Frontiers in Aging Neuroscience最新文献

{"title":"Diagnostic value of olfactory function testing for Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.","authors":"Yuxuan Liu, Yunpeng Cao, Hongquan Wei","doi":"10.3389/fnagi.2025.1551939","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1551939","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is clinically classified into prodromal (asymptomatic), mild cognitive impairment (MCI) due to AD, and dementia due to AD. This study investigates the diagnostic value of olfactory function testing for AD and MCI.</p><p><strong>Methods: </strong>Systematic searches of PubMed, Web of Science, Cochrane, and EMBASE databases were conducted up to February 1, 2024. Methodological quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies. Effect sizes were combined using a random-effects model (DerSimonian-Laird method), and statistical analyses were conducted using STATA 15.1 and Meta-Disc 1.4 software.</p><p><strong>Results: </strong>Twenty-five studies with 13,611 participants were included. For diagnosing AD, combined sensitivity (SE) was 0.79 (95% CI: 0.71-0.85), specificity (SP) was 0.78 (95% CI: 0.69-0.84), and AUC was 0.85 (95% CI: 0.82-0.88). For MCI, SE was 0.67 (95% CI: 0.54-0.78), SP was 0.79 (95% CI: 0.71-0.86), and AUC was 0.81 (95% CI: 0.77-0.84). Combined SE and SP for diagnosing AD and MCI were 0.58 (95% CI: 0.46-0.68) and 0.88 (95% CI: 0.78-0.93), with an AUC of 0.78 (95% CI: 0.74-0.82). SE and SP for AD or MCI were 0.83 (95% CI: 0.36-0.98) and 0.94 (95% CI: 0.82-0.98), with an AUC of 0.96 (95% CI: 0.94-0.98).</p><p><strong>Conclusion: </strong>This systematic review and meta-analysis reveal that olfactory function testing, as a simple, non-invasive, and cost-effective assessment method, demonstrates high diagnostic efficacy in the early identification of AD and MCI, showing promising clinical application.</p><p><strong>Systematic review registration: </strong>CRD42024520871.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1551939"},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181473","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":"Predicting brain age for veterans with traumatic brain injuries and healthy controls: an exploratory analysis.","authors":"John P Coetzee, Xiaojian Kang, Victoria Liou-Johnson, Ines Luttenbacher, Srija Seenivasan, Elika Eshghi, Daya Grewal, Siddhi Shah, Frank Hillary, Emily L Dennis, Maheen M Adamson","doi":"10.3389/fnagi.2025.1472207","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1472207","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is associated with increased dementia risk. This may be driven by underlying biological changes resulting from the injury. Machine learning algorithms can use structural MRIs to give a predicted brain age (pBA). When the estimated age is greater than the chronological age (CA), this is called the brain age gap (BAg). We analyzed this outcome in men and women with and without TBI.</p><p><strong>Objective: </strong>To determine whether factors that contribute to BAg, as estimated using the brainageR algorithm, differ between men and women who are US military Veterans with and without TBI.</p><p><strong>Methods: </strong>In an exploratory, hypothesis-generating analysis, we analyzed data from 85 TBI patients and 22 healthy controls (HCs). High-resolution T1W images were processed using FreeSurfer 7.0. pBAs were calculated from T1s. Differences between the two groups were tested using the Mann-Whitney U. Associations between the BAg and other factors were tested using partial Pearson's <i>r</i> within groups, controlling for CA, followed by construction of regression models.</p><p><strong>Results: </strong>After correcting for multiple comparisons, TBI patients and HCs differed on PCL score (higher for TBI patients) and cortical thickness (CT) in both hemispheres (higher for HCs). Among women TBI patients, BAg was correlated with pBA and hippocampal volume (HV), and among men TBI patients, BAg was correlated with pBA and CT. Among both men and women HCs, BAg was correlated only with CA. Four hierarchical regression models were constructed to predict BAg in each group, which controlled for CA and excluded pBA for multicollinearity. These models showed that HV predicted BAg among women with TBI, while CT predicted BAg among men with TBI, while only CA predicted BAg among HCs.</p><p><strong>Interpretation: </strong>These results offer tentative support to the view the factors associated with BAg among individuals with TBI differ from factors associated with BAg among HCs, and between men and women. Specifically, BAg among individuals with TBI is predicted by neuroanatomical factors, while among HCs it is predicted only by CA. This may reflect features of the algorithm, an underlying biological process, or both.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1472207"},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179890","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":"Mirodenafil improves cognitive function by reducing microglial activation and blood-brain barrier permeability in ApoE4 KI mice.","authors":"Yejin Park, Subin Moon, Harry Jung, Songyi Park, Ju Won Kim, Dan-Gyeong Song, Yong-Ho In, Sang Won Han, Jong-Hee Sohn, Chan Hee Lee","doi":"10.3389/fnagi.2025.1579411","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1579411","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) has significant public health concerns in the aging society. AD can compromise brain function and lead to severe neurological abnormalities associated with dementia. The human Apolipoprotein E (ApoE4) gene is a strong risk factor for AD. However, comprehensive analyses and improvements of mouse models expressing ApoE4 remain largely unexplored.