Hanna Joensen, Elisabeth Framke, Luigi Pontieri, Melinda Magyari
Objectives: Comparison of recorded diagnoses of multiple sclerosis (MS) and related disorders and disease-modifying therapies (DMTs) in The Danish Multiple Sclerosis Registry (DMSR) with other nationwide health registries. The aim of the study is to describe and compare information on diagnoses of MS and related disorders and treatments with DMTs available in three national registries, highlighting the key differences relevant to MS research and providing insight for researchers for their choice of data source(s) suitable for their study.
Materials and methods: DMSR is a disease registry encompassing information on persons with MS and related disorders. The Danish National Patient Registry (DNPR) is a registry of activities at Danish hospitals. The Danish National Hospital Medication Registry (DNHMR) contains information on in-hospital prescription medications. The population comprised all persons in DMSR in 2023 who were alive or born after and residing in Denmark on January 1, 1995 (N = 26,474). For this population, we identified DNPR contacts with diagnoses of MS or related disorders and initiated DMTs in DNHMR. Diagnostic and demographic characteristics were reported as recorded in DMSR for the total population, and the subset included in DMSR but not in DNPR. Characteristics of the part of the population identified in DNPR were reported as recorded in DNPR. We calculated the proportions of DMT treatments in DMSR identified in DNHMR.
Results: Of the 26,474 persons, 23,857 (90.1%) were recorded with a diagnosis of MS or a related disorder in DNPR. Most (86.6%) of the 2617 persons not identified in DNPR were diagnosed before 1995. The proportion of persons with MS recorded without specification of the disease phenotype was 23.5% in the DMSR and 76.2% in the DNPR. After 2005, only 1.8% of persons with MS were recorded with an unspecified phenotype in DMSR. Of a total of 18,168 initiated DMT treatments in DMSR, 7230 (39.8%) were identified in DNHMR, with proportions ranging from 0.0% (mitoxantrone) to 88.5% (ocrelizumab).
Conclusions: DMSR is suitable for disease-specific research addressing treatment efficacy, disease development, and long-term outcomes. In contrast, DNPR is well suited for broad epidemiological studies involving various health conditions and hospital utilization. The DNHMR will, when matured, be useful for studies involving medical treatment and comedication. However, as each registry has limitations, for most studies the best approach will be combining registries, depending on the research question.
{"title":"Diagnoses of Multiple Sclerosis and Related Disorders and Disease-Modifying Therapies: A Comparison of the Danish Multiple Sclerosis Registry With Other Danish Health Registries.","authors":"Hanna Joensen, Elisabeth Framke, Luigi Pontieri, Melinda Magyari","doi":"10.1002/brb3.71235","DOIUrl":"10.1002/brb3.71235","url":null,"abstract":"<p><strong>Objectives: </strong>Comparison of recorded diagnoses of multiple sclerosis (MS) and related disorders and disease-modifying therapies (DMTs) in The Danish Multiple Sclerosis Registry (DMSR) with other nationwide health registries. The aim of the study is to describe and compare information on diagnoses of MS and related disorders and treatments with DMTs available in three national registries, highlighting the key differences relevant to MS research and providing insight for researchers for their choice of data source(s) suitable for their study.</p><p><strong>Materials and methods: </strong>DMSR is a disease registry encompassing information on persons with MS and related disorders. The Danish National Patient Registry (DNPR) is a registry of activities at Danish hospitals. The Danish National Hospital Medication Registry (DNHMR) contains information on in-hospital prescription medications. The population comprised all persons in DMSR in 2023 who were alive or born after and residing in Denmark on January 1, 1995 (N = 26,474). For this population, we identified DNPR contacts with diagnoses of MS or related disorders and initiated DMTs in DNHMR. Diagnostic and demographic characteristics were reported as recorded in DMSR for the total population, and the subset included in DMSR but not in DNPR. Characteristics of the part of the population identified in DNPR were reported as recorded in DNPR. We calculated the proportions of DMT treatments in DMSR identified in DNHMR.</p><p><strong>Results: </strong>Of the 26,474 persons, 23,857 (90.1%) were recorded with a diagnosis of MS or a related disorder in DNPR. Most (86.6%) of the 2617 persons not identified in DNPR were diagnosed before 1995. The proportion of persons with MS recorded without specification of the disease phenotype was 23.5% in the DMSR and 76.2% in the DNPR. After 2005, only 1.8% of persons with MS were recorded with an unspecified phenotype in DMSR. Of a total of 18,168 initiated DMT treatments in DMSR, 7230 (39.8%) were identified in DNHMR, with proportions ranging from 0.0% (mitoxantrone) to 88.5% (ocrelizumab).</p><p><strong>Conclusions: </strong>DMSR is suitable for disease-specific research addressing treatment efficacy, disease development, and long-term outcomes. In contrast, DNPR is well suited for broad epidemiological studies involving various health conditions and hospital utilization. The DNHMR will, when matured, be useful for studies involving medical treatment and comedication. However, as each registry has limitations, for most studies the best approach will be combining registries, depending on the research question.</p>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":"e71235"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wencai Wang, Yinuo Chen, Zijie Xiong, Zun Wang, Wei Ye, Xianfeng Li
Background: Cognitive impairment (CI) greatly affects global health and quality of life. Donepezil, a widely used treatment for CI, particularly in Alzheimer's disease, has been extensively studied; however, a comprehensive bibliometric analysis summarizing global research trends remains limited.
