Post-stroke Cognitive Impairment Research Articles

Magnetic targeting enhances the neuroprotective function of human mesenchymal stem cell-derived iron oxide exosomes by delivering miR-1228-5p

BackgroundTreating mitochondrial dysfunction is a promising approach for the treatment of post-stroke cognitive impairment (PSCI). HuMSC-derived exosomes (H-Ex) have shown powerful therapeutic effects in improving mitochondrial function, but the specific effects are unclear and its brain tissue targeting needs to be further optimized.ResultsIn this study, we found that H-Ex can improve mitochondrial dysfunction of neurons and significantly enhance the cognitive behavior performance of MCAO mice in OGD/R-induced SHSY5Y cells and MCAO mouse models. Based on this, we have developed an exosome delivery system loaded with superparamagnetic iron oxide nanoparticles (Spion-Ex) that can effectively penetrate the blood-brain barrier (BBB). The research results showed that under magnetic attraction, Spion-Ex can more effectively target the brain tissue and significantly improve mitochondrial function of neurons after stroke. Meanwhile, we further confirmed that miR-1228-5p is a key factor for H-Ex to improve mitochondrial function and cognitive behavior both in vivo and in vitro. The specific mechanism is that the increase of miR-1228-5p mediated by H-Ex can inhibit the expression of TRAF6 and activate the TRAF6-NADPH oxidase 1 (NOX1) pathway, thereby exerting protective effects against oxidative damage. More importantly, we found that under magnetic attraction, Spion-Ex exhibited excellent cognitive improvement effects by delivering miR-1228-5p.ConclusionsOur research found that H-Ex has a good therapeutic effect on PSCI by increasing the expression of miR-1228-5p in PSCI, while H-Ex loaded with Spion-Ex exhibited more excellent effects on improving mitochondrial function and cognitive impairment under magnetic attraction, which can be used as a novel strategy for the treatment of PSCI.

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

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. 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. 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-1β) 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. LF-rTMS with XNKQ acupuncture can improve cognitive function and reduce inflammatory immune response, and has better clinical efficacy in PSCI patients.

A network meta-analysis of different acupuncture therapy in the treatment of poststroke cognitive impairment and dementia.

Poststroke cognitive impairment and dementia (PSCID) is a major cause of stroke-related morbidities and mortalities. Over the last few years, there has been growing evidence supporting the effectiveness of needle-related treatments in PSCID. Our goal was to rate the included therapies and assess the clinical effectiveness of various needle-related treatments in patients with PSCID. We searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed), Wanfang, FDA.gov, and ClinicalTrials.gov. A mix of subject terms and free words was used to search the databases. The retrieval period was from the inception date of the database to February, 2023. We included SRs and MAs from acupuncture RCTs of patients with PSCID. The Cochrane Risk Assessment Scale was used to evaluate the risk of bias in the included studies. State 17.0 was used for network meta-analysis in accordance with the Bayesian framework. There were 34 studies total of 2690 patients. The cumulative ranking curve (SUCRA) revealed that CT + CFT + EA was the most efficient intervention to improve (Mini-Mental State Examination, MMSE) efficiency, followed by CT + CFT + AP to improve (Montreal Cognitive Assessment, MoCA) efficiency, CT + CFT + ACU for improving (Activities of Daily Living scale, ADL) scores, and CT + CFT + EA to improve clinical efficiency. The results show that Different acupuncture methods can improve cognitive function and daily living ability in patients with PSCID. Network meta-analysis revealed that both CT + CFT + ACU and CT + CFT + EA appeared to be more beneficial for daily living activities, while CT + CFT + EA and CT + CFT + AP appeared to be more helpful for cognitive performance in patients with PSCID. Treatments including acupuncture are safer and have a reduced incidence of negative side effects.

