Proteomic Spectrum of Serum Exosomes in Ischemic Stroke Patients Is Associated with Cognitive Impairment in the Post-Stroke Period.

Ischemic stroke (IS) and subsequent neuropsychiatric disorders are among the leading causes of disability worldwide. Several strategies have been previously proposed to utilize exosomes for assessing the risk of IS-related diseases. The aim of this work was to evaluate serum exosomal proteins in IS patients during the chronic post-stroke period and to search for their associations with the development of post-stroke mild cognitive impairment (MCI). Comparative quantitative proteomic analysis of serum exosomes of patients without post-stroke MCI (19 patients mean age 52.0 ± 8.1 years) and patients with post-stroke MCI (11 patients, mean age 64.8 ± 5.6 years) revealed significant differences in the levels of 62 proteins out of 186 identified. Increased levels of the proteins associated with immune system and decreased levels of the proteins involved in lipid metabolism were observed in the patients with MCI compared to the patients without MCI in the chronic post-stroke period. The obtained data suggest that the higher level of immune system activation in the patients during a relatively long period after IS may be one of the risk factors for the development of post-stroke cognitive disorders and suggest participation of exosomal transport in these processes.

Transcutaneous auricular vagus nerve stimulation for long-term post-stroke cognitive impairment: a DTI case report.

Purpose: Long-term post-stroke cognitive impairment (PSCI) exhibits an accelerated rate of long-term cognitive decline, which can impair communication, limit social engagement, and increase rate of institutional dependence. The aim of this case report is to provide evidence for the potential of home-based transcutaneous auricular vagus nerve stimulation (taVNS) for home-bound patients with severe, long-term PSCI. Methods: A 71-year-old male suffered a stroke two and a half years ago, which imaging reported foci of cerebral infarction visible in the left temporal and parietal lobes. The patient was performed taVNS twice a day for 30 min, 5 times a week for 8 weeks. The patient was evaluated the changes of cognitive function and brain white matter at 4 time points: baseline (t0), 4 weeks without taVNS after baseline (t1), 4 weeks of intervention (t2), and 8 weeks of intervention (t3). The effect of taVNS on white matter changes was visualized by DTI. Results: After 8 weeks of taVNS treatment, the scores of Montreal cognitive assessment improved and the time to complete the shape trails test decreased. The DTI results showed that white matter in bilateral dorsal lateral prefrontal cortex remodeled after taVNS. Conclusion: Eight-week home-based taVNS may be beneficial to long-term PSCI. Further studies of home-based taVNS treating patients with long-term PSCI are needed.

Galantamine combined with cognitive rehabilitation on post-stroke cognitive impairment: a proof-of-concept study.

PURPOSE: We conducted a proof-of-concept study to evaluate the effects of galantamine treatment versus placebo combined to cognitive rehabilitation (CR) after stroke. MATERIALS AND METHODS: In this 12-week, double blinded, randomized, controlled trial, patients were assigned to either combined approach of galantamine and CR (G-CR) or placebo and CR (P-CR). Primary outcome was the proportion of patients who crossed over from vascular cognitive disorder (VCD) to no-VCD at 12 weeks. Secondary outcomes included changes in cognition, mood, quality of life and the N-back fMRI paradigm, assessed at baseline, 6 and 12 weeks and after an 8-week washout period. RESULTS: Ten patients were allocated to G-RC group, 12 to the P-RC group. After 12 weeks, 40.1% of all patients converted to no-VCD with similar proportions between groups. Both groups showed improvements in episodic and working memory, executive and quality of life after 6 weeks of CR. Decreased depression and anxiety were noted, and all benefits persisted after the washout period. An interaction effect was observed in the right parietal lobule during the N-back task. CONCLUSIONS: Interventions lead to improved cognition and distinct cortical reorganization without being able to establish correlation between neural changes and behavioral measures.

Effect of tDCS combined with virtual reality for post-stroke cognitive impairment: a randomized controlled trial study protocol.

BACKGROUND: Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. METHODS: This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects' speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. DISCUSSION: Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Low frequency-repetitive transcranial magnetic stimulation combined with Xingnao Kaiqiao acupuncture improves post-stroke cognitive impairment and has better clinical efficacy.

