Pub Date : 2026-01-01DOI: 10.1016/j.cccb.2025.100524
Bowen Wang , Yi Zeng , Virginia Byers Kraus , Xin Gao , Jixiang Ma , Xuemei Bai , Jun Na , Wei Zhe , Zhaoxue Yin
Objective
This study investigated the gender-dependent association of cardiovascular health, assessed by Life’s Essential 8 (LE8), with cognitive function in Chinese older adults.
Methods
Logistic regression was used to explore the relationships between LE8 scores and incident cognitive impairment as well as cognitive decline. Gender differences were examined by subgroup analyses. A generalized linear model (GLM) was used to assess the mean difference of Mini-Mental State Examination (MMSE) scores across LE8 groups.
Results
Based on logistic regression, LE8 scores were inversely correlated with prevalence of baseline cognitive impairment (OR = 0.49, 95%CI: 0.30,0.84). Higher LE8 scores were associated with reduced risk of incident cognitive impairment among participants with normal cognition at baseline (OR = 0.56, 95%CI: 0.31,0.99), although there was no significant relationship between high LE8 scores and cognitive decline. Based on subgroup analyses, there was a significant gender-based association of LE8 with incident cognitive impairment (P = 0.022), but not with cognitive decline (P = 0.424). In the female subgroup, higher LE8 scores were associated with low risk of incident cognitive impairment (OR = 0.29, 95%CI: 0.13,0.64). Based on GLM analysis, the adjusted mean MMSE score of the high LE8 group was higher than that of the low LE8 group among all participants with follow-up (adjusted mean difference = 0.44, 95%CI: 0.03,0.85); similar results were observed among those with normal cognition at baseline.
Conclusion
A higher LE8 score was significantly associated with better cognitive function in Chinese female but not male older adults.
{"title":"Gender-dependent association between cardiovascular health and cognitive function in chinese older adults: a community based cohort study","authors":"Bowen Wang , Yi Zeng , Virginia Byers Kraus , Xin Gao , Jixiang Ma , Xuemei Bai , Jun Na , Wei Zhe , Zhaoxue Yin","doi":"10.1016/j.cccb.2025.100524","DOIUrl":"10.1016/j.cccb.2025.100524","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the gender-dependent association of cardiovascular health, assessed by Life’s Essential 8 (LE8), with cognitive function in Chinese older adults.</div></div><div><h3>Methods</h3><div>Logistic regression was used to explore the relationships between LE8 scores and incident cognitive impairment as well as cognitive decline. Gender differences were examined by subgroup analyses. A generalized linear model (GLM) was used to assess the mean difference of Mini-Mental State Examination (MMSE) scores across LE8 groups.</div></div><div><h3>Results</h3><div>Based on logistic regression, LE8 scores were inversely correlated with prevalence of baseline cognitive impairment (<em>OR</em> = 0.49, 95%<em>CI</em>: 0.30,0.84). Higher LE8 scores were associated with reduced risk of incident cognitive impairment among participants with normal cognition at baseline (<em>OR</em> = 0.56, 95%<em>CI</em>: 0.31,0.99), although there was no significant relationship between high LE8 scores and cognitive decline. Based on subgroup analyses, there was a significant gender-based association of LE8 with incident cognitive impairment (<em>P</em> = 0.022), but not with cognitive decline (<em>P</em> = 0.424). In the female subgroup, higher LE8 scores were associated with low risk of incident cognitive impairment (<em>OR</em> = 0.29, 95%<em>CI</em>: 0.13,0.64). Based on GLM analysis, the adjusted mean MMSE score of the high LE8 group was higher than that of the low LE8 group among all participants with follow-up (adjusted mean difference = 0.44, 95%<em>CI</em>: 0.03,0.85); similar results were observed among those with normal cognition at baseline.</div></div><div><h3>Conclusion</h3><div>A higher LE8 score was significantly associated with better cognitive function in Chinese female but not male older adults.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100524"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.cccb.2025.100525
Anna Marseglia , Roxana O. Carare , Jessica L. Teeling , Saima Hilal , Vera Yuan Cai , Russell Chander , Hugues Chabriat , Deborah Gustafson , Atticus H. Hainsworth , Gurpreet Kaur Hansra , Sarah-Naomi James , Audrey Low , Julie Ottoy , Satoshi Saito , Annemieke ter Telgte , Hilde van den Brink , Frank J. Wolters , Prashanthi Vemuri
{"title":"The international society of vascular behavioural and cognitive disorders: highlights from VasCog 2025 in the UK.","authors":"Anna Marseglia , Roxana O. Carare , Jessica L. Teeling , Saima Hilal , Vera Yuan Cai , Russell Chander , Hugues Chabriat , Deborah Gustafson , Atticus H. Hainsworth , Gurpreet Kaur Hansra , Sarah-Naomi James , Audrey Low , Julie Ottoy , Satoshi Saito , Annemieke ter Telgte , Hilde van den Brink , Frank J. Wolters , Prashanthi Vemuri","doi":"10.1016/j.cccb.2025.100525","DOIUrl":"10.1016/j.cccb.2025.100525","url":null,"abstract":"","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100525"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.cccb.2026.100528
Michael S Stringer , Xingfeng Shao , Hedok Lee , Antoine Vallatos , Carmen Arteaga-Reyes , Una Clancy , Francesca Chappell , Cameron Manning , Maria Valdes-Hernandez , Daniela Jaime Garcia , Rosalind Brown , Fergus N Doubal , Helene Benveniste , Michael J Thrippleton , Danny JJ Wang , Joanna M Wardlaw , Mild Stroke Study 3 study group
Background
Subtle blood-brain barrier (BBB) leakage has been detected in small vessel disease (SVD). While established methods rely on gadolinium-based contrast agents (GBCA), diffusion-weighted arterial spin labelling (DW-ASL) is a promising alternative which assesses water exchange rate (kw) without injected contrast. However, DW-ASL has not been widely applied in sporadic SVD. We aimed to determine how kw varied with GBCA BBB leakage measures, baseline and 1-year change in SVD burden.