Asthenia and vascular cognitive impairment in young patients after stroke

Post-stroke cognitive impairment (PSCI) is found in most patients over 50 years of age. At a young age, PSCI has a negative impact on daily activities, quality of life and return to work, regardless of physical recovery. Often PSCI are combined with asthenia, but there is very little information on the prevalence of post-stroke asthenia (PSA). Currently, the treatment of PSCI and PSA in young patients with citicoline is still controversial.Objective: to evaluate the prevalence of PSCI and PSA in young patients and the efficacy and safety of the domestic drug Noocil (citicoline) in the treatment of PSCI and PSA in stroke patients of young age.Material and methods. The work was conducted in two stages: the first stage was a longitudinal study of cognitive status using neurocognitive scales and assessment of signs of asthenia in patients aged 18 to 45 years; the second stage was an open prospective observational study of 47 patients aged 18 to 45 years with confirmed ischemic stroke (IS) who were randomly assigned to groups with Noocil administration (main group; n=26) or without treatment (control group; n=21). Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) and asthenia by manifestations of general fatigue (Multidimensional Fatigue Inventory, MFI-20).Results. High frequency of PSCI (51%) and the severity of asthenia according to MFI-20 scale were found in the hospital sample of young patients with IS. A direct correlation was found between the severity of PSA and the degree of cognitive decline. The positive effect of Noozil on cognitive functions, emotional state and severity of asthenia in the study group was noted. At the end of treatment, the mean MoCA score was 27.4±1.4 in the main group and 25.9±1.1 in the control group (p<0.01), and the mean MFI-20 score was 37.4±7.4 in the main group and 43.7±5.1 in the control group (p<0.01).Conclusion. The high incidence of PSCI and PSA and the positive effect of Noocil on the non-motor consequences of stroke in young patients and the high safety profile of the drug were shown.

Possibilities of using innovative non-drug technologies in the rehabilitation of patients with early post-stroke cognitive impairment

BACKGROUND: One of the leading factors complicating social adaptation after ischemic stroke is cognitive and motor impairment. AIM: This study aimed to evaluate the effect of rehabilitation using virtual reality technologies and the influence of the main clinical and functional parameters on virtual reality (VR) therapy in patients with different degrees of cognitive decline in the acute period of ischemic stroke. MATERIALS AND METHODS: This study examined 170 patients diagnosed with ischemic stroke with cognitive decline according to the Montreal Cognitive Assessment. Depending on the volume of therapy, the patients were divided into two groups: group 1 included 120 patients who received additional therapy using VR technologies (62 patients with moderate cognitive impairment, 58 patients with dementia), and group 2 consisted of 50 patients who received only basic therapy and standard methods of early rehabilitation. In group 1, on days 4–5 following basic therapy, rehabilitation using VR was performed. The Barthel Index (BI) scale, Rankin Scale (mRS), and National Institute of Health Stroke Scale (NIHSS) were used to examine cognitive and functional status, and tests were performed to assess cognitive functions, as well as neuroimaging scales ASPECTS, STRIVE, and MTA. The effectiveness of rehabilitation (ΔRE) was measured by the indicator of changes in the parameters of the VR system before and after treatment. RESULTS: A more significant improvement of the patient’s independence and regression of perceptual and executive functions was demonstrated in group 1 than in the control group. In patients with MCI, significant improvement was observed in all cognitive and functional parameters except semantic information processing, attention, and constructive praxis. In patients with dementia, improvement was noted in NIHSS, speech and amnestic disorders. In group 1, ΔRE was found to be associated with the parameters of perception, attention, semantic information processing, IQCODE, and NIHSS and the presence of hypertension and repeated stroke. In patients with MCI, ΔRE was correlated with lesion size, attention level, BI, mRS, and NIHSS and with age, sex, degree of IQCODE and STRIVE, semantic aphasia, and perceptual impairment in patients with dementia. CONCLUSION: The present study revealed a polymorphism of factors influencing the effectiveness of VR therapy in patients with varying degrees of cognitive decline. Modern approaches to VR rehabilitation of patients with post-stroke cognitive impairment require the development of individual methods of rehabilitation using immersion environment focused on the structure, etiology, and severity of cognitive deficit considering the degree of the patient’s functional state.

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

ABSTRACT 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.

