (1)) used for assessing MCI based on the modified Jak/Bondi criteria. We developed automated measures that assessed participants’ LMd performance by using LLM-derived text embeddings to estimate the semantic similarity between the standard LMd test story (72 words) and the transcriptions of verbal retellings (average 62 words). We implemented four measures using state-of-the-art LLMs for short-text embedding: E5, MiniLM, MPNet, and the Universal Sentence Encoder (USE). We evaluated these measures against the LMd score through two analyses. First, we used a generalized linear mixed model to assess the association between each measure and MCI status, adjusting for age, sex, and education. Second, we used logistic regression to assess the association between each measure at baseline and the conversion from cognitively normal to MCI within 15 years, adjusting for age, sex, education, and the conversion duration. 587 LMd recordings from 282 FHS participants (age at baseline: 53.7±9.8, 48.9% Female) were analyzed, with 78 recordings corresponding to MCI cases (Table 1). The LLM-derived measures were correlated with the LMd score (Figure 1). Most LLM-derived measures were negatively associated with MCI status (Table 2), with USE-derived measure showing the strongest association (OR=0.539, P < 0.001). All LLM-derived measures were negatively associated with normal-to-MCI conversion (Table 2), with USE-derived measure being most sensitive (OR=0.344, P < 0.001). With further validation, these novel LLM-derived measures can potentially serve as digital markers for MCI.
38. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
The Centiloid (CL) scale standardizes amyloid PET imaging for consistent measurements across multicenter studies. However, varying thresholds for amyloid positivity create challenges in identifying individuals at risk for cognitive decline and specific pathological profiles. This study aims to define optimal CL thresholds using a three-level classification system and validate their relevance in distinguishing tau pathology, cognitive status, and clinical outcomes in a memory clinic cohort. A total of 580 participants, ranging from cognitively unimpaired to those with dementia, underwent amyloid-PET scans ([18F]florbetapir or [18F]flutemetamol). Subsets underwent [18F]Flortaucipir-PET (n = 185) and CSF biomarker analysis (n = 190). Participants were classified into three categories based on predefined thresholds: NEGATIVE (CL<12), GRAY-ZONE (12≤CL≤37), and POSITIVE (CL>37). Associations between amyloid categories, tau status, CSF biomarkers, and cognitive performance were evaluated with Chi-squared and Kruskal-Wallis tests, while prognostic implications were assessed using linear mixed-effects models. ROC analyses and Youden’s Index were applied to determine additional CL thresholds for tau pathology and cognitive decline. Predefined thresholds stratified participants effectively: 99% of POSITIVE individuals were visually amyloid-positive, while 44% of GRAY-ZONE individuals showed discordant visual classification. CSF levels decreased significantly across groups, with NEGATIVE individuals showing the highest and POSITIVE individuals the lowest levels (p <0.01). GRAY-ZONE individuals exhibited intermediate characteristics, with higher tau burden and faster cognitive decline than NEGATIVE individuals (p <0.01), but less severe than POSITIVE individuals (p <0.01). ROC analyses identified optimal CL thresholds for specific outcomes. A threshold of 13 CL distinguished stable individuals from decliners (AUC=0.677), and thresholds of 14 and 51 CL accurately distinguished tau-positive from tau-negative cases (AUC>0.841). Lower threshold were associated with early mesial temporal tau positivity, while higher threshold indicated advanced tau pathology. Our findings demonstrate the importance of moving beyond binary amyloid classification and identify at least 3 meaningful levels. The GRAY-ZONE group shows distinct clinical and biomarker profiles, with lower CL thresholds identifying individuals at higher risk for cognitive decline and early mesial temporal tau deposition, while higher CL values pinpoint individuals with amyloid and advanced tau pathology. Properly identifying these individuals is crucial for personalized treatment strategies, particularly as amyloid-targeting therapies become more widely accessible.
