Post-stroke Cognitive Impairment Research Articles

Scientific Evidence of Acupuncture for Post-Stroke Cognitive Impairment: An Overview of Systematic Reviews and Meta-Analyses.

Acupuncture may be effective to treat post-stroke cognitive impairment (PSCI). We aimed to evaluate the reliability of the systematic reviews/meta-analyses (SRs/MAs) evidence regarding acupuncture treatment of PSCI. The methodological quality was appraised with Methodological Quality of Systematic Reviews 2 (AMSTAR-2). We evaluated reporting quality with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and evidence quality with Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. The inclusion criteria were met by fifteen reviews. All studies assessed by AMSTAR-2 had critically poor methodological quality due to the limitations on the lack of the provision of the list of excluded trails, screening of duplicate study, and protocol registration. For reporting quality, response rate of "yes" was less than 50% in Q5 (protocol and registration topic), Q8 (Search) and Q23 (Additional analysis). Evidence quality of outcome measures was low or worse with GRADE because when the data was qualitatively synthesized, low quality and small sample size trials provided the data. Acupuncture may be beneficial for PSCI. Because of limitations and inconsistent conclusions, further research is needed to provide higher evidence for acupuncture on PSCI.

Impact of Serum Cystatin C Level on Long-Term Cognitive Impairment After Acute Ischemic Stroke and Transient Ischemic Attack.

Cognitive impairment after stroke/transient ischemic attack (TIA) has a high prevalence. Cystatin C (CysC) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer's disease. We aimed to explore the possible correlations of serum CysC level with cognitive impairment in patients who had mild ischemic stroke and TIA after 1 year. We measured serum CysC level in 1025 participants with a minor ischemic stroke/TIA from enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were divided into four groups according to quartiles of baseline CysC levels. Patients' cognitive functions were assessed by Montreal Cognitive Assessment (MoCA)-Beijing at day 14 and at 1 year. Multiple logistic regression models were performed to evaluate the relationship between CysC and post-stroke cognitive impairment (PSCI) at 1-year follow-up. Cognitive impairment was defined as MoCA-Beijing ≤22. Most patients were in 60s (61.52±10.97 years old) with a median (interquartile range) National Institute of Health Stroke Scale(NIHSS) score of 3.00 (4.00) and greater than primary school level of education, and 743 participants (72.49%) were male. Among the 1025 participants, 331 participants (32.29%) patients suffered PSCI at 1-year follow-up. A U-shaped association was observed between CysC and 1-year PSCI [quartile (Q)1 vs Q3: adjusted odds ratio (aOR) 2.69, 95% CI 1.67-4.34, p < 0.0001; Q2 vs Q3: aOR 1.63, 95% CI 1.03-2.57, p = 0.0354; Q4 vs Q3: aOR 1.83, 95% CI 1.16-2.87, p = 0.009]. Moreover, the U-shaped trends were also found between CysC level and the subscores of attention, recall, abstraction and language in MoCA. CysC showed a U-shaped correlation with 1-year overall cognitive function. It is probable that measurement of the serum CysC level would aid in the early diagnosis of PSCI.

Potential of a Brain–Computer Interface for Correcting Poststroke Cognitive Impairments

Potential of a Brain–Computer Interface for Correcting Poststroke Cognitive Impairments

The continuous performance test aids the diagnosis of post-stroke cognitive impairment in patients with right hemisphere damage.

The purpose of the study was to investigate the time course difference of relative changes in oxygenated hemoglobin (Oxy-Hb) concentration in the prefrontal cortex (PFC) between controls and patients with post-stroke cognitive impairment (PSCI) who had right hemisphere damage (RHD) using the continuous performance test (CPT) and functional near-infrared spectroscopy (fNIRS) technology. The study aimed to evaluate the feasibility of CPT in the diagnosis and evaluation of PSCI with RHD. A total of 16 patients with RHD (RHD group) and 32 normal subjects (control group) were recruited. The Montreal Cognitive Assessment Scale was used to assess post-stroke cognitive impairment. The CPT and fNIRS were employed to investigate task-related changes in Oxy-Hb levels. The RHD group showed significantly lower accuracy and hit rates than the control group; however, the average reaction time was significantly longer in the former. Although the two groups showed no statistically significant difference in terms of left and right PFC integral values, the mean values were greater in the RHD group. The centroid value of the right PFC was significantly higher in the RHD group than in the control group. The time course of Oxy-Hb concentrations in the PFC differed between the two groups. In the RHD group, neural compensation was observed in both prefrontal lobes; however, the rate of compensation was slower on the affected side. The CPT may be helpful in the clinical diagnosis of PSCI with RHD. It may therefore be used to evaluate the effectiveness of cognitive interventions.

