Journal of Investigative Medicine最新文献

{"title":"Access to mechanical thrombectomy for stroke in the UK: the unacceptable postcode lottery.","authors":"Soma Banerjee, Kyriakos Lobotesis, Joseph Kwan, Alan Isaacs, Deborah Lowe","doi":"10.1136/svn-2025-004559","DOIUrl":"https://doi.org/10.1136/svn-2025-004559","url":null,"abstract":"","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sox10 glial-neuron nuclear communication mediates anti-apoptosis neuroprotection after ischaemic stroke.","authors":"Maojiao Huang, Xinye Huang, Yunru Chen, Zixin Zhang, Ju Wang, Qiao Yin, Junjie Liu, Fanbin Xie, Wanting Huang, Falei Yuan, Chunyun Luo, Xiaosong He","doi":"10.1136/svn-2025-004934","DOIUrl":"https://doi.org/10.1136/svn-2025-004934","url":null,"abstract":"<p><strong>Background: </strong>Neuronal apoptosis is a hallmark of ischaemic stroke, yet effective neuroprotective therapies remain scarce. Recent studies suggest that Sox10-lineage cells (SOL) can transfer nuclear material to neurons. However, whether this process contributes to neuronal survival after stroke remains unknown.</p><p><strong>Methods: </strong>Sox10-iCreERT2:Ai9 mice subjected to distal middle cerebral artery occlusion (dMCAO) were used to investigate SOL to neuron material transfer after ischaemic injury. High-resolution confocal imaging, AAV-based lineage tracing and single-nucleus RNA sequencing were employed to identify tdTomato-positive neurons and characterise their transcriptional profiles. Behavioural tests and histological analyses were performed to evaluate the neuroprotective effects of tamoxifen treatment.</p><p><strong>Results: </strong>A subset of neurons from cortical layer 6 expressed tdTomato protein derived from SOL, suggesting intercellular material transfer. Notably, tdTomato⁺ neurons exhibited enhanced Bcl2 expression. High-dose tamoxifen (160 mg/kg) increased the number of tdTomato⁺ neurons by approximately fourfold compared with low-dose treatment. Correspondingly, the proportion of apoptotic neurons (TUNEL⁺/NeuN⁺) in the high-dose tamoxifen group was reduced from 33.4% to 19.3%, and infarct volume decreased from 11.68% to 7.26% of the ipsilateral hemisphere after ischaemic stroke. Functionally, high-dose tamoxifen significantly improved sensorimotor recovery, as evidenced by faster adhesive removal (6.9 s vs 22.2 s) and reduced forelimb error rates in the grid-walk test.</p><p><strong>Conclusions: </strong>We identify Sox10 lineage-associated tdTomato⁺ neurons in the ischaemic cortex, with their prevalence higher under high-dose tamoxifen and associated with reduced neuronal loss and improved neurological outcomes. These findings suggest a potential link between Sox10 lineage-related cellular plasticity and neuroprotection.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional outcomes of minimally invasive surgery treatment for patients with small supratentorial spontaneous intracerebral haematoma less than 30 mL: a propensity score matching study.","authors":"Hanyu Sun, Xinqun Luo, Zhang Guo, Lingyun Zhuo, Dekui Cheng, Zhuyu Gao, Qiu He, Zheng Yan, Dezhi Kang, Wenhua Fang, Fuxin Lin","doi":"10.1136/svn-2024-003893","DOIUrl":"10.1136/svn-2024-003893","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the efficacy of frameless robot-assisted stereotactic aspiration coupled with catheter thrombolysis (SA-CT) in treating supratentorial spontaneous intracerebral haemorrhage (sICH) with small haematoma volumes (<30 mL).</p><p><strong>Methods: </strong>We analysed the clinical and long-term outcome data for patients who had haematoma volumes <30 mL and underwent SA-CT between August 2019 and June 2023. Then, we matched the patients receiving conservative treatment during the same period from a multicentre intracerebral haemorrhage database using propensity score matching. The outcomes included the restoration of independent standing ability and mortality within 1 year after onset.</p><p><strong>Results: </strong>340 patients were included in the final analysis. A greater proportion of patients in the surgery group regained the ability to stand independently within 1 year (89.1% vs 78.1%, p=0.049). The Kaplan-Meier curve showed that the cumulative standing rate in the surgery group was higher than that in the conservative group (90.4% vs 82.0%, p=0.007) within 1 year, and the median time to regain standing was shorter in the surgery group (30 days vs 34 days). The mortality rates were lower in the surgery group (p<0.05). Multivariate Cox regression analysis revealed that frameless robot-guided SA-CT (adjusted HR 1.80; 95% CI 1.37 to 2.38; p<0.001), age, haematoma volume, the severe Glasgow Coma Scale scores and pneumonia were independent factors associated with standing recovery within 1 year after onset.