Comparative Efficacy of Cognitive Training for Post-Stroke Aphasia: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Although cognitive training has shown potential for treating post-stroke aphasia (PSA), its efficacy varies across studies, and the optimal training approaches remain unclear. OBJECTIVE: To evaluate and compare the effects of distinct cognitive training interventions, either combined with or independent of speech and language therapy (SLT), on language function in individuals with PSA. METHODS: A systematic search encompassing PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical Databases was conducted for randomized controlled trials (RCTs). A network meta-analysis evaluated interventions, including computer-assisted cognitive training (CCT), conventional cognitive training (CT), virtual reality (VR)-based cognitive training (vrCT), telerehabilitation computer-assisted cognitive training (tCCT), working memory (WM) training, and attention training (AT). RESULTS: Eleven RCTs comprising 501 participants were included. Individuals with PSA who underwent combined WM training with SLT led to significantly enhanced Western Aphasia Battery (WAB) Aphasia Quotient (AQ), as well as in spontaneous speech, auditory comprehension, repetition, and naming, compared to those receiving SLT alone. This combination was more effective than both CCT with SLT and tCCT with SLT in improving WAB AQ. Similarly, it outperformed both CCT with SLT and vrCT with SLT in enhancing WAB spontaneous speech. Additionally, both AT and CT combined with SLT were more effective than SLT alone in enhancing WAB spontaneous speech. Specifically, AT combined with SLT proved more effective than vrCT with SLT in this area. Moreover, vrCT combined with SLT significantly improved auditory comprehension compared with SLT alone. CONCLUSIONS: Combining WM training and SLT and integrating vrCT with SLT both significantly enhance language function in individuals with PSA, compared with SLT alone. Our findings advocate for the use of these cognitive training approaches as promising strategies for language rehabilitation in this population. PROSPERO registration number: CRD42023462361.

Cognitive impairment is associated with BDNF-TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure.

Heart failure (HF) is often accompanied by cognitive impairment (CI). Brain-derived neurotrophic factor (BDNF) deficiency is closely associated with CI. However, the role and mechanism of BDNF in HF with CI is still not fully understood. Here, the case-control study was designed including 25 HF without CI patients (HF-NCI) and 50 HF with CI patients (HF-CI) to investigate the predictive value of BDNF in HF-CI while animal and cell experiments were used for mechanism research. Results found that BDNF levels in serum neuronal-derived exosomes were downregulated in HF-CI patients. There was no significant difference in serum BDNF levels among the two groups. HF rats showed obvious impairment in learning and memory; also, they had reduced thickness and length of postsynaptic density (PSD) and increased synaptic cleft width. Expression of BDNF, TrkB, PSD95, and VGLUT1 was significantly decreased in HF rats brain. In addition, compared with sham rats, amino acids were significantly reduced with no changes in the acetylcholine and monoamine neurotransmitters. Further examination showed that the number of synaptic bifurcations and the expression of BDNF, TrkB, PSD95, and VGLUT1 were all decreased in the neurons that interfered with BDNF-siRNA compared with those in the negative control neurons. Together, our results demonstrated that neuronal-derived exosomal BDNF act as effective biomarkers for prediction of HF-CI. The decrease of BDNF in the brain triggers synaptic structural damage and a decline in amino acid neurotransmitters via the BDNF-TrkB-PSD95/VGLUT1 pathway. This discovery unveils a novel pathological mechanism underlying cognitive impairment following heart failure.

Herbal formulas for detoxification and dredging collaterals in treating carotid atherosclerosis: a systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy and safety of the Chinese medicine detoxification and dredging collaterals in treating carotid atherosclerosis (CAS). Methods: A systematic and comprehensive search of nine relevant domestic and international databases were conducted from their inception until June 2022. The methodological quality of the included trials was evaluated, and the efficacy and safety were comprehensively analyzed. After applying the inclusion and exclusion criteria to the randomized controlled trials (RCTs), the research quality evaluation and data extraction were conducted, followed by a meta-analysis of the selected articles. The Cochrane's Bias risk assessment was utilized to evaluate the quality of the evidence. Results: Of the 2,660 studies initially retrieved, 14 studies were included, involving a total of 1,518 patients. The results of the meta-analysis indicated that the clinical efficacy of the Detoxification and Collateral Dredging method in the treatment of CAS was superior to that of western medicine treatment alone, and the difference was statistically significant [RR = 1.23, 95% CI (1.13, 1.34)] Furthermore, carotid intima-media thickness [Mean Difference (MD) = -0.10, 95% CI (-0.13, -0.08)] and Crouse plaque score [MD = -0.54, 95% CI (-0.75, -0.32)] were significantly lower in the Detoxification and Collateral Dredging group compared to the pure western medicine treatment group. The difference was statistically significant. In addition, serum total cholesterol [MD = -0.70, 95% CI (-0.85, -0.55)] and low-density lipoprotein cholesterol [MD = -0.70, 95% CI (-0.85, -0.55)] were lower in the Detoxification and Collateral Dredging group than in the Western medicine group, with all differences being statistically significant. Serum high-density lipoprotein cholesterol was higher in the Detoxification and Collateral Dredging group compared to the pure western medicine group, and the difference was statistically significant [MD = 0.17, 95% CI (0.11, 0.23)]. Conclusion: The use of Chinese medicine Detoxification and Collateral Dredging approach in the treatment of CAS may offer benefits in improving carotid atherosclerotic plaque and reducing blood lipid levels, with a safety profile superior to that of western medicine treatment alone.