Altered neurovascular coupling in patients with vascular cognitive impairment: a combined ASL-fMRI analysis.

This study aims to examine the role of neurovascular coupling (NVC) in vascular cognitive impairment (VCI) by investigating the relationship between white matter lesion (WML) burden, NVC, and cognitive deficits. Additionally, we aim to explore the potential of NVC as a tool for understanding the neural mechanisms underlying VCI. This study included thirty-eight small vessel disease cognitive impairment (SVCI) patients, 34 post-stroke cognitive impairment (PSCI) patients, and 43 healthy controls (HC). Comprehensive assessments, including neuroimaging and neuropsychological testing, were conducted to evaluate cognitive function. WML burden was measured and correlated with NVC coefficients to examine the relationship between white matter pathology and NVC. Mediation analysis was employed to explore the link relationship between NVC, WML burden, and cognitive function. The present study showed that NVC was significantly reduced in the SVCI and PSCI groups compared with HCs at both whole-brain and brain region level. The analysis revealed notable findings regarding NVC in relation to WML burden and cognitive function in VCI patients. Specifically, reduced NVC coefficients were observed within higher order brain systems responsible for cognitive control and emotion regulation. Mediation analysis demonstrated that NVC played a mediating role in the relationship between WML burden and cognitive impairment. This study reveals the mediating role of NVC in the relationship between WML burden and cognitive function in VCI patients. The results demonstrate the potential of the NVC as an accurate measure of cognitive impairment and its ability to identify specific neural circuits affected by WML burden.

The effects and mechanisms of acupuncture for post-stroke cognitive impairment: progress and prospects.

Stroke is one of the important causes of both disability and death worldwide, which is very common in older adults. Post-stroke cognitive impairment (PSCI) is a common secondary damage of stroke, which is the main cause of long-term disability and decreased quality of life in stroke patients, which brings a heavy burden to society and families. Acupuncture, as one of the oldest and widely used worldwide techniques in Chinese medicine, is recommended by the World Health Organization (WHO) as an alternative and complementary strategy for improving stroke care. This review comprehensively summarizes literature from the last 25 years, showing that acupuncture can exert strong beneficial effect on PSCI. The mechanisms of acupuncture on PSCI involves anti-neuronal apoptosis, promoting synaptic plasticity, alleviating central and peripheral inflammatory reactions, and regulating brain energy metabolism disorders (including improving cerebral blood flow, glucose utilization and mitochondrial structure and function, etc.), etc. The effects and mechanisms of acupuncture on PSCI reviewed in this study provides scientific and reliable evidence for acupuncture application for PSCI.

Association of Temporalis Muscle Mass with Early Cognitive Impairment in Older Patients with Acute Ischemic Stroke.

The prognostic value of temporal muscle mass has been studied in various neurological disorders. Herein, we investigated the association between temporal muscle mass and early cognitive function in patients with acute ischemic stroke. This study included 126 patients with acute cerebral infarction aged ≥65 years. Temporal muscle thickness (TMT) was measured using T2-weighted brain magnetic resonance imaging at admission for acute stroke. Within 2 weeks of stroke onset, skeletal mass index (SMI) and cognitive function were assessed using bioelectrical impedance analysis and the Korean version of the Montreal Cognitive Assessment (MoCA), respectively. Pearson's correlation analyzed the correlation between TMT and SMI, and multiple linear regression analyzed independent predictors of early post-stroke cognitive function. TMT and SMI were significantly positively correlated (R = 0.36, p < 0.001). After adjusting for covariates, TMT was an independent predictor of early post-stroke cognitive function, stratified by the MoCA score (β = 1.040, p = 0.017), age (β = -0.27, p = 0.006), stroke severity (β = -0.298, p = 0.007), and education level (β = 0.38, p = 0.008). TMT may be used as a surrogate marker for evaluating skeletal muscle mass because it is significantly associated with post-stroke cognitive function during the acute phase of ischemic stroke; therefore, TMT may help detect older patients at a high risk of early post-stroke cognitive impairment.