Trajectory of Cognitive Decline Before and After Stroke in 14 Population Cohorts

Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up. The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024. Incident stroke. The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores. The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (-0.25 SD; 95% CI, -0.33 to -0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from -0.17 SD to -0.22 SD), as well as accelerated decline in global cognition (-0.038 SD per year; 95% CI, -0.057 to -0.019 SD per year) and all domains except memory (ranging from -0.020 to -0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was -0.049 SD per year (95% CI, -0.051 to -0.047 SD) in global cognition. In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.

Multivariate and network lesion mapping reveals distinct architectures of domain-specific post-stroke cognitive impairments

BackgroundThe purpose of this study was to identify patterns of structural disconnection and multivariate lesion-behaviour relationships associated with post-stroke deficits across six commonly impacted cognitive domains: executive function, language, memory, numerical processing, praxis, and visuospatial attention. MethodsStroke survivors (n = 593) completed a brief domain-specific cognitive assessment (the Oxford Cognitive Screen (OCS)) during acute hospitalisation. Network-level and multivariate (sparce canonical correlation) lesion mapping analyses were conducted to identify focal neural correlates and distributed patterns of structural disconnection associated with impairment on each of the 16 OCS measures. ResultsNetwork-level and multivariate lesion mapping analyses identified significant correlates for 12/16 and 10/16 OCS measures, respectively which were largely consistent with correlates reported in past work. Language impairments were reliably localised to network- and voxel-level correlates centred in left fronto-temporal regions. Memory impairments were associated with disconnection in a large network of left hemisphere regions. Number processing deficits were associated with damage to voxels centred in the left insular/opercular cortex, as well as disconnection within the surrounding white matter tracts. Within the domain of attention, different subtypes of visuospatial neglect were linked to distinct but partially overlapping patterns of disconnection and voxel-level damage. Praxis impairment was not linked to any voxel-level regions but was significantly associated with disconnection within the left hemisphere dorsal attention network. ConclusionThese results highlight the utility of routine, domain-specific cognitive assessment and imaging data for theoretically-driven lesion mapping analyses, while providing novel insight into the complex anatomical correlates of common and debilitating post-stroke cognitive impairments.

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

BackgroundPost-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.MethodsThis 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.DiscussionOur 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 registrationChictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

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

To investigate the impact of acupuncture on post-stroke cognitive impairment (PSCI). 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. A meta-analysis and systematic review of randomized controlled trials (RCTs). 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. 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. 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. 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.

Prevalence of poststroke anxiety and its associations with global cognitive impairment: An individual participant data analysis

Background and purposeAnxiety is frequent after stroke; however, little is known about its determinants. This study aims to assess the prevalence and correlates of post stroke anxiety (PSA) within 3–6 months following ischemic stroke. MethodsThree cohort studies from the STROKOG consortium were involved. Demographic and clinical data were standardized. PSA and PSD were assessed using inventories. The criteria for post-stroke cognitive impairment (PSCI) were at least one cognitive domain impaired if applicable, or a Montreal Cognitive Assessment (MoCA) score. Descriptive analyses were conducted to ascertain the prevalence of anxiety. Comparisons between anxious and non-anxious patients in the total sample were made using χ2 and t-tests. A two-step individual participant data (IPD) meta-analysis was employed to identify factors associated with PSA. Results584 patients were included. The total prevalence of PSA was 35 % (95%CI = [31.23;38.97]) and ranged from 27 % to 45 % across cohorts. In the total sample, there was a higher proportion of females in the anxiety group than the non-anxiety group (χ2 = 19.62; p < 0.001). Anxious patients had lower education, (χ2 = 6.59; p = 0.03), higher stroke severity (t = 2.77; p = 0.002), and higher rates of PSD (χ2 = 118.09; p < 0.001), and PSCI (χ2 = 23.81, p < 0.001). The analysis demonstrates that the odds of presenting with PSA is larger in patients with PSCI (OR = 1.84, 95%CI = [1.14; 2.91]). ConclusionsAnxiety is frequent after stroke, especially in females, and is associated with depression and cognitive impairment.

