Frontiers in Aging Neuroscience最新文献

{"title":"Regulation of BBB function and pathological evolution of PD by microenvironment \"spatiotemporal gradient\": unique advantages of microfluidic chips.","authors":"Sixun Yu, Lingli Jiang, Min Song, Tao Yang, Ma Yuan, Xin Chen, Haifeng Shu","doi":"10.3389/fnagi.2025.1599509","DOIUrl":"10.3389/fnagi.2025.1599509","url":null,"abstract":"<p><p>Parkinson's disease (PD), a prevalent neurodegenerative disorder, exhibits an exceedingly intricate pathological process characterized by multifaceted neuronal loss, inflammatory responses, protein misfolding, and blood-brain barrier (BBB) dysfunction. In the pathogenesis of PD, the BBB serves not only as a protective interface for the central nervous system but also actively contributes to the regulation of neural microenvironment homeostasis. Consequently, its impaired functionality can markedly exacerbate disease progression. Within the <i>in vivo</i> microenvironment, factors such as chemical gradients, fluid shear stress, and physical-mechanical signals play pivotal roles in modulating cellular behavior and organ function. The spatiotemporal dynamics of these gradients critically influence BBB integrity and neuroinflammatory responses. However, traditional <i>in vitro</i> models struggle to faithfully replicate such multidimensional dynamic microenvironmental changes. Recently, microfluidic chip technology has emerged as a transformative platform capable of simulating <i>in vivo</i> conditions through precise control of microenvironmental spatiotemporal gradients. This review examines the advancements of microfluidic chips in reproducing <i>in vivo</i> dynamic microenvironment gradients, regulating BBB function, and elucidating the pathological evolution of PD. It delves into the fundamental principles of microfluidic technology, gradient generation and control methodologies, and provides examples of BBB organoid models and PD pathological environment simulations constructed on this platform. Additionally, it systematically evaluates the technical bottlenecks, standardization challenges, and data integration issues associated with current model development, while exploring the potential for future technological convergence and interdisciplinary collaboration in advancing PD precision simulation and personalized treatment.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1599509"},"PeriodicalIF":4.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of inflammatory biomarkers underlies extracellular vesicle mediated functional recovery in an aged monkey model of cortical injury.","authors":"Ryan P McCann, Bethany Bowley, Monica Pessina, Qiong Yang, Hongqi Xin, Sarah A DeVries, Mingjin Wang, Yi Zhang, Michael Chopp, Zhenggang Zhang, Douglas L Rosene, Ella Zeldich, Maria Medalla, Tara L Moore","doi":"10.3389/fnagi.2025.1605144","DOIUrl":"10.3389/fnagi.2025.1605144","url":null,"abstract":"<p><p>Cortical injury results in inflammation and cell death that can cause disability, especially in the aged population. Previous studies from our group have demonstrated the efficacy of bone marrow mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) as a therapeutic to mitigate damage and enhance recovery in our aged monkey model of cortical injury. In the first 3-5 weeks following injury to the hand representation of the primary motor cortex, monkeys treated intravenously with MSC-EVs exhibited a more rapid and complete recovery of fine motor grasp compared to vehicle-treated monkeys. However, whether recovery and treatment are associated with temporal changes in peripheral or central biomarkers of inflammation remain unknown. The current study used the highly sensitive Olink^® Proximity Extension Assay to assess inflammatory protein biomarkers in blood and CSF across a 6-week recovery period in aged female monkeys. MSC-EV treatment promoted a sustained downregulation of pro-inflammatory proteins in plasma across the entire recovery period, and a transient downregulation of anti-inflammatory proteins at 2 weeks post-injury. Functional annotation and pathway analyses showed that the plasma proteins downregulated with MSC-EV treatment were associated with the suppression of pro-inflammatory signaling. Further, immunolabeling of perilesional brain tissue harvested 6-weeks post injury showed an increase in homeostatic microglial phenotypes with MSC-EV treatment. Downregulation of inflammatory markers in plasma and brain tissue were positively correlated with improved functional recovery. These data suggest that MSC-EVs facilitate recovery of function after brain injury, in part, via sustained suppression of both peripheral and central pro-inflammatory signaling across recovery.