Multimorbidity, the coexistence of two or more chronic conditions, is rising in China’s aging population, with limited data on prevalence and regional drivers. Using 2020 China Longitudinal Aging Social Survey data for adults aged ≥ 60, supplemented by official regional statistics, we defined multimorbidity from 22 self-reported conditions. A Generalized Linear Mixed Model (GLMM) with village/community-level random effects was used to identify individual-level correlates of multimorbidity, while Random Forests (RF) evaluated county-level determinants. Among 11,372 participants (mean [Standard Deviation, SD] 71.6 [6.6] years), 46.03

Stroke remains a major global public health challenge, with persistent disparities in its burden across countries, and an increasing burden among young adults aged 15-49 has emerged as a growing concern. However, comprehensive evaluations of stroke and its subtypes among young adults in Asia remain limited. This study utilizes data from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), covering the period from 1990 to 2021, to assess the burden of stroke in Asia and provide evidence-based policy and resource allocation. In this study, we extracted GBD 2021 data to estimate the absolute numbers and rates of prevalence, incidence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to stroke and its subtypes among young adults (15-49 years) in Asia from 1990 to 2021, with data stratified by year, age group, and sex. In addition, we analyzed major risk factors and projected future trends through 2050. Our analysis showed that in 2021, stroke accounted for 14.70 million (95% UI 13.39–16.01 million) DALYs and 1.14 million (95% UI 0.99–1.32 million) new cases in Asia, with a DALY rate of 620.24 (95% UI 564.66–675.12) per 100,000 and an incidence rate of 48.22 (95% UI 41.81–55.69) per 100,000. From 1990 to 2021, absolute numbers of prevalence, incidence, mortality, DALYs, YLLs, and YLDs increased by 43.56%, 44.82%, 10.68%, 11.02%, 7.64%, and 38.54%, respectively. Although the rates of prevalence and incidence showed slight increases of 0.07% and 0.96%, the rates of mortality, DALYs, YLLs, and YLDs decreased by 22.84%, 22.61%, 24.96%, and 3.42%, respectively. Among stroke subtypes, both ischemic stroke (IS) and intracerebral hemorrhage (ICH) showed increases in the absolute numbers across six metrics, with IS demonstrating more pronounced growth. Subarachnoid hemorrhage (SAH) showed increases in the incidence, prevalence, and YLDs, while its rates of mortality, DALYs, and YLLs declined. The rates of all six metrics decreased for ICH and SAH, whereas the rates of prevalence, incidence, and YLDs for IS increased, alongside reductions in the rates of mortality, DALYs, and YLLs. The absolute numbers and rates of all six metrics increased with age across both sexes, with males consistently showing higher absolute numbers and the highest burden observed in the 45-49 age group. Apart from the prevalence and YLD rates, males demonstrated higher incidence, mortality, DALYs, and YLL rates across all age groups, peaking at 45-49 years. Moreover, the leading contributors to stroke-related DALYs included high systolic blood pressure, smoking, and air pollution. From 2021 to 2050, the prevalence and incidence of stroke will continue to rise, while mortality and DALYs rates are expected to decline. Overall, from 1990 to 2021, the burden of stroke and its subtypes among young adults in Asia has increased significantly, with notable differences across age groups and sex, and with population growth and demographic changes, this burden is expected to further intensify in the future. Therefore, future research and public health policies should focus more on targeted interventions addressing the specific needs of young adults to effectively control and alleviate the burden of stroke.