New insights into the roles of oligodendrocytes regulation in ischemic stroke recovery

Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths.

Multivariate logistic regression analysis of clinical characteristics and risk factors of cognitive impairment after cerebral ischemic stroke: implications for clinical treatment.

Stroke ranks first among disease fatalities, and those who do survive stroke are prone to cognitive impairment. The aim of this study was to explore the clinical characteristics of post stroke cognitive impairment (PSCI) and the risk factors of PSCI using multivariate logistic regression. January 2018 to January 2021, the clinical data of 120 patients treated for cerebral ischemic stroke (CIS) at Chengde Central Hospital were retrospectively analyzed. In this study, patients were divided into 2 groups: a control group and a cognitive impairment group. The clinical characteristics of cognitive impairment following CIS were determined using multivariate logistic regression analysis to examine the risk factors and identify clinical implications. This study included the assessment of overall cognitive function and daily living activities of 120 participants, 68 of whom experienced cognitive impairment, representing an incidence of 57%, while 43% patients represented no cognitive impairment after CIS. After the careful analysis of the data, there were remarkable differences in age, sex, education level, stroke history, infarction area, and infarction location (P<0.05). There was no remarkable difference in the history of hypertension, diabetes, atrial fibrillation, carotid intima thickness, smoking, or drinking (P>0.05). The degree of white matter degeneration, brain atrophy, and dominant hemisphere involvement was higher in the cognitive impairment group (P<0.05). The results of multivariate logistic regression analysis indicated that sex, age, education level, stroke history, infarction size, and infarction location were the main risk factors for cognitive impairment after CIS (P<0.05). Patients with cognitive impairment after CIS have imaging features of white matter degeneration, brain atrophy, and involvement of dominant hemispheres. The results of multivariate logistic regression analysis indicated that sex, age, education level, stroke history, infarct size, and infarct location were main risk factors of cognitive impairment after CIS.

Incidence and risk factors of post-stroke cognitive impairment in convalescent elderly patients with first-episode acute ischemic stroke.

A total of 350 first-time AIS elderly patients (aged ≥60 years) were collected and analyzed. Multivariate Logistic regression analysis showed that the lesion site, frontal temporal, cerebral white matter degeneration, age ≥75 years, BMI ≥28, onset in autumn/winter, hospitalization expenses >20,000 yuan/month, high DBPV, high NIHSS score, and high HAMD score were risk factors for PSCI. Higher education level was a protective factor. In conclusion, the incidence of PSCI in elderly AIS patients was relatively high and related to the several factors, which indicated that more attention should be paid for such patients to prevent PSCI.

Research trends and hotspots of post-stroke cognitive impairment: a bibliometric analysis.