39. Basic Science and Pathogenesis.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Cardiovascular diseases (CVDs) such as peripheral artery disease (PAD) and coronary artery disease (CAD) are risk factors for Alzheimer’s disease (AD) and related dementias (ADRD). The APOE-ε4 variant, which codes for a cholesterol transporter protein, is the largest AD genetic risk factor, increases LDL cholesterol and triglycerides, and augments the risk of cardiovascular disease. In this study of participants in the US Department of Veterans Affairs’ Million Veteran Program (MVP), we examined the interactive effects of APOE-ε4 status with CVDs (PAD, CAD, myocardial infarction, hypertension, and hyperlipidemia) on ADRD prevalence. Our cohort included MVP participants of European ancestry age 65 and older with available genotype data (n = 11,112 ADRD cases and 170,361 controls). Cross-sectional logistic regression analyses were performed using the GEM (Gene-Environment interaction analysis in Millions of samples) software package and included fitting an omnibus test for gene by environment (GxE) interactions between additively-coded ε4 and the CVDs as a group, followed by GxE analysis of individual CVDs. Additive-scale interactions were measured using the Relative Excess Risk due to Interaction (RERI) statistic. ADRD was derived from International Classification of Diseases (ICD) codes using our validated algorithm. We used validated algorithms for MI and PAD identified in the VA’s Centralized Interactive Phenomics Resource (CIPHER). CAD, hypertension, and hyperlipidemia cases were identified using Phecodes. CVDs showed both strong main-effect associations with ADRD (ORs 1.55 to 1.82, all p < 1099; see Table). Both the omnibus test (p = 5x10-12) and the individual CVD interaction terms were significant (p from 7x10-8 to 0.025). RERI estimates indicated significant positive additive-scale interactions (see example figure illustrating additive hypertension x ε4 interaction). These additive-scale interactions are more directly interpretable than multiplicative-scale interactions. They indicate that the prevalence of ADRD associated with cardiovascular disease increases with the number of inherited APOE-ε4 alleles (e.g. from 3.3% greater ADRD frequency associated with hypertension at age 80 for those with 0 ε4 copies to 5.6% for those with 2 copies; see Figure). Combining genetic testing with information about health comorbidities could contribute to more accurate dementia risk assessment within the Veteran population, and likely within other populations as well.
40. Basic Science and Pathogenesis.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Vascular cognitive impairment and dementia (VCID) is a leading cause of cognitive decline and often coexists with neurodegenerative pathologies such as Alzheimer’s disease (AD). Despite its clinical significance, the genetic architecture of VCID remains poorly understood. Genome-wide association studies (GWAS) have identified only APOE as significantly associated with VCID. The GIGAVCID project aims to conduct the largest GWAS of VCID and examine its genetic overlap with other traits. It is a collaborative effort between the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and the European Alzheimer’s Disease DNA BioBank (EADB) consortia alongside major contributions from international cohorts (deCODE, HUNT, CHB, JPSC AD). This study includes 16 cohorts with over 1.1 million individuals (74.8 ± 12.3 years, 56% female), including more than 15,000 VCID cases. Genotyping data were imputed using the TOPMed reference panel, and additional stratification was performed based on APOEε4 genotype. Study-specific analyses were adjusted for age, sex, and population structure. We then applied standardized quality control, data harmonization, and meta-analysis using METAL, followed by conditional analyses and fine mapping. We identified genome-wide associations with VCID at the APOE and BIN1 loci, both of which have been previously implicated in AD (Figure 1). Our novel findings include loci at or adjacent to the PARD3 and COL4A1 genes. PARD3 plays a critical role in neurodevelopment by regulating neuronal differentiation, migration, and synaptic plasticity. COL4A1 has been associated with cerebral small vessel disease (cSVD), a condition characterized by vascular fragility in the brain, increasing the risk of hemorrhagic strokes. Finally, we will present insights derived from pathway analyses and bioinformatic interrogation of the identified loci, providing a broader mechanistic understanding of their potential roles in VCID. Our findings reinforce the critical role of APOE and BIN1 in VCID while identifying novel loci, including COL4A1 and PARD3. These discoveries suggest shared genetic mechanisms among VCID, AD, and cSVD. Our results provide valuable insights into the genetic architecture of VCID and underscore the need for further research to elucidate the biological pathways underlying vascular contributions to dementia. Future directions include functional annotation to validate and further characterize these genetic associations.