Methods
We recruited patients with mild ischaemic stroke (lacunar or cortical) all characterised for SVD features. We assessed kw using DW-ASL and GBCA measures of BBB leakage (permeability-surface area product (PS), blood plasma volume and exchange rate of GBCA) using dynamic-contrast enhanced MRI. We used separate linear regression models to assess how kw varied with GBCA-derived metrics, baseline and 1-year change in WMH volume in co-variate-adjusted analyses.
Results
We included 24 with complete MRI (61±10 years; 71% male). Patients with higher kw tended to have more severe baseline SVD (e.g. subcortical grey matter (SGM): B=14.59 min-1/%WMH volume, 95% confidence interval (95%CI)=-1.00,28.18, p=0.04) and greater 1-year increase (B=0.0013 %WMH volume increase/min-1, 95%CI=-0.0001, 0.0026, p=0.06). We generally found kw and GBCA BBB leakage measures were not meaningfully associated (e.g. SGM kw∼PS: B=-0.23 min-1/10-4 min-1, 95%CI=-7.47, 7.01, p=0.95).
Conclusion
BBB water exchange estimated using DW-ASL tended to be greater with higher WMH burden and progression, suggesting kw may be a sensitive measure of BBB dysfunction in SVD. However, non-concordance between kw and GBCA metrics suggests the two methods probe different aspects of BBB function.
{"title":"Gadolinium- and water-based blood-brain barrier dysfunction measures in patients with sporadic small vessel disease","authors":"Michael S Stringer , Xingfeng Shao , Hedok Lee , Antoine Vallatos , Carmen Arteaga-Reyes , Una Clancy , Francesca Chappell , Cameron Manning , Maria Valdes-Hernandez , Daniela Jaime Garcia , Rosalind Brown , Fergus N Doubal , Helene Benveniste , Michael J Thrippleton , Danny JJ Wang , Joanna M Wardlaw , Mild Stroke Study 3 study group","doi":"10.1016/j.cccb.2026.100528","DOIUrl":"10.1016/j.cccb.2026.100528","url":null,"abstract":"<div><h3>Background</h3><div>Subtle blood-brain barrier (BBB) leakage has been detected in small vessel disease (SVD). While established methods rely on gadolinium-based contrast agents (GBCA), diffusion-weighted arterial spin labelling (DW-ASL) is a promising alternative which assesses water exchange rate (<em>k<sub>w</sub></em>) without injected contrast. However, DW-ASL has not been widely applied in sporadic SVD. We aimed to determine how <em>k<sub>w</sub></em> varied with GBCA BBB leakage measures, baseline and 1-year change in SVD burden.</div></div><div><h3>Methods</h3><div>We recruited patients with mild ischaemic stroke (lacunar or cortical) all characterised for SVD features. We assessed <em>k<sub>w</sub></em> using DW-ASL and GBCA measures of BBB leakage (permeability-surface area product (<em>PS</em>), blood plasma volume and exchange rate of GBCA) using dynamic-contrast enhanced MRI. We used separate linear regression models to assess how <em>k<sub>w</sub></em> varied with GBCA-derived metrics, baseline and 1-year change in WMH volume in co-variate-adjusted analyses.</div></div><div><h3>Results</h3><div>We included 24 with complete MRI (61±10 years; 71% male). Patients with higher <em>k<sub>w</sub></em> tended to have more severe baseline SVD (e.g. subcortical grey matter (SGM): B=14.59 min<sup>-1</sup>/%WMH volume, 95% confidence interval (95%CI)=-1.00,28.18, p=0.04) and greater 1-year increase (B=0.0013 %WMH volume increase/min<sup>-1</sup>, 95%CI=-0.0001, 0.0026, p=0.06). We generally found <em>k<sub>w</sub></em> and GBCA BBB leakage measures were not meaningfully associated (e.g. SGM <em>k<sub>w</sub></em>∼<em>PS</em>: B=-0.23 min<sup>-1</sup>/10<sup>-4</sup> min<sup>-1</sup>, 95%CI=-7.47, 7.01, p=0.95).</div></div><div><h3>Conclusion</h3><div>BBB water exchange estimated using DW-ASL tended to be greater with higher WMH burden and progression, suggesting <em>k<sub>w</sub></em> may be a sensitive measure of BBB dysfunction in SVD. However, non-concordance between <em>k<sub>w</sub></em> and GBCA metrics suggests the two methods probe different aspects of BBB function.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100528"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.cccb.2025.100526
Sheelakumari Raghavan , Scott A. Przybelski , Robert I. Reid , Michael G. Kamykowski , Jonathan Graff-Radford , Val J. Lowe , David S. Knopman , Clifford R. Jack Jr , Ronald C. Petersen , Prashanthi Vemuri
Background
Diffusion MRI (dMRI) has been proposed for quantifying early tissue changes in cerebral small vessel disease (SVD). We evaluated the regional dependance of predictors of white matter (WM) damage and compared the utility of longitudinal WM changes in the commonly available diffusion MRI measures for vascular contribution to cognitive impairment and dementia (VCID) prevention trials.
Methods
We included 718 participants (mean age: 71.1(9.6) years, 56 % males) with at least two dMRI scans, amyloid-PET, and structural imaging. We computed single-shell dMRI measures (fractional anisotropy, mean diffusivity, free water, peak-width skeletonized mean diffusivity (PSMD) and assessed: i) regional dependance of predictors of baseline WM damage using voxel-level analyses; ii) longitudinal associations between dMRI measures and cognition; and iii) sample size estimates for a hypothetical clinical trial considering the regional and global dMRI measures as markers for VCID. We also included white matter hyperintensities (WMH) and our recently proposed composite vascular WM score (combination of WMH and fractional anisotropy of the genu) as a comparison.
