Post-stroke Cognitive Decline Research Articles

Predictors of Poststroke Cognitive Decline among Stroke Survivors in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Stroke is a devastating medical disorder associated with significant morbidity and mortality among adults and the elderly worldwide. Although numerous primary studies have been conducted to determine the pooled predictors of poststroke cognitive decline among stroke survivors in Sub-Saharan Africa, these studies presented inconsistent findings. Hence, the review aimed to determine the pooled predictors of poststroke cognitive decline among stroke survivors in Sub-Saharan Africa. The eligible studies were accessed through Google Scholar, Scopus, PubMed, and Web of Science databases. A manual search of the reference lists of included studies was performed. A weighted inverse-variance random-effects model was used to determine the pooled predictors of poststroke cognitive decline among stroke survivors in Sub-Saharan Africa. A total of 1,710 stroke survivors from 10 primary studies were included in the final meta-analysis. Increased age (≥45 years) (adjusted odds ratio [AOR] = 1.32, 95% CI: 1.13, 1.54), lower educational level (AOR = 4.58, 95% CI: 2.98, 7.03), poor functional recovery (AOR = 1.75, 95% CI: 1.42, 2.15), and left hemisphere stroke (AOR = 4.88, 95% CI: 2.98, 7.99) were significantly associated with poststroke cognitive decline. Increased age, lower educational level, poor functional recovery, and left hemisphere stroke were the pooled independent predictors of poststroke cognitive decline in Sub-Saharan Africa Healthcare providers, and other concerned bodies should give attention to these risk factors as the early identification may help to improve the cognitive profile of stroke survivors.

ZOom Delivered Intervention Against Cognitive decline (ZODIAC) COVID-19 pandemic adaptations to the Post-Ischaemic Stroke Cardiovascular Exercise Study (PISCES): protocol for a randomised controlled trial of remotely delivered fitness training for brain health

BackgroundStroke increases subsequent dementia risk yet there are no specific post-stroke therapies to protect cognition. Cardiorespiratory exercise is recommended for secondary prevention of stroke and may be neuroprotective. The Post Ischaemic Stroke Cardiovascular Exercise Study (PISCES) aims to reduce post-stroke secondary neurodegeneration and cognitive decline. During the pandemic, we pivoted to a ZOom Delivered Intervention Against Cognitive decline (ZODIAC) protocol, reducing pandemic-amplified barriers to exercise.MethodsWe present pandemic adaptions for a multicentre phase IIb assessor-blinded randomised controlled trial of ischaemic stroke survivors testing the efficacy and feasibility of an 8-week home-based exercise intervention delivered at 2 months post-stroke. We compare cardiorespiratory exercise (intervention arm) versus balance and stretching (active control arm). Participants are assessed with magnetic resonance imaging (MRI), fitness, blood, microbiome, and neuropsychological tests at three study visits: before and after the exercise intervention and at 12 months. Modifications to the original protocol include pre-exercise safety home visits, commercial delivery of exercise equipment to facilitate assessor blinding, and reconsideration of statistical plan to allow pooling of the studies. We have reduced in-person study visits from 27 to 3. Primary outcome remains between-group (intervention versus control) difference in brain volume change; secondary outcome is between-group difference in global cognitive ability to allow remote administration of a validated cognitive scale.DiscussionRemotely delivered exercise interventions reduce participant burden and may reduce barriers to recruitment. A decrease in the number of in-person study visits can be supported by greater information capture via self-reported questionnaires and phone surveys.Trial registrationProspectively ACTRN12616000942459. Registered on July 2016.

Associations Between Stroke Type, Ischemic Stroke Subtypes, and Post-Stroke Cognitive Trajectories.