Methods: Relevant English-language articles and reviews published between 2000 and 2025 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were employed to analyze publication trends, collaborative networks, journal distribution, co-citation patterns, and keyword co-occurrence.
Results: A total of 1907 publications were identified. The United States led in both output and citation impact, with the University of Toronto emerging as the most influential institution. The U.S. Department of Health and Human Services provided the greatest funding support. The Journal of Alzheimer's Disease was the primary publishing outlet, and Etsuro Mori was the most prolific and influential author. Keyword analysis revealed "Donepezil," "Alzheimer's disease," and "Mild cognitive impairment" as dominant terms. Recent hotspots-such as "acetylcholinesterase," "oxidative stress," "neuroinflammation," "tau protein," and "mechanism"-reflect a shift toward mechanistic and preclinical research.
Conclusion: Research on donepezil for CI has shown consistent growth, evolving from clinical application toward mechanistic exploration and disease modification. Future studies are expected to focus on individualized therapy, combination strategies, and underexplored CI subtypes, aiming to enhance the therapeutic potential and clinical value of donepezil.
背景：认知障碍（CI）严重影响全球健康和生活质量。多奈哌齐是一种广泛用于CI治疗，特别是阿尔茨海默病的药物，已被广泛研究；然而，总结全球研究趋势的综合文献计量分析仍然有限。方法：从Web of Science Core Collection检索2000 - 2025年间发表的相关英文文章和综述。利用CiteSpace和VOSviewer分析论文发表趋势、协同网络、期刊分布、共被引模式和关键词共现情况。结果：共确定了1907份出版物。美国在产出和引文影响方面都处于领先地位，多伦多大学（University of Toronto）成为最有影响力的机构。美国卫生与公众服务部提供了最大的资金支持。《阿尔茨海默病杂志》（Journal of Alzheimer's Disease）是主要的出版渠道，森悦郎（Etsuro Mori）是最多产、最有影响力的作者。关键词分析显示，“多奈哌齐”、“阿尔茨海默病”和“轻度认知障碍”是主要词汇。最近的热点——如“乙酰胆碱酯酶”、“氧化应激”、“神经炎症”、“tau蛋白”和“机制”——反映了向机制和临床前研究的转变。结论：多奈哌齐治疗CI的研究呈现持续增长趋势，从临床应用向机制探索和疾病改良发展。未来的研究将集中在个体化治疗、联合治疗策略和未开发的CI亚型上，旨在提高多奈哌齐的治疗潜力和临床价值。
{"title":"Donepezil Research in Cognitive Impairment: A Bibliometric and Scientometric Analysis of Global Trends and Pharmacological Perspectives.","authors":"Wencai Wang, Yinuo Chen, Zijie Xiong, Zun Wang, Wei Ye, Xianfeng Li","doi":"10.1002/brb3.71251","DOIUrl":"10.1002/brb3.71251","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment (CI) greatly affects global health and quality of life. Donepezil, a widely used treatment for CI, particularly in Alzheimer's disease, has been extensively studied; however, a comprehensive bibliometric analysis summarizing global research trends remains limited.</p><p><strong>Methods: </strong>Relevant English-language articles and reviews published between 2000 and 2025 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were employed to analyze publication trends, collaborative networks, journal distribution, co-citation patterns, and keyword co-occurrence.</p><p><strong>Results: </strong>A total of 1907 publications were identified. The United States led in both output and citation impact, with the University of Toronto emerging as the most influential institution. The U.S. Department of Health and Human Services provided the greatest funding support. The Journal of Alzheimer's Disease was the primary publishing outlet, and Etsuro Mori was the most prolific and influential author. Keyword analysis revealed \"Donepezil,\" \"Alzheimer's disease,\" and \"Mild cognitive impairment\" as dominant terms. Recent hotspots-such as \"acetylcholinesterase,\" \"oxidative stress,\" \"neuroinflammation,\" \"tau protein,\" and \"mechanism\"-reflect a shift toward mechanistic and preclinical research.</p><p><strong>Conclusion: </strong>Research on donepezil for CI has shown consistent growth, evolving from clinical application toward mechanistic exploration and disease modification. Future studies are expected to focus on individualized therapy, combination strategies, and underexplored CI subtypes, aiming to enhance the therapeutic potential and clinical value of donepezil.</p>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":"e71251"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12891979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To review how the immune microenvironment and oxidative stress modulate the initiation, maturation, and hemorrhagic conversion of cerebral cavernous malformations (CCM) and to appraise the therapeutic potential of immune-directed interventions.
Finding
This project conducts systematic research on the pathogenesis of cerebral cavernous malformation (CCM), focusing on the complex interactions between genetic mutations (KRIT1, CCM2, PDCD10) and the immune microenvironment, oxidative stress, inflammatory responses, and vascular dysfunction. The study confirms that CCM development relies not only on genetic mutations but also on the synergistic effects of a “second hit” mechanism and microenvironmental stressors. Immune cell infiltration (e.g., B cells, T cells, neutrophils) and oxidative stress responses play pivotal roles in lesion progression; Blood-brain barrier disruption and immune thrombosis further exacerbate the pathological process. These findings provide theoretical foundations for understanding CCM's multifactorial pathogenic network and establish scientific bases for personalized therapeutic strategies targeting the immune microenvironment and oxidative stress.
Conclusion
Genetic mutations trigger the formation of initial CCM lesions, while environmental and immune factors promote disease progression, increasing the risk of abnormal cerebral vascular formation or rupture.