</p><p><strong>Methods: </strong>ApoE4 knock-in (KI) mice were used to investigate the role of humanized ApoE4 in hippocampal histological changes and cognitive impairment. Cerebrovascular perfusion, blood-brain barrier (BBB) integrity, microgliosis, and amyloid-beta 42 (Aβ₄₂) accumulation were examined. Cognitive functions were assessed using the Morris water maze, Y-maze, and novel object recognition tests. Mirodenafil, a potent and selective phosphodiesterase 5 inhibitor (PDE5i), was orally administered to ApoE4 KI mice for 4 weeks. An <i>in vitro</i> BBB model and BV2 microglial cells were used to investigate endothelial permeability and inflammation.</p><p><strong>Results: </strong>ApoE4 KI mice exhibited not only reduced cerebrovascular perfusion and CLN-5 expression but also increased microgliosis and Aβ₄₂ accumulation in the hippocampus. These phenomena were accompanied by impaired cognitive functions. Mirodenafil administration reversed the histological and behavioral alterations induced by ApoE4 KI. <i>In vitro</i>, mirodenafil treatment mitigated Aβ₄₂-induced endothelial permeability and lipopolysaccharide-induced microglial inflammation.</p><p><strong>Discussion: </strong>These findings suggest that mirodenafil enhances cerebrovascular function, preserves BBB integrity, and mitigates neuroinflammation in ApoE4 KI mice, leading to cognitive improvement. PDE5 inhibition may serve as a promising therapeutic approach for addressing ApoE4-associated cerebrovascular and cognitive dysfunction.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1579411"},"PeriodicalIF":4.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179738","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":"Knowledge map of artificial intelligence in neurodegenerative diseases: a decade-long bibliometric and visualization study.","authors":"Junwei Huang, Shuqi Wang, Xuankai Liao, Danting Su, Rubing Lin, Tao Zhang, Long Zhao","doi":"10.3389/fnagi.2025.1586282","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1586282","url":null,"abstract":"<p><strong>Background: </strong>As the incidence of neurodegenerative diseases increases, the related AI research is getting more and more advanced. In this study, we analyze the literature in this field over the last decade through bibliometric and visualization methods with the aim of mining the prominent journals, institutions, authors, and countries in this field and analyzing the keywords in order to speculate on possible future research trends.</p><p><strong>Methods: </strong>Our study extracted 1,921 relevant publications spanning 2015-2025 from the Web of Science Core Collection database. We conducted comprehensive bibliometric analyses and knowledge mapping visualizations using established scientometric tools: CiteSpace and Bibliometrix.</p><p><strong>Results: </strong>A total of 1921 documents were included in the study, the number of publications in this field showed an overall increasing trend, and the average number of citations showed a downward trend since 2019. Among the journals, <i>Scientific Reports</i> had the highest number of publications. In addition, we identified 22 core journals. Institution wise, University of London has the highest participation. Among the authors, the highest number of publications is Benzinger, Tammie. The highest number of citations is Fingere Elizabeth. At the national level, the United States is number one in the world in terms of influence in this field, and China is ranked number two, both of which are well ahead of other countries and are major contributors to this field. The analysis of keywords showed the centrality of Alzheimer disease, machine learning, Parkinsons disease, and deep learning. All the studies were clustered based on keywords to get seven clusters: 0. immune infiltration; 1. Parkinsons disease; 2. multiple sclerosis; 3. mild cognitive impairment; 4. deep learning; 5. machine learning; 6. freesurfer; 7. scale. In addition, we also found the continuation of the trending topics, which are Parkinsons disease, deep learning, and machine learning.</p><p><strong>Conclusion: </strong>Based on the relationship between keywords and time, we speculate that there are four possible research trends: 1. Precision diagnosis with multimodal data fusion. 2. Pathological mechanism analysis and target discovery. 3. Interpretable AI and clinical translation. 4. Technology differentiation for subdivided diseases.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1586282"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173312","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":"Identification and validation of pyroptosis-related genes in Alzheimer's disease based on multi-transcriptome and machine learning.","authors":"Yuntai Wang, Yilin Li, Lu Zhou, Yihuan Yuan, Chuanfei Liu, Zimeng Zeng, Yuanqi Chen, Qi He, Zhuoze Wu","doi":"10.3389/fnagi.2025.1568337","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1568337","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) progression is characterized by persistent neuroinflammation, where pyroptosis-an inflammatory programmed cell death mechanism-has emerged as a key pathological contributor. However, the molecular mechanisms through which pyroptosis-related genes (PRGs) drive AD pathogenesis remain incompletely elucidated.