Results
Vascular risk was consistently associated with dMRI changes in the genu of the corpus callosum. All SVD markers correlated with cognitive performance longitudinally. Global free water and the composite score provided the smallest sample size estimates, especially in participants with prevalent vascular disease (aged 70–89).
Conclusions
dMRI markers had significant frontal lobe changes due to vascular risk and were sensitive to cognitive decline. The composite vascular WM score, global free water, and WMH emerged as promising VCID biomarkers, but further validation is needed in multiple populations.
{"title":"Evaluating regional and global diffusion measures as biomarkers for vascular contributions to cognitive impairment and dementia","authors":"Sheelakumari Raghavan , Scott A. Przybelski , Robert I. Reid , Michael G. Kamykowski , Jonathan Graff-Radford , Val J. Lowe , David S. Knopman , Clifford R. Jack Jr , Ronald C. Petersen , Prashanthi Vemuri","doi":"10.1016/j.cccb.2025.100526","DOIUrl":"10.1016/j.cccb.2025.100526","url":null,"abstract":"<div><h3>Background</h3><div>Diffusion MRI (dMRI) has been proposed for quantifying early tissue changes in cerebral small vessel disease (SVD). We evaluated the regional dependance of predictors of white matter (WM) damage and compared the utility of longitudinal WM changes in the commonly available diffusion MRI measures for vascular contribution to cognitive impairment and dementia (VCID) prevention trials.</div></div><div><h3>Methods</h3><div>We included 718 participants (mean age: 71.1(9.6) years, 56 % males) with at least two dMRI scans, amyloid-PET, and structural imaging. We computed single-shell dMRI measures (fractional anisotropy, mean diffusivity, free water, peak-width skeletonized mean diffusivity (PSMD) and assessed: i) regional dependance of predictors of baseline WM damage using voxel-level analyses; ii) longitudinal associations between dMRI measures and cognition; and iii) sample size estimates for a hypothetical clinical trial considering the regional and global dMRI measures as markers for VCID. We also included white matter hyperintensities (WMH) and our recently proposed composite vascular WM score (combination of WMH and fractional anisotropy of the genu) as a comparison.</div></div><div><h3>Results</h3><div>Vascular risk was consistently associated with dMRI changes in the genu of the corpus callosum. All SVD markers correlated with cognitive performance longitudinally. Global free water and the composite score provided the smallest sample size estimates, especially in participants with prevalent vascular disease (aged 70–89).</div></div><div><h3>Conclusions</h3><div>dMRI markers had significant frontal lobe changes due to vascular risk and were sensitive to cognitive decline. The composite vascular WM score, global free water, and WMH emerged as promising VCID biomarkers, but further validation is needed in multiple populations.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100526"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.cccb.2026.100529
Bonnie Yin Ka Lam , An Ran Ran , Yuan Cai , Huijing Zheng , Jize Wei , Yuen Tung Ng , Michael Ying Hong Chan , Ha Ying Chiu , Ho Ko , Carol Y. Cheung , Vincent Chung Tong Mok
Introduction
The i-Cog Brain Health is a validated deep learning model for differentiating Alzheimer’s disease dementia from cognitively unimpaired subjects based on retinal photographs. This study aimed to apply the i-Cog Brain Health in subjects without dementia and assess whether this tool may detect alterations in the retinal vessel network in healthy older adults.
Methods
Community subjects were recruited from the BEAT AD (Brain Health Evaluation And Tailor-made Measures for Prevention of Alzheimer’s Disease) service programme. Clinical data, vascular risk factors, lifestyle information and cognitive function were assessed. Tailor-made recommendations were provided to optimise risk factor control. Fundus photographs were obtained using the Topcon NW500 non-mydriatic retinal camera. Subjects were classified into positive or negative using i-Cog Brain Health based on quantitative measurements of retinal vessels.
Results
Among the 185 subjects (mean age: 68.14 ± 5.17 years; males: 32.97%), 29 (15.68%) were classified as positive by i-Cog Brain Health. Those subjects were significantly older (p = 0.001) and had wider venular branching width (p = 0.008). Regression analyses showed the venule branching coefficient significantly predicted i-Cog Brain Health positive cases (OR 1.54, 95% CI: 1.05–2.27, p = 0.027), after adjustments for age and mean arterial pressure.
Conclusions
The i-Cog Brain Health reflected older age and wider venular branching width, which are associated with dementia. The i-Cog Brain Health showed the potential to differentiate retinal features associated with dementia at an early stage and serve as a risk stratification tool.
