Frontiers in Aging Neuroscience最新文献

{"title":"Integrative single-cell and cell-free plasma RNA transcriptomics identifies biomarkers for early non-invasive AD screening.","authors":"Li Wu, Renxin Zhang, Yichao Wang, Shaoxing Dai, Naixue Yang","doi":"10.3389/fnagi.2025.1571783","DOIUrl":"10.3389/fnagi.2025.1571783","url":null,"abstract":"<p><strong>Introduction: </strong>Data-driven omics approaches have rapidly advanced our understanding of the molecular heterogeneity of Alzheimer's disease (AD). However, limited by the unavailability of brain tissue, there is an urgent need for a non-invasive tool to detect alterations in the AD brain. Cell-free RNA (cfRNA), which crosses the blood-brain barrier, could reflect AD brain pathology and serve as a diagnostic biomarker.</p><p><strong>Methods: </strong>Here, we integrated plasma-derived cfRNA-seq data from 337 samples (172 AD patients and 165 age-matched controls) with brain-derived single cell RNA-seq (scRNA-seq) data from 88 samples (46 AD patients and 42 controls) to explore the potential of cfRNA profiling for AD diagnosis. A systematic comparative analysis of cfRNA and brain scRNA-seq datasets was conducted to identify dysregulated genes linked to AD pathology. Machine learning models-including support vector machine, random forest, and logistic regression-were trained using cfRNA expression patterns of the identified gene set to predict AD diagnosis and classify disease progression stages. Model performance was rigorously evaluated using area under the receiver operating characteristic curve (AUC), with robustness assessed through cross-validation and independent validation cohorts.</p><p><strong>Results: </strong>Notably, we identified 34 dysregulated genes with consistent expression changes in both cfRNA and scRNA-seq. Machine learning models based on the cfRNA expression patterns of these 34 genes can accurately predict AD patients (the highest AUC = 89%) and effectively distinguish patients at early stage of AD. Furthermore, classifiers developed based on the expression of 34 genes in brain transcriptome data demonstrated robust predictive performance for assessing the risk of AD in the population (the highest AUC = 94%).</p><p><strong>Discussion: </strong>This multi-omics approach overcomes limitations of invasive brain biomarkers and noisy blood-based signatures. The 34-gene panel provides non-invasive molecular insights into AD pathogenesis and early screening. While cfRNA stability challenges clinical translation, our framework highlights the potential for precision diagnostics and personalized therapeutic monitoring in AD.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1571783"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301532","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":"Triglyceride-glucose indices predict all-cause mortality after stroke in NHANES 1999-2018.","authors":"Jiaqian Zheng, Weiwen Mao, Mengqian Sang, Xinyu Pan, Yiluo Xie, Yichi Xie","doi":"10.3389/fnagi.2025.1617419","DOIUrl":"10.3389/fnagi.2025.1617419","url":null,"abstract":"<p><strong>Objective: </strong>The present study explores the prognostic relevance of triglyceride-glucose-based indices in assessing post-stroke survival among affected individuals.</p><p><strong>Methods: </strong>This study utilized a multifaceted analytical approach to assess how triglyceride-glucose-based indicators relate to death risk in stroke patients. This study was analyzed using a multivariate Cox proportional risk regression model incorporating sampling weights, while a restricted cubic spline function was introduced to assess trends in non-linear associations between exposure variables and outcomes. In addition, interaction terms were set and stratified analyses were conducted to verify the robustness and heterogeneity of the model results.</p><p><strong>Results: </strong>This research ultimately included 796 individuals diagnosed with stroke. When adjusting for a wide range of potential confounders, those in the top TyG-BMI quartile exhibited the most pronounced reduction in mortality risk compared to individuals in the lowest category, with a hazard ratio of 0.20 (95% CI: 0.08-0.50), highlighting its protective potential across TyG-BMI. In contrast, individuals falling within the fourth quartile of the TyG-WHtR index demonstrated the strongest positive correlation with the risk of all-cause mortality (Hazard Ratio = 4.61, 95% CI: 1.77-12.00). Moreover, analysis using restricted cubic splines indicated a significant non-linear association between TyG-BMI levels and mortality outcomes (<i>p</i> < 0.05). No statistical interactions were observed between mortality outcomes and demographic or clinical variables including age, sex, smoking, asthma, coronary artery disease, diabetes, or hypertension across any TyG-related indices (<i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>The study outcomes suggest that stroke patients with reduced TyG-BMI and elevated TyG-WHtR levels tend to face increased mortality risks. Nonetheless, addressing obesity may be crucial in exploring potential causal pathways.