Background: Post-stroke cognitive impairment (PSCI) is a major complication of stroke that affects more than one-third of stroke survivors, threatening their quality of life and increasing the risk of disability and death. Although various studies have described the etiology, epidemiology, and risk factors of PSCI, there are a limited number of comprehensive and accurate reports on research trends and hotspots in this field. Therefore, this review aimed to evaluate research trends, hotspots, and frontiers in PSCI using bibliometric analysis. Methods: We screened the literature spanning 20 years in the Web of Science Core Collection: Science Citation Index Expanded (SCI-Expanded) database from 1 January 2003 to 31 December 2022. We included all eligible literature reports based on our comprehensive search strategy, inclusion criteria, and exclusion criteria. The analysis of annual publications, countries/regions, institutions, journals, co-cited references, and keywords was conducted using CiteSpace and VOSviewer, and the hotspots and major findings of PSCI were summarized. Results: A total of 1,024 publications were included in this review. We found that the number of publications on PSCI increased annually. These publications were published in 75 countries or regions by over 400 institutions. Although Chinese institutions had the highest number of publications, their international influence was limited. The United States showed a strong influence in the field. The journal "Stroke" published the most publications (57) with a high impact factor and was considered the most co-cited journal. The most frequently cited references focused on the prevalence, incidence, neuropsychological assessment scales, criteria, and guidelines of PSCI. The strongest citation burst keywords for PSCI were "neurotrophic factor" and "synaptic plasticity", which were regarded as research focuses and research hotspots, respectively. Conclusion: This review provided a comprehensive summary of the literature of PSCI, identified the authoritative and frequently cited literature and journals, clarified the trends in PSCI research, and highlighted the hotspots in this field. Currently, studies on the mechanisms and treatment of PSCI are limited, and we hope that this review has effectively highlighted the research trajectory of PSCI and will lay the foundation for more innovative research in the future.

Does resveratrol improve cognition in humans? A scientometric study to an in-depth review.

In order to understand the different processes and mechanisms of cognitive function and resveratrol (RES) as an active participant in pathophysiological events that affect cognitive function. First, the Web of Science (core collection) was selected as the data source. To ensure the comprehensiveness and accuracy of the search data, the index was selected as "SCI-EXPANDED", and the search formula was TS = resveratrol AND TS = ("cognitive" OR "memory" OR "cognition" OR "mood"). Next, details of authors, keywords, journals, countries, institutions, references, and more were analyzed by CiteSpace and VOSviewer software. Finally, we explored the mechanism by which RES could improve cognitive impairment, that involves healthy young adults, healthy elderly, post-menopausal women, and diseases involving Alzheimer's disease (AD), diabetes-related cognitive impairment, mental illness, post-stroke cognitive impairment, and neonatal hypoxic-ischemic injury. 287 valid papers were obtained. The scientometric results demonstrated 287 papers used in this study came from 1601 authors from 443 organizations in 38 countries, published in 169 journals, and cited 13,680 literatures from 2431 journals. Depression, AD, cerebral ischemia, diabetic cognitive impairment, and cognitive function in the elderly are all keywords of the co-occurrence network. This study supports the hypothesis that chronic RES intake may positively affect brain function. But it has become challenging to determine the optimal dose, time and duration of RES and improve the bioavailability of RES, which many researchers need to overcome.

Stimulation of Angiotensin II Type 2 Receptor Modulates Pro-Inflammatory Response in Microglia and Macrophages: Therapeutic Implications for the Treatment of Stroke.

Sustained microglial activation contributes to the development of post-stroke cognitive impairment (PSCI). Compound 21 (C21), an angiotensin II type 2 receptor agonist, has shown some neurovascular protection after stroke. This study aimed to investigate the direct anti-inflammatory effects of C21 on macrophages, as well as brain innate immune cells. Murine microglial cell line (C8-B4) and RAW 264.7 macrophages were exposed to lipopolysaccharide (LPS) and co-treated with C21. Pro-inflammatory mediators were assessed via RT-qPCR and ELISA. Cellular reactive oxygen species (ROS) were evaluated via CellROXGreen staining, and nitrate production was assessed using Griess assay. C21 suppressed LPS-induced inflammation and ROS generation in both cells. In microglia, C21 blunted LPS-induced mRNA expression of IL-1β, IL-12b, COX-1, iNOS, and IL-6. A similar pattern was observed in macrophages, where C21 suppressed LPS-induced IL-1β, TNF-α, and CXCL1 expression. These anti-inflammatory effects in microglia and macrophages were associated with increased neuroprotective gene expression, including GDNF and BDNF, in a dose-dependent manner. Our findings suggest a protective effect of C21 against the inflammatory response, in both macrophages and microglia, via suppression of the release of pro-inflammatory cytokines/chemokines and the generation of ROS while stimulating the production of neurotrophic factors.