i-Cog脑健康是一个经过验证的深度学习模型，用于区分阿尔茨海默病痴呆症和基于视网膜照片的认知未受损受试者。本研究旨在将i-Cog脑健康应用于无痴呆的受试者，并评估该工具是否可以检测健康老年人视网膜血管网络的改变。方法从BEAT AD （Brain Health Evaluation And tailored Measures for Prevention for Alzheimer 's Disease）服务项目中招募社区受试者。评估临床资料、血管危险因素、生活方式信息和认知功能。为优化风险因素控制提供了量身定制的建议。眼底照片采用Topcon NW500无散光视网膜相机拍摄。使用基于视网膜血管定量测量的i-Cog脑健康将受试者分为阳性或阴性。结果185例患者（平均年龄：68.14±5.17岁，男性：32.97%）中，29例（15.68%）i-Cog脑健康检查呈阳性。这些受试者明显更老（p = 0.001），静脉分支宽度更宽（p = 0.008）。回归分析显示，在调整年龄和平均动脉压后，小静脉分支系数显著预测i-Cog脑健康阳性病例（OR 1.54, 95% CI: 1.05-2.27, p = 0.027）。结论i-Cog脑健康反映年龄较大，静脉分支宽度较宽，与痴呆相关。i-Cog脑健康显示了在早期阶段区分与痴呆相关的视网膜特征的潜力，并可作为风险分层工具。
{"title":"Deep learning retinal imaging model identifies poor brain health among older adults without dementia","authors":"Bonnie Yin Ka Lam , An Ran Ran , Yuan Cai , Huijing Zheng , Jize Wei , Yuen Tung Ng , Michael Ying Hong Chan , Ha Ying Chiu , Ho Ko , Carol Y. Cheung , Vincent Chung Tong Mok","doi":"10.1016/j.cccb.2026.100529","DOIUrl":"10.1016/j.cccb.2026.100529","url":null,"abstract":"<div><h3>Introduction</h3><div>The i-Cog Brain Health is a validated deep learning model for differentiating Alzheimer’s disease dementia from cognitively unimpaired subjects based on retinal photographs. This study aimed to apply the i-Cog Brain Health in subjects without dementia and assess whether this tool may detect alterations in the retinal vessel network in healthy older adults.</div></div><div><h3>Methods</h3><div>Community subjects were recruited from the BEAT AD (<strong>B</strong>rain Health <strong>E</strong>valuation <strong>A</strong>nd <strong>T</strong>ailor-made Measures for Prevention of <strong>A</strong>lzheimer’s <strong>D</strong>isease) service programme. Clinical data, vascular risk factors, lifestyle information and cognitive function were assessed. Tailor-made recommendations were provided to optimise risk factor control. Fundus photographs were obtained using the Topcon NW500 non-mydriatic retinal camera. Subjects were classified into positive or negative using i-Cog Brain Health based on quantitative measurements of retinal vessels.</div></div><div><h3>Results</h3><div>Among the 185 subjects (mean age: 68.14 ± 5.17 years; males: 32.97%), 29 (15.68%) were classified as positive by i-Cog Brain Health. Those subjects were significantly older (<em>p</em> = 0.001) and had wider venular branching width (<em>p</em> = 0.008). Regression analyses showed the venule branching coefficient significantly predicted i-Cog Brain Health positive cases (OR 1.54, 95% CI: 1.05–2.27, <em>p</em> = 0.027), after adjustments for age and mean arterial pressure.</div></div><div><h3>Conclusions</h3><div>The i-Cog Brain Health reflected older age and wider venular branching width, which are associated with dementia. The i-Cog Brain Health showed the potential to differentiate retinal features associated with dementia at an early stage and serve as a risk stratification tool.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100529"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.cccb.2025.100527
Tímea Tünde Takács , Judit Kárpáti , Edina Szabó , Károlyné Pálvölgyi , Panna Pálinkás , Orsolya Antal , Júlia Baross , Bernadett Bruckner , Sam Webb , Nele Demeyere , Bence Gunda
Background
Post-stroke cognitive impairment (PSCI) is a frequent yet underdiagnosed consequence of stroke, with significant implications for quality of life, functional outcomes and long-term prognosis. Despite its importance, cognitive screening remains insufficiently integrated into post-stroke care protocols, particularly in Hungary.
Objective
This study aimed to adapt and pilot the Oxford Cognitive Screen (OCS) for Hungarian stroke patients, addressing the urgent need for a culturally and linguistically appropriate, stroke-specific cognitive screening tool that is freely available in Hungarian.
Methods
The Hungarian adaptation followed a rigorous 11-step linguistic validation process, including cultural adaptation, forward and back translations, reviews, and pilot testing. Ten stroke patients at Semmelweis University were assessed using the adapted OCS within three weeks of symptom onset. Data on test performance, feasibility, and patient feedback were collected from 10 pilot patients and 6 examiners.
Results
The adaptation and pilot testing process, completed in approximately three months, confirmed the usability of the tool, with most patients finding it engaging. The median number of impaired tasks was two. No major issues arose, and the tool was well received by both patients and examiners.
Conclusion
The Hungarian version of the OCS offers a practical, user-friendly cognitive screening tool tailored for stroke patients. Its implementation could enhance early detection of PSCI, improve patient safety by supporting targeted rehabilitation, and ultimately contribute to better long-term outcomes. This initiative represents a foundational step toward integrating cognitive screening into stroke protocols in Hungary, addressing a significant gap in rehabilitation and healthcare equity.
{"title":"The need for post-stroke cognitive screening - the rationale behind the Hungarian adaptation of the Oxford Cognitive Screen (OCS) and its pilot study","authors":"Tímea Tünde Takács , Judit Kárpáti , Edina Szabó , Károlyné Pálvölgyi , Panna Pálinkás , Orsolya Antal , Júlia Baross , Bernadett Bruckner , Sam Webb , Nele Demeyere , Bence Gunda","doi":"10.1016/j.cccb.2025.100527","DOIUrl":"10.1016/j.cccb.2025.100527","url":null,"abstract":"<div><h3>Background</h3><div>Post-stroke cognitive impairment (PSCI) is a frequent yet underdiagnosed consequence of stroke, with significant implications for quality of life, functional outcomes and long-term prognosis. Despite its importance, cognitive screening remains insufficiently integrated into post-stroke care protocols, particularly in Hungary.</div></div><div><h3>Objective</h3><div>This study aimed to adapt and pilot the Oxford Cognitive Screen (OCS) for Hungarian stroke patients, addressing the urgent need for a culturally and linguistically appropriate, stroke-specific cognitive screening tool that is freely available in Hungarian.</div></div><div><h3>Methods</h3><div>The Hungarian adaptation followed a rigorous 11-step linguistic validation process, including cultural adaptation, forward and back translations, reviews, and pilot testing. Ten stroke patients at Semmelweis University were assessed using the adapted OCS within three weeks of symptom onset. Data on test performance, feasibility, and patient feedback were collected from 10 pilot patients and 6 examiners.</div></div><div><h3>Results</h3><div>The adaptation and pilot testing process, completed in approximately three months, confirmed the usability of the tool, with most patients finding it engaging. The median number of impaired tasks was two. No major issues arose, and the tool was well received by both patients and examiners.</div></div><div><h3>Conclusion</h3><div>The Hungarian version of the OCS offers a practical, user-friendly cognitive screening tool tailored for stroke patients. Its implementation could enhance early detection of PSCI, improve patient safety by supporting targeted rehabilitation, and ultimately contribute to better long-term outcomes. This initiative represents a foundational step toward integrating cognitive screening into stroke protocols in Hungary, addressing a significant gap in rehabilitation and healthcare equity.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100527"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-07DOI: 10.1016/j.cccb.2025.100523
Xuan Vinh To , Javier Urriola , Viktor Vegh , Patrick Donnelly , Liam Maclachlan , Kate Mahady , Eduardo Miguel Apellaniz , Ryan Lim , Guido Gonzalez , Ricardo Wenger , Paul Cumming , Craig Winter , Fatima Nasrallah
Objectives
Cerebral microbleeds (CMBs), which present as foci of hypointensities on T2*-weighted Magnetic Resonance Imaging (MRI) are associated with weakened vessel walls. CMBs are also a frequent finding in traumatic brain injury (TBI) in association with poor outcome. We investigated whether a combination of susceptibility weighted imaging (SWI) and dynamic contrast enhanced (DCE) MRI could accurately identify characteristics of CMBs that are most relevant to TBI.