</p><p><strong>Methods: </strong>We integrated multiple transcriptomes of AD patients from the GEO database and analyzed the expression of PRGs in combined datasets. Machine learning algorithms and comprehensive bioinformatics analysis (including immune infiltration and receiver operating characteristic (ROC)) were applied to identify the hub genes. Additionally, we validated the expression patterns of these key genes using the expression data from AD mice and constructed potential regulatory networks through time series and correlation analysis.</p><p><strong>Results: </strong>We identified 91 PRGs in AD using the weighted gene co-expression network analysis (WGCNA) and differentially expressed genes analysis. By application of the protein-protein interaction and machine learning algorithms, seven pyroptosis feature genes (CHMP2A, EGFR, FOXP3, HSP90B1, MDH1, METTL3, and PKN2) were identified. Crucially, MDH1 and PKN2 demonstrated superior performance in terms of immune cell infiltration, ROC curves, and experimental validation. Furthermore, we constructed the long non-coding RNA and mRNA (lncRNA-mRNA) regulatory network of these characteristic genes using the gene expression profiles from AD mice at varying ages, revealing the potential regulatory mechanism in AD.</p><p><strong>Conclusion: </strong>This study provides the first comprehensive characterization of pyroptosis-related molecular signatures in AD. Seven hub genes were identified, with particular emphasis on MDH1 and PKN2. Their superior performances were validated through comprehensive bioinformatic analysis in both patient and mouse transcriptomes, as well as the experimental data. Our findings establish foundational insights into pyroptosis mechanisms in AD that may inform novel treatment strategies targeting neuroinflammatory pathways.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1568337"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173344","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":"Iron responsive elements mRNA regulate Alzheimer's amyloid precursor protein translation through iron sensing.","authors":"Mateen A Khan","doi":"10.3389/fnagi.2025.1483913","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1483913","url":null,"abstract":"<p><p>Iron responsive element (IREs) mRNA and iron regulatory proteins (IRPs) regulate iron homeostasis. 5'-untranslated region motifs of APP IREs fold into RNA stem loops bind to IRP to control translation. Through the 5'-UTR APP IREs, iron overload accelerated the translation of the Alzheimer's amyloid precursor protein (APP). The protein synthesis activator eIF4F and the protein synthesis repressor IRP1 are the two types of proteins that IREs bind. Iron regulates the competitive binding of eIF4F and IRP1 to IRE. Iron causes the IRE and eIF4F to associate with one other, causing the dissociation of IRPs and altered translation. In order to control IRE-modulated expression of APP, messenger RNAs are becoming attractive targets for the development of small molecule therapeutics. Many mRNA interference strategies target the 2-D RNA structure, but messenger RNAs like rRNAs and tRNAs can fold into complicated, three-dimensional structures that add another level of complexity. IREs family is one of the few known 3-D mRNA regulatory elements. In this review, I present IREs structural and functional characteristics. For iron metabolism, the mRNAs encoding the proteins are controlled by this family of similar base sequences. Iron has a similar way of controlling the expression of Alzheimer's APP as ferritin IRE RNA in their 5ÚTR. Further, iron mis regulation by IRPs can be investigated and contrasted using measurements of expression levels of APP, amyloid-<i>β</i> and tau formation. Accordingly, IRE-modulated APP expression in Alzheimer's disease has great therapeutic potential through targeting mRNA structures.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1483913"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173309","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":"Corrigendum: Prebiotic effect of fructooligosaccharides from <i>Morinda officinalis</i> on Alzheimer's disease in rodent models by targeting the microbiota-gut-brain axis.","authors":"Diling Chen, Xin Yang, Jian Yang, Guoxiao Lai, Tianqiao Yong, Xiaocui Tang, Ou Shuai, Gailian Zhou, Yizhen Xie, Qingping Wu","doi":"10.3389/fnagi.2025.1593725","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1593725","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnagi.2017.00403.].</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1593725"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173342","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":"Unravelling the interplay: brain regional atrophy and neuropsychological function in early Alzheimer's disease.","authors":"Doyun Heo, Min-Seong Kim, Yun-Jin Lee, Seon-Kyeong Kim, Yong Sung Kim, Wonjae Sung, Hee-Jin Kim","doi":"10.3389/fnagi.2025.1508849","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1508849","url":null,"abstract":"<p><strong>Objectives: </strong>The structural changes in the brain differ between normal aging and Alzheimer's dementia (AD). The results of cognitive function tests reflect structural changes in the brain in AD. This study aimed to determine the specific relationship between regional brain volume and neuropsychological subtest scores.