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1617419"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301535","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":"Association of neutrophil-percentage-to-albumin ratio with mortality in older stroke survivors.","authors":"Jie Huang, Xiaowei Zhang, Luyao Ding, Jiaxiang Yu, Mingshen Lin","doi":"10.3389/fnagi.2025.1611289","DOIUrl":"10.3389/fnagi.2025.1611289","url":null,"abstract":"<p><strong>Background: </strong>The neutrophil-percentage-to-albumin ratio (NPAR) functions as an integrative marker representing inflammatory response and nutritional health. However, its association with mortality in elderly stroke survivors has not been explored.</p><p><strong>Methods: </strong>This cohort study analyzed data from 1,026 elderly stroke survivors in the National Health and Nutrition Examination Survey (NHANES, 1999-2018). The association of NPAR with mortality was analyzed using Cox proportional hazards regression, restricted cubic splines (RCS), Kaplan-Meier survival analysis, and time-dependent receiver operating characteristic (ROC) curves. Subgroup analyses and interaction tests were also performed.</p><p><strong>Results: </strong>During the 6.65-year median follow-up, elevated NPAR showed independent associations with increased all-cause and cardiovascular mortality. Quartile-based analysis revealed 69 and 87% greater mortality hazards for the highest versus lowest NPAR groups, respectively. RCS analysis revealed a non-linear threshold effect at NPAR = 14.5, beyond which the risk of all-cause mortality increased sharply. NPAR demonstrated stable predictive accuracy, with time-dependent AUC ranging from 0.664 to 0.607 for all-cause mortality and 0.652-0.609 for cardiovascular mortality over 3-10 years. Subgroup analyses confirmed consistency across different sex, BMI, lifestyle habits, and comorbidity categories.</p><p><strong>Conclusion: </strong>This study underscores a strong positive correlation between NPAR and prognosis in older adult stroke survivors in the United States, indicating its potential as a novel biomarker for prognostic assessment.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1611289"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301467","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":"Potential cerebrospinal fluid metabolomic biomarkers and early prediction model for Parkinson's disease.","authors":"Yifan Zhang, Yuexin Yan, Xiangxu Kong, Haijun Zhang, Shengyuan Su","doi":"10.3389/fnagi.2025.1582362","DOIUrl":"10.3389/fnagi.2025.1582362","url":null,"abstract":"<p><strong>Objective: </strong>To identify key cerebrospinal fluid (CSF) metabolomic biomarkers associated with Parkinson's disease (PD) and prodromal PD, providing insights for intervention strategy development.</p><p><strong>Methods: </strong>Six hundred and thirty-nine participants from the Parkinson's Progression Markers Initiative (PPMI) cohort were included: 300 PD patients, 112 healthy controls (HC), and 227 prodromal PD patients. Regression analysis and OPLS-DA identified metabolic biomarkers, while pathway analysis examined their relationship to clinical features. An XGBoost-based early prediction model was developed to assess the distinction between PD, prodromal PD, and HC. A two-sample bidirectional Mendelian randomization analysis was performed to examine the association between differential metabolites and Parkinson's disease.</p><p><strong>Results: </strong>Sixty-four metabolites were significantly altered in PD patients compared to HC, with 58 elevated and 6 reduced. In prodromal PD, 19 metabolites were increased, and 34 were decreased. Key metabolic pathways involved glutathione and amino acid metabolism. Dopamine 3-O-sulfate correlated with PD progression, levodopa-equivalent dose, and non-motor symptoms. The XGBoost model demonstrated high specificity in predicting the onset of PD. The MR analysis results showed a positive correlation between higher genetic predictions of dopamine 3-O-sulfate levels and the risk of Parkinson's disease. In contrast, the reverse MR analysis found that Parkinson's disease susceptibility significantly increased dopamine 3-O-sulfate levels.</p><p><strong>Conclusion: </strong>The differential expression of CSF metabolites reveals early cellular metabolic changes, providing insights for early diagnosis and monitoring PD progression. A bidirectional causal relationship exists between genetically determined PD susceptibility and metabolites.