Materials and Methods
Thirty TBI patients were recruited from a neurosurgical unit. We acquired structural three-dimensional T1-weighted, T2-weighted dark fluid, SWI, and DCE-MRI images on a 3T MRI. DCE-MRI data was fitted for a linear graphic (Patlak-Gjedde) model to calculate voxel-wise volume transfer constant (Ktrans) maps. Ktrans ranges of normal-appearing brain (NAB) areas were quantified and two sub-classes of CMBs—leaky and non-leaky CMBs—were identified. Characteristics and spatial distribution of the quantified imaging metrics and the immunological blood panel results were then compared across mild versus moderate–severe TBI groups, as classified by Glasgow Coma Scale.
Results
More severe TBI was associated with CMBs exhibiting leaky BBB as quantified by DCE-MRI. Higher blood levels of interferon gamma (IFN-γ) were associated with lower number of CMBs in TBI patients at more than 8 days post-TBI.
Discussion
combined DCE-MRI and SWI confirmed that CMBs with leaky BBBs are more prevalent in moderate-severe TBIs compared. Higher levels of IFN-γ appeared to have been associated with fewer CMBs in the sub-acute stage of TBI.
{"title":"Relevance of cerebral microbleeds with leaky blood brain barrier in traumatic brain injury and protective role of interferon-gamma: A cohort study","authors":"Xuan Vinh To , Javier Urriola , Viktor Vegh , Patrick Donnelly , Liam Maclachlan , Kate Mahady , Eduardo Miguel Apellaniz , Ryan Lim , Guido Gonzalez , Ricardo Wenger , Paul Cumming , Craig Winter , Fatima Nasrallah","doi":"10.1016/j.cccb.2025.100523","DOIUrl":"10.1016/j.cccb.2025.100523","url":null,"abstract":"<div><h3>Objectives</h3><div>Cerebral microbleeds (CMBs), which present as foci of hypointensities on T2*-weighted Magnetic Resonance Imaging (MRI) are associated with weakened vessel walls. CMBs are also a frequent finding in traumatic brain injury (TBI) in association with poor outcome. We investigated whether a combination of susceptibility weighted imaging (SWI) and dynamic contrast enhanced (DCE) MRI could accurately identify characteristics of CMBs that are most relevant to TBI.</div></div><div><h3>Materials and Methods</h3><div>Thirty TBI patients were recruited from a neurosurgical unit. We acquired structural three-dimensional T1-weighted, T2-weighted dark fluid, SWI, and DCE-MRI images on a 3T MRI. DCE-MRI data was fitted for a linear graphic (Patlak-Gjedde) model to calculate voxel-wise volume transfer constant (K<sup>trans</sup>) maps. K<sup>trans</sup> ranges of normal-appearing brain (NAB) areas were quantified and two sub-classes of CMBs—leaky and non-leaky CMBs—were identified. Characteristics and spatial distribution of the quantified imaging metrics and the immunological blood panel results were then compared across mild versus moderate–severe TBI groups, as classified by Glasgow Coma Scale.</div></div><div><h3>Results</h3><div>More severe TBI was associated with CMBs exhibiting leaky BBB as quantified by DCE-MRI. Higher blood levels of interferon gamma (IFN-γ) were associated with lower number of CMBs in TBI patients at more than 8 days post-TBI.</div></div><div><h3>Discussion</h3><div>combined DCE-MRI and SWI confirmed that CMBs with leaky BBBs are more prevalent in moderate-severe TBIs compared. Higher levels of IFN-γ appeared to have been associated with fewer CMBs in the sub-acute stage of TBI.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"10 ","pages":"Article 100523"},"PeriodicalIF":2.8,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2024.100372
Katie Harris , Jessica Gong , Stephen MacMahon , Ying Xu , Sultana Shajahan , Stephen Harrap , Neil Poulter , Michel Marre , Pavel Hamet , Giuseppe Mancia , Craig Anderson , Mark Woodward , John Chalmers
Background and aims
Accumulating evidence indicates that reducing high blood pressure (BP) prevents dementia and mild cognitive impairment (MCI). Furthermore, although diabetes is a risk factor for dementia and MCI, there is uncertainty of the effect of intensive glucose control on these endpoints. This study aimed to determine the effects of BP-lowering (vs placebo) and intensive glucose-lowering (vs standard control) treatments according to baseline cognition and other characteristics on dementia and cognitive decline (CD) in people with type 2 diabetes mellitus (T2DM).
Methods
The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial involved 11,140 individuals with T2DM. The effects of BP-lowering and intensive glucose-lowering treatments were explored in subgroups of baseline Mini-Mental State Examination (MMSE), categorised as cognitively normal (scores ≥28) and cognitive impairment (scores <28). The primary outcome was a composite of dementia/CD that accounted for the competing risk of death. Multinomial regression models, adjusted for common cardiovascular risk factors, were used to estimate odds ratios (OR) with 95 % confidence intervals (CI) of the effects of the treatments on dementia/CD. Homogeneity of effects by subgroups were evaluated using interaction terms in the models. A two-sided p value <0.05 was regarded as statistically significant.