</p><p><strong>Methods: </strong>Ninety-three patients with definitive diagnosis of AD (confirmed by PET) were retrospectively enrolled. An automated program Quick Brain Volumetry (QBraVo) was used to measure the regional gray matter (GM) volume of the participants. Each score of the Seoul Neuropsychological Screening Battery (SNSB) subset test was statistically analyzed to observe correlations between regional brain volumes and cognitive function. Results of the SNSB subset test were compared to the degree of brain volume atrophy.</p><p><strong>Results: </strong>The Controlled Oral Word Association Test (COWAT), Trail making test for the elderly (TMT-e), and Korean version Boston naming test (K-BNT) were strongly correlated with GM volume atrophy, mainly in the temporal lobe. Memory functions, including Seoul verbal learning test (SVLT), Rey complex figure test (RCFT) recall and recognition tests, were significantly correlated with both the temporal and frontal regions. Various tests reflecting frontal and executive functions did not reveal significant correlations with the frontal regions. The BNT test scores reflecting language function did not correlate with frontal atrophy. Tests reflecting visuospatial capability (RCFT) were also related to inferior frontal and temporal atrophies.</p><p><strong>Conclusion: </strong>In patients with AD, the results of most cognitive function tests are related to the degree of atrophy of the temporal and frontal cortices. Further research is necessary to determine the extent to which cognitive function test results are associated with brain atrophy.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1508849"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173350","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":"Research status of visuospatial dysfunction and spatial navigation.","authors":"Rui Bao, Shijie Chang, Ruixiang Liu, Yunning Wang, Yifu Guan","doi":"10.3389/fnagi.2025.1609620","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1609620","url":null,"abstract":"<p><p>Visuospatial function is a critical aspect of cognitive abilities, encompassing visual perception, attention, memory, and adaptive responses to spatial changes. This paper reviews studies on human visuospatial function, spatial navigation, and factors contributing to visuospatial impairments. After introducing fundamental concepts of visuospatial function and spatial navigation, classical methods for assessing visuospatial performance are summarized. By examining recent advances in spatial navigation studies, this paper discusses factors influencing spatial navigation capabilities and explores how spatial navigation paradigms can be used to investigate visuospatial cognitive impairments. Finally, current limitations in spatial navigation research are highlighted. Overall, the current research has not yet reached definitive conclusions regarding visuospatial aspects. However, this paper aims to enhance the understanding of visuospatial dysfunction and spatial navigation, providing valuable references for future research.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1609620"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173318","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":"Plasma neurofilament light chain mediates the effect of subsyndromal symptomatic depression on cognitive decline in older adults.","authors":"Chunhua Zhang, Bingyu Li, Kok Pin Ng, Guojuan Huang, Xijin Wang, Min Kong, Maowen Ba","doi":"10.3389/fnagi.2025.1547394","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1547394","url":null,"abstract":"<p><strong>Objective: </strong>Subsyndromal symptomatic depression (SSD) is associated with an increased risk of cognitive impairment in non-demented older adults. However, the mechanism underlying this relationship remains unclear. This study aimed to investigate whether plasma neurofilament light chain (NfL) mediates the relationship between SSD and cognitive decline.</p><p><strong>Materials and methods: </strong>Data of 707 non-demented older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were analyzed. Geriatric Depression Scale (GDS) scores were collected at baseline, while plasma NfL levels and cognitive assessments were obtained at baseline, 1-year, and 2-year follow-up visits. SSD was defined as a GDS score of 1-5. Mediation analyses were performed to examine whether the rate of change in plasma NfL levels mediated the relationship between SSD and cognitive decline.</p><p><strong>Results: </strong>Participants with SSD exhibited a greater increase in plasma NfL levels and more pronounced declines in global cognition, memory, executive function, language, and processing speed over 2 years compared to non-SSD participants. The rate of change in plasma NfL levels significantly mediated the relationship between SSD and accelerated cognitive decline, particularly in global cognition, memory, language, and processing speed.</p><p><strong>Conclusion: </strong>Plasma NfL, which is related to neuroaxonal damage, may partially mediate the association between SSD and accelerated cognitive decline in non-demented older adults. These findings suggest that dynamic changes in plasma NfL levels may reflect early neurobiological alterations associated with SSD and could help identify individuals at increased risk of cognitive deterioration over a 2-year period.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1547394"},"PeriodicalIF":4.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173315","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}