It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline. This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke. On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations. Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

Impact of playful objects on wellbeing, emotions and engagement in patients with dementia and post-stroke cognitive impairment

Stroke is a major public health concern, and finding ways to support the wellbeing and emotional regulation of stroke patients with post-stroke cognitive decline or dementia is vitally important. HUG™ was developed to be used as a psychosocial intervention to reduce anxiety and provide comfort and pleasure to those with cognitive impairment. The aim of the ludic artefacts using gesture and haptics evaluation and making playful objects for wellbeing, emotional regulation and engagement for dementia post-stroke cognitive impairment (LAUGH EMPOWERED PSCI) study, a 2-year collaborative project between the NHS and Sunrise Senior Living, is to improve the lives of older people living with advanced stages of dementia and those living with post-stroke cognitive impairment (PSCI). Post-intervention qualitative data were gathered from NHS health professionals (n=20) via a series of interviews. A qualitative interpretive grounded practical theory methodology underpinned by a ‘compassionate design’ approach was used to analyse qualitative interviews. Two key themes were identified: evidence of improvement in patient care, and difficulties and negative responses to using HUG™ (patient and staff), with respective sub-themes also identified. Findings from this study reveal that HUG™ can be used successfully in a hospital context to improve patient wellbeing and reduce anxiety. Although not every patient who received a HUG™ responded positively, the device did have a significant positive impact on the quality of life and care of those who did. It is clear from this research that, although HUG™ is not the right solution for every patient, it is a useful alternative to prescribed medication for some patients who are anxious and distressed.

Risk factors and predictive markers of post-stroke cognitive decline-A mini review.

Stroke is one of the top causes of death and disability worldwide. Cognitive impairments are found in more than 70% of individuals who have survived a stroke. Cognitive decline is a major contributor to disability, dependency, and morbidity. The prevalence and severity of dementia vary depending on different characteristics of the stroke and other clinical risk factors. Here we discuss the effects of stroke territory, patients' age, sex, cerebral blood flow, acute reperfusion therapy, and cognitive reserve of post-stroke cognitive decline. Potential predictive molecular and genetic biomarkers of post-stroke cognitive impairments are also discussed.

Abstract TP13: Association Between Education Level and Post-Stroke Cognitive Decline - A Pooled Cohort Analysis of Four Cohorts

Introduction: We evaluated whether education level is associated with post-stroke cognitive decline and whether age modifies the association. Methods: We analyzed pooled data from 2,019 stroke survivors from the Atherosclerosis Risk in Communities, REasons for Geographic and Racial Differences in Stroke, Cardiovascular Health, and Framingham Offspring studies from 1971-2019. Participants ≥18 years with incident stroke and free of dementia were included (52% female and 39% Black). Repeated cognitive tests were administered in person or by telephone by trained cohort staff. Linear mixed-effects models were used to examine the association between education (less than high school, completed high school, some college, college graduate or more) and post-stroke cognitive decline for global cognition (primary outcome), executive function, and memory harmonized across cohorts and to examine effect modification by age. Median (IQR) follow-up was 4.1 (1.8, 7.2) years. Results: Compared to those with less than a high school education (n=339), stroke survivors with some college education (n=484) and stroke survivors with a college degree or more (n=583) had higher first post-stroke cognitive scores (Models M1a, M1b, and M1c, Table). Having some college education was associated with slower post-stroke decline in global cognition (Model M1a) compared to those with less than a high school education. Having some college education or a college degree was associated with faster post-stroke decline in executive function (Model M1b, Table) compared to those with less than a high school education. Significant interactions by age were lacking for all outcomes. Conclusions: Higher education level was associated with higher initial post-stroke cognitive scores, slower decline in global cognition, and faster decline in executive function, regardless of age. Stroke might narrow the gap in executive function between stroke survivors with higher and lower education.

Abstract 72: Association Between Stroke Subtype and Post-Stroke Cognitive Decline: A Pooled Cohort Analysis of Four Cohorts

Introduction: Associations between stroke subtype and post-stroke cognitive decline are unclear. We determined if post-stroke cognitive trajectories differed between 1) hemorrhagic vs. ischemic stroke and 2) ischemic stroke subtypes. Methods: We identified 1,150 eligible dementia-free individuals with incident stroke (93% ischemic, 7% hemorrhagic, 50% women, 31% Black, median age, 65) from 4 cohort studies from 1971-2019: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Offspring Study, and Reasons for Geographic and Racial Differences in Stroke. Of the ischemic strokes, 22% were small-vessel occlusion, 8% large artery atherosclerosis, 21% cardioembolic, and 49% cryptogenic/other determined etiology. Linear mixed-effects models were used to estimate longitudinal changes in cognition after incident stroke. Global cognition (primary outcome), executive function, and memory were harmonized across studies and standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median (IQR) follow-up was 5.9 (3.2, 9.2) years. Results: Survivors of ischemic stroke had significant declines in global cognition, executive function, and memory (Table). For example, global cognition declined -0.35 points/year (95%CI, -0.43, -0.26); P <0.001. Initial post-stroke cognitive scores and post-stroke cognitive trajectories did not differ between hemorrhagic and ischemic stroke, except for lower initial post-stroke memory scores (adjusted difference, -1.39 points; 95% CI, -2.77, -0.01; P =0.049). Survivors of small-vessel occlusions had significant declines in global cognition, executive function, and memory (Table). Initial post-stroke cognitive scores and post-stroke cognitive trajectories did not differ by ischemic stroke subtype. Conclusions: Our results suggest that stroke survivors experience long-term post-stroke cognitive decline regardless of subtype.

