Risk Of Post-stroke Cognitive Impairment Research Articles

Post-stroke cognitive impairment remains highly prevalent and disabling despite state-of-the-art stroke treatment.

State-of-the-art stroke treatment significantly reduces lesion size and stroke severity, but it remains unclear whether these therapeutic advances have diminished the burden of post-stroke cognitive impairment (PSCI). In a cohort of patients receiving modern state-of-the-art stroke care including endovascular therapy, we assessed the frequency of PSCI and the pattern of domain-specific cognitive deficits, identified risk factors for PSCI, and determined the impact of acute PSCI on stroke outcome. In this prospective monocentric cohort study, we examined patients with first-ever anterior circulation ischemic stroke without pre-stroke cognitive decline, using a comprehensive neuropsychological assessment ⩽10 days after symptom onset. Normative data were stratified by demographic variables. We defined PSCI as at least moderate (<1.5 standard deviation) deficits in ⩾2 cognitive domains. Multivariable regression analysis was applied to define risk factors for PSCI. We analyzed 329 non-aphasic patients admitted from December 2020 to July 2023 (67.2 ± 14.4 years old, 41.3% female, 13.1 ± 2.7 years of education). Although most patients had mild stroke (median National Institutes of Health Stroke Scale (NIHSS) 24 h = 1.00 (0.00; 3.00); 87.5% with NIHSS ⩽ 5), 69.3% of them presented with PSCI 2.7 ± 2.0 days post-stroke. The most severely and often affected cognitive domains were verbal learning, episodic memory, executive functions, selective attention, and constructive abilities (39.1%-51.2% of patients), whereas spatial neglect was less frequent (18.5%). The risk of PSCI was reduced with more years of education (odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.23-0.99) and right hemisphere lesions (OR = 0.47, 95% CI = 0.26-0.84), and increased with stroke severity (NIHSS 24 h, OR = 4.19, 95% CI = 2.72-6.45), presence of hyperlipidemia (OR = 1.93, 95% CI = 1.01-3.68), but was not influenced by age. After adjusting for stroke severity and depressive symptoms, acute PSCI was associated with poor functional outcome (modified Rankin Scale > 2, F = 13.695, p < 0.001) and worse global cognition (Montreal Cognitive Assessment (MoCA) score, F = 20.069, p < 0.001) at 3 months post-stroke. Despite modern stroke therapy and many strokes having mild severity, PSCI in the acute stroke phase remains frequent and associated with worse outcome. The most prevalent were learning and memory deficits. Cognitive reserve operationalized as years of education independently protects post-stroke cognition.

High-Serum Brain-Derived Neurotrophic Factor Levels Are Associated With Decreased Risk of Poststroke Cognitive Impairment.

BDNF (brain-derived neurotrophic factor) is widely implicated in the pathophysiological process of stroke, but the effect of BDNF on poststroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between baseline serum BDNF and the risk of PSCI at 3 months in a multicenter study based on a preplanned ancillary study of the CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke). We examined serum BDNF levels at baseline and used the Mini-Mental State Examination and Montreal Cognitive Assessment to evaluate cognitive function at 3-month follow-up after ischemic stroke. PSCI was defined as Mini-Mental State Examination score <27 or Montreal Cognitive Assessment score <25. Logistic regression analyses were performed to evaluate the association between serum BDNF and the risk of 3-month PSCI. In this ancillary study, a total of 660 patients with ischemic stroke with hypertension were included, and 593 patients (mean age, 59.90±10.44 years; 410 males and 183 females) were finally included in this analysis. According to mini-mental state examination score, after adjustment for age, sex, education, baseline National Institutes of Health Stroke Scale score, APOE ɛ4 carriers, and other potential confounders, the odds ratio of PSCI for the highest tertile of BDNF was 0.60 ([95% CI, 0.39-0.94]; P=0.024) compared with the lowest tertile. Multiple-adjusted spline regression model showed a linear association of serum BDNF levels with PSCI at 3 months (P value for linearity=0.010). Adding serum BDNF to conventional prognostic factors slightly improved the risk reclassification of PSCI (net reclassification improvement: 27.46%, P=0.001; integrated discrimination index: 1.02%, P=0.015). Similar significant findings were observed when PSCI was defined by the Montreal Cognitive Assessment score. Elevated serum BDNF levels were associated with a decreased risk of PSCI at 3 months, suggesting that serum BDNF might be a potential predictive biomarker for PSCI among patients with ischemic stroke with hypertension.

