{"title":"<i>In vivo</i> quantification of superficial cortical veins on susceptibility-weighted imaging with artificial intelligence image segmentation and the potential mechanism of human cognitive decline.","authors":"Qi Xie, Hai-Xia Xu, Ya-Jie Wang, Hui-Xian Chen, Xiao-Fang Tu, Peng-Peng Han, Jun Wu","doi":"10.3389/fnagi.2025.1557397","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1557397","url":null,"abstract":"<p><strong>Objective: </strong>Changes in superficial cerebral veins (SCV) caused by different cognitive levels were observed using MR susceptibility-weighted imaging (MR-SWI) to explore the vascular mechanism underlying human brain aging and potential biomarkers of cognitive decline <i>in vivo</i>.</p><p><strong>Methods: </strong>Three hundred and sixty-four participants (184 males,180 females and aged 18-79 years) were included in this study. The quantitative features of SCVs in the cerebral hemispheres were collected via MR-SWI and were processed with an artificial intelligence (AI) image segmentation algorithm. The changes in the morphology and structure of the SCVs were analyzed with SPSS software.</p><p><strong>Results: </strong>The quantitative value of SCV were significantly greater in males than in females. In higher age groups, the total number of SCVs and the number of SCVs in the left and right cerebral hemispheres significantly decreased. The number of SCVs in hypertensive patients was significantly lower than that in non-hypertensive patients. Additionally, the diameter, curvature and length of SCVs in the right cerebral hemispheres were significantly lower in anemic patients than in non-anemic patients. The number and length of SCVs in the bilateral cerebral hemispheres were negatively correlated with the rate of cognitive abnormalities. Among tea drinkers in the youth group, the number of SCVs in both hemispheres were negatively correlated with total tau protein (T-tau), and the curvature of SCVs in the right hemisphere was negatively correlated with phospho-tau181(P-tau181) and T-tau concentrations in venous blood. There was a negative correlation between the T-tau concentration in venous blood and tea consumption. The curvature of SCVs in the right cerebral hemisphere had a significant impact on cognitive decline, with a strong positive correlation. The length of SCV in the right hemisphere of the brain had a significant negative correlation with cognitive decline, however, this correlation was relatively weak.</p><p><strong>Conclusion: </strong>The quantitative value of SCV was negatively correlated with cognitive decline. Daily tea consumption may have a positive impact on the quantitative features of SCVs in the young group. As SCVs are a component of the glymphatic system, their blood flow may affect the clearance of toxic proteins.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1557397"},"PeriodicalIF":4.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354315","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":"Kynurenine pathway: a possible new mechanism for exercise in the prevention and treatment of Alzheimer's disease.","authors":"Gangqiang Li, Shuang Li, Wenhui Zhou","doi":"10.3389/fnagi.2025.1617690","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1617690","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common neurodegenerative disease in clinical practice. The kynurenine pathway (KP) is a potential intersection of factors associated with the development of AD (central nervous inflammation, glutamate excitotoxicity, and tau phosphorylation, among others). Pharmacological modulators targeting KP enzymes, such as inhibitors or agonists, and their major neuroprotective metabolites are beneficial in alleviating AD progression. Exercise significantly improves AD symptoms and also impacts KP pharmacokinetics. Promoting the production of neuroprotective active metabolites by KP may be one of the central mechanisms by which exercise improves AD symptoms. This article reviews the possible role of KP in AD neurodegeneration and AD exercise prevention and treatment.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1617690"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344556","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}
Noelia Peña Arauzo, Christoph Theyer, Florian Krismer, Atbin Djamshidian, Werner Poewe, Corinne Horlings, Beatrice Heim, Laura Zamarian, Philipp Mahlknecht
{"title":"Cognitive changes preceding Parkinson's disease: a systematic review and meta-analysis of prospective population-based studies.","authors":"Noelia Peña Arauzo, Christoph Theyer, Florian Krismer, Atbin Djamshidian, Werner Poewe, Corinne Horlings, Beatrice Heim, Laura Zamarian, Philipp Mahlknecht","doi":"10.3389/fnagi.2025.1627221","DOIUrl":"https://doi.org/10.3389/fnagi.2025.1627221","url":null,"abstract":"<p><strong>Introduction: </strong>Various non-motor symptoms have been studied as part of the prodromal phase of Parkinson's disease (PD). However, studies assessing cognitive changes are scarce.</p><p><strong>Methods: </strong>We systematically searched PubMed and SCOPUS to identify prospective, population-based studies that reported on cognitive performance in individuals without PD at baseline, the incidence of PD at follow-up, and comparisons of cognitive performance between participants who developed PD and controls.