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1582362"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301533","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":"Blood essential trace elements and Alzheimer's disease biomarkers in midlife.","authors":"Xin Wang, Kelly M Bakulski, Carrie A Karvonen-Gutierrez, Sung Kyun Park, David Morgan, Brian P Jackson, Roger L Albin, Henry L Paulson","doi":"10.3389/fnagi.2025.1539749","DOIUrl":"10.3389/fnagi.2025.1539749","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, impacting millions globally. Essential trace elements are implicated in key age-related physiologic processes but have not been fully examined with respect to AD etiology. This study investigates associations between serum levels of essential trace elements (manganese, iron, cobalt, copper, zinc, selenium, and molybdenum) and AD biomarkers (Aβ42, Aβ42/Aβ40 ratio, p-tau181, and total tau) in midlife women.</p><p><strong>Methods: </strong>This cross-sectional study included 194 midlife women (median age = 53.3 years) from the Study of Women's Health Across the Nation, Michigan site. Serum levels of trace elements were measured using inductively coupled plasma-mass spectrometry, and AD biomarkers were quantified using single molecule array assays. Multivariable linear regression models assessed potential associations and Bayesian kernel machine regression (BKMR) was used to account for complex co-exposures and non-linear relationships.</p><p><strong>Results: </strong>In the multivariable linear regression models, a doubling of serum molybdenum level was associated with 9.4% higher Aβ42/40 ratio (95% CI: 0.8, 18.6%; <i>p</i> = 0.03), and a doubling of serum cobalt level with 17.5% higher p-tau181 level (95% CI: 3.1, 33.8%; <i>p</i> = 0.02). Copper showed an inverse association with the Aβ42/40 ratio, while zinc was positively associated with the Aβ42/40 ratio, though these associations were marginally significant. BKMR analysis confirmed these associations.</p><p><strong>Conclusion: </strong>This study identified statistically significant associations of serum molybdenum and cobalt levels with AD biomarkers, suggesting a potential protective effect of molybdenum against Aβ aggregation and exacerbation of pathologic tau phosphorylation by cobalt. These findings underscore the need for further longitudinal studies to explore the role of essential trace elements in AD pathogenesis.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1539749"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301469","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":"Effect of transcranial magnetic stimulation combined with transcutaneous auricular vagus nerve stimulation on mild cognitive impairment: a study protocol for a randomized controlled trial.","authors":"Jingjing Zhang, Jun Ma, Yao Rao, Jiali Wu, Hui Xu, Jiawei Ni, Zhiwei Zhao, Cong Wang, Chunlei Shan","doi":"10.3389/fnagi.2025.1600921","DOIUrl":"10.3389/fnagi.2025.1600921","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive brain stimulation techniques have been widely used in patients with mild cognitive impairment (MCI) to accelerate the recovery of their cognitive functions. However, the clinical efficacy of single non-invasive stimulation techniques in treating MCI still requires further improvement. The combination of two non-invasive neuromodulation techniques can enhance the synergistic effects of the treatment. Repetitive transcranial magnetic stimulation (rTMS) regulates the cortical-subcortical network in a \"top-down\" manner, while transcutaneous auricular vagus nerve stimulation (taVNS) modulates the brainstem-limbic system-cortical pathway in a \"bottom-up\" fashion. We will combine rTMS and taVNS, anticipating synergistic regulation through dual pathways to achieve multi-level neural remodeling effects and improve MCI.</p><p><strong>Methods: </strong>This study will investigate the effectiveness of combined rTMS and taVNS therapy in improving the cognitive function of MCI patients. We will enroll 88 participants and randomly assign them to single-stimulation groups and combined-stimulation groups. The single-stimulation groups will be further randomized in a 1:1 ratio into a rTMS + sham taVNS stimulation group and a taVNS + sham rTMS stimulation group; the combined-stimulation groups will be randomized in a 1:1 ratio into an rTMS + taVNS group and an rTMS sham stimulation + taVNS sham stimulation group. All patients will receive treatment for 4 weeks. Assessments will be conducted before treatment (T0), 4-week treatment (T1), and 4-week post-treatment follow-up (T2). The primary outcome measure will be the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-B), while secondary outcome measures will include the Rivermead Behaviour Memory Test (RBMT), the modified Barthel Index (MBI) for activities of daily living, and the latency and amplitude of event-related potential (ERP) P300.