</p><p><strong>Conclusions: </strong>Frameless robot-guided SA-CT for small supratentorial haematoma with contralateral hemiplegia seems safe and potentially facilitates the recovery of independent standing ability and reduces the mortality rates.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"111-121"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the effectiveness and safety of rescue balloon angioplasty versus stenting in acute large vessel occlusion after thrombectomy.","authors":"Yu Jiang, Chao Li, Mingchao Shi, Kangjia Song, Menglu Cong, Wenbin Zhang, Lanqi Li, Shouchun Wang","doi":"10.1136/svn-2024-003851","DOIUrl":"10.1136/svn-2024-003851","url":null,"abstract":"<p><strong>Background: </strong>Intracranial atherosclerotic stenosis (ICAS) is a leading cause of failed mechanical thrombectomy (MT). To achieve successful recanalisation, rescue strategies such as balloon angioplasty and stenting are frequently employed. In this study, we aimed to investigate the comparative efficacy and safety of these strategies.</p><p><strong>Methods: </strong>We retrospectively analysed the data of 321 patients with ICAS-related large vessel occlusion (LVO) treated with rescue balloon angioplasty (n=212) or stenting (n=109) after MT. The primary outcome was favourable outcomes (modified Rankin Scale score of 0-2) at 3 months. Multivariate logistic regression identified predictors of outcomes, including subgroup analyses for anterior and posterior circulation.</p><p><strong>Results: </strong>Overall, data of 321 patients (median age, 60 (IQR, 53-67) years; 80.4% male) were analysed from an initial cohort of 1601 patients. At 3 months, the balloon group demonstrated a trend towards a higher rate of favourable outcomes (34.9% vs 45.8%; OR 0.62, 95% CI 0.36 to 1.09, p=0.098). The stent group showed a trend towards a higher incidence of symptomatic intracranial haemorrhage (11.0% vs 4.2%; OR 2.22, 95% CI 0.80 to 6.14, p=0.124). In the posterior circulation subgroup, favourable outcomes were significantly lower in the stent group (20.5% vs 41.5%; OR 0.32, 95% CI 0.10 to 0.98, p=0.047).</p><p><strong>Conclusion: </strong>Balloon angioplasty after MT may improve clinical outcomes to some extent in ICAS-related LVO with a lower incidence of intracranial haemorrhage compared with stenting, while stenting is an effective measure to prevent long-term restenosis.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"28-35"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically predicted white matter microstructure mediates the relationship between risk factors and lacunar stroke.","authors":"Jie Zhang, Min Wu, Douglas Neville, Yue Zou, Kaisi Ren, Qing Ye, Shuchang Zhong, Haiying Xiang, Wenshi Wang, Xiangming Ye, Benyan Luo, Li Zhang","doi":"10.1136/svn-2025-004208","DOIUrl":"10.1136/svn-2025-004208","url":null,"abstract":"<p><strong>Background and purpose: </strong>Lacunar stroke is a complex, multifactorial disease with significant genetic underpinnings. However, the mechanisms through which genetic predispositions and risk factors contribute to its pathogenesis remain poorly understood. We investigated whether genetically predicted white matter (WM) microstructure mediates causal relationships between risk factors and lacunar stroke.</p><p><strong>Methods: </strong>Data from genome-wide association studies were used to perform two-sample Mendelian randomisation (MR) analyses. Genetic variants associated with risk factors (n=34 461-898 130), lacunar stroke (n=232 596) and eight MRI-derived WM microstructural metrics across 48 tracts (n=20 859-20 860) were analysed. Univariable MR assessed causal effects of risk factors on lacunar stroke. Two-step MR analysis evaluated mediation roles of WM microstructure, whereas multivariable MR accounted for confounders.