</p><p><strong>Results: </strong>Twelve studies were identified, including a total of 524,807 participants, of whom 2,939 developed PD. Four studies found differences in global cognition and a meta-analysis showed that individuals who developed PD scored 0.3 points lower than controls on the Mini-Mental State Examination at baseline. Cognitive changes were most frequently observed in tests of executive function, processing-speed and attention, and less frequently in visuospatial/visuoconstructive skills and memory. Due to the heterogeneity of the assessment methods used, it was not possible to conduct further meta-analyses.</p><p><strong>Conclusions: </strong>Cognitive changes may be part of the clinical picture in prodromal PD cohorts derived from the general population. Further population-based studies with large samples and long-term follow-up are needed to better understand their extent and significance.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024547252, identifier: CRD42024547252.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1627221"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344631","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}
Leila C Moore, Nell Maltman, Jonathan S Lee-Confer, Megan J Kobel
{"title":"Biomarkers of balance and gait deficits in <i>FMR1</i> premutation carriers: a mini-review.","authors":"Leila C Moore, Nell Maltman, Jonathan S Lee-Confer, Megan J Kobel","doi":"10.3389/fnagi.2025.1637819","DOIUrl":"10.3389/fnagi.2025.1637819","url":null,"abstract":"<p><p>Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation (PM) of the <i>FMR1</i> gene on the X chromosome. FXTAS is characterized by intention tremor, ataxia, and cognitive decline. Age-related cognitive-behavioral and sensorimotor (i.e., balance and gait) abnormalities are also present in PM carriers who do not develop FXTAS. Digital biomarkers of gait and balance have been proposed to be promising markers in characterizing prodromal changes in FXTAS (i.e., preFXTAS) and identifying age-related changes in the <i>FMR1</i> phenotype in those who do not develop FXTAS. In this mini-review, gait and balance findings in PM carriers are reviewed to highlight potential future applications. Variability measures of gait and postural sway reveal measurable impairments in individuals with FXTAS, particularly under conditions challenging sensory integration or assessing cognitive-motor interactions. However, there are limited studies quantifying these domains in <i>FMR1</i> PM carriers without FXTAS, and there is significant variability in the patient populations assessed (i.e., differing ages, relative lack of information in females) thus restricting conclusions about the progression of balance and gait in FXTAS and possible prodromal markers. Future research should prioritize longitudinal tracking of gait and balance in PM carriers, along with potential cognitive interactions and the characterization of sensory contributions to postural control. This mini-review aims to synthesize current findings on digital balance and gait biomarkers in FMR1 premutation carriers and to explore their potential utility for early FXTAS detection.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1637819"},"PeriodicalIF":4.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344545","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":"The association between chronic rhinosinusitis and the risk of dementia: a longitudinal study.","authors":"Xinyu Zhang, Zhongmin Yin, Jia Luo, Runsheng Yang, Weijing Wang, Dongfeng Zhang","doi":"10.3389/fnagi.2025.1609790","DOIUrl":"10.3389/fnagi.2025.1609790","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation status could increase the risk of dementia, and chronic rhinosinusitis (CRS) could cause chronic inflammation status. Therefore, CRS may be associated with dementia. The aim of our study was to investigate the association between CRS and the risk of dementia in the UK Biobank (UKB) cohort.</p><p><strong>Materials and methods: </strong>A total of 3,64,945 participants were included in this cohort study. CRS information was obtained from the first occurrence date of CRS (Field 131,468) at baseline. A Cox regression model and mediation analysis were performed to measure the association between CRS and dementia.</p><p><strong>Results: </strong>Chronic rhinosinusitis was significantly associated with an increased risk of Alzheimer's disease (AD) (hazard ratio [HR]: 1.33, 95% CI: 1.04-1.71) but was not associated with the risk of all-cause dementia (hazard ratio [HR]: 1.04, 95% CI: 0.86-1.26) or vascular dementia (VD) (hazard ratio [HR]: 0.65, 95% CI: 0.40-1.07). The male participants, individuals with hypertension, former smokers, participants with less than a college-level education, and participants with a medium-level polygenic risk score for Alzheimer's disease (PRS-AD) were more susceptible to AD. Mediation analysis using the comprehensive inflammatory index showed that the systemic immune-inflammation index (SII) could explain 0.0042 of this association.</p><p><strong>Conclusion: </strong>Chronic rhinosinusitis may be associated with a higher risk of AD, and the association was mediated, in a very small part, by the SII.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1609790"},"PeriodicalIF":4.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344581","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}