Background This study aimed to investigate and validate the association of the discordance between apoB (apolipoprotein B) and low‐density lipoprotein cholesterol (LDL‐C) or non–high‐density lipoprotein cholesterol with cognitive function and explore the mediating role of cerebral large‐ and small‐vessel diseases on this association, for which previous evidence was limited. Methods Community‐dwelling adults aged >50 years from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study were included in this cross‐sectional study. Global cognitive function was evaluated using the Montreal Cognitive Assessment. The association of the residuals between apoB and LDL‐C or non–high‐density lipoprotein cholesterol levels with Montreal Cognitive Assessment score was explored using multivariate linear regression. The simple mediating effects of neuroimaging markers of cerebral large atherosclerotic disease and cerebral small‐vessel disease on this association were analyzed. Results This study included 2916 participants (age: 61.01±6.63 years, female sex: 1553 [53.26%]). Total Montreal Cognitive Assessment scores and visuospatial/executive function, naming, attention, language, abstraction, delayed memory, and orientation subscores differed significantly among 3 groups stratified by the residuals between apoB and LDL‐C. Increased residuals between apoB and LDL‐C were associated with decreased Montreal Cognitive Assessment score postadjustment. Intracranial atherosclerotic plaque presence and burden mediated 13.36% and 10.87% of this association, respectively; the mediation effect of intracranial atherosclerotic plaque presence postadjustment was 5.67%. The validation study confirmed these findings, with 10.04% and 9.08% postadjustment mediation effects of the presence and burden of intracranial atherosclerotic plaque, respectively, on the association. Conclusions High discordance between apoB and LDL‐C was associated with poor cognitive function, partially mediated by intracranial atherosclerotic plaque.

BackgroundCarotid bifurcation geometry influences local hemodynamics and may contribute to plaque formation and carotid disease. Interethnic differences in carotid bulb geometry remain incompletely characterized. However, Asian populations are known to have less atherosclerosis burden in the extracranial carotid arteries compared to White populations.MethodsIn a cross-sectional study (2022–2025), 200 adults without relevant carotid stenosis were enrolled consecutively (100 White participants in Germany; 100 Asian participants in China). Carotid geometry was assessed bilaterally using predefined diameter ratios; Carotid bulb (CB)/Internal carotid artery (ICA) diameter was the prespecified primary outcome. Linear mixed-effects models accounted for within-subject correlation; adjusted models included age, sex, BMI, diabetes, hypertension, dyslipidemia, smoking, and atrial fibrillation.ResultsIn unadjusted models, significant ethnic differences were observed across all primary geometry ratios. CB/ICA was lower in Asian versus White participants (EMM 1.57 vs. 1.68; p < 0.001). After adjustment, the CB/ICA difference remained robust (Asian minus White −0.09; 95% CI -0.14 to −0.04; p < 0.001). Additional adjusted differences were observed for CB/CCA, ICA/CCA, ECA/ICA, and outflow/inflow, whereas no significant difference persisted for ECA/CCA. Analyses of absolute diameters showed no significant interethnic difference in ICA diameter, while carotid bulb diameter was smaller in Asian participants.ConclusionCarotid bifurcation geometry differs between Asian and White adults independent of vascular risk factors. These anatomical differences may have implications for carotid hemodynamics and plaque formation across populations.

Background:The effect of colchicine on subsequent stroke among patients with and without symptomatic intracranial artery stenosis (sICAS) and whether age modifies such effect are not known. Methods:In this prespecified subgroup analysis of CHANCE-3, a randomized, double-blind, placebo-controlled clinical trial conducted at 244 centers in China between 11 August 2022 and 13 April 2023 (ClinicalTrials.gov number, NCT05439356), we included 7567 patients with ischemic stroke or transient ischemic attack and assessments of intracranial arteries at baseline. The primary efficacy outcome was a new stroke at 90 days. The main secondary outcome was a combined vascular event including ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, and vascular death. The primary safety outcome was any serious adverse event within 90 days. Findings:In patients with sICAS, 141 (10.5%) patients on colchicine and 115 (8.5%) on placebo had recurrent stroke within 90 days (adjusted HR 1.30, 95% CI 1.01-1.69; p = 0.04); in patients without sICAS, the corresponding event rates were 4.2% and 5.2% (adjusted HR 0.80, 95% CI 0.62-1.05; p = 0.10) (adjusted interaction p = 0.01). A significant interaction was also observed between sICAS status and the effect of colchicine on the secondary outcome of combined vascular events (adjusted p = 0.02). The interaction was more apparent in the elderly patients (adjusted p < 0.001). In the elderly patients with sICAS (n = 1648), the risk of stroke was higher in the colchicine group (n = 829, 50.3%) compared to the placebo group (n = 819, 49.7%) (adjusted HR 1.58, 95% CI 1.13-2.20; p < 0.001). There was no interaction of status of sICAS with treatment groups on primary safety outcome of any serious adverse event (p = 0.54). In patients with sICAS, 24 (1.8%) patients on colchicine and 7 (0.5%) on placebo had diarrhea within 90 days (p = 0.002). In patients without sICAS, diarrhea occurred in 43 (1.8%) patients on colchicine and in 20 (0.8%) patients on placebo (p = 0.004). Interpretation:The effect of colchicine on subsequent stroke within 90 days may differ according to the presence of sICAS. Aging might be associated with an increased risk of early recurrent stroke in the patients with sICAS receiving colchicine treatment. Future prospective studies are needed to confirm these results. Funding:National Key R&D Program of China, National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. China Kunming Pharmaceuticals supplied colchicine and placebo. Guangdong Wesail Biotech Co. provided assistance in measurement of hsCRP levels.