Results
BP-lowering treatment (vs. placebo) was associated with a lower odds of dementia/CD in participants with cognitive impairment (OR 0.76, 95 % CI (0.59–0.99)) but not in those cognitively normal (OR 1.05, 95 % CI (0.92–1.21); p for interaction 0.03). Those with a history of cardio-renal-metabolic syndrome did not experience a benefit of active BP lowering treatment compared with placebo on dementia/CD. There were no further subgroup effects of BP-lowering treatment. The effect of intensive glucose lowering (vs standard control) on the odds of dementia/CD did not vary by baseline cognition subgroup. However, it did vary by level of blood glucose at baseline (<7.9 mmol/L OR 1.12, 95 % CI (0.96–1.30) vs ≥ 7.9 mmol/L 0.87 (0.75–1.00); p for interaction 0.02) and duration of T2DM (<10 years OR 0.92 (0.81–1.05) vs ≥10 years 1.16 (0.97–1.38); p for interaction 0.04).
Conclusions
This study suggests greater effects of BP-lowering treatment in those with early loss of cognitive function than in those cognitively normal. There were also differential effects of intensive glucose-lowering on dementia and CD according to levels of blood glucose and duration of diabetes in people with T2DM.
Clinical trial registration
ADVANCE is registered with ClinicalTrials.gov: number NCT00145925
背景和目的：越来越多的证据表明，降低高血压（BP）可以预防痴呆和轻度认知障碍（MCI）。此外，虽然糖尿病是痴呆和轻度认知障碍的危险因素，但强化血糖控制对这些终点的影响尚不确定。本研究旨在根据基线认知和其他特征确定降压（相对于安慰剂）和强化降糖（相对于标准对照）治疗对2型糖尿病（T2DM）患者痴呆和认知能力下降（CD）的影响。方法：在糖尿病和血管疾病中的作用：Preterax和Diamicron改良释放控制评价（ADVANCE）试验纳入11,140例T2DM患者。在基线迷你精神状态检查（MMSE）的亚组中，研究了降压和强化降糖治疗的效果，分为认知正常（评分≥28）和认知障碍(评分结果：降压治疗（与安慰剂相比）与认知障碍参与者的痴呆/CD发生率较低相关（OR 0.76, 95% CI(0.59-0.99)），但与认知正常参与者无关(OR 1.05, 95% CI (0.92-1.21)；P为相互作用0.03)。与安慰剂相比，那些有心肾代谢综合征病史的患者在痴呆/CD方面没有得到主动降压治疗的益处。降压治疗没有进一步的亚组效应。强化降糖（与标准对照）对痴呆/CD几率的影响在基线认知亚组中没有变化。然而，它确实因基线血糖水平而异(结论：这项研究表明，与认知功能正常的人相比，早期认知功能丧失的人降压治疗的效果更大。根据2型糖尿病患者的血糖水平和糖尿病病程，强化降糖对痴呆和CD的影响也存在差异。临床试验注册：ADVANCE在ClinicalTrials.gov注册：编号NCT00145925。
{"title":"Effect of randomised blood pressure lowering treatment and intensive glucose control on dementia and cognitive decline according to baseline cognitive function and other subpopulations of individuals with type 2 diabetes: Results from the ADVANCE trial","authors":"Katie Harris , Jessica Gong , Stephen MacMahon , Ying Xu , Sultana Shajahan , Stephen Harrap , Neil Poulter , Michel Marre , Pavel Hamet , Giuseppe Mancia , Craig Anderson , Mark Woodward , John Chalmers","doi":"10.1016/j.cccb.2024.100372","DOIUrl":"10.1016/j.cccb.2024.100372","url":null,"abstract":"<div><h3>Background and aims</h3><div>Accumulating evidence indicates that reducing high blood pressure (BP) prevents dementia and mild cognitive impairment (MCI). Furthermore, although diabetes is a risk factor for dementia and MCI, there is uncertainty of the effect of intensive glucose control on these endpoints. This study aimed to determine the effects of BP-lowering (vs placebo) and intensive glucose-lowering (vs standard control) treatments according to baseline cognition and other characteristics on dementia and cognitive decline (CD) in people with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial involved 11,140 individuals with T2DM. The effects of BP-lowering and intensive glucose-lowering treatments were explored in subgroups of baseline Mini-Mental State Examination (MMSE), categorised as cognitively normal (scores ≥28) and cognitive impairment (scores <28). The primary outcome was a composite of dementia/CD that accounted for the competing risk of death. Multinomial regression models, adjusted for common cardiovascular risk factors, were used to estimate odds ratios (OR) with 95 % confidence intervals (CI) of the effects of the treatments on dementia/CD. Homogeneity of effects by subgroups were evaluated using interaction terms in the models. A two-sided p value <0.05 was regarded as statistically significant.</div></div><div><h3>Results</h3><div>BP-lowering treatment (vs. placebo) was associated with a lower odds of dementia/CD in participants with cognitive impairment (OR 0.76, 95 % CI (0.59–0.99)) but not in those cognitively normal (OR 1.05, 95 % CI (0.92–1.21); p for interaction 0.03). Those with a history of cardio-renal-metabolic syndrome did not experience a benefit of active BP lowering treatment compared with placebo on dementia/CD. There were no further subgroup effects of BP-lowering treatment. The effect of intensive glucose lowering (vs standard control) on the odds of dementia/CD did not vary by baseline cognition subgroup. However, it did vary by level of blood glucose at baseline (<7.9 mmol/L OR 1.12, 95 % CI (0.96–1.30) vs ≥ 7.9 mmol/L 0.87 (0.75–1.00); p for interaction 0.02) and duration of T2DM (<10 years OR 0.92 (0.81–1.05) vs ≥10 years 1.16 (0.97–1.38); p for interaction 0.04).</div></div><div><h3>Conclusions</h3><div>This study suggests greater effects of BP-lowering treatment in those with early loss of cognitive function than in those cognitively normal. There were also differential effects of intensive glucose-lowering on dementia and CD according to levels of blood glucose and duration of diabetes in people with T2DM.</div></div><div><h3>Clinical trial registration</h3><div>ADVANCE is registered with ClinicalTrials.gov: number NCT00145925</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"8 ","pages":"Article 100372"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100475
Christian Crouzet , Jihua Liu , Bernard Choi , David H Cribbs
Introduction
Introduction: Three Alzheimer disease-modifying anti-Aβ antibodies (aducanumab, lecanemab, and donanemab) have been approved since 2021. However, Amyloid Related Imaging Abnormalities (ARIAs) remain problematic, with rare serious adverse events and deaths linked to amyloid-immunotherapy (six deaths from macro- hemorrhages and eight from severe inflammatory ARIA-E). Investigating the underlying adverse cerebrovascular responses to passive anti-Aβ immunotherapy is critical to improve patient safety. The mechanisms driving these potentially fatal events remain poorly understood, necessitating robust preclinical models. This study aimed to investigate ARIAs following Ab immunotherapy in 5XFAD mice with different genetic backgrounds to develop better models for studying adverse cerebrovascular responses.