Efficacy of scalp stimulation for multidomain cognitive impairment in patients with post-stroke cognitive impairment and dementia: A network meta-analysis and meta-regression of moderators.

BACKGROUND: Scalp stimulation has gained more traction for post-stroke cognitive impairment and dementia (PSCID); the interaction between stimulation targets and parameters influences the response to the stimulation. However, the most efficacious treatment for improving different domains of cognitive impairment remains unknown. OBJECTIVE: We aimed to conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of various scalp stimulation protocols used in PSCID treatment. METHODS: Randomized controlled trials of scalp stimulation in patients with PSCID were searched in eight databases over the past 20 years. Standardized mean differences (SMDs) for global and subdomain cognitive scores were pooled in Bayesian NMA. Moderators were examined using meta-regression analysis. RESULTS: A total of 90 trials, with 6199 patients, were included. Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected dorsolateral prefrontal cortex (DLPFC) was highly suggested for alleviating global severity (SMD = 1.11, 95% CI (0.64, 1.57)). High-frequency rTMS over the left DLPFC was recommended for language use (1.85 (1.18, 2.52)), executive function (0.85 (0.36, 1.33)), orientation deficits (0.59 (0.07, 1.13)), and attention (0.85 (0.27, 1.43)). Anodal transcranial direct current stimulation over the affected DLPFC (2.03 (0.72, 3.34)) was recommended for treating memory impairment. Meta-regression analyses showed significant associations within attention, language and orientation. CONCLUSION: Overall, different cognitive domains have different optimal scalp stimulation prescriptions, and activating the affected key brain regions and inhibiting the unaffected area is still the most effective treatment.

Indole-3-propionic acid, a product of intestinal flora, inhibits the HDAC6/NOX2 signaling and relieves doxorubicin-induced cardiomyocyte damage.

The heart failure-gut hypothesis indicates that damage to intestinal mucosa leads to increased microbial translocation, resulting in alterations in metabolites entering the blood circulation. This process promotes the development of heart failure. This study aimed to reveal the involvement of indole-3-propionic acid (IPA), a microbiota-derived tryptophan metabolite, in heart failure. Human cardiomyocytes AC16 was treated with doxorubicin to induce in vitro heart failure model, the influences of IPA on the cellular viability, apoptosis, inflammation and oxidative stress were evaluated. Molecular docking and western blotting were used to initially illustrate the potential relationship between IPA and HDAC6. Through HDAC6 overexpression, its mediating role in the regulatory mechanism of IPA in the above aspects was further investigated. IPA was found to reduce the apoptosis, inflammation and oxidative stress in doxorubicin-treated cells. The visualized structure displayed that IPA bound to HDAC6 and that IPA reduced HDAC6 level. Additionally, HDAC6 overexpression reversed the regulation of IPA in the above aspects, indicating the HDAC6/NOX2 signals mediated the mechanism of IPA. Together, the present study revealed that IPA reduced oxidative stress, inflammatory response and apoptosis in cardiomyocytes via inhibiting the HDAC6/NOX2 signaling. The findings suggest that gut microbiota metabolites have potential in the treatment of heart failure.

Value of contrast-enhanced MR angiography for the follow-up of treated brain arteriovenous malformations: systematic review and meta-analysis.

OBJECTIVE: To estimate the diagnostic value of contrast-enhanced MR angiography (CE-MRA) in identifying residual brain arteriovenous malformations (AVMs) after treatment. METHODS: We retrieved appropriate references from the electronic databases of PubMed, Web of Science, Embase, and Cochrane Library, and then evaluated the methodology quality of included references using the QUADAS-2 tool. We calculated the pooled sensitivity and specificity by applying a bivariate mixed-effects model and detected the publication bias using Deeks' funnel plot. The values of I2 were used to test heterogeneity and meta-regression analyses were performed to search for the causes of heterogeneity. RESULTS: We included 7 eligible studies containing 223 participants. Compared with a gold standard, the overall sensitivity and specificity of CE-MRA in detecting residual brain AVMs were 0.77 (95% CI 0.65-0.86) and 0.97 (95% CI 0.82-1.00), respectively. Based on the summary ROC curve, the AUC was 0.89 (95% CI 0.86-0.92). Heterogeneity could be observed in our study, especially for the specificity (I2 = 74.23%). Furthermore, there was no evidence of publication bias. CONCLUSIONS: Our study provides evidence that CE-MRA has good diagnostic value and specificity for the follow-up of treated brain AVMs. Nevertheless, considering the small sample size, heterogeneity, and many factors that may affect the diagnostic accuracy, future large-sample, prospective studies are necessary to validate the results. KEY POINTS: • The pooled sensitivity and specificity of contrast-enhanced MR angiography (CE-MRA) in detecting residual arteriovenous malformations (AVMs) were 0.77 (95% CI 0.65-0.86) and 0.97 (95% CI 0.82-1.00). • The four-dimensional CE-MRA showed less sensitivity than the three-dimensional CE-MRA for treated AVMs. • CE-MRA is helpful to identify residual AVMs and reduce excessive DSA during follow-up.