Abstract 73: Wallerian Axon Degeneration is Required for Chronic Neuroinflammation and Infarct-Induced Neurodegeneration

Background: Ischemic stroke triggers a chronic B-lymphocyte response in the stroke core that is required for delayed post-stroke cognitive decline in mice. Because immune cells primarily infiltrate into connected subcortical axonal tracts after stroke, we hypothesized that degenerating axons promulgate a persistent neuroinflammation that is critical for late cognitive decline. To test this, we utilized mice deficient in Sarm1 ( Sarm1-/-), a molecular trigger of axon degeneration and the loss of which leads to axonal protection after injury. Methods: Wildtype and Sarm1-/- male mice (N=9 per condition) underwent distal MCA stroke followed by transient hypoxia, which reliably leads to infarct-induced neurodegeneration 7 weeks after injury. Innate (monocytes) and adaptive (T, B lymphocytes) immune cell infiltration were evaluated via immunohistochemistry 1 & 7 weeks after stroke. Cognition was assessed using the Barnes maze at both time points after stroke. Results: Absence of Sarm1 resulted in robust axonal protection after ischemic stroke. In connected thalamic region, mean immunostained intensity of axons was 166 in wildtype vs. 267 in Sarm1-/- (p < 0.005) 1 week, and 106 vs. 201 (p < 0.005) 7 weeks after stroke. Compared to wildtype mice, Sarm1-/- mice had an attenuated innate immune response in connected subcortical white matter 1 week after stroke (% area of CD68+ reactivity was 35 ± 5% in WT vs. 19 ± 4% in Sarm1-/- (p < 0.01), while peri-infarct CD68 was not different. Moreover, loss of Sarm1 reduced B220+ B-cell infiltration into the infarct 7 weeks after stroke. Percent area of B220+ reactivity was 30 ± 8% in WT vs 15 ± 7% in Sarm1-/- (p <0.05). Compared to wildtype littermates, Sarm1-/- mice were resistant to chronic post-stroke cognitive decline on the Barnes maze. There was no difference in cognition between cohorts 1 week after stroke but there was at 7 weeks. The mean escape latency was 97 ± 11 sec in wildtype vs 57 ± 9 sec in Sarm1-/ - mice (P<0.05). Conclusion: We report that Sarm1 -mediated axonal degeneration is critical for chronic neuroinflammation and delayed cognitive decline after ischemic stroke. Directly targeting axon degeneration by modulating Sarm1 activity provides a novel therapeutic approach to ameliorate infarct-induced neurodegeneration.

Poststroke Cognitive Decline: Is Functional Connectivity the Key to Tangible Therapeutic Targets?

Poststroke Cognitive Decline: Is Functional Connectivity the Key to Tangible Therapeutic Targets?

Effects of Oxiracetam and Physical Activity in Preventing Post-Stroke Cognitive Decline: A Randomized Controlled Trial

Effects of Oxiracetam and Physical Activity in Preventing Post-Stroke Cognitive Decline: A Randomized Controlled Trial

Abstract 15908: A Meta-Analysis Revealing an Association Between High Sensitivity C-Reactive Protein Levels and Cognitive Impairment After 3-Months of Ischemic Stroke