A modified Delphi survey to build expert consensus on the structure and content of an enhanced care pathway for cognitive changes after stroke in the UK

BackgroundEnhancing long-term support for post-stroke cognitive impairment is a top research priority. Addressing current gaps in UK post-stroke cognitive care provision requires a pragmatic and scalable intervention that can be integrated within the existing stroke care pathway. This study aimed to develop consensus on an initial set of core features for a UK-based monitoring and psychoeducational intervention for cognitive changes after stroke.MethodsAn expert panel of UK healthcare professionals and researchers participated in an online modified Delphi survey. Candidate intervention features were identified from clinical guidelines, existing literature, research team/collaborator expertise, and PPI group lived experience. Survey participants indicated whether they agreed/disagreed/had no opinion about including each candidate feature in the intervention and free-text responses were invited. We analysed responses for consensus (≥ 75% agreement) using descriptive statistics, with items not reaching consensus carried into subsequent rounds. Template analysis was used to identify similarities/differences in viewpoints for items that did not reach consensus.ResultsThree survey rounds were completed by 36, 29 and 26 participants, respectively. Participants agreed reviews should include a stroke-specific cognitive screen (97% agree) and assessment of other psychological changes (low mood, anxiety, fatigue: 94%, 90%, 89% agree, respectively). They agreed stroke survivors should be offered at least one review, regardless of their cognitive profile in hospital. They agreed on the importance of various cognition-focused psychoeducation topics, and formal (100% agree) and informal (79% agree) training for those conducting reviews. Consensus was not reached on the review mode (in person/remote options: 67% agree), offering reviews one-year post-discharge to patients without acute cognitive impairments (68% disagree), or including a dementia screen (63% disagree) and/or neuropsychological assessment battery (58% disagree). However, there were similarities in participant viewpoints. For example, participants emphasised the importance of onwards referral where clinically indicated. ConclusionsThe UK-based post-stroke monitoring and psychoeducation intervention was originally conceptualised as a cognitive care pathway, but expert participants agreed on the importance of simultaneously addressing related psychological changes (e.g. low mood, anxiety). There was clear consensus on a minimum set of intervention features. Recommendations outlined here may usefully inform local service improvements.

Effect of Blood Glucose Gap on Post-stroke Cognitive Impairment in Acute Ischemic Stroke Patients

Objective: To analyze the effect of the blood glucose gap on post-stroke cognitive impairment in acute ischemic stroke patients. Methods: 300 stroke patients admitted to the hospital between December 2021 and December 2022 were selected and divided into three groups according to the value of blood glucose gap: the group with no elevation of blood glucose gap (n = 124), the group with mild elevation of blood glucose gap (n = 97), and the group with elevated blood glucose gap (n = 79). The same treatment regimen was applied to these three groups and cognitive function was assessed using MMSE and MoCA at 3, 6, and 12 months after discharge. Results: The NIHSS and MoCA scores of the patients in the group with elevated blood glucose gap were significantly higher than those in the mildly elevated group and the non-elevated group at 3, 6, and 12 months after discharge, and the MMSE and MoCA scores of the patients in the group with mildly elevated blood glucose gap were significantly higher than those in the non-elevated group at 3, 6, and 12 months after discharge, and there were statistically significant differences between all the groups (P &lt; 0.05). Conclusion: Patients with an elevated glycemic gap in acute ischemic stroke showed more pronounced cognitive impairment than those with no elevated glycemic deficit, and the severity of cognitive impairment increased with the degree of glycemic deficit.

Effectiveness of Neurofeedback Training in Poststroke Cognitive Impairment

Effectiveness of Neurofeedback Training in Poststroke Cognitive Impairment

StrokeCog-R: Protocol for a Pilot Randomised Controlled Trial Of A Novel Cognitive Rehabilitation Intervention For Post-Stroke Cognitive Impairment

