Background: Previous studies found that antihypertensive medications (AHMs) acting on the renin-angiotensin system had the potential to reduce the progression from mild cognitive impairment to dementia. However, it remains unclear whether this association differs between ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers. methods: We conducted a retrospective cohort study in the Alzheimer’s Disease Neuroimaging Initiative among 403 participants with hypertension and mild cognitive impairment at baseline. Information on AHMs received during the follow-up period, including angiotensin receptor blockers, ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics, were self-reported. Cox proportional hazards models adjusted for potential confounders were used in the time to event analysis with progression to dementia as outcome. Results: Of the 403 participants, the mean (SD) age was 74.0 (7.3) years, 152 (37.7%) were female, 158 (39.2%) progressed to dementia over a median follow-up time of 3.0 years. Angiotensin receptor blockers were associated with a lower risk of progression to dementia as compared to ACE inhibitors (adjusted hazard ratio=0.45 [95% CI, 0.25–0.81]; P =0.023), other classes of AHMs (beta-blockers, calcium channel blockers, diuretics; adjusted hazard ratio, 0.49 [95% CI, 0.27–0.89]; P =0.037), and none of AHMs (adjusted hazard ratio, 0.31 [95% CI, 0.16–0.58]; P =0.001). Conclusions: In patients with hypertension and mild cognitive impairment, angiotensin receptor blockers were associated with a lower risk of progression to dementia compared with ACE inhibitors and other classes of AHMs. Our findings may have important implications for clinical practice but still warrant further investigations in larger prospective cohorts or clinical trials.

To date, there is no homogeneous evidence of whether earlier age at menopause is associated with incident dementia. In addition, the underlying mechanism and driven mediators are largely unknown. We aimed to fill these knowledge gaps. This community-based cohort study included 154,549 postmenopausal women without dementia at enrolment (between 2006 and 2010) from the UK Biobank who were followed up until June 2021. We followed up until June 2021. Age at menopause was entered as a categorical variable (<40, 40–49, and ≥50 years) with ≥50 years taken as a reference. The primary outcome was all-cause dementia in a time-to-event analysis and the secondary outcomes included Alzheimer's disease, vascular dementia, and other types of dementia. In addition, we investigated the association between magnetic resonance (MR) brain structure indices with earlier menopause, and explored the potential underlying driven mediators on the relationship between earlier menopause and dementia. 2266 (1.47%) dementia cases were observed over a median follow-up period of 12.3 years. After adjusting for confounders, women with earlier menopause showed a higher risk of all-cause dementia compared with those ≥50 years (adjusted-HRs [95% CIs]: 1.21 [1.09–1.34] and 1.71 [1.38–2.11] in the 40–49 years and <40 years groups, respectively; P for trend <0.001). No significant interactions between earlier menopause and polygenic risk score, cardiometabolic factors, type of menopause, or hormone-replacement therapy strata were found. Earlier menopause was negatively associated with brain MR global and regional grey matter indices, and positively associated with white matter hyperintensity. The relationship between earlier menopause and dementia was partially mediated by menopause-related comorbidities including sleep disturbance, mental health disorder, frailty, chronic pain, and metabolic syndrome, with the proportion (95% CI) of mediation effect being 3.35% (2.18–5.40), 1.38% (1.05–3.20), 5.23% (3.12–7.83), 3.64% (2.88–5.62) and 3.01% (2.29–4.40), respectively. Multiple mediator analysis showed a combined effect being 13.21% (11.11–18.20). Earlier age at menopause was associated with risk of incident dementia and deteriorating brain health. Further studies are warranted to clarify the underlying mechanisms by which earlier age at menopause is linked to an increased risk of dementia, and to determine public health strategies to attenuate this association. 10.13039/501100001809 National Natural Science Foundation of China , the Science and Technology Program of Guangzhou, the 10.13039/501100015956 Key Area Research and Development Program of Guangdong Province , the 10.13039/501100002858 China Postdoctoral Science Foundation , and the 10.13039/501100021171 Guangdong Basic and Applied Basic Research Foundation .

Introduction: Successful reperfusion does not always lead to good neurological outcomes and impaired microcirculation can be one of the underlying causes. Intra-arterial alteplase after mechanical thrombectomy (MT) may improve microcirculation contributing to neurological recovery, but prospective randomised studies are still needed to validate its efficacy and safety. We aim to assess the efficacy and safety of intra-arterial alteplase after MT for acute ischaemic stroke (AIS) with large-vessel occlusion (LVO). Methods and analysis: The Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy (PEARL) study is a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. We consecutively screen AIS patients with anterior circulation LVO and National Institute of Health Stroke Scale of 6–25, who reach stable expanded Thrombolysis in Cerebral Infarction scores of 2b50-3 on angiography after MT. Eligible participants are 1:1 randomly assigned to the experimental group and the control group. Participants in the experimental group will receive intra-arterial alteplase (0.225 mg/kg and a maximum dose of 20 mg) after MT and standard medical treatment, while those in the control group will receive standard medical treatment alone after the procedure. The primary outcome is the proportion of patients with a 90-day modified Rankin scale of 0–1. A total of 324 participants are required to test the superiority hypothesis with 80% power at a two-tailed significance level of 0.05. Ethics and dissemination: This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY-2023-390-02) and will be conducted following the Declaration of Helsinki. Ethical approvals have been obtained separately for all centres participating in the study. Study results will be published in peer-reviewed academic journals. Trial registration number: NCT05856851 .

The evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality. In this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a “watch-and-wait” policy). Of 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41). Among head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic. National Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).

BACKGROUND: Randomized trials have demonstrated the benefit of endovascular treatment (EVT) in moderate-to-severe acute basilar artery occlusion (BAO), but its benefit in acute mild BAO remains uncertain. This multicenter, retrospective cohort study aimed to explore the efficacy of EVT in acute BAO with a low National Institutes of Health Stroke Scale. METHODS: Patients with acute BAO and National Institutes of Health Stroke Scale <10, hospitalized at 5 stroke centers in China between January 2020 and December 2023, were included and divided into EVT and standard medical treatment groups. The primary outcome was 90-day functional independence, defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes include proportions of 90-day modified Rankin Scale score of 0 to 1 and 0 to 3. Symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality were assessed as safety outcomes. RESULTS: Three hundred fifteen patients with BAO with National Institutes of Health Stroke Scale <10 were enrolled (229 [72.7%] male; median [interquartile range] age, 65 [58–72] years; median [interquartile range] baseline National Institutes of Health Stroke Scale score, 6 [3–8] points), 161 (51.1%) of whom underwent EVT and 154 (48.9%) received standard medical treatment. The EVT group had a higher rate of 90-day functional independence (68.9% versus 44.8%; adjusted odds ratio, 3.69 [95% CI, 2.04–6.68]; P <0.001). There was no significant difference in 90-day mortality (4.3% versus 4.5%; adjusted odds ratio, 1.22 [95% CI, 0.37–4.03]; P =0.80). However, EVT was associated with a higher risk of symptomatic intracerebral hemorrhage (8.2% versus 3.9%; adjusted odds ratio, 3.86 [95% CI, 1.18–12.61]; P =0.03). CONCLUSIONS: In this cohort of patients with acute mild BAO, EVT was associated with an improved 90-day functional outcome compared with standard medical treatment alone, although the risk of symptomatic intracerebral hemorrhage was increased.