Background We aimed to investigate the relationships between metabolic syndrome (MetS) and its severity score (Metsss) with asymptomatic intracranial arterial stenosis (aICAS) while also assessing the additional effect of high-sensitivity C reactive protein (hsCRP).Methods This cross-sectional study included 2390 individuals who underwent health examinations at our centre from June 2019 to August 2023. Participants received physical examinations, laboratory tests and magnetic resonance angiography evaluations. MetS was defined by the modified acknowledged criteria and quantified by Metsss. Logistic regression, interaction analysis and mediation analysis were employed.Results Among the 2390 participants, 135 (5.65%) had aICAS, and 726 (30.40%) had MetS. After adjusting for confounders, MetS was significantly associated with aICAS (OR: 1.68, 95% CI: 1.16 to 2.43, p=0.006). The prevalence of aICAS increased significantly from 3.6% to 8.6% as the number of MetS components increased. Higher quartiles of Metsss also significantly increased aICAS risk (P for trend <0.001). After multivariable adjustment, MetS (p=0.001) and elevated Metsss (p<0.001) were only associated with posterior circulation aICAS (vs anterior). Furthermore, participants with both MetS and elevated hsCRP levels had a greater risk for aICAS (OR: 2.32, 95% CI: 1.36 to 3.96, p=0.002). hsCRP mediated the association between MetS and alCAS in participants ≤65 years old.Conclusions MetS and Metsss were independently associated with the risk of aICAS. The mediating effect of hsCRP on the relationship between MetS and aICAS appears to be age-dependent. These findings offer valuable insights into clinical decision making of aICAS and further improve the primary stroke prevention.