Ashley H Duche, Oliver Tan, Andrius Baskys, Rachita K Sumbria, Moom R Roosan
{"title":"Predictive gene expression signatures for Alzheimer's disease using post-mortem brain tissue.","authors":"Ashley H Duche, Oliver Tan, Andrius Baskys, Rachita K Sumbria, Moom R Roosan","doi":"10.3389/fnagi.2025.1591946","DOIUrl":"10.3389/fnagi.2025.1591946","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau protein aggregates in the brain. These pathological features manifest in specific regions, but mechanisms rendering some areas more susceptible to early AD-related changes remain poorly understood. To address this, we developed predictive gene expression signatures to explore molecular mechanisms underlying regional vulnerability to AD pathology.</p><p><strong>Methods: </strong>Post-mortem brain tissues from participants of the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) were used to derive gene expression signatures from six brain regions affected at varying stages of AD progression. Differential gene expression analysis identified genes with altered expression patterns which were used to develop predictive gene signatures using Adaptive Signature Selection and InteGratioN (ASSIGN) to predict pathway activity. Predictions of AD activity were validated against known AD status across clinical markers of AD pathology, including Aβ plaque deposition, tau aggregates, cognitive assessments, and clinical diagnoses. Dysregulation of key biological pathways was then analyzed using g: Profiler and ClueGO. Additionally, genetic and sociodemographic factors impacting AD prediction were assessed, and potential drug repurposing candidates identified using Connectivity Map (CMAP).</p><p><strong>Results: </strong>Predictive gene expression signatures from six AD-affected brain regions distinguished AD activity in control and AD post-mortem brain tissue, corresponding to clinical markers of disease severity. The signatures revealed common underlying mechanisms of regional vulnerability, including upregulation of extracellular matrix (ECM)-related processes and downregulation of hormonal signaling pathways. Notably, <i>S100A4</i> was consistently upregulated across all regions, while <i>CRH</i> expression was downregulated except in the cerebellum. Additionally, findings underscored the influence of APOE genotype (e3/e4) and sex on disease progression. Drug repurposing analysis identified FGFR inhibitors, specifically orantinib and bromodomain inhibitors, as promising therapeutic candidates.</p><p><strong>Conclusion: </strong>Molecular signatures underlying regional vulnerability to AD provide a framework for understanding genetic and systemic factors in disease progression. Findings highlight specific molecular pathways, including ECM-related processes and hormonal regulation, as key drivers of susceptibility. Finally, identified drug repurposing candidates present promising therapeutic avenues for further investigation.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1591946"},"PeriodicalIF":4.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328627","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":"Role of lipocalin-2 in amyotrophic lateral sclerosis.","authors":"Zhuoya Wang, Wen Cao, Dongsheng Fan","doi":"10.3389/fnagi.2025.1672903","DOIUrl":"10.3389/fnagi.2025.1672903","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized pathologically by degeneration of upper and lower motor neurons, ultimately leading to muscle weakness and respiratory failure. Lipocalin-2 (LCN2) is a secreted protein involved in lipid transport that plays a key role in inflammatory responses and the regulation of iron homeostasis. The role of LCN2 in ALS has attracted increasing attention, as significantly elevated LCN2 expression has been observed in the blood and postmortem tissues of ALS patients. Functionally, LCN2 participates in neuroinflammation, iron dysregulation, cell death, and peripheral immune immunity, proposing a central-peripheral linkage hypothesis mediated by LCN2. Clinically, LCN2 shows promise as both a biomarker and a therapeutic target, with multiple strategies demonstrating potential to mitigate ALS pathology. Moving forward, it is essential to integrate multi-omics to deeply decipher LCN2-mediated molecular networks, advance patient stratification, and accelerate its clinical translation.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1672903"},"PeriodicalIF":4.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328567","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}
Ji Sun Lim, Soyoung Kwak, Mi-Hee Yu, Mee-Na Park, Hye Suk Baek, Junho Kang, Jeong-Ho Hong, Jin Kyung Kim, Hye Won Lee, Sang-Woo Lee, Shin Kim, Hae Won Kim