41. Aging well in an aging society: Italy at the forefront of global aging and the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
Italy, one of the world’s super-aged societies, faces profound demographic transformations amid relevant regional disparities in sociodemographic trends, institutional structures, and economic conditions. These features make it an ideal laboratory to study both the challenges and opportunities of population aging. This article introduces Age-It, a Research Program designed to leverage Italy’s position at the forefront of global aging to advance transdisciplinary research and inform evidence-based policies and practices on aging. Age-It adopts a life course perspective encompassing individual, family, and societal levels. It conceptualizes “aging well” as the outcome of multi-agent, multi-context processes unfolding from early life through old age. Furthermore, Age-It moves beyond a multidisciplinary approach by fostering true cross-fertilization between biomedical, sociodemographic, and technological sciences. Structured as an umbrella initiative, the program brings together multiple interlinked projects that address diverse dimensions of aging through transdisciplinary and collaborative research. The program addresses key limitations in Italy’s current aging research and policy landscape: fragmented data, disciplinary silos, and weak connections between research and policymaking. By integrating biomedical, technological, and socioeconomic perspectives into structured, theory-driven research centers (Spokes), Age-It provides a coordinated and innovative platform for studying aging. Leveraging Italy’s unique demographic profile and internal heterogeneity, Age-It promotes sustainable aging by harnessing the opportunities embedded in demographic change. The program ranges from the biology of aging to mental and physical health prevention, long-term care, labor market dynamics, and social participation-ultimately aiming to reshape how aging is perceived and managed in aging societies.
42. Caring in the XXI century: the sustainability of long-term care in aging societies-mapping challenges and developing solutions within the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
The process of population aging characterizing Italian society will lead to a greater demand for long-term care (LTC) services, while simultaneously reducing the availability of caregivers. Spoke 5 activities develop interdisciplinary solutions to meet the challenges and seize the opportunities that emerge from this transformation. The article summarizes the outputs from Spoke 5 of the Age-It research program, highlighting their implications for practitioners and policymakers. The research activities contribute to: (a) mapping care needs and resources; (b) developing innovative digital tools to monitor caregivers’ well-being and support them; (c) advancing integrative planning for age-friendly environments; (d) developing e-learning platforms addressing caregivers’ needs; (e) identifying existing policy shortcomings. Spoke 5 developed an index of LTC risks that measures the balance between the demand and the potential supply of care at the municipal level; critical areas only partially overlap with traditional socioeconomic cleavages. The analysis of informal care distribution reveals that high socioeconomic status (SES) individuals outsource more demanding caregiving tasks, whereas low-SES families face high-intensity care demands. Innovative digital tools and e-learning platforms are presented. The analysis of policies supporting Italian informal caregivers indicates that they are characterized by a significant geographical and institutional fragmentation. The progression of macro sociodemographic trends has pushed Italy’s existing “care equilibrium” to its limits; innovative solutions are needed. Adopting a multidimensional and multidisciplinary approach, focusing on the goal of supporting caregivers’ well-being and training, and overcoming policy fragmentation are key to creating an LTC system that is socially and economically sustainable.
43. Multicomponent interventions and technologies to reduce the burden of frailty, functional, and cognitive decline: insights from the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
Preventing age-related complications is a critical priority for health systems. Within the Age-It program, Spoke 8 aims to evaluate scalable, multicomponent, technology-assisted interventions to prevent frailty and mitigate functional and cognitive decline in older adults across different care settings. Spoke 8 includes three clinical studies conducted in community, hospital, and long-term care settings, supported by cross-cutting work packages on digital infrastructure, technology development, and economic evaluation. The intervention model integrates physical, cognitive, nutritional, and psychosocial components, supported by digital tools, biomarkers of aging, and a centralized data platform. The project is expected to generate evidence on the effectiveness, feasibility, and cost-effectiveness of multidomain interventions implemented across diverse real-world settings, including community, hospital, and long-term care. Technology-assisted strategies-such as wearable sensors and digital cognitive tools-may enhance adherence and enable remote monitoring, while also supporting more personalized care delivery. The integration of artificial intelligence will facilitate the interpretation of complex clinical and biological data, improving risk stratification and the early identification of individuals most likely to benefit from targeted interventions. Together, these approaches may help reduce hospitalizations, delay functional decline, and promote aging in place. This initiative supports the transition toward more integrated and equitable care models for older adults. Through the implementation of scalable, person-centered interventions within routine services, the project offers policy-relevant strategies to address frailty and functional decline-contributing to the redesign of aging care in Italy and providing insights applicable across diverse health systems facing the challenges of population aging countries.