Background:Stroke is a leading cause of mortality and disability globally, with high rates of adverse outcomes. We aimed to develop and test a clinically accessible and explainable predictive model for post-stroke composite outcomes that could identify patients at high-risk for targeted interventions. Methods:This modelling study used artificial intelligence to develop and validate a prognostic predictive model for post-stroke outcomes at 3 months and over 5 years, using comprehensive data from the third China National Stroke Registry (CNSR-III; 2015-2018). The development cohort comprised 11,313 patients from CNSR-III. Validation cohort 1 (n = 2627 from CNSR-III; internal validation) were selected at random on the basis of hospital assignment. Validation cohort 2 (external validation) included 5158 patients with a history of ischaemic stroke, excluding those diagnosed with TIA, from the CHANCE-2 trial (2019-2021) done at 202 centres in China. Validation cohort 3 (external validation: disability and mortality) involved 3855 patients with a history of acute ischaemic stroke or TIA from a single centre in the Clinical Research Center for Stroke-Fifth Division (CRCS-5) cohort (2011-2024) in South Korea. We evaluated 309 hospitalisation variables, including baseline characteristics, medical history, hospitalisation data, biomarkers, geographical factors, National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Scale (mRS), and stroke polygenic risk scores, using an extreme gradient boosting tree model. Feature importance was assessed via Shapley values. Primary outcomes were 3-month stroke recurrence, disability (mRS >2), and mortality. Secondary outcomes were assessed at six additional time points over 5 years. A nested cross-validation scheme was employed for feature selection and internal validation in 80% of patients (n = 11,313) from CNSR-III cohort. Testing was performed in the remaining 20% of patients (n = 2627) from CNSR-III (validation cohort 1). External validation was performed in validation cohorts 2 and 3. Findings:Global and domain-specific delta-NIHSS(admission-discharge) emerged as the strongest predictor of stroke recurrence, disability, and mortality. The Delta-NIHSS-based Predictor for Post-Stroke Composite Outcomes (DISCO) model, integrating 16 delta-NIHSS(admission-to-discharge) measures, age, gender, TOAST subtypes, history of TIA, stroke, diabetes and mRS at discharge, achieved the area under the receiver operating curve (AUCs) of 0.805 and 0.815 for recurrence and mortality and of 0.852 for disability at 3 months in validation cohort 2. The 1% patients with highest-risk exhibited a 19.27-fold relative risk (RR) for recurrence, 36.59-fold RR for disability, and 225.5-fold RR for mortality at 3 months. The DISCO model is available at https://www.discosysu.cn. Interpretation:The DISCO model, incorporating 23 clinical variables, demonstrates high accuracy, robustness, clinical accessibility, and explainability in predicting post-stroke outcomes. The predictive strength of delta-NIHSS(admission-discharge) provides mechanistic insights into stroke outcomes and could potentially inform future acute stroke treatment and rehabilitation strategies. Future studies, with external validation across diverse ancestries and mechanistic studies elucidating the predictive power of delta-NIHSS in stroke recovery, are warranted. Funding:National Key Research and Development Program of China, National Natural Science Foundation of China, Young Elite Scientists Sponsorship Program by the China Association for Science and Technology, and Young Talents Supporting Program of Capital Medical University.

Background Remnant cholesterol (RC) is considered to be one of the most significant and important risk factors for atherosclerotic cardiovascular disease (ASCVD). Nonetheless, the association between RC and unstable carotid plaque remains unclear. Our primary objective is to ascertain whether RC exhibits an independent and significant association with unstable carotid plaque in a neurologically healthy population.Methods In the cross-sectional study, we enrolled neurologically healthy participants who visited our centre for health checkups between 2021 and 2022. All eligible participants underwent a standardised questionnaire, physical examinations and laboratory testing. The carotid plaque was evaluated with a standard carotid ultrasound and an advanced ultrasound imaging technique called superb microvascular imaging. The correlation between lipids and unstable carotid plaque was primarily assessed utilising univariate and multivariate logistic regression.Results The study totally enrolled 1100 participants who had an average age of 57.00 years (IQR: 49.00–63.00), with 67.55% being men. Among the participants, 321 (29.18%) had unstable carotid plaque. In the multivariate logistic regression analysis, higher RC had an independent association with an elevated incidence of unstable carotid plaque compared with the lowest concentrations of RC (OR=1.673, 95% CI 1.113 to 2.515, p=0.0134), but not other lipids. In addition, apolipoprotein A1 was negatively related to unstable carotid plaque (OR=0.549, 95% CI 0.364 to 0.830, p=0.0045).Conclusions Elevated concentrations of RC are independently and excellently correlated with unstable carotid plaque within a neurologically healthy population.