Differentially Expressed miR-511-3p in Stroke Patients Predicts the Presence of Post-Stroke Cognitive Impairment.

Stroke is common cerebrovascular disease in the elderly, which is characterized by neurological defects caused by cerebral vessels. Multiple studies have shown that miRNAs play important roles in stroke. In addition, a large number of evidence suggest that stroke increases the risk and severity of cognitive impairments. miR-511-3p expression levels were detected by real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-511-3p in distinguishing stroke patients from healthy controls and to assess risk of post-stroke cognitive impairment (PSCI) in stroke patients. Pearson correlation coefficient was used to determine the relationship between miR-511-3p expression level and Montreal Cognitive Assessment Scale (MoCA) scores. Serum miR-511-3p expression levels were decreased in stroke patients, and the decrease was more significant in PSCI patients. ROC curve results showed that miR-511-3p had high diagnostic accuracy in distinguishing healthy controls from stroke patients. Moreover, the expression level of miR-511-3p can be used as an independent predictor for the occurrence of PSCI and is positively correlated with MoCA scores of PSCI patients. miR-511-3p may be involved in the occurrence and development of stroke. In addition, miR-511-3p may be a novel biomarker for predicting PSCI occurred in stroke patients. These results may help improve the quality of prognosis of stroke.

Association between Systemic Immune Inflammation Index and Cognitive Impairment after Acute Ischemic Stroke

Post-stroke cognitive impairment (PSCI) is one of the major complications after ischemic stroke. PSCI has been shown to be associated with low-grade systemic inflammation. As a novel inflammatory marker, the systemic immune-inflammation (SII) index could reflect clinical outcomes in severe cardiovascular diseases. We therefore performed a prospective study to investigate the correlation between the SII index and the risk of PSCI in patients with ischemic stroke. We prospectively enrolled 254 patients with ischemic stroke with symptoms onset <72 h. The SII index was detected within 24 h after admission. The Montreal Cognitive Scale (MoCA) was utilized to evaluate cognitive function, and PSCI was defined as a MoCA score of <25 points. During the 3-month follow-up, 70 participants (27.6%) had mild cognitive impairment and 60 (23.6%) had severe cognitive impairment. In binary logistic regression analysis, each one-standard deviation increase in the SII index was significantly associated with the prevalence of PSCI after adjusting for age, sex, and other confounders (odds ratio 2.341; 95% confidence interval, 1.439-3.809, p = 0.001). Similar significant findings were observed when SII was defined as a categorical variable. In addition, the multiple-adjusted spline regression model showed a linear association between the SII index and cognitive impairment (p = 0.003 for linearity). Our study indicated that an increased SII index was closely related to PSCI at 3 months in patients with ischemic stroke. Further research is required to evaluate the efficacy of inflammation management in these patients.

White matter microstructure and verbal fluency

Poor performance on verbal fluency tasks is associated with an increased risk of post-stroke cognitive impairment. Grey matter regions supporting verbal fluency have been identified via lesion–symptom mapping, but the links between verbal fluency and white matter structure remain less well described. We examined white matter correlates of semantic (Category Fluency Animals) and phonemic or lexical fluency (COWAT FAS) after stroke, accounting for stroke severity measured with the National Institutes of health Stroke Scale (NIHSS), age, sex, and level of education. White matter fibre density and cross-section measures were automatically extracted from 72 tracts, using MRtrix and TractSeg software in 72 ischaemic stroke survivors assessed 3 months after their event. We conducted regression analyses separately for phonemic and semantic fluency for each tract. Worse semantic fluency was associated with lower fibre density in several tracts, including the arcuate fasciculus, superior longitudinal fasciculus, inferior occipito-frontal fasciculus, inferior longitudinal fasciculus, optic radiation, striato-occipital, thalamo-occipital tracts, and inferior cerebellar peduncle. Our stroke sample was heterogenous with largely non-overlapping and predominantly right-lateralised lesions (lesion distribution: left N = 27, right N = 43, bilateral N = 2), dissimilar to previous studies of verbal fluency. Yet, the tracts we identified as correlates of semantic fluency were all left-lateralised. No associations between phonemic fluency performance and fibre density metrics in any of the white matter tracts we extracted survived correction for multiple comparisons, possibly due to the limitations in the selection of tracts and sample characteristics. We conclude that when accounting for the effects of stroke severity, sex, age, and education, semantic fluency is associated with white matter microstructure in the left arcuate fasciculus, superior longitudinal fasciculus, and several occipital tracts, possibly reflecting the disconnection in the sagittal stratum. Our results obtained with fixel-based analysis, complement previous findings obtained with lesions–symptom mapping and neurodegenerative approaches.