BACKGROUND: Enhancing post-stroke cognitive impairment (PSCI) is a key aspect of prognosis for stroke patients. Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) is currently a widely utilised method for treating PSCI. With the increasing promotion of traditional Chinese medicine, Xingnao Kaiqiao (XNKQ) acupuncture has been progressively incorporated into clinical treatment. This paper observes the effect of LF-rTMS with XNKQ acupuncture on patients with PSCI. METHODS: Totally, 192 patients with PSCI were consecutively recruited and treated either with LF-rTMS and XNKQ acupuncture (observation group) or LF-rTMS only (control group) for 4 weeks. The pre- and post-treatment Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, P300 latency and amplitude, inflammatory factor levels were compared and clinical efficacy was assessed. RESULTS: Both groups exhibited increased MMSE/MoCA scores, and P300 amplitude, and shortened P300 latency, and the observation group had higher scores and P300 amplitude, and shorter P300 latency than the control group. Both groups displayed decreased inflammatory factor levels (Tumour necrosis factor-α, interleukin (IL)-6, IL-10, IL-1ß) after treatment, which were lower in the observation group than the control group. Inflammatory factor levels in PSCI patients were negatively interrelated with MMSE, MoCA score and P300 amplitude, and positively with P300 latency. The observation group showed an increased number of patients showing cured and significantly effective results, a decreased number of patients showing effective and invalid results, and an observably elevated total effective rate. CONCLUSION: LF-rTMS with XNKQ acupuncture can improve cognitive function and reduce inflammatory immune response, and has better clinical efficacy in PSCI patients.

Effect of Acupuncture on Cognitive Function in Patients With Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

AIMS AND OBJECTIVE: To investigate the impact of acupuncture on post-stroke cognitive impairment (PSCI). BACKGROUND: PSCI is a major barrier to stroke patients' rehabilitation, and acupuncture is one of the treatments. However, the benefit of acupuncture on PSCI is unclear. DESIGN: A meta-analysis and systematic review of randomized controlled trials (RCTs). METHODS: Up to February 1, 2024, databases in PubMed, MEDLINE, Scopus, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched. The risk of bias was investigated using the Cochrane Handbook for systematic reviews of treatments. Random-effect and fix-effect models were used to report the effects. RESULTS: There were 29 randomized clinical trials with 2477 participants included. The findings demonstrated that the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scores were higher in the acupuncture group than medicine group (mean difference [MD] = 1.74, 95% confidence interval (CI) CI [1.26, 2.23], I2 = 59%, p < 0.01). Compared to medicine group, the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score exhibited a significant decrease and demonstrated improvement in the acupuncture group. Statistically significant outcomes were observed in the Barthel Index scores and P300 event-related potential (ERP). According to subgroup analysis, acupuncture was superior to conventional therapy for improving cognitive function in PSCI patients at 4 weeks after treatment. CONCLUSION: Acupuncture therapy has shown promise in ameliorating cognitive deficits and enhancing daily functional abilities in individuals diagnosed with PSCI. But future research should focus on the duration and implement large sample, high-quality RCTs. RELEVANCE TO CLINICAL PRACTICE: Clinical workers in practical clinical work can select appropriate acupoints according to the actual conditions of patients, as well as confirm the treatment course of PSCI patients, while paying attention to observing and evaluating the therapeutic efficacy of acupuncture, to improve the health outcomes of patients in a patient-centered way.

Effect of non-invasive brain stimulation on post-stroke cognitive impairment: a meta-analysis.

Background: Previous studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may be an effective and safe alternative treatment for post-stroke cognitive impairment (PSCI). Similarly, the application of transcranial direct current stimulation (tDCS) during stroke rehabilitation has been shown to improve cognitive function in PSCI patients. However, there have been conflicting results from some studies. Therefore, this study aims to conduct a meta-analysis to evaluate the effects of tDCS and rTMS on PSCI. Methods: The meta-analysis search for articles published from the initial availability date to 5 February 2024 in databases. The extracted study data were entered into STATA 12.0 software for statistical analysis. Results: This meta-analysis provides evidence that both rTMS and tDCS have a positive impact on general cognitive function in PSCI patients [immediate effect of rTMS: standard mean difference (SMD) = 2.58, 95% confidence interval (CI) = 1.44 to 3.71; long-term effect of rTMS: SMD = 2.33, 95% CI = 0.87-3.78; immediate effect of tDCS: SMD = 2.22, 95% CI = 1.31-3.12]. Specifically, rTMS was found to significantly improve attention, language, memory, and visuospatial functions, while it did not show a significant therapeutic effect on executive function (attention: SMD = 3.77, 95% CI = 2.30-5.24; executive function: SMD = -0.52, 95% CI = -3.17-2.12; language: SMD = 3.43, 95% CI = 1.50-5.36; memory: SMD = 3.52, 95% CI = 1.74-5.30; visuospatial function: SMD = 4.71, 95% CI = 2.61-6.80). On the other hand, tDCS was found to significantly improve executive and visuospatial functions but did not show a significant improvement in attention function and memory (attention: SMD = 0.63, 95% CI = -0.30-1.55; executive function: SMD = 2.15, 95% CI = 0.87-3.43; memory: SMD = 0.99, 95% CI = -0.81-2.80; visuospatial function: SMD = 2.64, 95% CI = 1.04-4.23). Conclusion: In conclusion, this meta-analysis demonstrates that both rTMS and tDCS are effective therapeutic techniques for improving cognitive function in PSCI. However, more large-scale studies are needed to further investigate the effects of these techniques on different cognitive domains in PSCI.