{"title":"The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation","authors":"Xuesai Zhu, Yizhi Yao, Tengbo Yu, Xiao Xiao","doi":"10.1002/brb3.71237","DOIUrl":"10.1002/brb3.71237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose of Review</h3>\u0000 \u0000 <p>To review how the immune microenvironment and oxidative stress modulate the initiation, maturation, and hemorrhagic conversion of cerebral cavernous malformations (CCM) and to appraise the therapeutic potential of immune-directed interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Finding</h3>\u0000 \u0000 <p>This project conducts systematic research on the pathogenesis of cerebral cavernous malformation (CCM), focusing on the complex interactions between genetic mutations (KRIT1, CCM2, PDCD10) and the immune microenvironment, oxidative stress, inflammatory responses, and vascular dysfunction. The study confirms that CCM development relies not only on genetic mutations but also on the synergistic effects of a “second hit” mechanism and microenvironmental stressors. Immune cell infiltration (e.g., B cells, T cells, neutrophils) and oxidative stress responses play pivotal roles in lesion progression; Blood-brain barrier disruption and immune thrombosis further exacerbate the pathological process. These findings provide theoretical foundations for understanding CCM's multifactorial pathogenic network and establish scientific bases for personalized therapeutic strategies targeting the immune microenvironment and oxidative stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Genetic mutations trigger the formation of initial CCM lesions, while environmental and immune factors promote disease progression, increasing the risk of abnormal cerebral vascular formation or rupture.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simone Migliore, Martina Marcaccio, Ilaria Di Pompeo, Massimo Marano, Giuseppe Curcio
Purpose
This systematic review examines executive dysfunction in Huntington's disease (HD), an inherited neurodegenerative disorder characterized by cognitive alterations that may emerge years before the onset of motor symptoms. The objective of this review is to provide an updated and comprehensive synthesis of executive function deficits observed across the clinical spectrum of HD—from presymptomatic to the more advanced symptomatic phases—and to examine how these deficits relate to underlying neurobiological changes identified through neuroimaging and neurophysiological studies.
Method
A systematic review was conducted encompassing studies published up to November 2024 and listed on PubMed database. Inclusion criteria focused on clinical and experimental studies involving executive functions in HD at different stages. A total of 3487 articles were screened, of which 115 met the eligibility criteria. The present review synthesizes recent longitudinal and multimodal findings, with a specific focus on the presymptomatic and prodromal phases, offering an integrative perspective that links cognitive, structural, and functional markers of executive dysfunction.
Finding
The findings reveal a selective, stage-dependent pattern of executive dysfunction. Early alterations are most consistently observed in psychomotor speed, cognitive flexibility, response inhibition, and working memory updating, whereas later stages exhibit broader impairments in planning and attention, accompanied by overall functional decline. Among neuroimaging markers, striatal atrophy, frontostriatal disconnection, and reduced prefrontal activation during executive tasks emerge as the most robust correlates of executive dysfunction.
Conclusion
These results underscore the relevance of early cognitive assessment for detecting subtle executive changes prior to overt motor symptoms, and the need for longitudinal, multimodal and computational approaches integrating behavioral, neuroimaging, and electrophysiological data. Future research should prioritize prospective tracking of presymptomatic individuals, the standardization of executive function measures, and the identification of biologically markers to inform early interventions and monitor treatment efficacy.
{"title":"Executive Impairment in Huntington's Disease: Insights From a Systematic Review of the Literature","authors":"Simone Migliore, Martina Marcaccio, Ilaria Di Pompeo, Massimo Marano, Giuseppe Curcio","doi":"10.1002/brb3.71238","DOIUrl":"10.1002/brb3.71238","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This systematic review examines executive dysfunction in Huntington's disease (HD), an inherited neurodegenerative disorder characterized by cognitive alterations that may emerge years before the onset of motor symptoms. The objective of this review is to provide an updated and comprehensive synthesis of executive function deficits observed across the clinical spectrum of HD—from presymptomatic to the more advanced symptomatic phases—and to examine how these deficits relate to underlying neurobiological changes identified through neuroimaging and neurophysiological studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A systematic review was conducted encompassing studies published up to November 2024 and listed on PubMed database. Inclusion criteria focused on clinical and experimental studies involving executive functions in HD at different stages. A total of 3487 articles were screened, of which 115 met the eligibility criteria. The present review synthesizes recent longitudinal and multimodal findings, with a specific focus on the presymptomatic and prodromal phases, offering an integrative perspective that links cognitive, structural, and functional markers of executive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Finding</h3>\u0000 \u0000 <p>The findings reveal a selective, stage-dependent pattern of executive dysfunction. Early alterations are most consistently observed in psychomotor speed, cognitive flexibility, response inhibition, and working memory updating, whereas later stages exhibit broader impairments in planning and attention, accompanied by overall functional decline. Among neuroimaging markers, striatal atrophy, frontostriatal disconnection, and reduced prefrontal activation during executive tasks emerge as the most robust correlates of executive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results underscore the relevance of early cognitive assessment for detecting subtle executive changes prior to overt motor symptoms, and the need for longitudinal, multimodal and computational approaches integrating behavioral, neuroimaging, and electrophysiological data. Future research should prioritize prospective tracking of presymptomatic individuals, the standardization of executive function measures, and the identification of biologically markers to inform early interventions and monitor treatment efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisco José Alcaide, Ignacio Alvarez Illan, Javier Ramírez, Juan Manuel Gorriz
Purpose
Autism spectrum condition (ASC) is a neurodevelopmental condition characterized by impairments in communication, social interaction, and restricted or repetitive behaviors. Extensive research has aimed to identify structural brain distinctions between individuals with ASC and neurotypical individuals using neuroimaging techniques. However, limited attention has been given to evaluating how variations in image acquisition protocols across different centers influence these observed differences.