Methods
Methods: Study 1: Ten 8-10-month-old 5XFAD.WSB.EiJ female mice received single IP injections of 3D6 anti-Aβ antibody (7.0 mg/kg), and five received IgG2a(k) isotype control (BioXCell). The 3D6.IgG2a monoclonal (from Dr. Ron Demattos, Eli Lilly) offers strong FcgR-mediated response with weak inhibitory activity and complement activation capability. Blood vessels were labeled with Lectin-Dylight-649 via retro-orbital injection.
Amyloid plaques and CAA were labeled with Amylo-glo RTD and H&E staining detected vasculitis/angiitis. Study 2: Earlier time points (12, 24, 36 hours) compared 5XFAD.WSB.EiJ versus 5XFAD.C57B/6J responses to 3D6.IgG2a (5 mice/timepoint). Evans blue assessed blood-brain barrier integrity loss.
Results
Results: Study 1 was designed for 8 weeks with weekly 3D6.IgG2a injections, but was aborted after the first injection when 7/10 mice died within 36 hours. The remaining 3 mice were perfused to salvage data. All 3D6.IgG2a-treated brains showed surface macro- hemorrhages (Figure 1), while the IgG2a controls had no visible bleeds. Study 2 revealed striking strain differences: 5XFAD.C57B/6J mice were resistant to 3D6.IgG2a at all timepoints, while 5XFAD.WSB.EiJ brains showed modest surface lesions at 12 hours, prominent hemorrhages by 24 hours, and distress signs by 27 hours.
Conclusions
Conclusions: Comparing anti-Ab immunotherapy responses between 5XFAD.C57B/6J versus 5XFAD.WSB.EiJ mice provide insights into aging, amyloid plaque, and CAA contributions to ARIA development. The 3D6 antibody was chosen because its humanized version (bapineuzumab) previously reduced Aβ pathology while inducing ARIA-E and ARIA-H in patients. ARIA-like responses in 5XFAD.WSB.EiJ mice may provide a valuable model for investigating causes of serious adverse events in human amyloid immunotherapy patients.
自2021年以来，三种阿尔茨海默病修饰抗a β抗体（aducanumab， lecanemab和donanemab）已获批。然而，淀粉样蛋白相关成像异常（ARIAs）仍然存在问题，与淀粉样蛋白免疫治疗相关的罕见严重不良事件和死亡（6例死于大出血，8例死于严重炎症性ARIAs - e）。研究被动抗a β免疫治疗潜在的不良脑血管反应对提高患者安全性至关重要。驱动这些潜在致命事件的机制仍然知之甚少，需要健全的临床前模型。本研究旨在研究不同遗传背景的5XFAD小鼠Ab免疫治疗后的ARIAs，为研究脑血管不良反应建立更好的模型。方法：研究1:10例8 ~ 10月龄5XFAD.WSB。EiJ雌性小鼠单次IP注射3D6抗a β抗体（7.0 mg/kg）， 5只接受IgG2a(k)同型对照（BioXCell）。3 d6。IgG2a单克隆（来自Dr. Ron Demattos, Eli Lilly）具有较强的fcgr介导应答，但具有较弱的抑制活性和补体激活能力。血管经眶后注射凝集素- dylight -649标记。淀粉样斑块和CAA用Amylo-glo RTD标记，H&；E染色检测血管炎/脉管炎。研究2：与5XFAD.WSB相比，更早的时间点（12,24,36小时）。EiJ和5XFAD。C57B/6J对3D6的响应IgG2a（5只小鼠/时间点）。埃文斯蓝评估血脑屏障完整性损失。结果：研究1设计为8周，每周3D6。但在第一次注射后流产，7/10的小鼠在36小时内死亡。其余3只小鼠灌注保存数据。所有3 d6。IgG2a处理的大脑显示表面大出血（图1），而IgG2a对照组没有明显出血。研究2显示了显著的菌株差异：5XFAD。C57B/6J小鼠3D6耐药。在所有时间点IgG2a，而5XFAD.WSB。12小时时，EiJ脑表面出现轻度损伤，24小时时出现明显出血，27小时时出现窘迫症状。结论：比较5XFAD患者抗ab免疫治疗反应。C57B/6J与5XFAD.WSB。EiJ小鼠提供了对衰老、淀粉样斑块和CAA对ARIA发展的贡献的见解。选择3D6抗体是因为其人源化版本（bapineuzumab）先前在诱导ARIA-E和ARIA-H的同时降低了Aβ病理。5XFAD.WSB中的类aria响应。EiJ小鼠可能为研究人类淀粉样蛋白免疫治疗患者严重不良事件的原因提供有价值的模型。
{"title":"A Novel Mouse Model for Investigating ARIAs in Response to Anti-Abeta Immunotherapy","authors":"Christian Crouzet , Jihua Liu , Bernard Choi , David H Cribbs","doi":"10.1016/j.cccb.2025.100475","DOIUrl":"10.1016/j.cccb.2025.100475","url":null,"abstract":"<div><h3>Introduction</h3><div>Introduction: Three Alzheimer disease-modifying anti-Aβ antibodies (aducanumab, lecanemab, and donanemab) have been approved since 2021. However, Amyloid Related Imaging Abnormalities (ARIAs) remain problematic, with rare serious adverse events and deaths linked to amyloid-immunotherapy (six deaths from macro- hemorrhages and eight from severe inflammatory ARIA-E). Investigating the underlying adverse cerebrovascular responses to passive anti-Aβ immunotherapy is critical to improve patient safety. The mechanisms driving these potentially fatal events remain poorly understood, necessitating robust preclinical models. This study aimed to investigate ARIAs following Ab immunotherapy in 5XFAD mice with different genetic backgrounds to develop better models for studying adverse cerebrovascular responses.</div></div><div><h3>Methods</h3><div>Methods: Study 1: Ten 8-10-month-old 5XFAD.WSB.EiJ female mice received single IP injections of 3D6 anti-Aβ antibody (7.0 mg/kg), and five received IgG2a(k) isotype control (BioXCell). The 3D6.IgG2a monoclonal (from Dr. Ron Demattos, Eli Lilly) offers strong FcgR-mediated response with weak inhibitory activity and complement activation capability. Blood vessels were labeled with Lectin-Dylight-649 via retro-orbital injection.