Neuropsychological Performance after Extended N-Pep-12 Dietary Supplementation in Supratentorial Ischemic Stroke.

Background: Cognitive deficits following ischemic stroke significantly impair quality of life, highlighting the need for effective interventions. This study evaluates the efficacy and safety of extended N-Pep-12 dietary supplementation in enhancing cognitive recovery post-stroke. Methods: In this randomized, open-label, controlled study, 106 patients with supratentorial ischemic stroke were enrolled to receive either 90mg N-Pep-12 or no supplementation daily for 360 days and were followed-up for 360 days. Cognitive function and emotional well-being were assessed using established neuropsychological scales at baseline, 90 days, and 360 days post-stroke. Safety was monitored through adverse events and mortality rates. Results: Significant improvements were observed in the N-Pep-12 group compared to controls, particularly in the Montreal Cognitive Assessment scores at both 90 and 360 days, and in the Digit Symbol Coding scores at 360 days, suggesting enhanced cognitive recovery with extended N-Pep-12 supplementation. A linear regression for a composite outcome analysis at day 360 further confirmed the efficacy of N-Pep-12 in contributing to cognitive improvement. Safety profiles were favorable, with no significant adverse effects attributed to N-Pep-12. Conclusions: Extended dietary supplementation with N-Pep-12 appears to offer a safe and effective approach to support cognitive recovery in ischemic stroke survivors. These findings underscore the potential of the supplement as an add-on intervention for managing post-stroke cognitive impairments.

[Effects of electroacupuncture on learning-memory function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury based on the BDNF/TrkB pathway].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Baihui" (GV 20) and "Sishencong" (EX-HN 1) on the expression of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, synaptophysin (SYN), and the levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the hippocampus of the ischemic side in rats with cerebral ischemia-reperfusion injury (CIRI), and to explore the effects and action mechanism of EA on post-CIRI learning-memory function. METHODS: Forty-eight SPF-grade male SD rats were randomly divided into a sham operation group, a model group, an EA group, and a non-acupoint group, with 12 rats in each group. The CIRI model was established in the model group, the EA group, and the non-acupoint group using the modified ZeaLonga suture method. The rats in the EA group were treated with EA at "Sishencong" (EX-HN 1) and "Baihui" (GV 20), with disperse-dense wave at frequency of 2 Hz/10 Hz and intensity of 1 mA. The rats in the non-acupoint group were treated with EA at non-meridian and non-acupoint points under the ribs bilaterally with the same parameters as the EA group. EA were conducted for 30 min each session, once daily, for 7 days. During the intervention, body weight was measured daily at a fixed time, and neurological deficits were assessed on the 1st, 3rd, and 7th days into intervention. Brain infarct volume was measured using small animal magnetic resonance imaging before and after the intervention. After the intervention, learning-memory function were evaluated using the Morris water maze. Hippocampal morphology was observed with HE staining. The positive expression of SYN in the hippocampus of the ischemic side was detected by immunohistochemistry. BDNF, TrkB, and SYN protein expressions in the hippocampus of the ischemic side were detected by Western blot. IL-1ß and IL-18 levels in the hippocampus of the ischemic side were measured by ELISA. RESULTS: From the 2nd to the 7th day into intervention, compared with the sham operation group, the body weight of rats in the model group was decreased (P<0.01); compared with the model group and the non-acupoint group, the body weight of rats in the EA group was increased (P<0.01). On the 1st day into intervention, compared with the sham operation group, neurological function scores of rats in the model group, the EA group, and the non-acupoint group were increased (P<0.01); on the 3rd and 7th days into intervention, neurological function scores of rats in the model group were higher than those in the sham operation group (P<0.01); on the 7th day, neurological function scores of rats in the EA group were lower than those in the model group and the non-acupoint group (P<0.05). Compared with the sham operation group, escape latency was prolonged (P<0.05), and the number of platform crossings was decreased (P<0.01) in the model group; compared with the model group and the non-acupoint group, escape latency was shortened (P<0.05), and the number of platform crossings was increased (P<0.01) in the EA group. Before intervention, the high signal infarcts were observed in the left ventricles of rats in the model group, the EA group, and the non-acupoint group; after intervention compared with the model group and the non-acupoint group, infarct volume in the EA group was decreased (P<0.01). Neuronal cells in the model group and the non-acupoint group were sparsely and disorderedly arranged, with deep-stained cytoplasm and shrunken nuclei; the number and arrangement of neuronal cells in the EA group were similar to the sham operation group, with less deep-stained cytoplasm and shrunken nuclei compared to the model group. Compared with the sham operation group, the positive expression of SYN, and BDNF TrkB, and SYN protein expressions in the hippocampus of the ischemic side were decreased (P<0.01, P<0.05), while levels of IL-1ß and IL-18 were increased (P<0.01) in the model group; compared with the model group and the non-acupoint group, the positive expression of SYN, and BDNF, TrkB and SYN protein expressions in the hippocampus of the ischemic side were increased (P<0.01, P<0.05), while levels of IL-1ß and IL-18 were decreased (P<0.01) in the EA group. CONCLUSION: EA at "Baihui" (GV 20) and "Sishencong" (EX-HN 1) may improve learning-memory function in rats with CIRI by activating the BDNF/TrkB signaling pathway, reducing neuroinflammatory response, and promoting the recovery of synaptic plasticity.