</p><p><strong>Results: </strong>Hypertension was identified as the strongest risk factor for lacunar stroke (OR=1.38; 95% CI: 1.28 to 1.50, p=4.43×10^-15). Only hypertension showed a significant causal association with genetically predicted WM microstructure. Elevated mean diffusivity (MD), isotropic volume fraction (ISOVF) and the tertiary eigenvalue in the anterior limb of the internal capsule (ALIC) were independently linked to increased lacunar stroke risk, beyond the influence of WM hyperintensities, dilated perivascular spaces and brain volume. Mediation analysis suggested that hypertension-induced lacunar stroke was partially mediated through bilateral MD and left ISOVF in the ALIC, with mediation proportions of 23.70%-33.44%.</p><p><strong>Conclusions: </strong>Hypertension may contribute to lacunar stroke pathogenesis in part through WM microstructure alterations, particularly in the ALIC. MD and ISOVF in the ALIC may serve as structural brain reserves and early biomarkers of hypertension-induced pathophysiology associated with lacunar stroke.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"69-81"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture reduces neuroinflammation and neuronal pyroptosis via downregulating Neat1 in rats after stroke.","authors":"Wanqing Lin, Zhaolian Cai, Xiaoyong Zhong, Xiaofang You, Renyu Yu, Bin Chen","doi":"10.1136/svn-2024-003964","DOIUrl":"10.1136/svn-2024-003964","url":null,"abstract":"<p><strong>Background: </strong>We investigated the potential contribution of the lncRNA Neat1 to the therapeutic efficacy of electroacupuncture (EA) after ischaemic stroke.</p><p><strong>Methods: </strong>EA stimulation was used to treat cerebral ischaemia/reperfusion injury (CIRI) in the rat model. Post-therapeutic intervention, infarct volume (IV), brain water content and neurological impairments were assessed. Furthermore, TUNEL and immunofluorescence staining were performed to examine cellular apoptosis, neuronal loss and neuroglial activation. Additionally, Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), western blotting, ELISA and electron microscopy were employed to assess the NLRC4 inflammasome pathway and neuronal pyroptosis in rats subjected to CIRI.</p><p><strong>Results: </strong>Present findings confirmed that EA successfully downregulated Neat1 and IV in response to CIRI. Moreover, the positive impacts of EA on neurobehavioural recovery, suppression of brain damage and reduction in MAP2 degradation were reversed by Neat1 overexpression. Neat1 overexpression also blocked the reduction in NLRC4 activation, including that of components such as NLRC4, Caspase-1 and gasdermin D, as well as the decrease in cellular apoptosis and neuronal pyroptosis induced by EA. Furthermore, Neat1 overexpression counteracted the suppressive effects of EA on proinflammatory microglial polarisation (Iba1⁺/CD11b⁺) and increased neurogenesis (Nestin⁺/Sox2⁺) in EA-treated rats. Finally, Neat1 overexpression inhibited the ability of EA to lower proinflammatory factors and elevated anti-inflammatory cytokines in the ischaemic striatum.</p><p><strong>Conclusions: </strong>These results highlight a novel anti-inflammatory mechanism of EA that involves the lncRNA Neat1/NLRC4 pathway, which regulates the inhibition of neuronal pyroptosis and neuroinflammation. This mechanism may work as an attainable therapeutic objective for EA-induced neuroprotection against ischaemic stroke.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"45-57"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of Y-3 intracalvariosseous injection versus intravenous injection in the treatment of acute large hemispheric infarction (SOLUTION-2): rationale and design of a multicentre, prospective, randomised, open-label, blind endpoint (PROBE) trial.","authors":"Nanxing Wang, Meiyang Zhang, Mo Yang, Wenqian Liu, Weiming Liu, Yunwei Ou, Mengyuan Zhou, Xuan Wang, Zhiwei Sun, Yuesong Pan, Yongjun Wang, Yilong Wang","doi":"10.1136/svn-2024-004011","DOIUrl":"10.1136/svn-2024-004011","url":null,"abstract":"<p><strong>Rationale: </strong>The blood-brain barrier (BBB) largely restricts the efficacy of neuroprotectants, which is an important approach in treating large hemispheric infarction (LHI). In this study, we harnessed intracalvariosseous (ICO) injection to bypass the BBB and facilitate drug delivery.</p><p><strong>Aim: </strong>To compare the efficacy and safety of ICO injection versus intravenous injection in the treatment of acute LHI within 24 hours of disease onset.