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1605144"},"PeriodicalIF":4.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered automatic gaze processing in older adults.","authors":"Roger Koenig-Robert, Boris Barrientos, Phoebe E Bailey, Kiley Seymour","doi":"10.3389/fnagi.2025.1592763","DOIUrl":"10.3389/fnagi.2025.1592763","url":null,"abstract":"<p><p>From understanding others' mental states to interpreting social cues, aging impairs social abilities. These impairments might not seem surprising given they rely on other cognitive functions such as memory, attention and decision-making, which are known to decline with age. It is, however, unclear to what degree impairments of more basic perceptual abilities, such as eye-gaze detection, contribute to or even precede the decline in social skills. Previous studies have obtained mixed results when investigating whether aging impairs fundamental perceptual processing of social information. Our study expands on previous findings by showing that aging impairs the ability to rapidly detect and discriminate gaze direction. Using breaking Continuous Flash Suppression (b-CFS), we tested whether preconscious automatic processing of direct eye contact was prioritized over the processing of averted gaze direction, as previously established in younger adults. Our results show that, on average, older adults (65-89 years old, <i>n</i> = 19) lack this direct gaze advantage and do not exhibit significant differences in detecting direct vs. averted gaze direction. These results provide important insights into age-related deficits in social cognition, suggesting social processing deficits may manifest at the earliest automatic stages of perceptual processing. Future work examining the relationship between alterations in gaze processing and decline in higher-level cognitive functions could inform the development of early detection tools and clinical interventions.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1592763"},"PeriodicalIF":4.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficiency of structural brain networks mediates age-associated differences in executive functioning in older adults.","authors":"Geraldine Rodríguez-Nieto, Caroline Seer, Hamed Zivari Adab, Antonio Jimenez-Marin, Sima Chalavi, Amirhossein Rasooli, Jesús M Cortés, Stefan Sunaert, Stephan P Swinnen","doi":"10.3389/fnagi.2025.1593868","DOIUrl":"10.3389/fnagi.2025.1593868","url":null,"abstract":"<p><strong>Introduction: </strong>Older age is associated with alterations in executive functioning (EF). Age-related alterations in the integrity of structural brain networks may contribute to EF decline, with potential consequences for independent living. Graph theory provides powerful metrics to examine the brain's structural connectome, but few studies have investigated the relationship of EF and structural brain networks, as described by graph-theoretical measures, in older adults. We aimed to investigate the mediatory role of network characteristics for the relationship between age and EF in older adults.</p><p><strong>Methods: </strong>Eighty-four older adults completed a battery of EF tasks to allow for the extraction of a latent Common-EF factor. White-matter tractograms were generated from diffusion neuroimaging using anatomically-constrained tractography (ACT) and spherical-deconvolution informed filtering of tractograms (SIFT2).</p><p><strong>Results: </strong>From the resulting networks, global efficiency (reflecting integration) as well as local efficiency (reflecting segregation) were calculated. Older age was associated with worse EF and decreased global and local efficiency. Both global and local efficiency were positively correlated with EF. Local efficiency mediated the negative correlation of age and EF, whereas no such relationship was found for global efficiency. Further regional efficiency analyses identified the nodes that contributed to the mediation effect of local efficiency.</p><p><strong>Discussion: </strong>These results shed light on the shared variability among the integrity of structural brain networks and EF at older age. A causal role of a reduced segregation in structural brain networks to support EF in older adults remains to be determined but would bear promising potential for preserving EF during aging.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1593868"},"PeriodicalIF":4.