44. Improving our understanding of the biology of aging: findings from the Age-It Research Program.
期刊: The journals of gerontology. Series B, Psychological sciences and social sciences 发表日期: 2025-Dec-01 链接: PubMed
摘要
Aging mechanisms at both cellular and organismal levels remain poorly understood, as do the factors influencing the variability in aging rates across organs and individuals. Our work aims to identify the key biological pathways that drive aging, determine the most relevant biomarkers of biological aging, and uncover actionable mechanisms to improve risk prediction for unsuccessful aging. To achieve these objectives, we employ a structured approach that includes (a) investigating the molecular and cellular mechanisms underlying aging, (b) identifying and validating biomarkers associated with biological aging, and (c) assessing potential therapeutic targets that could modulate aging-related processes. These efforts are being carried out within the framework of the Age-It initiative, leveraging interdisciplinary methodologies and advanced analytical tools. Ongoing studies within Age-It are generating insights into aging-related pathways and biomarkers. Preliminary findings highlight specific molecular signatures associated with biological aging and suggest potential intervention points for mitigating age-related decline. Understanding the biological underpinnings of aging will enhance our ability to predict and potentially modify aging trajectories. By identifying reliable biomarkers and actionable pathways, this research may contribute to the development of targeted interventions to promote healthy aging. The Age-It initiative represents a collaborative effort to translate these findings into practical applications for aging research and health care policy.
45. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Cerebral blood flow (CBF) plays a pivotal role in maintaining brain function and metabolism, serving as a crucial parameter for assessing brain health. Similarly, the estimated glomerular filtration rate (eGFR) measures kidney function and determines kidney disease stages. CBF and eGFR assess the vascular health of two essential organs-the brain and the kidney. We enrolled 785 healthy middle-aged and older adults undergoing regular health check-ups at our Health Promotion Center. Participants underwent blood tests for creatinine, cholesterol, and diabetes markers, and brain MRIs using a 3T system with pseudo-continuous arterial spin labeling (pCASL) to measure CBF. Based on their eGFR, calculated from creatinine levels, participants were classified into three stages. We conducted voxel-based and region-of-interest analyses to compare CBF as well as brain tissue volumes across stages and to examine their associations with eGFR and creatinine levels. The study comprised 368 participants in Stage 1 (high eGFR), 287 in Stage 2 (moderate eGFR), and 130 in Stage 3 (low eGFR). Significantly higher CBF was observed in Stages 1 and 2 compared to Stage 3, notably in the hippocampus and parahippocampal gyrus. CBF showed a positive correlation with eGFR levels and a negative correlation with creatinine levels across all defined brain areas. CBF was sensitive to differences between eGFR stages, higher in Stage 1 compared to Stages 2 and 3, suggesting its utility as an early marker for brain integrity changes. Its positive correlation with eGFR and inverse relation with creatinine support its role in monitoring early cerebral perfusion changes linked to renal function. This study underscores the interconnectedness of renal and brain health, proposing CBF as a potential early biomarker for cerebral changes in a healthy population.
46. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Alzheimer’s disease (AD) and cardiovascular disease (CVD) share overlapping risk factors and pathological pathways, yet the mechanisms linking subclinical atherosclerosis to early brain alterations remain poorly understood. The PESA-Brain study builds on the unique strengths of the PESA cohort to explore the relationships between cardiovascular burden, cerebrovascular health, and early markers of AD pathology in asymptomatic, middle-aged individuals. PESA-Brain is a longitudinal study that includes 1,000 participants aged 50-55 from the PESA cohort, which provides extensive cardiovascular and biomarker data collected over more than a decade. The study aims to investigate how subclinical atherosclerosis and other cardiovascular risk factors contribute to early brain alterations. Recruitment for PESA-Brain is expected to be completed by April 2025. Current analyses focus on integrating cardiovascular metrics with multimodal data to evaluate the potential pathways linking vascular and neurodegenerative processes. PESA-Brain hypothesizes that subclinical atherosclerosis, through mechanisms such as impaired cerebral perfusion and neurovascular dysfunction, may drive early brain alterations associated with AD pathology. By identifying these pathways in midlife, the study seeks to uncover modifiable factors that can inform strategies for early prevention and intervention. PESA-Brain offers a unique opportunity to understand the early interactions between cardiovascular health and brain integrity, offering critical insights into the role of vascular factors in the development of neurodegeneration and dementia. This study’s findings are expected to contribute significantly to the global effort to combat Alzheimer’s disease.
47. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Recent studies indicate that soluble tau phosphorylated at threonine 231 (p-tau231) rises most prominently in the earliest preclinical stages of Alzheimer’s disease (AD), preceding overt amyloid-beta (Aβ) PET positivity. Elevated p-tau231 levels may promote emerging Aβ deposition, but the biological mechanisms linking early tau phosphorylation to subsequent Aβ accumulation remain unclear. Microglial reactivity may play a key role in Aβ dynamics, given their involvement in both facilitating Aβ clearance (protective) and promoting Aβ buildup via neuroinflammation (detrimental). We studied 187 cognitively unimpaired (CU) individuals from the ALFA+ cohort who underwent repeated Aβ-PET imaging over an average of 3.4 (SD=0.55) years (Table 1). Using linear regression models and mediation analysis, we tested the associations between cerebrospinal fluid (CSF) p-tau231 levels, longitudinal Aβ accumulation measured by PET (annual centiloid change), and CSF sTREM2 levels, a biomarker of TREM2-mediated microglial reactivity. Models were adjusted for baseline centiloid levels, age, APOE-ε4 status, and sex. Higher CSF p-tau231 levels were associated with faster Aβ-PET accumulation (β [95% CI]: 0.98 [0.26-1.69], p <0.01). Elevated p-tau231 was also linked to increased CSF sTREM2 (β [95% CI]: 0.18 [0.11-0.25], p <0.001). Notably, higher sTREM2 was associated with reduced rates of Aβ accumulation (β [95% CI]: -1.67 [-2.83 to -0.51], p <0.01), attenuating the relationship between p-tau231 and Aβ-PET accumulation by 27% (Figure 1). These findings suggest that soluble tau phosphorylation at early disease stages may enhance TREM2-mediated microglial reactivity, which may in turn be a protective mechanism against Aβ aggregation. This may suggest that elevated p-tau231 in the preclinical phase may initiate a microglial response that slows fibrillar Aβ accumulation (e.g., via phagocytosis). This may later transition to detrimental inflammation as the disease progresses. Enhancing microglial function in preclinical AD might therefore be a promising therapeutic strategy to delay or prevent Aβ buildup.
48. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
FDG-PET has been a widely used imaging modality for evaluating hypometabolism in Alzheimer’s disease (AD) for decades. This study investigates differences in biomarker profiles between patients with AD and non-AD patterns of FDG-PET. Additionally, we aim to explore whether the AD FDG-PET pattern complements the diagnostic performance of plasma p-tau217 for detecting beta-amyloid (Aβ) and tau pathology. We included 51 participants diagnosed with amnestic mild cognitive impairment or mild dementia. The participants were classified by radiologist-reported FDG-PET patterns as either AD (n = 32) or non-AD (n = 19). AD patterns were defined by typical AD-related hypometabolism (involving posterior cingulate, precuneus, and posterior temporal and parietal lobes). Aβ-PET centiloid (AβCL), Aβ positivity (A+), tau standardized uptake value ratio (SUVR) in Braak III and/or IV, tau-PET status (T+), and plasma biomarkers, including p-tau217, p-tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels, were determined. ROC analyses identified optimal cut-off values for p-tau217, which were further assessed alongside FDG-PET patterns for their diagnostic performance for A+ and A+T+. Participants with AD FDG-PET patterns, compared to those with non-AD patterns, exhibited higher proportions of A+ (28/32 (87.5%) vs. 9/19 (47.4%), p = 0.002) and A+T+ (22/32 (68.8%) vs. 2/19 (10.5%), p <0.001). They also showed elevated AβCL levels and tau SUVRs across Braak III-IV regions (all p <0.001, Figure 1A-1D). Plasma biomarkers, including p-tau217, were markedly higher in the AD pattern group (all p <0.001, Figure 1E-1H). The AD FDG-PET pattern demonstrated high diagnostic accuracy, while plasma p-tau217 alone (at optimal cut-off values) showed excellent performance for predicting A+ and A+T+ (Table 1). Combining FDG-PET patterns with p-tau217 (cut-off ≥ 4.874 pg/mL) enhanced specificity for A+T+ prediction (from 0.556 to 0.741) while maintaining high sensitivity (from 1.0 to 0.917) (Table 1). The determination of p-tau217 cut-off values will be illustrated with ROC curves (Figure 2A-B). FDG-PET patterns, particularly when combined with plasma p-tau217, improve diagnostic specificity for A+ and A+T+ pathology. These findings emphasize the complementary value of integrating imaging and fluid biomarkers for accurate AD diagnosis.