Healthcare Professionals' Perspectives on Post-Diagnostic Care for People with Vascular Cognitive Impairment: When Help Is Needed in a "No-Man's Land".

Background: Post-diagnostic care for people with vascular cognitive impairment (VCI) typically involves multiple professions and disjointed care pathways not specifically designed to aid VCI needs. Objective: Exploring perspectives of healthcare professionals on post-diagnostic care for people with VCI. Methods: We conducted a qualitative focus group study. We used purposive sampling to include healthcare professionals in different compositions of primary and secondary care professionals per focus group. Thematic saturation was reached after seven focus groups. Transcripts were iteratively coded and analyzed using inductive thematic analysis. Results: Forty participants were included in seven focus groups (4-8 participants). Results showed knowledge and awareness of VCI as prerequisites for adequate post-diagnostic care, and for pre-diagnostic detection of people with VCI (theme 1). In light of perceived lack of differentiation between cognitive disorders, participants shared specific advice regarding post-diagnostic care for people with VCI and informal caregivers (theme 2). Participants thought current care for VCI was fragmented and recommended further integration of care and collaboration across settings (theme 3). Conclusions: People with VCI and their caregivers risk getting stuck in a "no man's land" between post-diagnostic care pathways; challenges lie in acknowledgement of VCI and associated symptoms, and alignment between healthcare professionals. Education about the symptoms and consequences of VCI, to healthcare professionals, people with VCI and caregivers, may increase awareness of VCI and thereby better target care. Specific attention for symptoms common in VCI could further tailor care and reduce caregiver burden. Integration could be enhanced by combining expertise of dementia and stroke/rehabilitation pathways.

Suppression of neuronal CDK9/p53/VDAC signaling provides bioenergetic support and improves post-stroke neuropsychiatric outcomes.

Bioenergy decline occurs with reperfusion following acute ischemic stroke. However, the molecular mechanisms that limit energy metabolism and their impact on post-stroke cognitive and emotional complications are still unclear. In the present study, we demonstrate that the p53 transcriptional response is responsible for neuronal adenosine triphosphate (ATP) deficiency and progressively neuropsychiatric disturbances, involving the downregulation of mitochondrial voltage-dependent anion channels (VDACs). Neuronal p53 transactivated the promoter of microRNA-183 (miR-183) cluster, thereby upregulating biogenesis of miR-183-5p (miR-183), miR-96-5p (miR-96), and miR-182-5p. Both miR-183 and miR-96 directly targeted and post-transcriptionally suppressed VDACs. Neuronal ablation of p53 protected against ATP deficiency and neurological deficits, whereas post-stroke rescue of miR-183/VDAC signaling reversed these benefits. Interestingly, cyclin-dependent kinase 9 (CDK9) was found to be enriched in cortical neurons and upregulated the p53-induced transcription of the miR-183 cluster in neurons after ischemia. Post-treatment with the CDK9 inhibitor oroxylin A promoted neuronal ATP production mainly through suppressing the miR-183 cluster/VDAC axis, further improved long-term sensorimotor abilities and spatial memory, and alleviated depressive-like behaviors in mice following stroke. Our findings reveal an intrinsic CDK9/p53/VDAC pathway that drives neuronal bioenergy decline and underlies post-stroke cognitive impairment and depression, thus highlighting the therapeutic potential of oroxylin A for better outcomes.