Introduction: Cognitive impairment has a significant impact on functional recovery and quality of life in stroke patients. Given the emerging role of high sensitivity C-reactive protein (hs-CRP) as a biomarker for predicting post-stroke cognitive decline, we conducted a meta-analysis to investigate this association. Methods: We systematically searched SCOPUS, PubMed, and Google Scholar databases until May 2023 using relevant keywords. Pooled effect sizes were estimated using a random-effects model, and I2 statistics and leave-one-out sensitivity analysis were performed to assess heterogeneity and robustness, respectively (p-value < 0.05 considered significant). Results: The final analysis included five studies spanning the years 2018-2023, with a total sample size of 9,625 patients, all from China, and predominantly male (57.85%). The median follow-up period was 3 months. Patients with higher hs-CRP levels had a higher burden of smoking, alcohol consumption, hypertension, diabetes, hyperlipidemia, and lower education levels. The meta-analysis revealed an increased risk of cognitive impairment after ischemic stroke associated with higher hs-CRP levels (adjusted odds ratio [aOR] 1.15; 95% CI: 1.01-1.30, p - 0.03). Substantial heterogeneity was observed among the studies (I2 = 79.23%; p < 0.01). However, a leave-one-out sensitivity analysis confirmed the robustness of the findings, indicating that no single study strongly influenced the overall results. Conclusion: This meta-analysis provides evidence of an association between elevated hs-CRP levels and cognitive impairment following ischemic stroke. However, the limited number of studies, mainly from a specific population, highlights the need for further research to enhance the generalizability of these findings.

Hospital-Acquired Infection at Time of Stroke and Cognitive Decline: The Cardiovascular Health Study

Introduction: Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke. Methods: We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged ≥65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by the Modified Mini-Mental State Examination (3MSE) and executive function by the Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors. Results: Among 5,443 participants ≥65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95% CI: −0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95% CI: 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95% CI: −0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year [95% CI: 0.003, 0.33]), as did SI participants (additional 0.27 points/year [95% CI: 0.19, 0.35]). Conclusion: Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention.

Genetic Variations and Altered Blood mRNA Level of Circadian Genes and BDNF as Risk Factors of Post-Stroke Cognitive Impairment Among Eastern Indians.

Post-stroke cognitive impairment (PSCI) is a clinical outcome in around 30% of post-stroke survivors. BDNF is a major gene in this regard. It is regulated by circadian rhythm. The circadian genes are correlated with stroke timings at molecular level. However, studies suggesting the role of these on susceptibility to PSCI are limited. We aim here to determine: (a) genetic risk variants in circadian clock genes, BDNF and (b) dysregulation in expression level of CLOCK, BMAL1, and BDNF that may be associated with PSCI. BDNF (rs6265G/A, rs56164415C/T), CLOCK (rs1801260T/C, rs4580704G/C), and CRY2 (rs2292912C/G) genes variants were genotyped among 119 post-stroke survivors and 292 controls from Eastern part of India. In addition, we analyzed their gene expression in Peripheral blood Mononuclear cells (PBMC) from 15 PSCI cases and 12 controls. The mRNA data for BDNF was further validated by its plasma level through ELISA (n = 38). Among the studied variants, only rs4580704/CLOCK showed an overall association with PSCI (P = 0.001) and lower Bengali Mini-Mental State Examination (BMSE) score. Its 'C' allele showed a correlation with attention deficiency. The language and memory impairments showed association with rs6265/BDNF, while the 'CC' genotype of rs2292912/CRY2 negatively influenced language and executive function. A significant decrease in gene expression for CLOCK and BDNF in PBMC (influenced by specific genotypes) of PSCI patients was observed than controls. Unlike Pro-BDNF, plasma-level mBDNF was also lower in them. Our results suggest the genetic variants in CLOCK, CRY2, and BDNF as risk factors for PSCI among eastern Indians. At the same time, a lowering expression of CLOCK and BDNF genes in PSCI patients than controls describes their transcriptional dysregulation as underlying mechanism for post-stroke cognitive decline.

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-ischemic stroke cognition in rats