Method
This analysis focuses on structural magnetic resonance imaging (sMRI) data from the Autism Brain Imaging Data Exchange I (ABIDE I) database, considering both subjects' condition and individual centers to identify disparities between ASC and control groups. Statistical analysis, employing permutation tests, utilizes two distinct statistical mapping methods: statistical agnostic mapping (SAM) and statistical parametric mapping (SPM).
Finding
Results from the SAM mapping method show greater consistency with existing literature. However, no statistically significant differences were found in any brain region. This outcome is attributed to factors such as limited sample sizes within certain centers, noise effects, and the challenges posed by multi-center databases in a heterogeneous condition such as autism.
Conclusion
The study indicates limitations in using the ABIDE I database to detect structural differences in the brain between neurotypical individuals and those diagnosed with ASC. Multi-center variability and sample size constraints significantly affect the reliability of findings in structural neuroimaging studies of autism.
{"title":"Unraveling the Autism Spectrum Heterogeneity: Insights From ABIDE I Database Using Data/Model-Driven Permutation Testing Approaches","authors":"Francisco José Alcaide, Ignacio Alvarez Illan, Javier Ramírez, Juan Manuel Gorriz","doi":"10.1002/brb3.71121","DOIUrl":"10.1002/brb3.71121","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Autism spectrum condition (ASC) is a neurodevelopmental condition characterized by impairments in communication, social interaction, and restricted or repetitive behaviors. Extensive research has aimed to identify structural brain distinctions between individuals with ASC and neurotypical individuals using neuroimaging techniques. However, limited attention has been given to evaluating how variations in image acquisition protocols across different centers influence these observed differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This analysis focuses on structural magnetic resonance imaging (sMRI) data from the Autism Brain Imaging Data Exchange I (ABIDE I) database, considering both subjects' condition and individual centers to identify disparities between ASC and control groups. Statistical analysis, employing permutation tests, utilizes two distinct statistical mapping methods: statistical agnostic mapping (SAM) and statistical parametric mapping (SPM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Finding</h3>\u0000 \u0000 <p>Results from the SAM mapping method show greater consistency with existing literature. However, no statistically significant differences were found in any brain region. This outcome is attributed to factors such as limited sample sizes within certain centers, noise effects, and the challenges posed by multi-center databases in a heterogeneous condition such as autism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study indicates limitations in using the ABIDE I database to detect structural differences in the brain between neurotypical individuals and those diagnosed with ASC. Multi-center variability and sample size constraints significantly affect the reliability of findings in structural neuroimaging studies of autism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12860423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wen-Bo Gao, Wen-Hui Wang, Si-Tong Zhou, Zi-Wei Lu, Xin Xiang, Jin Hu, Ting-Yu Jin, Chao-Bo Ni, Ming Yao, Hua-Dong Ni
Background
Postoperative delirium (POD) is a frequent complication among elderly surgical patients and is associated with adverse outcomes and increased mortality. Current preventive and therapeutic strategies remain limited. Repetitive transcranial magnetic stimulation (rTMS) has recently shown promise in enhancing cognitive function across various neurological and psychiatric conditions.
Objective
This trial aimed to investigate the efficacy of preoperative rTMS on POD in elderly patients undergoing elective non-cardiac surgery.
Methods
This double-blind, randomized controlled trial included 254 patients aged 60 years or older undergoing elective non-cardiac surgery, randomly assigned to either active rTMS group or sham rTMS group. Patients received two sessions of 10 Hz rTMS over the left DLPFC, at 110% RMT, totaling 1080 pulses before surgery. The primary outcome was the incidence of POD within 7 days after surgery.
Results
In the intention-to-treat analysis of 249 patients (median age 69 years [IQR 63 to 73] years; 46.2% women), the incidence of POD was significantly lower in the active rTMS group (10 of 124 [8.1%]) compared with the sham rTMS group (36 of 125 [28.8%]) (relative risk, 0.22; 95% CI 0.10 to 0.46; p < 0.001). Compared with the sham rTMS group, patients in the active rTMS group had significantly lower pain intensity and sleep quality on postoperative days 1 and 3 (p < 0.001 for each), lower anxiety and depression scores on postoperative days 3 and 7 (p < 0.001 for each), and lower frailty scores on postoperative days 1 and 7 (p < 0.001 for each), while there was no significant differences in PONV scores at any time pointy (p > 0.05 for each).
Conclusions
Preoperative high-frequency rTMS targeting left DLPFC was associated with a reduced incidence of POD in elderly patients undergoing elective non-cardiac surgery.