Circulating circular RNAs as novel biomarkers and functional prediction for the early diagnosis in post-stroke cognitive impairment: A single-center prospective study in China.

BACKGROUND: Early evaluation and intervention for post-stroke cognitive impairment are crucial for improving the prognosis of acute ischemic stroke. The search for specific diagnostic markers and feasible therapeutic targets is extremely urgent.The characteristics of circular RNAs make them promising candidates. AIMS: To screen circular RNAs as novel biomarkers and therapeutic targets for post-stroke cognitive impairment in large-artery atherosclerosis anterior circulation cerebral infarction patients. METHODS: In this prospective observational study, patients with first-ever large-artery atherosclerosis anterior circulation cerebral infarction were recruited. The Montreal Cognitive Assessment was used to assess the cognitive statuses of patients. Venous blood samples were collected on the seventh day after stroke onset. A circRNA microarray was used to identify differentially expressed circular RNAs in the discovery cohort (four patients with post-stroke cognitive impairment and four patients with post-stroke cognitive normal characteristics), and validation was performed in the validation cohorts (45 patients with post-stroke cognitive impairment and 30 patients with post-stroke cognitive normal characteristics) using quantitative real-time polymerase chain reaction. Receiver operating characteristic curves of the validated circular RNAs and the NIHSS score were constructed, and the area under the curve, sensitivity, and specificity were calculated. Correlation analysis was performed to explore the relationship between the copy number of circular RNAs and the cognitive status. The functions of the differentially expressed circular RNAs were predicted using bioinformatics analysis. RESULTS: CircRNA microarray analysis revealed 189 human circular RNAs (152 upregulated and 37 downregulated) that were differentially expressed in the plasma samples of patients with post-stroke cognitive impairment and PSCN characteristics. The expression of hsa_circ_0089763, hsa_circ_0064644, and hsa_circ_0089762 was validated using quantitative real-time polymerase chain reaction. The area under the curve, sensitivity, and specificity of hsa_circ_0089762 in post-stroke cognitive impairment diagnosis were 0.993, 97.8%, and 96.7%, respectively, and the correlation coefficient between hsa_circ_0089762 expression and the Montreal Cognitive Assessment score was -0.693 (p < 0.001), which made it an ideal biomarker. Bioinformatic analysis revealed that the targeted mRNAs of the three circular RNAs were enriched in pathologically related signaling pathways of post-stroke cognitive impairment, such as the MAPK and PI3K-Akt signaling pathways. Based on the circRNA-miRNA-mRNA network, the three circular RNAs play a crucial role in numerous pathological processes of acute ischemic stroke and post-stroke cognitive impairment by sponging miRNAs such as MiR-335, MiR-424, and MiR-670. By building the protein-protein interaction network, we identified cluster 1 according to the MCODE score; cluster 1 was composed of ERBB4, FGFR1, CACNA2D1, NRG1, PPP2R5E, CACNB4, CACNB2, CCND1, NTRK2, and PTCH. CONCLUSION: Hsa_circ_0089762, hsa_circ_0064644, and hsa_circ_0089763 are potential novel biomarkers and focal points for exploring intervention targets in post-stroke cognitive impairment of large-artery atherosclerosis anterior circulation cerebral infarction patients. REGISTRATION NUMBER: ChiCTR2000035074.

Improving diagnostic accuracy of the Montreal Cognitive Assessment to identify post-stroke cognitive impairment.