49. Basic Science and Pathogenesis.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Alzheimer’s disease (AD) is characterized by tau and amyloid-β (Aβ) pathologies, influenced by factors such as sex, aging, APOE genotype, and sleep. Sleep is essential for memory consolidation, but its interaction with these factors and AD biomarkers remains unclear. This study examined how sex, APOEε4 status, and CSF AD biomarkers (Aβ42/40, p-tau) affect the relationship between sleep and overnight memory retention in older adults. Sixty-six Wisconsin Registry for Alzheimer’s Prevention participants (41 women, 25 ε4-carriers, mean age 61.8±6.1 years) encoded word pairs in the evening, underwent overnight polysomnography, and completed a morning memory test. Memory retention was calculated as the morning-evening difference, with sleep stages quantified. CSF biomarkers (p-tau, Aβ42/40) were assessed using the exploratory NeuroToolKit panel on Cobas® analyzers (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) under strict quality control. Moderated mediation analysis (PROCESS model 11) examined relationships between sleep stages (predictor), memory retention (outcome), biomarkers (mediators), and sex/APOEε4 status (moderators). A sex×APOEε4 interaction predicted memory (p = 0.02) where female ε4-non-carriers exhibited more forgetting than ε4-carriers (p = 0.02). Male ε4-carriers had worse memory retention than female ε4-carriers (p = 0.01). Female ε4-carriers had more N3-sleep stage (p = 0.01), correlating with better memory retention (r=0.72, p = 0.02), while male ε4-carriers had more N2-sleep (p = 0.04), also linked to better memory retention (r=0.68, p = 0.03). Moderated mediation analysis demonstrated that N2-sleep negatively predicted p-tau levels across participants (p = 0.03), suggesting a potential protective effect, while higher p-tau was linked to lower overnight memory retention (p = 0.04). A significant interaction between sex and APOEε4 (p = 0.05), N2 and APOEε4 (p = 0.07-trend), and a main effect of APOEε4 (p = 0.04) on Aβ42/40 levels suggest that APOEε4 status is a determinant of Aβ42/40. The findings indicate that the relationship between N2-sleep and Aβ42/40 is not uniform but are moderated by whether an individual carries the APOEε4 allele. No significant associations were found with N3-sleep (p > 0.05). Our findings show that NREM sleep stages influence overnight memory retention in older men and women, depending on APOE genotype and CSF AD biomarkers, suggesting that sex differences in long-term memory retention are shaped by interactions between sleep and AD pathology.
50. Basic Science and Pathogenesis.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Fundamental questions remain about the key mechanisms that initiate Alzheimer’s disease (AD), the factors that promote its progression, and the relationship with cognitive impairment. Therapeutic interventions have been successful at clearing amyloid plaque accumulation, though fail to rescue and prevent cognitive decline. To understand the association between amyloid burden and cognition decline, we are studying non-human primates that carry a C410Y point mutation in the presenilin-1 (PSEN1) gene that confers early onset AD in human carriers, and the association of cognitive function with amyloid progression measured by fluid and neuroimaging biomarkers. Marmosets carrying PSEN1 mutations and age-and sex-matched non-carrier controls are studied longitudinally from birth throughout their lifespan. Beginning at 6-weeks of age and at 6-month intervals, plasma biomarkers of amyloid-beta (Aβ1-40, Aβ1-42), total tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were analyzed. Marmosets were trained on a cognitive battery that was delivered annually using a touchscreen including tests of spatial working memory and reversal learning (delayed-match and delayed-non-match-to-position), recognition memory (delayed-match-to-sample), a serial reaction time task to measure attention and a progressive ratio task to measure motivation. Amyloid uptake was measured with 11C-PiB-PET. Beginning at 12-months of age PSEN1 marmosets demonstrate significant increases in plasma Aβ42:40 relative to non-carriers. PSEN1 marmosets were indistinguishable from non-carriers in task acquisition across the cognitive testing battery with no significant impairment in measures of visual and spatial working memory capacities, attention, or motivation up to 2 years of age. When compared to age and sex matched unmanipulated WT control marmosets, PSEN1 marmosets have similar 11C-PiB uptake values, indicative of little to no difference between cortical amyloid burden. Increases in brain and plasma amyloid beta do not correlate with cognitive changes in young PSEN1 carrier animals, indicating a lack of direct association between amyloid progression and cognition. Longitudinal study of these marmosets provides the opportunity to study the earliest primate-specific mechanisms that contribute to the molecular and cellular root causes of cognitive decline associated with early onset AD and disease progression.
