BACKGROUND: Vascular cognitive impairment (VCI) persistently impairs cognition and the ability to perform activities of daily living, seriously compromising patients\' quality of life. Previous studies have reported that disorders of serum iron metabolism and iron deposition in the brain can lead to inflammation, abnormal protein aggregation and degeneration, and massive neuronal apoptosis in the central nervous system, which in turn leads to a progressive decline in cognitive processes. Our previous clinical studies have found acupuncture to be a safe and effective intervention for treating VCI, but the specific mechanisms require further exploration.
OBJECTIVE: The objective of the trial is to evaluate the clinical efficacy of Tongdu Xingshen acupuncture and to investigate whether it can improve VCI by regulating brain iron deposition and body iron metabolism.
METHODS: In total, 42 patients with VCI and 21 healthy individuals will participate in this clinical trial. The 42 patients with VCI will be randomized into acupuncture and control groups, while the 21 healthy individuals will be in the healthy control group. Both the control and acupuncture groups will receive conventional medical treatment and cognitive rehabilitation training. In addition, the acupuncture group will receive electroacupuncture treatment with Tongdu Xingshen for 30 minutes each time, 6 times a week for 4 weeks. Meanwhile, the healthy control group will not receive any intervention. All 3 groups will undergo baseline assessments of brain iron deposition, serum iron metabolism, and neuropsychological tests after enrollment. The acupuncture and control groups will be evaluated again at the end of 4 weeks of treatment, as described earlier. By comparing neuropsychological test scores between groups, we will examine the efficacy of Tongdu Xingshen acupuncture in treating VCI. Additionally, we will test the correlations between neuropsychological test scores, brain iron deposition, and body iron metabolism indexes to explore the possible mechanisms of Tongdu Xingshen acupuncture in treating VCI.
RESULTS: Participants are currently being recruited. The first participant was enrolled in June 2023, which marked the official start of the experiment. As of the submission of the paper, there were 23 participants. The recruitment process is expected to continue until June 2025, at which point the processing and analysis of data will begin. As of May 15, 2024, up to 30 people have been enrolled in this clinical trial.
CONCLUSIONS: This study will provide data on the effects of Tongdu Xingshen acupuncture on cerebral iron deposition as well as somatic iron metabolism in patients with VCI. These results will help to prove whether Tongdu Xingshen acupuncture can improve VCI by regulating brain iron deposition and body iron metabolism, which will provide the clinical and theoretical basis for the wide application of acupuncture therapy in VCI rehabilitation.
BACKGROUND: China Clinical Registration Agency ChiCTR2300072188; https://tinyurl.com/5fcydtkv.
UNASSIGNED: PRR1-10.2196/56484.

UNASSIGNED: Carotid artery stenosis or occlusion (CASO) is a major cause of vascular cognitive impairment (VCI). There is currently no effective treatment for VCI induced by CASO. Resveratrol, a type of polyphenol, improves cognitive performance in rat CASO models via pleiotropic effects. Furthermore, we previously reported the longevity gene, SIRT1, which can be activated by resveratrol, improves cognitive and cerebral blood flow impairment in mouse CASO models by activating endothelial nitric oxide synthase. However, clinical evidence remains limited.
UNASSIGNED: The REsveratrol for VAscular cognitive impairment investigating cerebral Metabolism and Perfusion (REVAMP) trial is a randomized, double-blind, placebo-controlled trial involving patients with asymptomatic CASO. Each participant will receive either 150 mg/day of resveratrol or a placebo for 35 weeks. The primary objective is to determine whether resveratrol improves cognitive impairment, as assessed using the Alzheimer\'s disease Assessment Scale-cognitive subscale 13. One of our secondary objectives is to determine whether resveratrol improves cerebral hemodynamic impairment as assessed via 15O-gas positron emission tomography. We will recruit 100 patients (50 per group).
UNASSIGNED: The REVAMP trial may provide valuable insights into new therapeutic options, as multitarget neuroprotection could potentially improve cognitive function along with enhancements in cerebral hemodynamic status in patients with asymptomatic CASO.Clinical trial registration: The REVAMP trial was prospectively registered in the Japan Registry of Clinical Trials (jRCTs051230013) on April 13, 2023.

Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood-brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability. We determined whether minocycline had a similar effect in patients with SVD.
MINERVA was a single-center, phase II, randomized, double-blind, placebo-controlled trial. Forty-four participants with moderate-to-severe SVD took minocycline or placebo for 3 months. Co-primary outcomes were microglial signal (determined using 11C-PK11195 positron emission tomography) and BBB permeability (using dynamic contrast-enhanced MRI).
Forty-four participants were recruited between September 2019 and June 2022. Minocycline had no effect on 11C-PK11195 binding (relative risk [RR] 1.01, 95% confidence interval [CI] 0.98-1.04), or BBB permeability (RR 0.97, 95% CI 0.91-1.03). Serum inflammatory markers were not affected.
11C-PK11195 binding and increased BBB permeability are present in SVD; minocycline did not reduce either process. Whether these pathophysiological mechanisms are disease-causing remains unclear.
ISRCTN15483452 HIGHLIGHTS: We found focal areas of increased microglial signal and increased blood-brain barrier permeability in patients with small vessel disease. Minocycline treatment was not associated with a change in these processes measured using advanced neuroimaging. Blood-brain barrier permeability was dynamic but MRI-derived measurements correlated well with CSF/serum albumin ratio. Advanced neuroimaging is a feasible outcome measure for mechanistic clinical trials.

BACKGROUND: The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH.
METHODS: We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90.
RESULTS: 291 were available for analysis under the trial\'s modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8-18). The median baseline ICH volume was 12.9 IQR (6.4-26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery.
CONCLUSIONS: Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration.

Vascular cognitive impairment（VCI） is a group of syndromes ranging from mild cognitive impairment to dementia caused by cerebrovascular disease, due to the lack of sensitivity and specific biomarkers, it is difficult to identify and diagnose early. Abnormal connectivity is observed in brain regions of patients with vascular cognitive disorders, locates mainly in the default mode network（DMN）, and changes in their abnormal functional connectivity correlated with the degree of patients\' cognitive impairment. Resting-state functional magnetic resonance imaging(rs-fMRI) is a commonly used method to detect the internal activity of the brain at resting state. The use of various rs-fMRI to study abnormal changes in the DMN in patients with VCI is useful to further investigate the pathogenesis of VCI and provide an objective basis for imaging. This article mainly reviews the application of rs-fMRI in the DMN in patients with VCI, bringing new perspectives for the correct diagnosis and assessment of VCI.
血管性认知障碍是由脑血管疾病导致的一种从轻度认知功能障碍至痴呆的综合征，由于缺乏敏感性和特异性生物标志物，早期不易鉴别和诊断。血管性认知障碍患者脑网络连接异常的脑区多位于默认网络，其异常变化的功能连接与患者的认知障碍程度相关。静息态功能磁共振成像技术是一种常用的检测静息态大脑内在活动的方法，应用静息态磁共振不同分析技术探索血管性认知障碍患者默认网络异常变化有助于深入研究血管性认知障碍的发病机制，并提供客观的影像依据。该文主要综述静息态功能磁共振成像技术在血管性认知障碍患者默认网络研究中的应用成果，为血管性认知障碍的精准诊断和评估提供新思路。.

Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non-intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke.
This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched.
Forty-eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing.
RIC is safe, feasible, and effective in the treatment of stroke. Large-scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment.

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52-87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15-30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies.
UNASSIGNED: http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015-001,235-20NCT00123456.

Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs.
To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs.
TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose.
The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv).
TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs.
European Union\'s Horizon 2020 programme.
NCT03082014.

Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis.
This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient\'s global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient\'s final follow-up was completed in September 2022.
This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

UNASSIGNED: Sex is a significant determinant of survival and functional outcome after stroke. Long-term cognitive outcome after acute lacunar stroke in the context of sex differences has been rarely reported.
UNASSIGNED: A cohort of small vessel disease (SVD) patients presenting with first-ever acute lacunar stroke and normal cognitive status has been evaluated 4 years after the qualifying event for the presence of cognitive impairment (CI) with a comprehensive neuropsychological battery. Differences in baseline clinical and neuroimaging characteristics were compared between sexes in relation to cognitive status.
UNASSIGNED: A total of 124 female and 150 male patients were analyzed. No difference was detected between the groups regarding age (p = 0.932) or frequency of common vascular risk factors (p > 0.1 for all). At the baseline assessment, women had more disabilities compared to men with a mean modified Rankin scale (mRS) score of 2.5 (1.5 in men, p < 0.0001). Scores of white matter hyperintensities (WMH) of presumed vascular origin and a total number of lacunes of presumed vascular origin on brain MRI were higher in women compared to men (p < 0.0001 for all). As many as 64.6% of patients had CI of any severity on follow-up, women more frequently (77.4%) than men (54.0%; p < 0.0001). Univariate logistic regression analysis showed that female sex, higher NIHSS and mRS scores, presence of depression, and increasing WMH severity were associated with an increased risk for CI. Multivariate regression analysis indicated that only depression (OR 1.74, 95%CI 1.25-2.44; p = 0.001) and WMH severity (OR 1.10, 95%CI 1.03-1.17; p = 0.004) were independently associated with the CI.
UNASSIGNED: At the long-term follow-up, women lacunar stroke survivors, compared to men, more frequently had CI in the presence of more severe vascular brain lesions, but this association was dependent on the occurrence of depression and severity of WMH, and could not be explained by differences in common vascular risk factors.