Corrigendum: Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia.

[This corrects the article DOI: 10.3389/fneur.2022.956931.].

Altered Functional Activity and Functional Connectivity of Seed Regions Based on ALFF Following Acupuncture Treatment in Patients with Stroke Sequelae with Unilateral Limb Numbness.

Objective: Limb numbness is a frequent symptom of post-stroke somatosensory dysfunction, which may be alleviated by non-invasive therapy such as acupuncture. However, the precise mechanism via acupuncture remains unknown. The goal of this study was to investigate how the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) changed between stroke patients with limb numbness and healthy people, as well as how acupuncture might work. Methods: 24 stroke sequelae patients with unilateral limb numbness and 14 matched healthy controls were enrolled in the study. The patients with limb numbness received acupuncture therapy three days a week for four weeks. We mainly assessed the clinical outcomes via the visual analogue scale (VAS). In addition, fMRI data from patients with unilateral limb numbness at baseline and after treatment (4th week) were collected, as well as data from healthy controls at baseline. Results: Compared with the healthy subjects, the patient group demonstrated significantly decreased ALFF in several brain regions, mainly associated with the sensorimotor network (SMN) and default mode network (DMN), including left superior frontal gyrus (SFG), right temporal fusiform cortex (TFC), right middle frontal gyrus (MFG), bilateral middle temporal gyrus (MTG), right putamen (PUT), right precentral gyrus (preCG), right planum polare (PP), and left supplementary motor area (SMA). These regions were chosen as the seeds for investigating the FC alteration induced by acupuncture. Several sensorimotor-related brain regions were activated by acupuncture, and the FC of the left supramarginal gyrus (SMG) with right MTG, as well as brain-stem, cerebellum vermis 9 with right MFG showed enhancement following acupuncture in the patient group, which had a significant correlation with clinical outcomes. Conclusion: Acupuncture treatment may be used to stimulate brain areas associated with somatosensory processing and to strengthen the FC of sensorimotor and cognitive brain networks in order to achieve therapeutic effect.

Safety and Efficacy of Edaravone in Patients with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: The efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide evidence-based medical guidance and advice for the clinical application of edaravone in the treatment of ALS. METHODS: PubMed, Embase, Chinese Biomedical Literature Database (CBM), Cochrane Library and Web of Science were searched through 09 March 2022 for randomized controlled trials (RCTs) on the safety and efficacy of edaravone versus placebo during follow-up of patients with ALS. A summary of the outcome measures with GRADE was performed. This study was registered on PROSPERO (ID: CRD 42022319997). RESULTS: Five RCTs with a total of 566 participants were included, and there was a significant difference (mean difference [MD] 1.33, 95% confidence interval [CI] 0.33-2.34; p = 0.009) in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score between the treatment and placebo groups. The edaravone group had an increased grip strength (MD 0.26, 95% CI 0.03-0.49; p = 0.03) and modified Norris Scale score (MD 2.81, 95% CI 1.18-4.43; p = 0.0007). However, there were no significant differences between groups for the change in forced vital capacity (FVC)% (MD 0.55, 95% CI - 3.15 to 4.24; p = 0.77), pinch strength (MD 0.05, 95% CI - 0.05 to 0.16; p = 0.33) or Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) score (MD - 4.76, 95% CI - 9.56 to 0.03; p = 0.05). The incidence of adverse events (AEs) (risk ratio [RR] 0.09, 95% CI 0.93-1.05; p = 0.65), serious adverse events (SAEs) (RR 0.72, 95% CI 0.52-1.00; p = 0.05) and the number of deaths (risk difference [RD] 0.00, 95% CI - 0.02 to 0.03; p = 0.83) were not statistically different from the placebo group. The quality of evidence was low only for SAEs, and the remaining outcome measures were of moderate quality. CONCLUSIONS: Compared with placebo, edaravone may provide potential clinical benefits in the treatment of ALS and may not increase the number of AEs and deaths. However, due to the low-quality evidence of the included studies and the small sample size, more high-quality and high-standard research evidence is needed to confirm these results. PROTOCOL REGISTRATION: This study was registered on PROSPERO (ID: CRD 42022319997).