Ischemic stroke affects millions of individuals worldwide and a high prevalence of survivors experience cognitive deficits. At present, the underlying mechanisms that drive post-stroke cognitive decline are not well understood. Microglia play a critical role in the post-stroke inflammatory response, but experimental studies show that an accumulation of chronically activated microglia can be harmful and associates with cognitive impairment. This study assessed the effect of acute post-stroke minocycline treatment on chronic microglia and astrocyte expression within the infarct and remote white matter regions, as well as its effect on various domains of cognitive function post-stroke. Nine-month-old male rats received an injection of endothelin-1 into the right dorsal striatum to induce transient focal ischemia, and then were treated with minocycline or saline for 4 days post-stroke. Rats were tested using a series of lever-pressing tasks and the Morris water maze to assess striatal-based learning, cognitive flexibility, and spatial learning and reference memory. We found that minocycline-treated rats had smaller stroke-induced infarcts and less microglia activation in the infarct area and remote white matter regions compared to saline-treated rats at 28 days post-stroke. The behavioural testing results differed according to the cognitive domain; whereas minocycline-treated rats trended towards improved striatal-based learning in a lever-pressing task, but cognitive flexibility was unaffected during the subsequent set-shifting task. Furthermore, minocycline treatment unexpectedly impaired spatial learning, yet it did not alter reference memory. Collectively, we show that post-stroke minocycline treatment can reduce chronic microglia activation even in remote brain regions, with domain-specific effects on cognitive function.

Inflammatory-associated proteomic predictors of cognitive outcome in subjects with ELVO treated by mechanical thrombectomy

BackgroundEmergent Large Vessel Occlusion (ELVO) stroke causes devastating vascular events which can lead to significant cognitive decline and dementia. In the subset of ELVO subjects treated with mechanical thrombectomy (MT) at our institution, we aimed to identify systemic and intracranial proteins predictive of cognitive function at time of discharge and at 90-days. These proteomic biomarkers may serve as prognostic indicators of recovery, as well as potential targets for novel/existing therapeutics to be delivered during the subacute stage of stroke recovery.MethodsAt the University of Kentucky Center for Advanced Translational Stroke Sciences, the BACTRAC tissue registry (clinicaltrials.gov; NCT 03153683) of human biospecimens acquired during ELVO stroke by MT is utilized for research. Clinical data are collected on each enrolled subject who meets inclusion criteria. Blood samples obtained during thrombectomy were sent to Olink Proteomics for proteomic expression values. Montreal Cognitive Assessments (MoCA) were evaluated with categorical variables using ANOVA and t-tests, and continuous variables using Pearson correlations.ResultsThere were n = 52 subjects with discharge MoCA scores and n = 28 subjects with 90-day MoCA scores. Several systemic and intracranial proteins were identified as having significant correlations to discharge MoCA scores as well as 90-day MoCA scores. Highlighted proteins included s-DPP4, CCL11, IGFBP3, DNER, NRP1, MCP1, and COMP.ConclusionWe set out to identify proteomic predictors and potential therapeutic targets related to cognitive outcomes in ELVO subjects undergoing MT. Here, we identify several proteins which predicted MoCA after MT, which may serve as therapeutic targets to lessen post-stroke cognitive decline.

Association of Income with Post-Stroke Cognition and the Underlying Neuroanatomical Mechanism.

To investigate the association between income and post-stroke cognition at 3 months, and the underlying neuroanatomical mechanism. Patients with first-ever ischemic stroke were enrolled and analyzed. Baseline information on income and neuroimaging measurements with predictive values for post-stroke cognitive impairment (PSCI) were collected within 7 days of the admission. Three months after the index stroke, all participants underwent a detailed neuropsychological test battery. The associations between income and PSCI and between income and brain structural measurements were investigated. A total of 294 patients were recruited for this study. Lower income was independently associated with poor cognitive performance on Stroop tests, Clinical Dementia Rating, Boston Naming Test, and Verbal Fluency Test. Regarding neuroimaging parameters, lower income was associated with a lower total brain volume (TBV)/total intracranial volume (TICV) ratio (p = 0.004). Lower income is associated with an increased chance of post-stroke cognitive decline, particularly in executive function and language domains. Since global brain atrophy (measured by TBV/TICV ratio) is a strong predictor for PSCI, its correlation with income may help explain the neuroanatomical mechanism between income and post-stroke cognition.