The use of enhanced intrinsic feedback for motor learning in stroke survivors: Clinical trial protocol

BackgroundStroke can lead to lasting sensorimotor deficits of the upper limb (UL) persisting into the chronic phase despite intensive rehabilitation. A major impairment of reaching after stroke is a decreased range of active elbow extension, which in turn leads to the use of compensatory movements. Retraining movement patterns relies on cognition and motor learning principles. Implicit learning may lead to better outcomes than explicit learning. Error augmentation (EA) is a feedback modality based on implicit learning resulting in improved precision and speed of UL reaching movements in people with stroke. However, accompanying changes in UL joint movement patterns have not been investigated. The objective of this study is to determine the capacity for implicit motor learning in people with chronic stroke and how this capacity is affected by post-stroke cognitive impairments. MethodsFifty-two subjects who have chronic stroke will practice reaching movements 3×/wk. for 9 wk. in a virtual reality environment. Participants will be randomly allocated to 1 of 2 groups to train with or without EA feedback. Outcome measures (pre-, post- and follow-up) will be: endpoint precision, speed, smoothness, and straightness and joint (UL and trunk) kinematics during a functional reaching task. The degree of cognitive impairment, lesion profile, and integrity of descending white matter tracts will be related to training outcomes. ConclusionsThe results will inform us which patients can best benefit from training programs that rely on motor learning and utilize enhanced feedback.Trial status: Ethical approval for this study was finalized in May 2022. Recruitment and data collection is actively in progress and is planned to finish in 2026. Data analysis and evaluation will occur subsequently, and the final results will be published.

Early post-stroke cognitive impairment and in-hospital predicting factors among stroke survivors in Ethiopia.

In low-and middle-income countries, post-stroke cognitive impairment (PSCI) is the least investigated stroke complication that clinically is given little attention. Finding patients who are at high risk of having cognitive problems after a stroke could allow targeted follow-up and help with prognosis discussions, which would then contribute to improved treatment outcomes. The main aim of this study was to determine the incidence and predictors of PSCI among stroke survivors in Northwest Ethiopia. The study was a multicenter prospective cohort study. The study participants were 403 stroke survivors who were alive on follow-up after 3 months of stroke onset at the neurology department of three hospitals in Northwest Ethiopia. To investigate the link between the outcome and the explanatory variables, analyses of bivariable and logistic multivariable regression were performed. A value of p of 0.05 or less was regarded as statistically significant, and data were presented as odds ratios and 95% confidence intervals. The mean age of the participants was 61.3 years (SD = 0.7), 56% were females, the mean time from symptom onset to hospital arrival was 46 h (SD = 3.32), and the mean National Institute of Health Stroke Scale (NIHSS) score at admission was 14.79 (SD = 0.25). PSCI was observed in 122 patients (30.3%) after 90 days of stroke onset, that is, 83 (20.6%) of female and 39 (9.7%) of male stroke survivors. The result of multivariable logistic regression analysis revealed PSCI was independently associated with age (adjusted OR = 1.04, 95% CI = 1.061-1.981), women (AOR = 1.390, 95% CI = 1.221-2.690), admission modified Rankin scale (mRS) (AOR = 1.629, 95% CI = 1.381-2.037), moderate Glasgow coma scale (GCS) score (AOR = 1.149, 95% CI = 1.402-3.281), and poor GCS score (AOR = 1.632, 95% CI = 1.610-4.361) and stage one (AOR = 1.428, 95% CI = 1.198-2.922) and stage two hypertension (AOR = 1.255, 95% CI = 1.107-2.609). Nearly one-third of stroke survivors developed PSCI. Moreover, further research is needed with a larger sample size, showing a time trend and longer follow-up duration.

Plasma exosome proteomics reveals the pathogenesis mechanism of post-stroke cognitive impairment.