</p><p><strong>Discussion: </strong>This study is a clinical randomized controlled trial, which innovatively combines two non-invasive modulation techniques to improve cognitive function in patients with MCI. This study can validate the clinical efficacy of the combined TMS + taVNS stimulation, providing a theoretical basis for the application of this technology in clinical settings.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1600921"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301529","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":"Risk factors and mediation role of sleep quality for depression in cognitively frail older adults: a cross-sectional study.","authors":"Xiaoxing Lai, Yonghua Cai, Hongwei Zhu, Zhiyuan Zhang, Xinyue Zhang, Yang Li, Jiazhen Liu, Xiaopeng Huo","doi":"10.3389/fnagi.2025.1541555","DOIUrl":"10.3389/fnagi.2025.1541555","url":null,"abstract":"<p><strong>Objective: </strong>Aimed to investigate the risk factors associated with depression in community-dwelling older adults with cognitive frailty and to examine the mediating role of sleep quality in the relationship between activities of daily living (ADL) and depression.</p><p><strong>Methods: </strong>A cross-sectional study was conducted using convenience sampling, enrolling older adults with cognitive frailty from six communities in Beijing from July 2023 to December 2023. Cognitive frailty was assessed using the Montreal Cognitive Assessment (MoCA) alongside with the Fried Frailty Phenotype, while depressive symptoms were measured with the Geriatric Depression Scale (GDS-15). Multivariate logistic regression analysis was used to identify risk factors influencing depression, and mediation analysis was employed to explore the mediating effect of sleep quality on the relationship between ADL and depression.</p><p><strong>Results: </strong>Among the 529 elderly participants with cognitive frailty, 128 (24.2%) were found to exhibit depressive symptoms. Multivariate logistic regression identified ADL [Mild Dependence: OR = 176.729 (95% CI 32.427-963.172), <i>p</i> < 0.001; Moderate Dependence: OR = 51.769 (95% CI 12.541-213.697), <i>p</i> < 0.001], loneliness [OR = 13.821 (95% CI 6.095-31.338), <i>p</i> < 0.001], and sleep quality [Suspected Insomnia: OR = 7.310 (95% CI 2.316-23.074), <i>p</i> = 0.001] were significantly associated with depression. Sleep quality was found to mediate the relationship between ADL and depression, accounting for 2.82% of the total effect.</p><p><strong>Conclusion: </strong>Dependence in ADL, loneliness, and poor sleep quality are potential risk factors of depression for cognitive frailty in aging adults. Moreover, sleep quality was found to mediate the relationship between ADL dependence and depressive symptoms.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1541555"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301534","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":"Bibliometric analysis of global research on PD-L1/PD-1 pathway and neurodegenerative diseases over the last two decades (2004-2023).","authors":"Jialin Wu, Chaojin Zhang, Qiang Cao, Wei Xuan, Xiaorong Huai, Jie Zhou, Jie Tian","doi":"10.3389/fnagi.2025.1570428","DOIUrl":"10.3389/fnagi.2025.1570428","url":null,"abstract":"<p><strong>Background: </strong>Programmed death receptor 1 (PD-1), encoded by the PDCD1 gene, functions as a pivotal immunosuppressive molecule. Neurodegenerative diseases (NDDs) encompass a diverse array of neurological disorders that adversely impact the lives of millions of individuals globally. The current study discusses the impacts of PD-L1/PD-1 signaling on NDDs.</p><p><strong>Methods: </strong>A comprehensive online search was conducted using the Web of Science Core Collection database (WOSCC), with a limited time frame set from 2004 to 2023. Data were analyzed with CiteSpace, VOSviewer, and bibliometric package to explore trends in research output, key authors, institutions, journals, and thematic developments.</p><p><strong>Results: </strong>This study analyzed 366 publications within the field of PD-L1/PD-1 and NDDs. During 2004-2023, there's an overall upward trajectory in the number of publications as the years progressed. The United States has a significant influence in this field, accounting for the highest number of publications. It also boasts the top two authors, six of the top 10 journals, and four of the top five institutions in terms of article count. Keyword burst analysis identified EAE, Parkinson's disease, adaptive immunity, immune checkpoint blockade, and cerebrospinal fluid are research hotspots in recent years.</p><p><strong>Conclusion: </strong>This field has garnered increasing research attention, with the United States being the primary contributor. Recent studies have concentrated on the mechanisms through which PD-L1/PD-1 influences NDDs, and research into cerebrospinal fluid may persist as a focal point in the years to come. While the neuroprotective vs. neurodegenerative effects of PD-L1/PD-1 signaling remain controversial, this pathway represents a promising diagnostic and therapeutic target for NDDs.