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sedentary behavior, cognition, and brain health in older adults: a systematic review.","authors":"Marissa A Gogniat, Junyeon Won, Carlos Cruz, Amaya Aranda, Aryan Verma, Swathi Gujral, Andrea M Weinstein, Afsara B Zaheed, Keith R Cole, Kelsie M Full, Beth E Snitz","doi":"10.3389/fnagi.2025.1622049","DOIUrl":"10.3389/fnagi.2025.1622049","url":null,"abstract":"<p><p>Sedentary behavior has been associated with poor health outcomes, especially in older adulthood. Given that sedentary behavior is a highly prevalent, modifiable health behavior, there has been a recent increased interest in examining how sedentary behavior relates to cognition and brain health. The current body of literature is limited and mixed. The purpose of this systematic review was to examine the associations of sedentary behavior with cognition and brain health in older adults across the cognitive spectrum. This study was pre-registered with PROSPERO (CRD42023477868). Six comprehensive databases were searched with pre-registered search terms. A total of 33 studies were included. Overall, results indicated that greater sedentary behavior was associated with worse cognition and brain health, although associations varied based on differences in measurement and classification of sedentary behavior. We discuss next steps and implications for future research.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1622049"},"PeriodicalIF":4.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative analysis of targeted lipidomics in the hippocampus of APP/PS1 mice employing the UHPLC-MS/MS method.","authors":"Shiyu Xiao, Xuemeng Wei, Bing Han, Xiaoqian Shi, Congzhen Wei, Rumeng Liang, Jingna Sun, Zheng Zhang, Zhengang Han, Li Shen","doi":"10.3389/fnagi.2025.1561831","DOIUrl":"10.3389/fnagi.2025.1561831","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is marked by the pathological features of amyloid-<i>β</i> plaque accumulation, as well as intracellular neurofibrillary tangles formation in the patients' brain. Aberrant lipid metabolism is increasingly recognized as one of the important contributors to AD.</p><p><strong>Purpose: </strong>The main goal of this research was to conduct quantitative detection of targeted lipidomics in hippocampal tissue of APPSwe/PS1dE9 mice in order to identify lipid metabolic biomarkers of early-onset AD mice.</p><p><strong>Methods: </strong>Our approach departs from conventional lipid detection methods, employing a highly accurate quantificational Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UHPLC-MS/MS) technique to analyze targeted lipid biomarkers. The innovative method was utilized to detect targeted lipids in the hippocampus of AD and wild-type mice. Statistical method was performed by Student's <i>t</i>-test and multivariate analysis. Differential metabolites were identified through fulfilling the standard of Variable Importance in Projection surpassing one and the significance probability lower than 0.05 thresholds.</p><p><strong>Results: </strong>Both groups utilized identical methodologies and adhered strictly to standardized treatment protocols. Sphingolipids (SPs), Glycerophospholipids (GPs), Glycolipids, Glycerides (GLs), Sterol Lipids (STs), and Free Fatty Acid (FA) were identified as prominent lipids exhibiting alterations in the hippocampus of AD models. Regarding glycolipid and glycerolipid composition, monogalactosyldiacylglycerols (MGDGs) and Triacylglycerols (TGs) constituted a significant proportion (<i>p</i> < 0.05, VIP > 1). Among glycerophospholipids, phosphatidylethanolamines (PEs) and phosphatidylcholines (PCs) emerged as significant constituents (<i>p</i> < 0.05, VIP > 1). Furthermore, hexosylceramides (HexCers) and ceramides (Cers) in the AD model's hippocampus, the prominent sphingolipids in the hippocampus of AD mice, existed as the two primary changed lipid metabolites. The levels of some TGs in GLs and CEs in STs showed a significant elevation (<i>p</i> < 0.05, VIP > 1). In contrast, most kinds of MGDGs, HexCers, Cers, PEs and FA (18:2) demonstrated a notable decrease in the hippocampus of AD group (<i>p</i> < 0.05, VIP > 1).</p><p><strong>Conclusion: </strong>The present research represents the important quantitative identification of distinct lipid biomarker profiles within the hippocampal portion of 7.5-month-aged AD mice. It encompasses glycolipid, GLs, GPs, SPs, STs, and FAs using a targeted HPLC-MS method for quantification. These findings suggest potential diagnostic lipid biomarkers in hippocampus of early-onset AD mice related to cellular membrane integrity, atherosclerosis, oxidative stress damage, and inflammation.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1561831"},"PeriodicalIF":4.