Abstract Background Post-stroke cognitive impairment (PSCI) affects 50% of patients six months post-stroke and is associated with increased disability, reduced quality of life, diminished independence, and a higher risk of long-term care and dementia. Addressing cognitive impairment is crucial to maximise patient recovery, facilitate the return to pre-stroke activities, and optimise secondary prevention efforts. However, cognitive rehabilitation is underrepresented in standard stroke rehabilitation protocols. This pilot randomised controlled trial (RCT) aims to evaluate a novel cognitive rehabilitation intervention, StrokeCog-R, designed to enhance cognitive function in stroke survivors with PSCI. The primary aims are to assess the feasibility of patient recruitment and retention and to determine the statistical power needed for a definitive trial. A secondary aim is to evaluate the efficacy and acceptability of the intervention for individuals with mild-to-moderate PSCI. Methods Sixty-four consecutive stroke patients with mild-to-moderate PSCI will be recruited and randomly assigned to either the intervention group (StrokeCog-R) or the control group (usual care). The intervention involves five weeks of group-based cognitive rehabilitation using “Rehearsal-Based” and “Compensatory-Based” strategies, supplemented with tailored home activities. Cognitive function, self-efficacy, and caregiver psychological wellbeing will be assessed pre- and post-intervention (or control) and at a four-month follow-up. Intervention acceptability will be documented through focus groups following each intervention. Recruitment is ongoing, and the first intervention group has concluded. Results Recruitment and retention rates, the feasibility of randomisation, patient acceptability, and resource utilisation will be evaluated. Additionally, the effectiveness of various communication techniques for retaining participants between the intervention period and the four-month follow-up will be assessed. These data will inform recruitment strategies and the determination of necessary effect sizes to power a definitive trial. Conclusion This study will provide critical insights for a definitive trial, potentially making a substantial contribution to the evidence base for cognitive rehabilitation in stroke patients.

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.

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.

A clinical protocol for the diagnosis of delirium after stroke in the post-acute setting: The “post-acute stroke delirium assessment” study

Post-stroke delirium (PSD) is an important complication to identify in the inpatient rehabilitation setting due to its negative impact on rehabilitation outcomes. Delirium diagnosis is challenging and is rendered more so in the presence of post-stroke language and cognitive impairments. As delirium is a clinical diagnosis, the majority of PSD studies use a Diagnostic and Statistical Manual (DSM)–based “expert clinical diagnosis” as the reference standard. However, a diagnostic protocol is rarely defined, which undermines transparency, interrater reliability, and reproducibility in delirium research. This report describes the clinical diagnostic protocol for the “Post-Acute Stroke Delirium Assessment” study, a quality improvement initiative to be conducted in adult stroke rehabilitation inpatients at a tertiary academic hospital. The main study goals are to explore how delirium features present in this patient group and to use this information to create a new screening tool specific for PSD in inpatient rehabilitation. This protocol evaluates 16 delirium features, including those encompassed by the DSM, fifth edition, text revision as well as other features absent from the DSM, and delineates how to determine whether each feature is “present, absent, or unable to assess.” This protocol may also be valuable in informing delirium diagnosis in other patient groups with or without neurological deficits.

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.

Markers of early post-stroke cognitive impairment

Aim. To identify significant indicators of cognitive dysfunction based on discriminant analysis and to assess the influence of the course, nature and localization of ischemic stroke on the cognitive status of the patient.Materials and methods. We examined 290 patients diagnosed with ischemic stroke in the carotid artery area. Depending on presence of cognitive dysfunction according to the Montreal Cognitive Assessment Scale (MoSA) patients were divided into 2 groups: 240 patients with cognitive decline (≤25 point by MoCA) and 50 patients without it. In order to verify the markers, anamnestic characteristics were assessed, cognitive-functional indicators (according to the scales of the National Institutes of Health, MoCA, Bartel, Rankin, IQCODE questionnaire, additional scales to assess praxis, semantic aphasia, perception and executive function), data of neuroimaging studies. For statistical analysis machine learning algorithms and Python with its libraries (Pandas and SciPy) were implied.Results. The main neuropsychological indicators for patients with early post-stroke cognitive impairment were decline in the areas of perception, executive function, memory and semantic information processing, affective disturbances and physical fatigue. Relevant indicators identified during estimation of the instrumental and clinical examination results were severity of IS, left frontal and right parietal localisations of ischemia focus, presence of cortical atrophy and leukoaraiosis.Conclusion. Based on multi-factor analysis of clinical and paraclinical parameters using machine learning algorithms, the main markers of cognitive decline of early post-stroke impairments were identified. This will allow us to optimise the choice of neurocognitive rehabilitation strategies and to personalise the approach in the further management of the stroke patient.