{"title":"Western diet-induced visceral adipose tissue inflammation promotes Alzheimer's disease pathology via microglial activation in a mouse model.","authors":"Ji Sun Lim, Soyoung Kwak, Mi-Hee Yu, Mee-Na Park, Hye Suk Baek, Junho Kang, Jeong-Ho Hong, Jin Kyung Kim, Hye Won Lee, Sang-Woo Lee, Shin Kim, Hae Won Kim","doi":"10.3389/fnagi.2025.1644988","DOIUrl":"10.3389/fnagi.2025.1644988","url":null,"abstract":"<p><strong>Introduction: </strong>Western diet (WD)-induced visceral adipose tissue (VAT) inflammation is characterized by adipocyte hypertrophy, hypoxia, and apoptosis. Epididymal white adipose tissue (eWAT), a representative VAT depot in rodents, plays a central role in WD-induced inflammation by secreting pro-inflammatory cytokines that contribute to systemic and neuroinflammation. However, the mechanistic link between WD-driven eWAT inflammation and Alzheimer's disease (AD) pathology remains unclear.</p><p><strong>Methods: </strong>WD feeding for 20 weeks was conducted to evaluate its effects on AD-related neuroinflammation and pathology in mice. Cerebral glucose metabolism was assessed using F-18 FDG-PET. RNA sequencing of eWAT and plasma cytokine profiling identified inflammation-associated factors. <i>In vitro</i> assays were performed to examine the effects of these cytokines on microglial activation, neuronal viability, and IL-6/STAT3 signaling.</p><p><strong>Results: </strong>WD group exhibited significantly increased levels of neuroinflammatory markers and increased hippocampal levels of AD-related proteins including amyloid-beta oligomers, amyloid precursor protein, and phosphorylated tau. Additionally, F-18 FDG PET imaging revealed reduced glucose metabolism in the thalamus and hippocampus of WD group compared to controls. RNA sequencing of eWAT and cytokine profiling of plasma identified CCL8, CCL9, CXCL13, and IL-18 as significantly elevated pro-inflammatory cytokines. <i>In vitro</i> analyses demonstrated that these eWAT-associated cytokines directly activate microglial cells via the IL-6/STAT3 signaling pathway, promoting hippocampal neuronal death.</p><p><strong>Discussion: </strong>These findings elucidate a critical pathway through which WD-induced eWAT inflammation exacerbates AD pathology through a systemic-to-neuroinflammation axis, highlighting the therapeutic potential of targeting eWAT-associated cytokines to mitigate diet-associated AD progression.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1644988"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12521253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307415","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}
Lidya K Yassin, Jurga Skrabulyte-Barbulescu, Shamsa H Alshamsi, Sara Saeed, Shamma H Alkuwaiti, Saif Almazrouei, Abeer Alnuaimi, Shamsa BaniYas, Dana Aldhaheri, Mahra Alderei, Safa Shehab, Mohammad I K Hamad
{"title":"The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.","authors":"Lidya K Yassin, Jurga Skrabulyte-Barbulescu, Shamsa H Alshamsi, Sara Saeed, Shamma H Alkuwaiti, Saif Almazrouei, Abeer Alnuaimi, Shamsa BaniYas, Dana Aldhaheri, Mahra Alderei, Safa Shehab, Mohammad I K Hamad","doi":"10.3389/fnagi.2025.1667448","DOIUrl":"10.3389/fnagi.2025.1667448","url":null,"abstract":"<p><p>The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1667448"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12521449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307435","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}
Themis P Exarchos, George A Dimakopoulos, Konstantinos Lazaros, Marios Krokidis, Aristidis Vrahatis, Gerasimos Grammenos, Antigoni Avramouli, Konstantina Skolariki, Roy Adams, Vasiliki Mahairaki, Esther S Oh, Jeannie Leoutsakos, Paul B Rosenberg, Constantine G Lyketsos, Panagiotis Vlamos
{"title":"Five-year dementia prediction and decision support system based on real-world data.","authors":"Themis P Exarchos, George A Dimakopoulos, Konstantinos Lazaros, Marios Krokidis, Aristidis Vrahatis, Gerasimos Grammenos, Antigoni Avramouli, Konstantina Skolariki, Roy Adams, Vasiliki Mahairaki, Esther S Oh, Jeannie Leoutsakos, Paul B Rosenberg, Constantine G Lyketsos, Panagiotis Vlamos","doi":"10.3389/fnagi.2025.1670609","DOIUrl":"10.3389/fnagi.2025.1670609","url":null,"abstract":"<p><strong>Introduction: </strong>This work presents a machine learning (ML) based risk prediction model for Alzheimer's disease and related dementias, utilizing real-world electronic health record (EHR) clinical data. While significant research has been conducted on dementia risk prediction, most studies rely on volunteer-based research cohorts rather than real-world clinical data. Using raw EHR data offers more realistic insights but poses challenges due to the extensive effort required to convert real-world EHR clinical data into a decision support system for daily clinical use.</p><p><strong>Methods: </strong>The dataset consists of a high-volume, ten-year export of raw EHR data from Epic, the Johns Hopkins (JH) Health System. In this study, we utilized multimodal JH EHR data to develop a patient-based model to predict dementia onset over a five-year period. The interpretable binary classification model identified prognostic rulesets for dementia based on clinical characteristics.</p><p><strong>Results: </strong>The model achieved a mean test accuracy of 0.722 (95% CI: 0.722-0.723) and an AUROC of 0.795 (95% CI: 0.794-0.795) using 5-fold cross-validation across different sample subsets.</p><p><strong>Discussion: </strong>Recognizing that neurodegenerative diseases are often driven by multiple contributing factors rather than a single cause, we identify risk pathways by leveraging multimodal data and modeling their combined effects, leading to accurate dementia predictions and improved clinical interoperability.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1670609"},"PeriodicalIF":4.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298893","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}