Given advantages in reperfusion therapy leading to mild stroke, less apparent cognitive deficits can be overseen in a routine neurological examination. Despite the widespread use of the Montreal Cognitive Assessment (MoCA), age- and education-specific cutoffs for the detection of post-stroke cognitive impairment (PSCI) are not established, hampering its valid application in stroke. We aimed to establish age- and education-specific MoCA cutoffs to better discriminate patients with and without acute PSCI. Patients with acute ischemic stroke underwent the MoCA and a detailed neuropsychological assessment. PSCI was defined as a performance < - 1.5 SD in ≥ 2 cognitive domains. As secondary data analysis, the discriminant abilities of the MoCAraw-score (not adding + 1 as correction for ≤ 12 years of education, YoE) cutoffs were automatically derived based on Youden Index and evaluated by receiver operating characteristic analyses across age- (< 55, 55-70, > 70 years old) and education-specific (≤ 12 and > 12 YoE) groups. 351 stroke patients (67.4 ± 14.1 years old; 13.1 ± 2.8 YoE) underwent the neuropsychological assessment 2.7 ± 2.0 days post-stroke. The original MoCA cutoff < 26 falsely classified 26.2% of examined patients, with poor sensitivity in younger adults (34.8% in patients < 55 years > 12 YoE) and poor specificity in older adults (55.0%, in > 70 years ≤ 12 YoE). By maximizing both sensitivity and specificity, the optimal MoCAraw cutoffs were: (i) < 28 in patients aged < 55 with > 12 YoE (sensitivity = 69.6%, specificity = 77.8%); (ii) < 22 and < 25 in patients > 70 years with ≤ 12 and > 12 YoE (sensitivity = 61.6%, specificity = 90.0%; sensitivity = 63.3%, specificity = 84.0%, respectively). In other groups the optimal MoCAraw cutoff was < 26. Age and education level should be considered when interpreting MoCA-scores. Though new age- and education-specific cutoffs demonstrated higher discriminant ability for PSCI, their performance in young stroke and adults with higher education level was low due to ceiling effects and MoCA subtests structure, and cautious interpretation in these patients is warranted.Trial registration: ClinicalTrials.gov Identifier: NCT05653141.

Exploring the Relationship between Abnormal Communication Efficiency of Cerebral Cortex and Multiple Cognitive Functions in Mild Subcortical Stroke: A Resting-State fMRI Study.

BACKGROUND: The purpose of this study was to explore the specific regions of abnormal cortical communication efficiency in patients with mild subcortical stroke and to investigate the relationship between these communication efficiency abnormalities and multidimensional cognition. METHODS: The research involved 35 patients with mild strokes affecting the basal ganglia and 29 healthy controls (HC). Comprehensive neuroimaging and neuropsychological assessments were conducted. Stroke patients were categorized into post-stroke cognitive impairment (PSCI) (MoCA ≤ 22) and non-cognitively impaired stroke patients (NPSCI) (MoCA ≥ 23) based on their cognitive performance. Additionally, 22 patients were reassessed three months later. RESULTS: PSCI patients, compared to HC and NPSCI groups, had significantly higher communication efficiency in specific brain regions. A notable finding was the significant correlation between increased communication efficiency in the medioventral occipital cortex and multidimensional cognitive decline. However, this increased communication efficiency in PSCI patients lessened during the three-month follow-up period. CONCLUSIONS: the heightened communication efficiency in the medio-ventral occipital cortex may represent a compensatory mechanism for cognitive impairment in PSCI patients, which undergoes adjustment three months after stroke.

Using Dual-Target rTMS, Single-Target rTMS, or Sham rTMS on Post-Stroke Cognitive Impairment.

BACKGROUND: The clinical application of 10 Hz repetitive transcranil magnetic stimulation (rTMS) remains limited despite its demonstrated effectiveness in enhancing cortical excitability and improving cognitive function. The present study used a novel stimulus target [left dorsolateral prefrontal cortex + primary motor cortex] to facilitate the enhancement of cognitive function through the bidirectional promotion of cognitive and motor functions; Methods: Post-stroke cognitive impairment patients (n = 48) were randomly assigned to receive either dual-target, single-target, or sham rTMS for 4 weeks. Before and after 4 weeks of treatment, participants were asked to complete the Montreal Cognitive Assessment (MoCA) test, the Modified Barthel Index (MBI), the Trail-making Test (TMT), and the Digital Span Test (DST). In addition, the levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in serum were also measured. RESULTS: After adjusting for pre-intervention (baseline) MoCA scores, the post-intervention MoCA scores varied significantly. After post-hoc analysis, differences existed between the post-treatment scores of the dual-target rTMS group and the sham rTMS group (the experimental group scores were significantly higher), and between those of the dual-target rTMS group and the single-target rTMS group (the dual-target rTMS scores were significantly higher). The serum VEGF levels of the dual-target rTMS group were significantly higher those that of the sham rTMS group. CONCLUSIONS: The present study presented data showing that a dual-target rTMS therapy is effective for Post-stroke cognitive impairment (PSCI). The stimulation exhibited remarkable efficacy, suggesting that dual-target stimulation (left dorsolateral prefrontal cortex+motor cortex (L-DLPFC+M1)) holds promise as a potential target for TMS therapy in individuals with cognitive impairment after stroke. CLINICAL TRIAL REGISTRATION: No: ChiCTR220066184. Registered 26 November, 2022, https://www.chictr.org.cn.