Background: An accurate, robust, clinically accessible, and explainable predictive model for post-stroke composite outcomes could identify high-risk patients for targeted interventions. However, such a model is currently lacking. This study leverages artificial intelligence to develop and validate a predictive model for post-stroke outcomes at three months and over five years, leveraging comprehensive data from the third China National Stroke Registry (CNSR-III), one of China largest nationwide multi-center ischemic stroke registries with five-year follow-up and the CHANCE-2 trial, a genotype-guided dual anti-platelet therapy trial in China. Methods: We evaluated 309 hospitalization variables, including baseline characteristics, medical history, hospitalization data, biomarkers, geographical factors, NIHSS/mRS scores, and stroke polygenic risk scores (PRS), using an extreme gradient boosting tree model. Feature importance was assessed via Shapley values. Primary outcomes were three-month stroke recurrence (5.6%), disability (mRS > 2, 13.75%), and mortality (1.18%). Secondary outcomes were assessed at six additional time points over five years. A nested cross-validation scheme was employed for feature selection and internal validation in 80% of patients (n=11,313) from CNSR-III cohort. External validation of the model was performed in the remaining 20% patients (n=2,627) from CNSR-III cohort and in CHANCE-2 trail (n=5,158). Results: Global and domain-specific delta-NIHSS(admission-discharge) emerged as the strongest predictor of stroke recurrence, disability and mortality. The Delta-NIHSS-Based Predictor for Post-Stroke Composite Outcomes (DISCO) model, integrating 16 delta-NIHSS(admission-to-discharge) and 8 clinically accessible variables, achieved AUCs > 0.8 for recurrence and disability and > 0.9 for mortality at three months. The highest-risk 1% patients exhibited a >10-fold relative risk (RR) for recurrence, >30-fold RR for disability, and >100-fold RR for mortality at three months. The DISCO model is clinically accessible at http://www.discosysu.cn. Conclusion: The DISCO model, incorporating 24 readily obtainable clinical variables, demonstrates high accuracy, robustness, clinical accessibility, and explainability in predicting post-stroke outcomes. The predictive strength of delta-NIHSS(admission-discharge) provides mechanistic insights into stroke outcomes and informs future acute stroke treatment and rehabilitation strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement The Study was funded by Grants from National Key Research and Development Program of China (2022YFE0209600, 2022YFC2502400, 2022YFC2502402, 2022YFC2502404), the National Natural Science Foundation of China (82471304), the Young Elite Scientists Sponsorship Program by CAST (2023QNRC001) and Young Talents Supporting Program of Capital Medical University (B2417) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethics Committee of Beijing Tiantan Hospital (Institutional Review Board approval number: KY2015-001-01), as well as the ethics committees of all participating centers. Detailed information regarding ethical approvals can be found in the publications with PMID: 31709123 and 34708996. Based on the existing cohort, we are able to conduct this study involving prognostic model development, validation and explanation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Post-stroke cognitive impairment (PSCI) imposes a significant economic and social burden on patients and their families. High-density lipoprotein cholesterol (HDL-C) is reported to have protective effects on cognitive function in older adults. This study assesses the effects of HDL-C during the acute period of stroke on PSCI. This sub-study of the China National Clinical Research Center Alzheimer's Disease and Neurodegenerative Disorder Research (CANDOR) prospectively enrolled patients with acute ischemic stroke. HDL-C levels and brain magnetic resonance imaging findings were examined at the acute stage. All participants completed neuropsychological assessment at 3 months. A total of 394 acute ischemic stroke patients were enrolled, 297 (75.4 %) were men, with mean age 58.14 ± 9.25 years, and all participants finished the baseline and 3-month cognitive assessments. HDL-C levels showed nonlinear relationships with post-stroke cognitive functions and brain structures. Participants were divided into five groups based on HDL-C levels: first-20th, 21st-40th, 41st-60th, 61st-80th, and 81st-last percentiles. The HDL-C middle group (1.03-1.15 mmol/L) had greater baseline global brain volume and regional brain volumes, the lowest incidence of PSCI at 3 months (50.0 %), and better MMSE and MoCA scores at baseline and at the 3-month follow-up, as well as better multi-domain Z scores (construction, executive function, language and memory) at the 3-month follow-up. Curve estimation further confirms the quadratic models (U-shaped curve) fit the relationships between HDL-C and baseline global and regional brain volume, and cognitive performance at 3-month visits. U-shaped associations of HDL-C with post-stroke cognitive function and baseline brain structures were identified. Either too high or too low HDL-C indicates a higher risk of poor post-stroke cognition. TRAIL REGISTRATION NUMBER: NCT04320368.