An observational and cross-sectional study on prevalence of cognitive impairment and short-term changes in cognitive function after ischemic stroke in a tertiary care hospital

Background: Stroke is a leading cause physical and cognitive disability. Aims and Objectives: The aims of this study were to investigate the prevalence and pattern of cognitive impairment (CI) after first-ever ischemic stroke. Materials and Methods: Sixty subjects with first-ever ischemic strokes, confirmed by magnetic resonance imaging (MRI), were selected. Their clinic-diagnostic and comorbidity data were collected. Mini mental state examination (MMSE) was done after 3–7 days on each patient. MRI was used to ascertain the side, vascular territory, extent, and neural tissues (cortical/subcortical) involved. CIs were categorized as normal, mild, and moderate-to-severe according to MMSE scores ≥ 24, 18–23, and 0–17, respectively. Data were summarized as mean±standard deviation (SD) for numerical variables and counts and percentages for categorical variables. Results: (1) Elderly (61–70 years), male and higher educated patients were more prevalent, hypertension (HTN) was the most common comorbidity. (2) Subcortical, middle cerebral artery (MCA), and anterior cerebral artery (ACA) lesions and non-dominant side involvement were common. (3) 80% patients had CI (65% mild and 15% moderate-to-severe). (4) CI was the most common in patients aged 71–80 years, of lower educational status and having both diabetes and HTN. MCA territory strokes and non-dominant side involvement resulted in more moderate/severe CI. (5) Registration followed by recall was least affected whereas language and praxis were more affected domains. Conclusion: Post-stroke cognitive decline is more common in elderly population and patients with lower education. CI is more in people with HTN and DM and in people with MCA territory infarct. Language and praxis were the most affected domain of all.

Longitudinal brain age prediction and cognitive function after stroke

Advanced age is associated with post-stroke cognitive decline. Machine learning based on brain scans can be used to estimate brain age of patients, and the corresponding difference from chronological age, the brain age gap (BAG), has been investigated in a range of clinical conditions, yet not thoroughly in post-stroke neurocognitive disorder (NCD). We aimed to investigate the association between BAG and post-stroke NCD over time. Lower BAG (younger appearing brain compared to chronological age) was found associated with lower risk of post-stroke NCD up to 36 months after stroke, even among those showing no evidence of impairments 3 months after hospital admission. For patients with no NCD at baseline, survival analysis suggested that higher baseline BAG was associated with higher risk of post-stroke NCD at 18 and 36 months. In conclusion, a younger appearing brain is associated with a lower risk of post-stroke NCD.

Post-stroke low-frequency whole-body vibration improves cognition in middle-aged rats of both sexes.

Low-frequency whole-body vibration (WBV; 40 Hz), a low impact form of exercise, intervention for a month following moderate transient middle-cerebral artery occlusion (tMCAO) reduces infarct volume and improves motor function in reproductively senescent, middle-aged female rats. Since post-stroke cognitive decline remains a significant problem, the current study aims to investigate the efficacy of WBV in ameliorating post-tMCAO cognitive deficits and to determine the underlying putative mechanism(s) conferring benefits of WBV in middle-aged rats. Middle-aged rats of both sexes were randomly assigned to tMCAO (90 min) or sham surgery followed by exposure to either WBV (twice a day for 15 min each for 5 days a week over a month) or no WBV treatment groups. Following the last WBV treatment, rats were tested for hippocampus-dependent learning and memory using a water maze followed by harvesting brain and blood samples for histopathological and inflammatory marker analyses, respectively. Results show that post-tMCAO WBV significantly lessens cognitive deficits in rats of both sexes. Post-tMCAO WBV significantly decreased circulating pro-inflammatory cytokines and increased serum levels of irisin, a muscle-derived hormone that may play a role in brain metabolism and inflammation regulation, which suggests putative beneficial mechanisms of WBV.

CD11bhigh B Cells Increase after Stroke and Regulate Microglia.

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed on the basis of expression levels of transcription factors (e.g., T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11bhigh subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11bhigh B cells in immune responses after stroke in young and aged mice. We evaluated the ability of CD11bhigh B cells to influence pro- and anti-inflammatory phenotypes of young and aged microglia (MG). We hypothesized that CD11bhigh B cells accumulate in the brain and contribute to neuroinflammation in aging and after stroke. We found that CD11bhigh B cells are a heterogeneous subpopulation of B cells predominantly present in naive aged mice. Their frequency increases in the brain after stroke in young and aged mice. Importantly, CD11bhigh B cells regulate MG phenotype and increase MG phagocytosis in both ex vivo and in vivo settings, likely by production of regulatory cytokines (e.g., TNF-α). As both APCs and adaptive immune cells with long-term memory function, B cells are uniquely positioned to regulate acute and chronic phases of the post-stroke immune response, and their influence is subset specific.