51. Biomarkers.
期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed
摘要
Given the idiopathic nature of many neurodegenerative diseases (ND), the contributions of environmental factors need to be considered. Here environment is defined as the milieu of chemicals, whether occupational and/or ecological exposures, rural and urban spheres, as well as social stressors. This is particularly of concern in absence of enforced regulatory oversight. It should not be assumed that this is an issue exclusive to developing countries, given concerns of environmental equity globally. Over the past 3 decades, numerous studies have implicated gene-environmental interactions as playing a role in precipitating neurotoxicity and neurodegenerative conditions. Indeed, several studies have drawn attention to the potential contribution of the environment, including fetal, to cognitive decline and neurological dysfunction. A pilot study of patients with MCI (n = 20) as determined by MMSE (<25) and a socioeconomically matched control group (n = 30). Sera were analyzed for the presence of neuroantibodies (NAb), IgM and IgG, against neurofilament triplet (NF), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) by ELISA, as well as levels of heavy metals (μg/dl) Cd, Pb, Cu, Mn and Al by ICP. There was a go highly significant (p = 0.00001) prevalence of Nab against NFL, IgM and IgG, as well as NFH and GFAP, IgG in MCI patients. Significant odds ratios were 23 (95% CI= 1.358 to 422), 8 (95% CI= 1.492 to 21.418), and 33 (95% CI=2.2906 to 146.5430), respectively, for NFL, IgM and NFH IgG. Stepwise multirgeression analysis indicated that urban environment, Al, and MCI diagnosis were significant determinants of Anti-NFL titers (R2=0.6; p = 0.00001; 95% CI=-0.112-2.60694), whereas diagnosis and Cr where determinants of Anti-NFH IgG (R2=0.37; p = 0.00001; 95% CI=-0.84799-1.83). In contrast Anti-GFAP IgG titers were significantly associated with Pb, Mn and MMSE (R2=0.47; p = 0.00001; 95% CI= -0.006-4.7). In turn MMSE was associated with urban environment, Pb, anti-NFM and anti-GFAP titers (R2=0.47; p = 0.00001; 95% CI= 10-16). This preliminary study with the strong association between serum NAb titers and environmental metals, as well as the association of clinical diagnosis with environment, metals and NAb underscores the need to consider these and other environmental factors in dementia, as well as other ND, as will be illustrated.
52. Comprehensive Clinical Profile of Amanita exitialis Poisoning: Integrating Toxin Detection and Autopsy Pathology.
期刊: Toxins 发表日期: 2025-Nov-29 链接: PubMed
摘要
Amanita exitialis is a lethal mushroom species found in southern China. Its amatoxins can cause acute liver injury with a high case-fatality rate. However, reports combining toxin detection in clinical specimens with autopsy pathology remain limited. We conducted a retrospective analysis of A. exitialis poisoning events treated at Chuxiong Yi Autonomous Prefecture People’s Hospital from 2019 to 2024. Toxins were measured in collected mushrooms, patient blood, and urine. Clinical data included demographics, complications, laboratory parameters, and autopsy findings. Associations between a time-weighted urinary amatoxin exposure metric and laboratory indices were assessed. Ten poisoning incidents involving 27 individuals were identified, including five deaths. We collected 10 mushroom samples, 120 urine samples, and 108 blood samples. α-amanitin, β-amanitin, phallacidin, and phallisacin were detected in mushrooms and urine. The detection rates of α-AMA, β-AMA, PCD, and PSC in urine samples were 31.67%, 5.00%, 38.33%, and 49.17%, respectively. Only three blood samples tested positive for α-AMA. The time-weighted urinary amatoxin exposure metric was positively correlated with total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR). Early symptoms included nausea, vomiting, diarrhea, abdominal pain, and distention; later findings involved injury to the liver, kidneys, intestines, heart, and lungs. On the fourth day following ingestion, there was a marked increase in bilirubin levels and a concurrent decrease in liver enzymes, indicating severe damage to the hepatocytes. Platelet count, white blood cell count, hemoglobin, and red blood cell count decreased over time. Autopsies demonstrated hepatic, renal, and myocardial injury, gastrointestinal mucosal exfoliation, and multiorgan hemorrhage. In summary, A. exitialis poisoning is primarily characterized by liver damage, accompanied by injuries to the kidneys, myocardium, and intestines, as well as multiorgan hemorrhaging, which may lead to blood toxicity. The detection rate of toxins in urine samples is relatively high, and early urine toxin testing can help clarify the diagnosis and guide treatment.