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABA, Glx, and GSH in the cerebellum: their role in motor performance and learning across age groups.","authors":"Shanti Van Malderen, Melina Hehl, Stefanie Verstraelen, Robbe Breugelmans, Georg Oeltzschner, Stephan P Swinnen, Koen Cuypers","doi":"10.3389/fnagi.2025.1626417","DOIUrl":"10.3389/fnagi.2025.1626417","url":null,"abstract":"<p><strong>Introduction: </strong>The cerebellum is essential for motor control and learning, relying on structural and functional integrity. Age-related atrophy leads to Purkinje cell loss, but subtle neurochemical changes in GABA, Glx (glutamate + glutamine), and glutathione (GSH) may precede degeneration and contribute to motor decline.</p><p><strong>Methods: </strong>25 younger (YA) and 25 older adults (OA) were included in this study. Magnetic resonance spectroscopy (MRS), using the MEGA-PRESS sequence, was used to investigate how age affects GABA, Glx and GSH levels in the right cerebellar hemisphere, and their relationship with motor performance, measured using a visuomotor bimanual tracking task (BTT).</p><p><strong>Results: </strong>In line with previous work YA outperformed OA on both the simple and complex task variants of the BTT. Furthermore, YA demonstrated faster short-term motor learning as compared to OA. On the metabolic level, no significant age group differences in cerebellar GABA, Glx or GSH levels, nor any task-related modulation of GABA or Glx were observed. Additionally, neither baseline neurometabolite levels nor their modulation predicted motor performance or learning.</p><p><strong>Discussion: </strong>These results align with previous research suggesting that neurometabolic aging is region-specific, with the cerebellum potentially being more resilient due to its slower aging process. Since neither baseline nor task-related modulation of GABA, Glx, or GSH predicted motor performance or learning, cerebellar neurometabolite concentrations may not directly underlie age-related behavioral changes. Instead, volumetric decline and changes in structural and functional connectivity in the aging cerebellum may play a more significant role in motor decline as compared to neurochemical alterations. Nonetheless, it is important to consider that motor performance and learning rely on distributed brain networks-including cortical and subcortical structures-which also undergo age-related changes and may contribute to observed behavioral declines. While our findings do not support a direct role of cerebellar neurometabolite levels in age-related motor performance differences, they underscore the complexity of neurochemical aging.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1626417"},"PeriodicalIF":4.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between tau-PET and quantitative susceptibility mapping in atypical Alzheimer's disease.","authors":"Neha Singh-Reilly, Ryota Satoh, Jonathan Graff-Radford, Mary M Machulda, Val J Lowe, Keith A Josephs, Jennifer L Whitwell","doi":"10.3389/fnagi.2025.1615718","DOIUrl":"10.3389/fnagi.2025.1615718","url":null,"abstract":"<p><strong>Background: </strong>Iron is an important component in neurofibrillary tangles, is known to co-localize with tangles in Alzheimer's disease (AD) and can be measured using quantitative susceptibility mapping (QSM). However, it is unclear if iron measured using QSM is regionally related to tau in atypical presentations of AD.</p><p><strong>Methods: </strong>Forty patients with atypical AD underwent a 3 T magnetic resonance imaging (MRI) scan with a five-echo gradient echo sequence to calculate QSM, Aβ, and [¹⁸F] AV-1451 positron emission tomography (PET). The relationship between QSM and tau-PET was assessed using voxel-based regression analysis using whole brain VoxelStats and region-of-interest (ROI)-based Spearman's correlation analyses using cortical and subcortical ROIs.</p><p><strong>Results: </strong>At the voxel-level, positive correlations between tau-PET and QSM were only observed in the left caudate. At the ROI-level, a positive association was observed between tau-PET and susceptibility in the occipital lobe and a negative association was observed between substantia nigra susceptibility and occipital tau-PET uptake, although these findings did not survive correction for multiple comparisons.</p><p><strong>Discussion: </strong>Our data provides little evidence that regional tau-PET uptake is related to susceptibility changes, suggesting that iron deposition may not be directly associated with tau accumulation in atypical AD.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1615718"},"PeriodicalIF":4.