Journals
2026 EN
Biber Sarah · Culhane Jessica E. · Prado Maria G.
+21 more
Abstract INTRODUCTION Integrating real‐world data (RWD) with clinical research datasets creates more complete, context‐rich resources to drive discovery and enable precision medicine in Alzheimer's disease and related dementias. The National Alzheimer's Coordinating Center conducted a proof‐of‐concept (POC) project to link its longitudinal Uniform Data Set (UDS) with electronic health records (EHRs), Medicare claims, and genomic data. METHODS In partnership with three Alzheimer's Disease Research Centers (ADRCs), we developed scalable data pipelines and a governance framework to collect, harmonize, and securely share linked data through the National Institute on Aging's LINKAGE Program. RESULTS We linked UDS and EHR data for 2206 participants and added Medicare claims for 1522. Nearly 500 participants have 5 or more years of linked data, with genomic profiles available for 93%. DISCUSSION This POC demonstrates the feasibility of integrating clinical, genomic, and RWD across ADRCs, offering a scalable model for broader implementation.
Journals
2026 EN
Carrillo Maria C · Mahinrad Simin
Abstract Over the past four decades, the partnership between the Alzheimer's Association, Alzheimer's Disease Research Centers (ADRCs), and the National Alzheimer's Coordinating Center (NACC) has been instrumental in advancing research, data infrastructure, and community impact in Alzheimer's disease (AD) and related dementias (ADRD). Established in 1984, ADRCs now span 36 centers conducting cutting‐edge translational research, supported by NACC's comprehensive infrastructure that harmonizes, standardizes, and centralizes ADRC data. The Alzheimer's Association has actively amplified these efforts through major research funding, federal advocacy, data‐sharing platforms, and community engagement programs. The partnership between the Alzheimer's Association, ADRCs, and NACC has accelerated discoveries in AD/ADRD, influenced public policy, and enhanced translation of research into real‐world practice. Their sustained collaboration represents a powerful and scalable model for addressing the growing burden of AD/ADRD and advancing progress in prevention, diagnosis, and care.
Journals
2026 EN
Hall Stephen · Garcia Leticia · Stahmer Marie
+3 more
Abstract BACKGROUND Roughly 7.2 million older Americans are living with Alzheimer's disease (AD). Research participation remains one of the largest barriers facing dementia research advancements. METHODS TrialMatch is a dementia research awareness tool. TrialMatch consolidates research opportunities to serve as an open‐access, centralized, and user‐friendly resource to identify research opportunities. Between August 2020 and June 2024, we tracked the number of research opportunities available, enrollment targets, and TrialMatch engagement. RESULTS TrialMatch maintained a database of over 700 opportunities and received 18,802 calls and 122,461 web sessions, and provided 17,725 referrals to opportunities. An estimated 1,867,403 participants are needed to populate all the ongoing studies in the United States. DISCUSSION By using a broad inclusion criteria, TrialMatch highlights the burden that AD/ADRD research faces with recruitment. While TrialMatch has demonstrated its ability to serve as an awareness tool, future analyses are needed to better evaluate the impact of the tool on enrollment.
Journals
2026 EN
Salvador Larissa · Giatti Luana · Souza Leonardo Cruz
+5 more
Abstract INTRODUCTION Cognitive reserve (CR) arises from cognitively enriching experiences over time and may buffer against cognitive decline. However, the mechanisms underlying CR in low‐ and middle‐income countries (LMICs) remain underexplored. This study investigated the latent structure of CR using socioeconomic and occupational indicators, and evaluated whether CR categories are associated with cognitive trajectories over 8 years. METHODS In the ELSA‐Brasil study, we derived a CR construct via principal component analysis from five indicators: education, occupational social class, occupational nature, technological stratum of work, and leisure‐time physical activity. Memory, verbal fluency, and executive functioning were assessed at three waves; longitudinal trajectories were analyzed using mixed‐models. RESULTS Participants with higher CR exhibited significantly slower age‐related cognitive decline across multiple domains, after controlling for demographic and health covariates. DISCUSSION In a middle‐income country with strong socioeconomic inequalities, early‐life socioeconomic conditions were key determinants of CR development, contributing to disparities in late‐life cognitive aging.
Journals
2026 EN
Aliberti Márlon Juliano Romero · AvelinoSilva Thiago Junqueira · Covinsky Kenneth E.
+14 more
Abstract INTRODUCTION Cognitive impairment in hospitalized older adults without delirium is often undiagnosed. We evaluated the diagnostic accuracy and prognostic value of two brief bedside screening tools—the 10‐point Cognitive Screener (10‐CS) and Short Portable Mental Status Questionnaire (SPMSQ). METHODS Multicenter prospective cohort of 2003 patients ≥65 years of age without delirium, admitted to 43 hospitals in five countries of the Creating a Hospital Assessment Network in Geriatrics (CHANGE) Study. Screening was completed within 48 h of admission. Dementia was defined as informant‐based Clinical Dementia Rating ≥1. RESULTS Dementia prevalence was 22%, with 35% undiagnosed. Both tools showed good accuracy for detecting dementia, with the 10‐CS slightly more accurate than SPMSQ (area under the curve [AUC] = 0.87 vs 0.85; p = 0.02). After adjustment, cognitive impairment detected by either tool was associated with increased risk of incident delirium, hospital‐associated disability in self‐care activities, and 90‐day mortality, but not prolonged stay. DISCUSSION Brief bedside screening identified dementia and predicted adverse outcomes, supporting its integration into routine hospital care.