OBJECTIVES:To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN:Multicentre, double blind, randomised, placebo controlled trial. SETTING:244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS:8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS:Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES:The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS:4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). CONCLUSIONS:The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. TRIAL REGISTRATION:ClinicalTrials.gov, NCT05439356.

BACKGROUND:The brain aging in the general population and patients with neurological disorders is not well understood. PURPOSE:To characterize brain aging in the above conditions and its clinical relevance. STUDY TYPE:Retrospective. POPULATION:A total of 2913 healthy controls (HC), with 1395 females; 331 multiple sclerosis (MS); 189 neuromyelitis optica spectrum disorder (NMOSD); 239 Alzheimer's disease (AD); 244 Parkinson's disease (PD); and 338 cerebral small vessel disease (cSVD). FIELD STRENGTH/SEQUENCE:3.0 T/Three-dimensional (3D) T1-weighted images. ASSESSMENT:The brain age was estimated by our previously developed model, using a 3D convolutional neural network trained on 9794 3D T1-weighted images of healthy individuals. Brain age gap (BAG), the difference between chronological age and estimated brain age, was calculated to represent accelerated and resilient brain conditions. We compared MRI metrics between individuals with accelerated (BAG ≥ 5 years) and resilient brain age (BAG ≤ -5 years) in HC, and correlated BAG with MRI metrics, and cognitive and physical measures across neurological disorders. STATISTICAL TESTS:Student's t test, Wilcoxon test, chi-square test or Fisher's exact test, and correlation analysis. P < 0.05 was considered statistically significant. RESULTS:In HC, individuals with accelerated brain age exhibited significantly higher white matter hyperintensity (WMH) and lower regional brain volumes than those with resilient brain age. BAG was significantly higher in MS (10.30 ± 12.6 years), NMOSD (2.96 ± 7.8 years), AD (6.50 ± 6.6 years), PD (4.24 ± 4.8 years), and cSVD (3.24 ± 5.9 years) compared to HC. Increased BAG was significantly associated with regional brain atrophy, WMH burden, and cognitive impairment across neurological disorders. Increased BAG was significantly correlated with physical disability in MS (r = 0.17). DATA CONCLUSION:Healthy individuals with accelerated brain age show high WMH burden and regional volume reduction. Neurological disorders exhibit distinct accelerated brain aging, correlated with impaired cognitive and physical function. LEVEL OF EVIDENCE:4 TECHNICAL EFFICACY: Stage 2.

Asymptomatic intracranial atherosclerotic stenosis (aICAS) is a major risk factor for cerebrovascular events. The study aims to construct and validate a nomogram for predicting the risk of aICAS. Participants who underwent health examinations at our center from September 2019 to August 2023 were retrospectively enrolled. The participants were randomly divided into a training set and a testing set in a 7:3 ratio. Firstly, in the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were performed to select variables that were used to establish a nomogram. Then, the receiver operating curves (ROC) and calibration curves were plotted to assess the model's discriminative ability and performance. A total of 2563 neurologically healthy participants were enrolled. According to LASSO-Logistic regression analysis, age, fasting blood glucose (FBG), systolic blood pressure (SBP), hypertension, and carotid atherosclerosis (CAS) were significantly associated with aICAS in the multivariable model (adjusted P < 0.005). The area under the ROC of the training and testing sets was, respectively, 0.78 (95% CI: 0.73-0.82) and 0.65 (95% CI: 0.56-0.73). The calibration curves showed good homogeneity between the predicted and actual values. The nomogram, consisting of age, FBG, SBP, hypertension, and CAS, can accurately predict aICAS risk in a neurologically healthy population.