The influence of eight cognitive training regimes upon cognitive screening tool performance in post-stroke survivors: a network meta-analysis.

Background: Traditional meta-analysis offers only direct comparative evidence. The optimal cognitive training for poststroke cognitive impairment (PSCI) remains largely undetermined. Objectives: This study aims to assess and compare the effectiveness of selected cognitive training methods for PSCI patients and to identify and rank the most effective intervention programs. Methods: Searches were conducted in PubMed, Embase, Cochrane Library, Web of science, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biomedical Database for randomized controlled trials up to September 30, 2023. Two researchers independently performed literature screening, data extraction, and quality assessment. Network meta-analysis was utilized to synthesize the main findings. The primary outcome focused on the intervention's impact on subjective cognitive function, with secondary outcomes including effects on activities of daily living, motor function, and functional independence. This study is registered with PROSPERO (CRD42023463282). Results: Fifty eligible randomized controlled trials were identified, revealing eight distinct interventions. These interventions collectively demonstrate efficacy in enhancing cognition. Traditional cognitive training significantly improves overall cognitive function, daily living function, motor function, and functional independence. In Loewenstein Occupational Therapy Cognitive Assessment, Barthel Index, Fugl-Meyer Assessment, and Functional Independence Measure scales, a combination of computer-based and traditional cognitive training outperformed the conventional control group MD = 29.97 (95%CI: 16.3, 44.2), MD = 18.67 (95%CI: 9.78, 27.45), MD = 28.76 (95%CI: 5.46, 51.79) and MD = 42.2 (95%CI: 5.25, 78.99). In the MMSE scale, virtual reality cognitive training combined with traditional training was most effective MD = 8.01 (95%CI: 3.6, 12.4). On the MoCA scale, the combination of exercise and cognitive training showed superior results MD = 6.68 (95%CI: 2.55, 10.78). Only the combined computer-based and traditional cognitive training, as well as traditional cognitive training alone, significantly enhanced functional independence, with no notable differences in other pairwise interventions. Conclusion: The network meta-analysis suggests that augmenting traditional training with other modalities may enhance overall effectiveness. Specifically, interventions incorporating computer-based cognitive training appear to surpass other methods in improving cognition, daily living function, motor skills, and functional independence. The findings of this network meta-analysis provide evidence-based guidance for clinical decision-making. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier in PROSPERO (CRD42023463282).

The role of ventral hippocampal-medial prefrontal glutamatergic pathway on the non-affected side in post-stroke cognitive impairment.

Elucidate the pathogenesis mechanism of post-stroke cognitive impairment (PSCI) can help to develop precision interventions. In this study, we established a mouse model of PSCI using the photochemical method, and behavioral tests including Y-maze and Novel object recognition task for accessing cognitive impairment were observed at week 2 post-stroke. Besides, synaptic plasticity, theta nerve oscillatory and the activity of glutamatergic neurons related to the ventral hippocampal-medial prefrontal glutamatergic neural pathway in the non-affected hemisphere (contralateral hemisphere to the lesion site) were observed. The result indicated the cognitive function declined at week 2 post-stroke. Synaptic plasticity, theta nerve oscillatory synchronization and the activity of glutamatergic neurons of the ventral hippocampal-medial prefrontal glutamatergic neural pathway in the non-affected hemisphere was down-regulated in the PSCI group compared to those of the SHAM group. Therefore, we concluded that the declined function of the ventral hippocampal-medial prefrontal glutamatergic pathway in the non-affected hemisphere is a biomarker in the occurrence of cognitive dysfunction after stroke.

Brain activation patterns in patients with post-stroke cognitive impairment during working memory task: a functional near-infrared spectroscopy study.