Journals
2026 EN
Rae Rosaria J. · Alberhasky Jessica Marie Hunter · Baillet Marion
+51 more
Abstract Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia‐related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex‐specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non‐disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex‐specific AD susceptibility and potential footholds for sex‐based interventions targeting these systems. We conclude by outlining immediate and long‐term actions to address the intersection of NSSs, sex, and AD.
Journals
2026 EN
Suemoto Claudia K. · Custodio Nilton · Aguilar Diego
+39 more
Abstract Latin America is undergoing rapid population aging alongside a rising burden of dementia. While the region holds substantial potential for dementia risk reduction, challenges remain, such as delayed diagnoses, limited access to specialized care and biomarker testing, persistent stigma, and deep‐rooted structural inequities. To address these gaps and foster regionally informed solutions, the Alzheimer's Association convened the 2025 Alzheimer's Association International Conference (AAIC) Satellite Symposium in Lima, Peru, on May 14–15, in collaboration with the Global Brain Health Institute (GBHI) and the Atlantic Fellows for Equity in Brain Health. The meeting aimed to bring core elements of the global AAIC meeting to regional Latin American settings, recognizing that national and cultural contexts demand tailored approaches to dementia prevention, risk reduction, treatment and care all aimed at promoting brain health in the region. This manuscript synthesizes the symposium's key discussions, scientific advances, and opportunities for collaboration across the region.
Journals
2026 EN
Cressman Erik N. K. · Hicks Samantha · Fowlkes Natalie W.
+2 more
Abstract Background The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease. Transgenic approaches hold promise in addressing this complex problem. One such model, the Oncopig, has been reported to develop tumors of up to 4 cm in diameter within 7–14 days at sites of in situ vector inoculation. However, the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail. Methods Herein, we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and replaced in the tissue. The study consisted of 3 animals in 3 cohorts (total of 9 animals) that were evaluated at 14, 21, and 28 days. CT imaging, immunohistochemistry, multiplex immunofluorescence, and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation. Results The tumors were hypovascular on CT and predominantly composed of CD45+ cells with a strong lymphohistiocytic component, with no carcinomas identified. Ki‐67 staining showed proliferation of CD45+ immune cells but no neoplastic component. To provide further insight, the results are evaluated in the context of tumor growth kinetics. Conclusion While progress has been made in generating targetable lesions, achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.
Journals
2026 EN
Vinogradova Elena Vladimirovna · Varavko Maria Alexandrovna · Ustyugov Yakov Yuryevich
+3 more
Abstract A lupus‐like condition induced by intraperitoneal administration of pristane (2,6,10,14‐tetramethylpentadecane) in mice is widely used as a model of systemic lupus erythematosus (SLE). Due to their phylogenetic distance from humans, murine models are not always suitable tool for studying the specific activity of therapeutic agents and the pathogenesis of SLE. In order to overcome species‐specific limitations of murine models, this approach was tested in non‐human primates—cynomolgus monkeys ( Macaca fascicularis ). Two intraperitoneal injections at a dose of 3.5 mL/kg, administered at weeks 1 and 23, recapitulated SLE features, including: production of antinuclear autoantibodies (ANA), membranoproliferative glomerulonephritis with immune complex (IC) deposition in the glomeruli. However, from week 27 five of eight pristane‐treated monkeys developed progressive respiratory failure. Two of these died at week 28 and the remaining were euthanized at week 32. The histology of the monkey lungs suggested exogenous lipoid pneumonia. Thus, while pristane induced serological autoimmunity and characteristic renal manifestations in Macaca fascicularis , the consequent lipoid pneumonia limited the observation period and prevented comprehensive evaluation of SLE manifestations beyond 32 weeks.
Journals
2026 EN
GranadosMartinez Cristina · AlfagemeLopez Nuria · NavarroOviedo Manuel
+8 more
Abstract Stroke induces profound neuroinflammation and systemic immune dysregulation, including disturbances in gut homeostasis. Experimental evidence suggests that intestinal barrier permeability (IBP) and bacterial translocation (BT) critically influence stroke outcomes. However, biological variability among commonly used rodent substrains has received limited attention. In this pilot study, we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers: RccHan (Envigo) and RjHan (Janvier). Naive animals ( n = 4) and rats subjected to permanent cerebral ischemia ( n = 8 per substrain) were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT. Immune cell populations in blood and bone marrow were analyzed using flow cytometry, and leukocyte infiltration into ischemic brain tissue was quantified using immunohistochemistry. Differences were considered statistically significant when p < 0.05. Both substrains developed significant infarcts and neurological deficits. RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs. In contrast, RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP. Although dissemination was broader in RccHan rats, overall bacterial burden was slightly lower compared with RjHan, and extraintestinal bacterial composition differed between groups. Particularly, RjHan rats exhibited stronger systemic and central immune activation, with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T‐cell infiltration within ischemic lesions. These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity, bacterial dissemination, and immune responses considering substrain‐related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.