Exploration and utilization of exosome biomarkers and their related functions provide the possibility for the diagnosis and treatment of post-stroke cognitive impairment (PSCI). To identify the new diagnostic and prognostic biomarkers of plasma exosome were uzed label-free quantitative proteomics and biological information analysis in PSCI patients. Behavioral assessments were performed, including the Mini-Mental Status Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Barthel index, the Morse Fall Seale (MFS) between control group (n = 10) and PSCI group (n = 10). The blood samples were collected to analyse the biomarker and differentially expressed proteins of plasma exosome using label-free quantitative proteomics and biological information. The exosomes marker proteins were determined by Western blot. The exosome morphology was observed by transmission electron microscopy. The scores of MMSE and MoCA were significantly decreased in the PSCI group. The PT% and high-density lipoprotein decreased and the INR ratio increased in PSCI group. The mean size of exosome was approximately 71.6 nm and the concentration was approximately 6.8E+7 particles/mL. Exosome proteomics identified 259 differentially expressed proteins. The mechanisms of cognitive impairment are related to regulate the degradation of ubiquitinated proteins, calcium dependent protein binding, cell adhesive protein binding, formation of fibrin clot, lipid metabolism and ATP-dependent degradation of ubiquitinated proteins in plasma exosome of PSCI patients. Plasma levels of YWHAZ and BAIAP2 were significantly increased while that of IGHD, ABCB6 and HSPD1 were significantly decreased in PSCI patients. These proteins might be target-related proteins and provide global insights into pathogenesis mechanisms of PSCI at plasma exosome proteins level.

The analysis of brain functional connectivity of post-stroke cognitive impairment patients: an fNIRS study.

Post-stroke cognitive impairment (PSCI) is a considerable risk factor for developing dementia and reoccurrence of stroke. Understanding the neural mechanisms of cognitive impairment after stroke can facilitate early identification and intervention. Using functional near-infrared spectroscopy (fNRIS), the present study aimed to examine whether resting-state functional connectivity (FC) of brain networks differs in patients with PSCI, patients with Non-PSCI (NPSCI), and healthy controls (HCs), and whether these features could be used for clinical diagnosis of PSCI. The present study recruited 16 HCs and 32 post-stroke patients. Based on the diagnostic criteria of PSCI, post-stroke patients were divided to the PSCI or NPSCI group. All participants underwent a 6-min resting-state fNRIS test to measure the hemodynamic responses from regions of interests (ROIs) that were primarily distributed in the prefrontal, somatosensory, and motor cortices. The results showed that, when compared to the HC group, the PSCI group exhibited significantly decreased interhemispheric FC and intra-right hemispheric FC. ROI analyses showed significantly decreased FC among the regions of somatosensory cortex, dorsolateral prefrontal cortex, and medial prefrontal cortex for the PSCI group than for the HC group. However, no significant difference was found in the FC between the PSCI and the NPSCI groups. Our findings provide evidence for compromised interhemispheric and intra-right hemispheric functional connectivity in patients with PSCI, suggesting that fNIRS is a promising approach to investigate the effects of stroke on functional connectivity of brain networks.

Cognitive Impairment After Ischemic and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association/American Stroke Association.

Cognitive impairment is a common consequence of stroke and has direct implications for poststroke functioning and quality of life, including the ability to maintain a job, live independently, sustain interpersonal relationships, and drive a vehicle. In this scientific statement, we critically appraise the literature on the prevalence, diagnosis, and management of poststroke cognitive impairment (PSCI) and provide a framework for clinical care while highlighting gaps that merit further study. We performed a scoping literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case-control studies, clinical guidelines, review articles, and editorials on the incidence and prevalence, natural history, diagnosis, and management of PSCI. Scoping reviews determine the scope of a body of literature on a given topic to indicate the volume of literature and the studies currently available and provide an overview of its focus. PSCI is common after stroke, especially in the first year, and ranges from mild to severe. Although cognitive impairment is reversible in some cases early after stroke, up to one-third of individuals with stroke develop dementia within 5 years. The pathophysiology is not yet fully elucidated but is likely attributable to an acute stroke precipitating a series of pathological events, often in the setting of preexisting microvascular and neurodegenerative changes. Screening for associated comorbidities and interdisciplinary management are integral components of the care of individuals with PSCI. There is a need for prospective studies evaluating the individual trajectory of PSCI and the role of the acute vascular event in the predisposition for Alzheimer disease and related dementias, as well as high-quality, randomized clinical trials focused on PSCI management.