{"title":"Efficacy of Repetitive Transcranial Magnetic Stimulation on Postoperative Delirium in Elderly Patients Undergoing Non-Cardiac Major Surgery: A Randomized Controlled Trial","authors":"Wen-Bo Gao, Wen-Hui Wang, Si-Tong Zhou, Zi-Wei Lu, Xin Xiang, Jin Hu, Ting-Yu Jin, Chao-Bo Ni, Ming Yao, Hua-Dong Ni","doi":"10.1002/brb3.71242","DOIUrl":"10.1002/brb3.71242","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Postoperative delirium (POD) is a frequent complication among elderly surgical patients and is associated with adverse outcomes and increased mortality. Current preventive and therapeutic strategies remain limited. Repetitive transcranial magnetic stimulation (rTMS) has recently shown promise in enhancing cognitive function across various neurological and psychiatric conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This trial aimed to investigate the efficacy of preoperative rTMS on POD in elderly patients undergoing elective non-cardiac surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This double-blind, randomized controlled trial included 254 patients aged 60 years or older undergoing elective non-cardiac surgery, randomly assigned to either active rTMS group or sham rTMS group. Patients received two sessions of 10 Hz rTMS over the left DLPFC, at 110% RMT, totaling 1080 pulses before surgery. The primary outcome was the incidence of POD within 7 days after surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the intention-to-treat analysis of 249 patients (median age 69 years [IQR 63 to 73] years; 46.2% women), the incidence of POD was significantly lower in the active rTMS group (10 of 124 [8.1%]) compared with the sham rTMS group (36 of 125 [28.8%]) (relative risk, 0.22; 95% CI 0.10 to 0.46; <i>p</i> < 0.001). Compared with the sham rTMS group, patients in the active rTMS group had significantly lower pain intensity and sleep quality on postoperative days 1 and 3 (<i>p</i> < 0.001 for each), lower anxiety and depression scores on postoperative days 3 and 7 (<i>p</i> < 0.001 for each), and lower frailty scores on postoperative days 1 and 7 (<i>p</i> < 0.001 for each), while there was no significant differences in PONV scores at any time pointy (<i>p</i> > 0.05 for each).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Preoperative high-frequency rTMS targeting left DLPFC was associated with a reduced incidence of POD in elderly patients undergoing elective non-cardiac surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Functional magnetic resonance imaging (fMRI) and deep learning models can classify Alzheimer's disease (AD) with high accuracy. These models are highly adaptable and work with a plethora of architectures, data types, and AD stages. However, fMRI deep learning models lack clinical application due to issues with small datasets, explainability, and reliability (e.g., data leakage).
Methods
In this study, we address these issues using multimodal and explainable artificial intelligence (XAI) methods. Specifically, we overcome data size limitations by supplementing fMRI data with clinical tests, use a strict leave-one-out cross-validation regime to control for data leakage, and apply perturbation ranking to explain the importance of features in our model. Our 3D convolutional neural network model was trained and validated on 52 participants from ADNI using five clinical tests and fMRI of the default mode network.
Findings
The resulting multimodal model classified AD from controls with an accuracy of 90% and outperformed the same architecture without clinical data (58% accuracy). Our feature rankings showed that clinical tests changed in importance within our model depending on the diagnostic group. For example, our model found the MoCA to be highly important for classifying controls but not for AD. This trend of feature importance was seen across almost all fMRI and clinical features.
Conclusion
Our model was highly accurate and highlighted the importance of combining fMRI and clinical data for AD classification. These findings have implications for the refinement of multimodal deep learning models; however, our small sample and need for external validation are also noted.
{"title":"Functional and Clinical: An Explainable Deep Learning Model for Multimodal Alzheimer's Disease Classification","authors":"Samuel L. Warren, Ahmed A. Moustafa","doi":"10.1002/brb3.71240","DOIUrl":"10.1002/brb3.71240","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Functional magnetic resonance imaging (fMRI) and deep learning models can classify Alzheimer's disease (AD) with high accuracy. These models are highly adaptable and work with a plethora of architectures, data types, and AD stages. However, fMRI deep learning models lack clinical application due to issues with small datasets, explainability, and reliability (e.g., data leakage).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we address these issues using multimodal and explainable artificial intelligence (XAI) methods. Specifically, we overcome data size limitations by supplementing fMRI data with clinical tests, use a strict leave-one-out cross-validation regime to control for data leakage, and apply perturbation ranking to explain the importance of features in our model. Our 3D convolutional neural network model was trained and validated on 52 participants from ADNI using five clinical tests and fMRI of the default mode network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>The resulting multimodal model classified AD from controls with an accuracy of 90% and outperformed the same architecture without clinical data (58% accuracy). Our feature rankings showed that clinical tests changed in importance within our model depending on the diagnostic group. For example, our model found the MoCA to be highly important for classifying controls but not for AD. This trend of feature importance was seen across almost all fMRI and clinical features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our model was highly accurate and highlighted the importance of combining fMRI and clinical data for AD classification. These findings have implications for the refinement of multimodal deep learning models; however, our small sample and need for external validation are also noted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiqi Wang, Mingyu Tang, Haiquan Gao, Yuhui Sha, Ming Yao, Yicheng Zhu, Bin Peng, Lixin Zhou, Jun Ni
Introduction
The study aimed to evaluate long-term medication persistence and adherence to secondary prevention therapies in young ischemic stroke survivors (aged 18–49 years) and identify factors influencing these outcomes.
Methods
The single-center prospective cohort study enrolled young ischemic stroke patients (aged 18–49 years) from March 2017 to March 2023. Medication persistence (continuation of all prescribed secondary prevention drugs) and adherence (assessed by the Morisky Medication Adherence Scale-8 (MMAS-8)) were evaluated, with reasons for discontinuation and influencing factors analyzed.