Increased efforts in neuroscience seek to understand how macro-anatomical and physiological connectomes cooperatively work to generate cognitive behaviors. However, the structure-function coupling characteristics in normal aging individuals remain unclear. Here, we developed an index, the Coupling in Brain Structural connectome and Functional connectome (C-BSF) index, to quantify regional structure-function coupling in a large community-based cohort. C-BSF used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) data from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (PRECISE) cohort (2007 individuals, age: 61.15 ± 6.49 years) and the Sydney Memory and Ageing Study (MAS) cohort (254 individuals, age: 83.45 ± 4.33 years). We observed that structure-function coupling was the strongest in the visual network and the weakest in the ventral attention network. We also observed that the weaker structure-function coupling was associated with increased age and worse cognitive level of the participant. Meanwhile, the structure-function coupling in the visual network was associated with the visuospatial performance and partially mediated the connections between age and the visuospatial function. This work contributes to our understanding of the underlying brain mechanisms by which aging affects cognition and also help establish early diagnosis and treatment approaches for neurological diseases in the elderly.

Background The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks. Methods This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0–1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0–90 min, 91–180 min and 181–270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment. Results Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0–90 min, 1.23 (95% CI 0.88 to 1.71) for 91–180 min and 1.21 (95% CI 0.88 to 1.65) for 181–270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI −0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI −2.66 to 6.20; p=0.58) for 0–180 min. Conclusions In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors and subsequent atherosclerosis play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n=2220) and Sydney Memory and Ageing Study (MAS, n=246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, vascular risk factors (VRF), and atherosclerosis (AS), and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

BACKGROUND:There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients. METHODS:In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic stroke who were eligible for standard intravenous thrombolysis but ineligible for endovascular thrombectomy were enrolled from 53 centres in China and randomly assigned (1:1) to receive intravenous tenecteplase (0·25 mg/kg, maximum dose of 25 mg) or intravenous alteplase (0·9 mg/kg, maximum dose of 90 mg). Participants had to be able to receive treatment within 4·5 h of stroke, have a modified Rankin Scale (mRS) score of no more than 1 before enrolment, and have a National Institutes of Health Stroke Scale score of 5-25. Patients and treating clinicians were not masked to group assignment; clinicians evaluating outcomes were masked to treatment type. The primary efficacy outcome was the proportion of participants who had a mRS score of 0-1 at 90 days, assessed in the modified intention-to-treat population (all randomly assigned participants who received the allocated thrombolytic), with a non-inferiority margin of 0·937 for the risk ratio (RR). The primary safety outcome was symptomatic intracranial haemorrhage within 36 h, assessed in all participants who received study drug and had a safety assessment available. The trial is registered with ClinicalTrials.gov, NCT04797013, and has been completed. FINDINGS:Between June 12, 2021, and May 29, 2022, 1430 participants were enrolled and randomly assigned to tenecteplase (n=716) or alteplase (n=714). Six patients assigned to tenecteplase and seven to alteplase did not receive study product, and five participants in the tenecteplase group and 11 in the alteplase group were lost to follow-up at 90 days. The primary outcome in the modified intention-to-treat population occurred in 439 (62%) of 705 in the tenecteplase group versus 405 (58%) of 696 in the alteplase group (RR 1·07, 95% CI 0·98-1·16). The lower limit of the RR's 95% CI was greater than the non-inferiority margin. Symptomatic intracranial haemorrhage within 36 h was observed in 15 (2%) of 711 in the tenecteplase group and 13 (2%) of 706 in the alteplase group (RR 1·18, 95% CI 0·56-2·50). Mortality within 90 days occurred in 46 (7%) individuals in the tenecteplase group versus 35 (5%) in the alteplase group (RR 1·31, 95% CI 0·86-2·01). INTERPRETATION:Tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy. FUNDING:National Science and Technology Major Project, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

主观认知下降指患者出现自我感觉认知下降但客观认知检测无异常,是最近研究的热点.近年来,关于主观认知下降的发病率、危险因素、干预治疗等方面的研究逐渐增多.本文汇总了国内外相关文献,对主观认知下降的特点进行综述,包括主观认知下降的定义、流行病学特征、病因、临床评估、鉴别诊断及干预治疗等,旨在探讨主观认知下降的临床意义,为后续临床研究提供参考.