Objective: To explore the activation patterns in the frontal cortex of patients with post-stroke cognitive impairment during the execution of working memory tasks. Methods: 15 patients with post-stroke cognitive impairment, 17 patients without cognitive impairment, and 15 healthy controls of similar age and sex were included. All participants under-went immediate recall task testing and near-infrared spectroscopy imaging to measure frontal cortex activation during the task. Results: The healthy control group performed the best in the immediate recall task, followed by the post-stroke non-cognitive impairment group. The post-stroke cognitive impairment group had the poorest performance. The near-infrared spectroscopy results revealed that during the immediate recall task, the healthy control group primarily activated the left frontal lobe region. In contrast, post-stroke patients exhibited reduced activation in the left frontal lobe and increased activation in the right frontal cortex, particularly in the right frontopolar and orbitofrontal regions, with the post-stroke cognitive impairment group displaying the most pronounced changes. Conclusion: Patients with post-stroke cognitive impairment exhibit reduced activation in the left prefrontal cortex during the working memory tasks. They rely on compensatory activation in the right prefrontal cortex, particularly in the frontopolar and orbitofrontal cortex, to successfully complete the task.

The relationship between social and psychological factors with cognitive impairment after stroke: a prospective study.

Objectives: To investigate the association between social and psychological factors and the risk of cognitive impairment following acute ischemic stroke. Materials and methods: A prospective study was conducted at Shanghai Tenth People's Hospital from June 2021 to July 2022. The study focused on social and psychological factors, which were assessed using the Social Support Rating Scale (SSRS), Self-Perceived Burden Scale (SPBS), and Hamilton Depression Scale (HAMD) within 3 days after admission to the hospital. Cognitive function was evaluated using the Montreal Cognitive Assessment at 3 months post-stroke. Logistic hierarchical regression models were used to examine the association between these three indicators and cognitive impairment following a stroke. Results: Among these patients, cognitive function was assessed in 211 cases at the 3-month follow-up after the initial stroke event. At 3 months post-stroke, 118(55.9%) of the participants experienced cognitive impairment, while 93(44.1%) did not. The scores on the SPBS and HAMD showed significant associations with cognitive impairment at 3 months after stroke. The scores of SPBS [scores: 30~39 vs.<20 points, odds ratio (OR)=2.993 (1.135-7.896); scores: ≥40 vs.<20points, OR=7.382 (1.117-48.799); P=0.043] and the HAMD [scores: >7 vs.≤7 points, OR=3.287(1.362~7.936); P=0.008]. There were no significant associations observed between SSRS and PSCI. Conclusion: Early screening for depressive symptoms and focusing on self-perceived burden can be beneficial for decision support for clinicians and improve cognitive function recovery at the 3-month mark post-stroke.

Risk Factors of Poststroke Cognitive Impairment: A Meta-Analysis.

OBJECTIVE: To explore the potential risk factors of post stroke cognitive impairment (PSCI) by conducting a meta-analysis. METHODS: Literature search was performed in databases (PubMed, Embase, Web of Science, CNKI) using keywords of PSCI. Cochrane ROB tool was adopted for evaluating the quality of the included studies. Afterwards, data was independently extracted by 2 investigators. Heterogeneity was quantified across studies by Chi-squared-based Q statistic test and I2 statistic. The random-effects model or fixed-effects model was employed to compute the pooled estimates depends on whether the heterogeneity was significant (I2 > 50% or P < .05) or not. Publication bias was evaluated by the funnel plot and Egger's test. Sensitivity analysis was accomplished through eliminating studies 1 at a time to evaluate the stability of the pooled estimates. RESULTS: 23 high-quality studies with 13322 patients were included. Compared with patients with no cognitive impairment, PSCI was more likely to develop in the elderly (pooled MD = 3.58, 95% CI = [1.82, 5.34]), female (pooled RR = 1.23, 95% CI = [1.07, 1.41]), or less-educated (pooled MD = -1.63, 95% CI = [-2.96, -.31]) patients with a history of hypertension (pooled RR = 1.07, 95% CI = [1.03, 1.11]), diabetes mellitus (pooled RR = 1.10, 95% CI = [1.03, 1.17]), atrial fibrillation (pooled RR = 1.38, 95% CI = [1.10, 1.74]), or stroke (pooled RR = 1.36, 95% CI = [1.09, 1.70]). Smoking did not affect the development of PSCI in patients (pooled RR = .96, 95% CI = [.78, 1.19]). Ischemic heart disease and region represented the sources of significant heterogeneity across studies. The pooled estimates were robust, and no publication bias was seen. CONCLUSION: Age, gender, education, hypertension, diabetes mellitus, atrial fibrillation, and stroke were the risk factors of PSCI. Controlling these risk factors can help prevent PSCI.