53. Are Online Maps and Booking Systems for Antenatal Vaccination Fit for Purpose? A Qualitative Study.
期刊: Vaccines 发表日期: 2025-Nov-28 链接: PubMed
摘要
Objective: Online maps and booking tools aim to reduce barriers to vaccination by helping users locate nearby clinics, understand service availability, and provide information about vaccination choices. The aim of this research was to explore the potential of online vaccination booking and mapping tools in facilitating antenatal vaccination uptake among Māori and Pacific hapū māmā (pregnant women) in Aotearoa. Methods: This was a qualitative descriptive study that used kaupapa Māori methodology. Focus groups with hapū māmā and semi-structured interviews with healthcare workers were conducted. Transcripts were analyzed thematically. Results: Seven hapū māmā and forty healthcare professionals participated. Three main themes were developed from interviews with hapū māmā: (i) limited awareness of online maps and bookings for vaccination services; (ii) the need for accessible, user-friendly information; and (iii) preference for flexible booking systems. Three themes were developed from the healthcare worker interviews: (i) difficulties with accessibility; (ii) promotion of tools; and (iii) usability of online platforms. Discussion: Although antenatal vaccinations are publicly funded, systemic and digital barriers persist, especially for Māori and Pacific communities. Online tools have the potential to support maternal vaccination, but require improved visibility, cultural relevance, and functionality to be effective.
54. Dhai, Ayah, and Anglo-Indian Mother: Rivalry in the Nursery in Nineteenth-Century British India.
期刊: Canadian journal of health history = Revue canadienne d’histoire de la sante 发表日期: 2025-Sep 链接: PubMed
摘要
In nineteenth-century British India, the Anglo-Indian mother and the female Indian servants hired to help her with nursing and childcare were seen as potential rivals in the nursery. In the late nineteenth century, a divide in the discourse of nursing opened between, on one hand, medical handbooks and domestic guides preferring the Anglo-Indian mother, if healthy, to the dhai (Indian wet nurse) or ayah (Indian nursemaid) as a provider of milk to her infants and, on the other, Anglo-Indian fictional works by Rudyard Kipling and Sara Jeannette Duncan elevating the dhai or ayah above her British counterpart as a source of early maternal sustenance, particularly for sons. In these fictional narratives, the dhai or the bottle-feeding nursemaid is seen as a beneficial figure, whose milk (whether mammary or bottled) supplies to Anglo-Indian sons not only physical robustness but also an intuitive understanding of Indian cultures crucial to their efficacy as future imperial rulers. In these narratives, male Anglo-Indian infants, nourished by Indian milk and endowed by birth with British “blood,” possess a quasi-biological hybridity that putatively ensures both an acculturation to native mores and an inborn loyalty to the British Raj that will allow them to serve, in adulthood, as model civil servants or army officers. These fictional works, moreover, reconceive the idea of motherhood: the eclipse of the Anglo-Indian mother, who is dead or simply ineffectual, and the temporary promotion of the dhai or ayah to maternal surrogate and facilitator of continued imperial dominance at a time of rising Indian nationalism. Résumé. Dans l’Inde britannique du XIXe siècle, les mères anglo-indiennes et les servantes indiennes engagées pour les aider à allaiter et à s’occuper des enfants étaient considérées comme des rivales potentielles pour ce qui était d’élever les enfants. À la fin du XIXe siècle, un fossé s’est creusé dans le discours sur l’allaitement entre, d’une part, les manuels médicaux et les guides domestiques qui préféraient la mère anglo-indienne, si elle était en bonne santé, à la dhai (nourrice indienne) ou à l’ayah (nounou indienne) comme source de lait pour ses nourrissons et, d’autre part, les œuvres de fiction anglo-indiennes de Rudyard Kipling et Sara Jeannette Duncan, qui élevaient la dhai ou l’ayah au-dessus de son homologue britannique en tant que source initiale d’alimentation dans un contexte de soins maternels, en particulier pour les fils. Dans ces récits fictifs, la dhai ou la nourrice qui donne le biberon est présentée comme une figure bienfaisante, dont le lait, qu’il soit maternel ou en bouteille, apporte aux enfants anglais d’origine indienne non seulement une robustesse physique, mais également une compréhension intuitive de la culture indienne, essentielle pour leur efficacité future en tant que leaders impériaux. Dans ces récits, les nourrissons anglo-indiens de sexe masculin, nourris au lait indien et dotés dès la naissance du « sang » britannique, possèdent une hybridité quasi biologique qui leur garantit à la fois une acculturation aux mœurs locales et une loyauté innée envers le Raj britannique, ce qui leur permettra, à l’âge adulte, de devenir des fonctionnaires ou des officiers de l’armée modèles. Ces œuvres de fiction repensent en outre la notion de maternité : l’éclipse de la mère anglo-indienne, morte ou simplement inefficace, et la promotion temporaire de la dhai ou ayah au rang de mère de substitution et de facilitatrice de la domination impériale continue à une époque où le nationalisme indien est en plein essor.