</p><p><strong>Methods and design: </strong>The efficacy and safety of Y-3 ICO injection versus intravenous injection in the treatment of acute LHI (SOLUTION-2) is a multicentre, prospective, randomised, open-label, blind endpoint trial. 134 patients with acute LHI from more than six centres will be enrolled and randomised in the trial to receive ICO or intravenous injection of Y-3 in a 1:1 ratio.</p><p><strong>Study outcomes: </strong>The primary efficacy outcome is the proportion of patients with a modified Rankin Scale score of 0-3 at 90 days after symptom onset. Primary safety outcomes include infection events related to ICO injection procedures.</p><p><strong>Discussion: </strong>Results from the SOLUTION-2 trial will contribute to the understanding of the efficacy and safety of the Y-3 ICO injection in patients with LHI.</p><p><strong>Trial registry: </strong>The efficacy and safety of Y-3 ICO injection versus intravenous injection in the treatment of acute LHI (SOLUTION-2). URL: https://clinicaltrials.gov/study/NCT06374667?cond=SOLUTION-2&intr=y-3&rank=1.</p><p><strong>Trial registration number: </strong>NCT06374667.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"130-135"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of histone deacetylases and sirtuins in the ischaemic stroke: a systematic review and meta-analysis of animal studies.","authors":"Ali Majdi, Shahin Yaraghi, Ali Moharrami, Amirreza Ghaffari Tabrizi, Morteza Dojahani, Erfan Alirezapour, Kamyar Mansori, Mehdi Eskandari, Hossein Mostafavi","doi":"10.1136/svn-2025-004159","DOIUrl":"10.1136/svn-2025-004159","url":null,"abstract":"<p><strong>Background: </strong>Treatment of ischaemic stroke requires exploration of novel neuroprotective strategies owing to the constraints of thrombolytic therapy. Recent research implies that modulation of histone deacetylases (HDAC) or sirtuins (SIRT) could be beneficial in achieving this goal.</p><p><strong>Methods: </strong>This systematic review and meta-analysis evaluates the effectiveness of HDAC/SIRT enzyme modulation in treating acute ischaemic stroke. It includes relevant studies but excludes human and in vitro research and non-primary studies. An electronic search was conducted across databases PubMed, Web of Science and Scopus until 20 March 2025. The methodological quality was assessed using a modified SYRCLE risk of bias tool. Infarct volume and neurological responses were extracted as key outcomes, and a random-effects meta-analysis of infarct volume was conducted for studies directly targeting HDAC/SIRT enzymes.</p><p><strong>Results: </strong>A review of 71 studies involving over 1600 animals focused on ischaemic stroke treatments, predominantly using male rodents in a transient middle cerebral artery occlusion model. Most treatments were administered intraperitoneally, starting from the inception of ischaemia until 5 days afterwards. Non-selective HDAC inhibitors and SIRT1 modulators were targeted most frequently. The meta-analysis on infarct volume with 95% CI showed an overall effect estimate of -1.529 and suggested that non-selective HDAC inhibitors exhibit the most promise in reducing infarct size. Additionally, agonists of SIRT3/7, SIRT6, SIRT1 and HDAC1, along with inhibitors of SIRT5, HDAC6 and HDAC3, may play a significant role in the treatment of ischaemic stroke. Importantly, neuroprotective treatments have been found to be most effective in reducing infarct volume when administered within 24 hours following ischaemia.</p><p><strong>Discussion: </strong>This study highlights the most promising neuroprotective trials for ischaemic stroke by focusing on infarct volume as a key outcome. However, relying exclusively on infarct volume may not fully capture the effectiveness of these treatments.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"6-20"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting clinical outcome in posterior circulation large-vessel occlusion patients with endovascular recanalisation: the GNC score.","authors":"Jia-Qi Wang, Si-Qi Qiu, Wei Li, Jing Qiu, Thanh Nguyen, Hui-Sheng Chen","doi":"10.1136/svn-2025-004131","DOIUrl":"10.1136/svn-2025-004131","url":null,"abstract":"<p><strong>Background and purpose: </strong>Acute ischaemic strokes caused by posterior circulation large-vessel occlusions (pc-LVOs) are associated with particularly poor prognoses, including significant disability and mortality rates. This study sought to develop and validate a novel scoring system for predicting functional outcomes in pc-LVO cases following successful endovascular recanalisation.