Clinical Features, Brain-Structure Changes, and Cognitive Impairment in Basal Ganglia Infarcts: A Pilot Study.

Stroke has been considered to raise the risk of dementia in several studies, but the relationship between brain structural changes and poststroke cognitive impairment (PSCI) is unclear. In this study, 23 PSCI patients with basal ganglia infarcts after 2 weeks and 29 age-matched controls underwent magnetic resonance imaging measuring cortical thickness and volume changes, as well as neuropsychological tests. CI was derived from a performance score <1.5 standard deviations for normally distributed scores. We compared Z scores in different cognitive domains and cortical thickness and volumes in two groups. Multiple linear regressions were used to investigate the relationship between cortical thickness and volumes and neuropsychological tests. A majority of PSCI patients were in their 50s (55.19±8.52 years). PSCI patients exhibited significantly decreased Z scores in multiple domains, such as memory, language, visuomotor speed, and attention/executive function. The volumes of the middle posterior corpus callosum, middle anterior corpus callosum, and hippocampus in PSCI patients were markedly lower than controls. The thickness of the right inferior temporal cortex and insula were significantly smaller than controls. It found that the reduced right hippocampus was related to executive dysfunction. Hippocampus dysfunction may be involved in language impairment (p<0.05) in PSCI patients with basal ganglia infarcts. These findings demonstrated that brain structure changed after ischemic stroke, and different gray-matter structural changes could lead to specific cognitive decline in PSCI patients with basal ganglia infarcts. Atrophy of the right hippocampus potentially serves as an imaging marker of early executive function of PSCI.

Inhibition of Ferroptosis in the Subacute Phase of Ischemic Stroke Worsens Aversive Learning In Diabetic Rats: A Randomized Double-Blind Preclinical Trial

Diabetes increases the risk of hemorrhagic transformation as well as post-stroke cognitive impairment (PCSI). We have shown that iron chelation in the subacute phase improves stroke cognitive outcomes in experimental models of diabetes. We hypothesized that inhibition of ferroptosis, iron-induced cell death, in the post-stroke period will prevent PSCI in diabetic animals. Methods: Male rats, housed in reverse light cycle, underwent sham or 60-min middle cerebral artery occlusion surgery 8 weeks after diabetes onset. After MRI, rats that met the preset inclusion criteria (adhesive removal time &gt; 35 sec. and either a modified Bederson score &lt;= 6 or weight loss &gt; 10% on Day 3) were randomized to ferroptosis inhibitor UAMC-3 (2mg/kg) or vehicle treatment for 2 weeks (n=8-12). Sensorimotor and cognitive outcomes were monitored for 8 weeks in the dark (active) cycle. Results: As confirmed by MRI, inclusion criteria predicted successful stroke surgery in 95% of the animals. There were significant acute neurological deficits. Long-term weight gain and survival were better in this cohort as compared to our historical data collected in regular light cycle experiments. Blood glucose levels were comparable. In contrast to our previous data, there were no significant differences in indices measured by novel object recognition (NOR), Y-maze, and sucrose preference tests after stroke but there was a trend for a greater number of animals showing a cognitive decline in treated cohorts. Step-through latency in the passive avoidance test (PAT) was lower in the treated stroke group. Open field (OF) suggested anxiety-like behavior in RX group. Conclusions: Preset inclusion criteria were effective in controlling for stroke severity. Ferroptosis inhibition impaired aversive learning and appeared to worsen cognitive outcomes in some of the animals. Better post-stroke weight gain/maintenance and greater engagement of animals in behavioral tests conducted in the “dark” cycle may explain the lack of a progressive memory decline after stroke. While further studies are required to better understand whether ferroptosis and housing lighting impacts stroke recovery in diabetes, based on current findings, inhibition of ferroptosis with UAMC-3 is not desirable. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.