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1570428"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301468","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":"Global and tract-specific differences between younger and older adults in DTI measures of white matter integrity.","authors":"Stephanie Matijevic, Lee Ryan","doi":"10.3389/fnagi.2025.1562660","DOIUrl":"10.3389/fnagi.2025.1562660","url":null,"abstract":"<p><p>Prior research utilizing diffusion tensor imaging (DTI) to examine cerebral white matter microstructural integrity among adults has established that increasing age is associated with poorer white matter health. While age effects on DTI measures of white matter integrity have been shown to vary in strength across different white matter tracts, tract-specific effects may be secondary to a global impact of age on white matter health. Furthermore, this global age effect could result in \"homogenizing\" increases in shared variance across tracts. The present study compared DTI measures in 36 white matter tracts between 71 younger adults (ages 18-37) and 129 older adults (ages 52-82), to (1) determine whether shared variance across white matter tracts increases with age, and (2) examine tract-specific variability in age-related alterations to white matter integrity. Diffusion weighted images were processed using probabilistic tractography in order to reconstruct callosal, association, and radiation tracts, from which average measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were derived. In comparing inter-tract correlation matrices for each DTI measure between age groups, we found stronger inter-tract correlations for older adults relative to younger adults overall. Additionally, general factors for FA, RD and AD, derived from separate factor analyses, accounted for greater proportions of shared variance across tracts among older adults compared to younger adults. For MD, however, the amount of shared variance captured by the general factor was similar between age groups. Older adults exhibited lower FA and higher MD and RD values compared to younger adults for the majority of tracts examined, although the strength of the age effect differed across tracts. Age group differences in AD were more variable. The present findings provide support for the notion that aging exerts a global, homogenizing impact on white matter integrity, alongside tract-specific age effects.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1562660"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301530","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":"Healthy aging in rats is associated with a decline in the ability to inhibit maladaptive responses, but not in measures of self-control by delayed gratification.","authors":"Adam T Brockett, Xavier Sciarillo, Xuan Li, Matthew R Roesch","doi":"10.3389/fnagi.2025.1579934","DOIUrl":"10.3389/fnagi.2025.1579934","url":null,"abstract":"<p><strong>Introduction: </strong>While it is often assumed that aging is associated with a general decline in cognitive health and decision-making, behavioral and neural evidence suggests that this decline may not be as broad as once thought. Cognitive health can be measured in various ways but is often subdivided into our ability to adapt motor plans to rapidly changing sensory information (inhibitory control) as well as our ability to make effectively delay gratification (self-control).</p><p><strong>Methods: </strong>To examine how aging impacts these aspects of cognitive health across the lifespan, we tested rats of various ages on the stop-change task, a measure of inhibitory control, and reset and no-reset versions of the diminishing returns task, a measure of self-control by delayed gratification.</p><p><strong>Results: </strong>In Experiment 1, we show that 10-12-month-old rats performed fewer trials compared to rats 3-4 months of age and exhibited significant differences in some measures of inhibitory, but not self, control as measured by diminishing returns. In Experiment 2, we show that 21-23-month-old rats show significant deficits in multiple measures of inhibitory control but largely resemble 14-15-month-old rats on measures of self-control. The results from both experiments highlight that aged rats tend to be less sensitive to delays in reward. Finally, we show that overexpression of an epigenetic enzyme (histone deacetylase 5)-thought to be elevated in aged individuals-worsens inhibitory control.</p><p><strong>Conclusion: </strong>Across these experiments we show that the impact of aging on cognitive health is not unitary, in that aging negatively impacts the adaptation of motor actions independent of self-control.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1579934"},"PeriodicalIF":4.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301531","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}