</p><p><strong>Methods: </strong>We derived a predictive model from the DETECT-China cohort and externally validated it using the DETECT2-China dataset. Poor outcome was defined as a modified Rankin Scale score of 4-6 at 90 days. Cerebral circulation time (CCT), measured via digital subtraction angiography (DSA), served as a key predictor. Multivariable logistic regression was employed to construct the scoring system.</p><p><strong>Results: </strong>The training cohort comprised 92 patients, of whom 52 (56.5%) experienced poor outcomes. Multivariate analysis identified prolonged CCT (adjusted OR (aOR) 1.365; 95% CI 1.105 to 1.686; p=0.004), elevated admission National Institutes of Health Stroke Scale (NIHSS) (aOR 1.235; 95% CI 1.120 to 1.363; p<0.001) and higher blood glucose levels (aOR 1.345; 95% CI 1.023 to 1.769; p=0.034) as independent predictors. These variables were integrated into the GNC score (Glucose-NIHSS-CCT). The GNC score demonstrated excellent predictive performance for clinical outcome, good discrimination and calibration in this cohort, as well as the bootstrap validation. Importantly, the excellent performance of this score was further validated in DETECT2-China.</p><p><strong>Conclusions: </strong>This is the first report that CCT based on DSA is an independent prognostic marker in pc-LVO patients with successful recanalisation post-endovascular treatment. The GNC score, incorporating readily available clinical and angiographic parameters, offers a reliable tool for outcome prediction in this high-risk population.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"21-27"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of accelerated biological ageing with incident dementia, cognitive functions and brain structure: a prospective cohort study based on UK Biobank.","authors":"Xiaowei Zheng, Wenyang Han, Yiqun Li, Minglan Jiang, Xiao Ren, Pinni Yang, Yiming Jia, Lulu Sun, Ruirui Wang, Mengyao Shi, Zhengbao Zhu, Yonghong Zhang","doi":"10.1136/svn-2024-003690","DOIUrl":"10.1136/svn-2024-003690","url":null,"abstract":"<p><strong>Background: </strong>Several small-sample studies have suggested that biological processes of ageing are implicated with dementia and cognitive function. We aimed to prospectively investigate the associations of biological age with incident dementia, cognitive functions and brain structure based on the UK Biobank.</p><p><strong>Methods: </strong>A total of 287 846 participants without dementia at baseline (followed until November 2022) were analysed. We measured biological age from clinical traits using the Klemera-Doubal method Biological Age (KDM-BA) and PhenoAge algorithms. Cox models were applied to evaluate the risk of dementia. Logistic regression models and linear regression models were used to assess the association between cognitive functions and brain structural measures.</p><p><strong>Results: </strong>During a median follow-up of 13.68 years, 4744 incident all-cause dementia (ACD) events (including 3013 Alzheimer's disease (AD) and 853 vascular dementia (VaD)) were recorded. Participants with older biological age were at increased risk of incident dementia (HR=1.35, 95% CI 1.23 to 1.48 for KDM-BA acceleration, 1.71 (1.52 to 1.91) for PhenoAge acceleration). Those with the highest level of KDM-BA and PhenoAge acceleration had the highest risk of ACD risk, with the corresponding HR of 1.80 (95% CI 1.60 to 2.03) and 1.19 (1.09 to 1.29), respectively. The associations between biological ageing with AD and VaD were also significant. Furthermore, a higher level of biological age was associated with worse performance in multiple cognitive domains and brain structural measures.</p><p><strong>Conclusion: </strong>A higher level of biological age may represent a potential risk factor for incident dementia and is associated with worse performance in multiple cognitive domains and brain structural measures.</p>","PeriodicalId":48733,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"58-68"},"PeriodicalIF":4.9,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}