Results
Among 226 patients (median age 35 years, 34.5% female), 80.1% remained persistent with their medication regimen over a median follow-up of 3.9 years. Patients with persistence had higher rates of large artery atherosclerosis (42% vs. 22.2%, p = 0.015) and comorbid diabetes (13.3% vs. 2.2%, p = 0.015). The median MMAS-8 score was 7 (6–7.38), with 24.2% showing high adherence, 63% moderate adherence, and 12.8% poor adherence. Poor adherence was associated with younger age (<35 years, p = 0.018), the absence of large artery atherosclerosis (p = 0.017), and a lower quality of life (p = 0.004). Multivariate analysis revealed that older age (p = 0.043) and large artery atherosclerosis (p = 0.047) were independent predictors of better adherence.
Conclusion
Young ischemic stroke patients demonstrated high medication persistence and moderate adherence, which were influenced by age, stroke etiology, and quality of life. These findings highlight the need for tailored secondary prevention strategies to improve outcomes in this population.
{"title":"Long-Term Secondary Preventive Medication Persistence and Adherence in Young Ischemic Stroke Survivors: A Prospective Single-Center Cohort Study","authors":"Qiqi Wang, Mingyu Tang, Haiquan Gao, Yuhui Sha, Ming Yao, Yicheng Zhu, Bin Peng, Lixin Zhou, Jun Ni","doi":"10.1002/brb3.71248","DOIUrl":"10.1002/brb3.71248","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The study aimed to evaluate long-term medication persistence and adherence to secondary prevention therapies in young ischemic stroke survivors (aged 18–49 years) and identify factors influencing these outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The single-center prospective cohort study enrolled young ischemic stroke patients (aged 18–49 years) from March 2017 to March 2023. Medication persistence (continuation of all prescribed secondary prevention drugs) and adherence (assessed by the Morisky Medication Adherence Scale-8 (MMAS-8)) were evaluated, with reasons for discontinuation and influencing factors analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 226 patients (median age 35 years, 34.5% female), 80.1% remained persistent with their medication regimen over a median follow-up of 3.9 years. Patients with persistence had higher rates of large artery atherosclerosis (42% vs. 22.2%, <i>p</i> = 0.015) and comorbid diabetes (13.3% vs. 2.2%, <i>p</i> = 0.015). The median MMAS-8 score was 7 (6–7.38), with 24.2% showing high adherence, 63% moderate adherence, and 12.8% poor adherence. Poor adherence was associated with younger age (<35 years, <i>p</i> = 0.018), the absence of large artery atherosclerosis (<i>p</i> = 0.017), and a lower quality of life (<i>p</i> = 0.004). Multivariate analysis revealed that older age (<i>p</i> = 0.043) and large artery atherosclerosis (<i>p</i> = 0.047) were independent predictors of better adherence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Young ischemic stroke patients demonstrated high medication persistence and moderate adherence, which were influenced by age, stroke etiology, and quality of life. These findings highlight the need for tailored secondary prevention strategies to improve outcomes in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weizhe Zhang, Ming Chen, Haozhang Huang, Puyi Sheng
Background
Rotator cuff tendinopathy (RCT) is a major contributor to over 30 million surgeries which are conducted to treat shoulder overuse injuries worldwide annually. Accumulating evidence indicates that neuropsychiatric disorders (ND) share pathogenic pathways with tendinopathy. However, unclarified causal relationships between these two disease spectra undermine the individualized design of treatment strategies benefiting patients with ND while minimizing the RCT risk. We aimed to unveil whether ND were genetically associated with increased RCT occurrence by conducting a two-sample Mendelian randomization (MR) algorithm.
Methods
Genome-wide association studies (GWAS) data of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), and RCT patients of European ancestry were retrieved for bidirectional two-sample Mendelian randomization (MR) analyses to establish causal relationships among these eight main types of ND and RCT. To detect false positive findings, MR-Egger, weighted median and causal analysis using summary effect estimates (CAUSE) were employed as sensitivity tests. Body shape, lifestyle, and socioeconomic parameters were adjusted as mediators in multivariable MR to validate the robustness of the results.
Results
Univariable MR revealed that genetic predisposition to ADHD (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.05–1.24, p = 0.001) and PTSD (OR 2.23, 95% CI 1.75–2.84, p < 0.001) significantly increased the RCT risk. MDD showed a similar association (OR 1.21, 95% CI 1.06–1.38, p = 0.004), which was attenuated after confounder adjustment (p = 0.78). Multivariable MR confirmed ADHD (OR 1.09, 95% CI 1.01–1.18, p = 0.02) and PTSD (OR 2.00, 95% CI 1.41–2.82, p < 0.001) as robust causal factors for RCT after adjusting for anthropometric, lifestyle, physical activity, and socioeconomic confounders.
Conclusion
Our study sheds new light on the need for early screening, targeted overuse injury prevention, and specialized clinical interventions to alleviate the RCT burden in ADHD and PTSD populations.