</div><div>Amyloid plaques and CAA were labeled with Amylo-glo RTD and H&E staining detected vasculitis/angiitis. Study 2: Earlier time points (12, 24, 36 hours) compared 5XFAD.WSB.EiJ versus 5XFAD.C57B/6J responses to 3D6.IgG2a (5 mice/timepoint). Evans blue assessed blood-brain barrier integrity loss.</div></div><div><h3>Results</h3><div>Results: Study 1 was designed for 8 weeks with weekly 3D6.IgG2a injections, but was aborted after the first injection when 7/10 mice died within 36 hours. The remaining 3 mice were perfused to salvage data. All 3D6.IgG2a-treated brains showed surface macro- hemorrhages (Figure 1), while the IgG2a controls had no visible bleeds. Study 2 revealed striking strain differences: 5XFAD.C57B/6J mice were resistant to 3D6.IgG2a at all timepoints, while 5XFAD.WSB.EiJ brains showed modest surface lesions at 12 hours, prominent hemorrhages by 24 hours, and distress signs by 27 hours.</div></div><div><h3>Conclusions</h3><div>Conclusions: Comparing anti-Ab immunotherapy responses between 5XFAD.C57B/6J versus 5XFAD.WSB.EiJ mice provide insights into aging, amyloid plaque, and CAA contributions to ARIA development. The 3D6 antibody was chosen because its humanized version (bapineuzumab) previously reduced Aβ pathology while inducing ARIA-E and ARIA-H in patients. ARIA-like responses in 5XFAD.WSB.EiJ mice may provide a valuable model for investigating causes of serious adverse events in human amyloid immunotherapy patients.</div></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"9 ","pages":"Article 100475"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.cccb.2025.100419
Alexandra Morozova , Maria del C. Valdés Hernández , Roberto Duarte Coello , Heather Whalley , Andrew McIntosh , Anca-Larisa Sandu Giuraniuc , Gordon D. Waiter , Christopher J McNeil , Douglas Steele , Joanna M. Wardlaw
Introduction
Stress, depressive symptoms, cardiovascular health, and physical strength are well-recognised factors contributing to microcirculatory changes in the brain, accentuating the multifactorial nature of these alterations. MRI-detectable brain perivascular spaces (PVS) have been proposed as neuroimaging markers reflecting microcirculatory dynamics. However, it remains unclear whether perivascular morphology is affected by these neuropsychiatric and physiological determinants, and which specific morphometric features are influenced by familial factors beyond established overall genetic contributions. Therefore, our study aims to investigate the associations between neuropsychiatric factors – hair cortisol, Quick Inventory of Depressive Symptomatology scale score, and hand grip strength – and PVS characteristics in a healthy aging population. In addition, it seeks to investigate the potential influence of familial factors on PVS characteristics through first-degree relatives.
Methods
We used the Stratifying Depression and Resilience Longitudinally (STRADL) family-based cohort to assess the association between these factors, familial influences, and PVS characteristics. Using an automated segmentation method on brain magnetic resonance images, we generated perivascular space volume, count, density (i.e., count per unit volume), and median length in the centrum semiovale (CSO) and the basal ganglia (BG) of 1183 participants, including 324 subjects with first-degree relatives within the cohort. The statistical analyses were conducted using Linear Mixed Effects Models built for each PVS measurement.
Results
Significant associations were identified between increasing PVS burden, advancing age and current depressive symptoms in both the BG and the CSO regions. Increased PVS burden in the CSO was associated with higher hair cortisol and weaker hand grip strength. Familial factors were significant in determining PVS volume and median length in the CSO, with age being a substantial contributor.
Conclusions
Chronic stress exposure and physical strength are reflected in the PVS morphology of the CSO, whereas depressive symptomatology affects both the BG and the CSO regions. Familial effects on CSO PVS volume and length were observed, contributing to our understanding of potential genetic and environmental influences on PVS morphology.
The regional variability in PVS burden provides insights into differences in the pathophysiology of perivascular clearance across brain regions, suggesting that specific changes in PVS characteristics may depend on the nature of influencing factors.
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