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing changes to individual-specific brain signature with age.","authors":"Monireh Taimouri, Vikram Ravindra","doi":"10.3389/fnagi.2025.1493855","DOIUrl":"10.3389/fnagi.2025.1493855","url":null,"abstract":"<p><p>The increasing prevalence of neurodegenerative diseases in an aging population underscores the critical need for reliable biomarkers distinguishing normal aging from pathological neurodegeneration. This study leverages neuroimaging to identify age-resilient biomarkers, establishing a baseline of neural features that are relatively stable across the aging process. Our research objectives are threefold: (a) Validate a methodology using leverage scores to identify age-robust neural signatures; (b) Confirm the consistency of these features across a diverse age cohort (18-87 years); and (c) Assess the stability of individual-specific neural characteristics across multiple brain parcellations (Craddock, AAL, and HOA). Using functional connectomes data from resting-state and task-based fMRI, we found that a small subset of features consistently capture individual-specific patterns, with significant overlap (~50%) between consecutive age groups and across atlases. Our approach effectively minimized inter-subject similarity while maintaining intra-subject consistency across different cognitive tasks. The stability of these signatures throughout adulthood and their consistency across different anatomical parcellations provide new perspectives on brain aging. They highlight both the preservation of individual brain architecture and subtle age-related reorganization. These findings enhance our understanding of age-related brain changes, potentially aiding in differentiating normal cognitive decline from neurodegenerative processes.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1493855"},"PeriodicalIF":4.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum uric acid to creatinine ratio in patients with early-onset post-stroke cognitive impairment: a retrospective cohort study.","authors":"Libin Liao, Weiquan Huang, Rongchao Ma, Wentong Hu, Hui Wu, Moxi Su, Dujuan Sha","doi":"10.3389/fnagi.2025.1580722","DOIUrl":"10.3389/fnagi.2025.1580722","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment is the major complication of acute ischemic stroke, which is a significant health concern imposing a heavy economic burden on families and society. Studies have shown that the serum uric acid (SUA) level is correlated to clinical outcomes of stroke and neurogenerative diseases. The serum uric acid to serum creatinine ratio (SUA/SCr) is an independent risk factor for poor outcomes of acute ischemic stroke and can potentially become an effective diagnostic indicator for cognitive decline. In this study, we aimed to investigate the association between SUA/SCr and early-onset post-stroke cognitive impairment.</p><p><strong>Methods: </strong>Consecutive acute ischemic stroke patients from our hospital were enrolled between June 2023 and September 2024. All blood samples were collected within 24 h after admission, and the cognitive function of patients was assessed within 2 weeks using the Chinese version of the Montreal Cognitive Assessment (MoCA). SUA/SCr was calculated by serum uric acid (umol/L)/serum creatinine (umol/L) and was split into three layers according to tertiles. The subjects were divided into a post-stroke cognitive impairment group and a non-post-stroke cognitive impairment group based on cognitive assessment. Binary logistic regression with different models, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curves were adopted to evaluate the predictive ability of SUA/SCr in early-onset post-stroke cognitive impairment.</p><p><strong>Results: </strong>The current study showed that the post-stroke cognitive impairment group had lower SUA/SCr (<i>p</i> = 0.005) and the lower tertile of SUA/SCr is associated with a higher prevalence of post-stroke cognitive impairment (<i>p</i> = 0.008). The multivariate logistic analysis indicated that SUA/SCr (OR = 0.560, 95% CI = 0.321-0.976, <i>p</i> = 0.024) was independently associated with early-onset post-stroke cognitive impairment, and the lowest tertile was independently associated with a 5.903-fold increased risk of post-stroke cognitive impairment after adjusting for confounders. The optimal cutoff value of SUA/SCr to predict post-stroke cognitive impairment was 4.874, which gave a sensitivity of 72.22% and a specificity of 63.16%.</p><p><strong>Conclusion: </strong>Our study revealed that SUA/SCr can be a potential indicator for post-stroke cognitive impairment in the early phase, a lower level of SUA/SCr upon admission was independently correlated to cognitive dysfunction after stroke.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1580722"},"PeriodicalIF":4.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}