背景：肩袖肌腱病变（RCT）是全球每年超过3000万例治疗肩部过度使用损伤手术的主要原因。越来越多的证据表明，神经精神疾病（ND）与肌腱病有共同的致病途径。然而，这两种疾病谱之间未明确的因果关系破坏了治疗策略的个性化设计，使ND患者受益，同时使RCT风险最小化。我们的目的是通过进行双样本孟德尔随机化（MR）算法来揭示ND是否与RCT发生率增加有关。方法：检索欧洲血统的注意缺陷/多动障碍（ADHD）、自闭症谱系障碍（ASD）、双相情感障碍（BD）、癫痫、重度抑郁症（MDD）、强迫症（OCD）、创伤后应激障碍（PTSD）、精神分裂症（SCZ）和RCT患者的全基因组关联研究（GWAS）数据，进行双向双样本孟德尔随机化（MR）分析，建立这8种主要ND与RCT之间的因果关系。为了检测假阳性结果，采用MR-Egger、加权中位数和使用总结效应估计（CAUSE）的因果分析作为敏感性检验。身体形状、生活方式和社会经济参数被调整为多变量MR的中介，以验证结果的稳健性。结果：单变量MR显示，ADHD遗传易感性（比值比[OR] 1.14, 95%可信区间[CI] 1.05-1.24, p = 0.001）和PTSD遗传易感性（比值比[OR] 2.23, 95% CI 1.75-2.84, p < 0.001）显著增加了RCT风险。MDD表现出类似的相关性（OR 1.21, 95% CI 1.06-1.38, p = 0.004），经混杂校正后减弱（p = 0.78）。多变量MR证实ADHD （OR 1.09, 95% CI 1.01-1.18, p = 0.02）和PTSD （OR 2.00, 95% CI 1.41-2.82, p < 0.001）是校正人体测量、生活方式、体力活动和社会经济混杂因素后的RCT的可靠原因。结论：我们的研究揭示了早期筛查、有针对性的过度使用损伤预防和专门的临床干预的必要性，以减轻ADHD和PTSD人群的RCT负担。
{"title":"Decoding Causal Associations Between Neuropsychiatric Disorders and Rotator Cuff Tendinopathy: A Two-Sample Mendelian Randomization Study","authors":"Weizhe Zhang, Ming Chen, Haozhang Huang, Puyi Sheng","doi":"10.1002/brb3.71246","DOIUrl":"10.1002/brb3.71246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rotator cuff tendinopathy (RCT) is a major contributor to over 30 million surgeries which are conducted to treat shoulder overuse injuries worldwide annually. Accumulating evidence indicates that neuropsychiatric disorders (ND) share pathogenic pathways with tendinopathy. However, unclarified causal relationships between these two disease spectra undermine the individualized design of treatment strategies benefiting patients with ND while minimizing the RCT risk. We aimed to unveil whether ND were genetically associated with increased RCT occurrence by conducting a two-sample Mendelian randomization (MR) algorithm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genome-wide association studies (GWAS) data of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), and RCT patients of European ancestry were retrieved for bidirectional two-sample Mendelian randomization (MR) analyses to establish causal relationships among these eight main types of ND and RCT. To detect false positive findings, MR-Egger, weighted median and causal analysis using summary effect estimates (CAUSE) were employed as sensitivity tests. Body shape, lifestyle, and socioeconomic parameters were adjusted as mediators in multivariable MR to validate the robustness of the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Univariable MR revealed that genetic predisposition to ADHD (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.05–1.24, <i>p</i> = 0.001) and PTSD (OR 2.23, 95% CI 1.75–2.84, <i>p</i> < 0.001) significantly increased the RCT risk. MDD showed a similar association (OR 1.21, 95% CI 1.06–1.38, <i>p</i> = 0.004), which was attenuated after confounder adjustment (<i>p</i> = 0.78). Multivariable MR confirmed ADHD (OR 1.09, 95% CI 1.01–1.18, <i>p</i> = 0.02) and PTSD (OR 2.00, 95% CI 1.41–2.82, <i>p</i> < 0.001) as robust causal factors for RCT after adjusting for anthropometric, lifestyle, physical activity, and socioeconomic confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study sheds new light on the need for early screening, targeted overuse injury prevention, and specialized clinical interventions to alleviate the RCT burden in ADHD and PTSD populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p><i>Toxoplasma gondii</i> (<i>T. gondii</i>) is a ubiquitous protozoan parasite capable of establishing lifelong latent infections in the central nervous system. Previous epidemiological studies have suggested a potential association between <i>T. gondii</i> infection and an increased risk of brain cancer, but the causal relationship remains unclear.</p> </section> <section> <h3> Methods</h3> <p>We conducted a bidirectional Mendelian randomization (MR) study to assess the causal relationship between <i>T. gondii</i> infection and brain tumor risk. Genetic instruments for <i>T. gondii</i> seropositivity were derived from a genome-wide association study (GWAS) in the UK Biobank, while genetic data for brain tumors were obtained from the FinnGen R12 dataset. Standard MR methods, including inverse-variance weighted (IVW), weighted median, and MR-Egger, were applied to infer causality, with generalized summary Mendelian randomization (GSMR) used for further validation. Sensitivity analyses, including heterogeneity and pleiotropy assessments, were performed to ensure robustness. Additionally, reverse MR analyses were conducted to evaluate whether brain tumors influence genetic liability to <i>T. gondii</i> seropositivity.</p> </section> <section> <h3> Results</h3> <p>Our MR analyses found no evidence of a causal relationship between genetic liability to <i>T. gondii</i> seropositivity, as indicated by P22 and SAG1 antibody levels, and the risk of brain tumors. Across all tumor subtypes, IVW, weighted median, MR-Egger, and GSMR analyses consistently yielded non-significant results. However, reverse MR analysis suggested that genetic liability to malignant brain tumors is associated with increased odds of <i>T. gondii</i> seropositivity. For P22, a strong association was observed across methods (IVW: OR = 1.234, <i>p</i> = 0.004; GSMR: OR = 1.228, <i>p</i> = 0.006). In contrast, for SAG1 the evidence was weaker, with IVW indicating a suggestive association (OR = 1.094, <i>p</i> = 0.048) and GSMR showing a borderline association (OR = 1.088, <i>p</i> = 0.052). Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or pleiotropy. No significant associations were observed for meningioma, glioblastoma, or benign brain tumors.</p> </section> <section> <h3> Conclusion</h3> <p>Our study provides no evidence for a causal relationship between genetic liability to <i>T. gondii</i> seropositivity and brain tumor risk. However, reverse MR suggests that genetic liability to malignant bra
背景：刚地弓形虫（弓形虫）是一种普遍存在的原生动物寄生虫，能够在中枢神经系统建立终身潜伏感染。先前的流行病学研究表明，弓形虫感染与脑癌风险增加之间存在潜在关联，但因果关系尚不清楚。方法：我们进行了双向孟德尔随机化（MR）研究，以评估弓形虫感染与脑肿瘤风险的因果关系。弓形虫血清阳性的遗传仪器来自英国生物银行的全基因组关联研究（GWAS），而脑肿瘤的遗传数据来自FinnGen R12数据集。标准MR方法，包括反方差加权（IVW）、加权中位数和MR- egger，用于推断因果关系，并使用广义总结孟德尔随机化（GSMR）进行进一步验证。进行敏感性分析，包括异质性和多效性评估以确保稳健性。此外，进行了反向磁共振分析，以评估脑肿瘤是否影响弓形虫血清阳性的遗传倾向。结果：我们的MR分析没有发现遗传倾向与弓形虫血清阳性（如P22和SAG1抗体水平所示）与脑肿瘤风险之间的因果关系。在所有肿瘤亚型中，IVW、加权中位数、MR-Egger和GSMR分析一致得出无显著性结果。然而，反向磁共振分析表明，恶性脑肿瘤的遗传易感性与弓形虫血清阳性的几率增加有关。对于P22，不同方法间观察到很强的相关性（IVW: OR = 1.234, p = 0.004; GSMR: OR = 1.228, p = 0.006）。相比之下，SAG1的证据较弱，IVW表明有暗有性关联（OR = 1.094, p = 0.048）， GSMR显示有边缘性关联（OR = 1.088, p = 0.052）。敏感性分析证实了这些发现的稳健性，没有证据表明存在异质性或多效性。脑膜瘤、胶质母细胞瘤或良性脑肿瘤无显著相关性。结论：我们的研究没有证据表明弓形虫血清阳性的遗传倾向与脑肿瘤风险之间存在因果关系。然而，反向磁共振表明，恶性脑肿瘤的遗传易感性可能与弓形虫感染的几率增加有关。
{"title":"Exploring the Causal Links Between Toxoplasma gondii Infection and Risk of Brain Tumors: A Bidirectional Mendelian Randomization Analysis","authors":"Pengqiang Shi, Gangao Wei, Zhenwei Li, Baoshun Du, Guodong Zhang, Jiaqi Zhang, Yungang Wang, Yunchao Chen, Zhang Cheng, Zhenguo Cheng","doi":"10.1002/brb3.71239","DOIUrl":"10.1002/brb3.71239","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Toxoplasma gondii</i> (<i>T. gondii</i>) is a ubiquitous protozoan parasite capable of establishing lifelong latent infections in the central nervous system. Previous epidemiological studies have suggested a potential association between <i>T. gondii</i> infection and an increased risk of brain cancer, but the causal relationship remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a bidirectional Mendelian randomization (MR) study to assess the causal relationship between <i>T. gondii</i> infection and brain tumor risk. Genetic instruments for <i>T. gondii</i> seropositivity were derived from a genome-wide association study (GWAS) in the UK Biobank, while genetic data for brain tumors were obtained from the FinnGen R12 dataset. Standard MR methods, including inverse-variance weighted (IVW), weighted median, and MR-Egger, were applied to infer causality, with generalized summary Mendelian randomization (GSMR) used for further validation. Sensitivity analyses, including heterogeneity and pleiotropy assessments, were performed to ensure robustness. Additionally, reverse MR analyses were conducted to evaluate whether brain tumors influence genetic liability to <i>T. gondii</i> seropositivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our MR analyses found no evidence of a causal relationship between genetic liability to <i>T. gondii</i> seropositivity, as indicated by P22 and SAG1 antibody levels, and the risk of brain tumors. Across all tumor subtypes, IVW, weighted median, MR-Egger, and GSMR analyses consistently yielded non-significant results. However, reverse MR analysis suggested that genetic liability to malignant brain tumors is associated with increased odds of <i>T. gondii</i> seropositivity. For P22, a strong association was observed across methods (IVW: OR = 1.234, <i>p</i> = 0.004; GSMR: OR = 1.228, <i>p</i> = 0.006). In contrast, for SAG1 the evidence was weaker, with IVW indicating a suggestive association (OR = 1.094, <i>p</i> = 0.048) and GSMR showing a borderline association (OR = 1.088, <i>p</i> = 0.052). Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or pleiotropy. No significant associations were observed for meningioma, glioblastoma, or benign brain tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides no evidence for a causal relationship between genetic liability to <i>T. gondii</i> seropositivity and brain tumor risk. However, reverse MR suggests that genetic liability to malignant bra","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"16 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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