Association Between Plasma L-Carnitine and Cognitive Impairment in Patients with Acute Ischemic Stroke.

L-carnitine has been shown to exert neuroprotective effects on cerebral ischemia, mainly by improving mitochondrial function and reducing inflammation. L-carnitine supplementation has also been promoted to enhance cognitive function. However, the relationship between L-carnitine and cognitive impairment after ischemic stroke has seldom been studied. We aimed to evaluate the association between plasma L-carnitine and poststroke cognitive impairment. The study sample population was drawn from the China Antihypertensive Trial in Acute Ischemic Stroke. Plasma L-carnitine were measured at baseline in 617 patients with ischemic stroke using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Cognitive function was evaluated using the Montreal Cognitive Assessment at 3-month follow-up after ischemic stroke. Plasma L-carnitine were inversely associated with cognitive impairment at 3 months after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartiles of L-carnitine was 0.60 (0.37, 0.98; p for trend = 0.04). Each 1-SD increase in log-transformed L-carnitine concentration was significantly associated with a 15% (95% CI: 1%, 29%) reduction in the risk of cognitive impairment after stroke. The addition of L-carnitine to the model including conventional risk factors significantly improved the risk reclassification for cognitive impairment (net reclassification improvement: 17.9%, integrated discrimination improvement: 0.8%; both p < 0.05). Furthermore, joint effects of L-carnitine and inflammation markers were observed, and patients with higher L-carnitine and a lower inflammatory status simultaneously had the lowest risk of poststroke cognitive impairment. The present study provided prospective evidence on the inverse association between plasma L-carnitine and cognitive impairment after ischemic stroke.

Gamma-glutamyl transferase levels are associated with the occurrence of post-stroke cognitive impairment: a multicenter cohort study

BackgroundGamma-glutamyl transferase (GGT) is involved in maintenance of physiological concentrations of glutathione in cells, and protects them from oxidative stress-induced damage. However, its role in post-stroke cognitive impairment (PSCI) remains unknown. Here, we investigated the effects of serum GGT on PSCI.MethodsWe conducted a prospective, multicenter cohort study. A total of 1, 957 participants with a minor ischemic stroke or transient ischemic attack whose baseline GGT levels were measured were enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were categorized into four groups according to quartiles of baseline GGT levels. Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) approach. Multiple logistic regression models were performed to evaluate the relationship between GGT and PSCI at 3 months follow-up.ResultsAmong the 1957 participants, 671 (34.29%) patients suffered PSCI at 3 months follow-up. The highest GGT level quartile group exhibited a lower risk of PSCI in the fully adjusted model [OR (95% CI): 0.69 (0.50-0.96)], relative to the lowest group. Moreover, incorporation of GGT to the conventional model resulted in slight improvements in PSCI outcomes after 3 months (NRI: 12.00%; IDI: 0.30%).ConclusionsSerum GGT levels are inversely associated with the risk of PSCI, with extremely low levels being viable risk factors for PSCI.

A High Neutrophil-to-Lymphocyte Ratio Predicts Higher Risk of Poststroke Cognitive Impairment: Development and Validation of a Clinical Prediction Model.

ObjectivePoststroke cognitive impairment (PSCI) is a serious complication of stroke. The neutrophil-to-lymphocyte ratio (NLR) is a marker of peripheral inflammation. The relationship between the NLR and PSCI is far from well studied, and the thesis of this study was to assess the predictive value of the NLR in patients with PSCI, and establish and verify the corresponding prediction model based on this relationship.MethodsA total of 367 stroke patients were included in this study. Neutrophils, lymphocytes, and NLRs were measured at baseline, and clinical and neuropsychological assessments were conducted 3 months after stroke. The National Institutes of Health Scale (NIHSS) was used to assess the severity of stroke. A Chinese version of the Mini Mental State Examination (MMSE) was used for the assessment of cognitive function.ResultsAfter three months of follow-up, 87 (23.7%) patients were diagnosed with PSCI. The NLR was significantly higher in PSCI patients than in non-PSCI patients (P < 0.001). Patient age, sex, body mass index, NIHSS scores, and high-density lipoprotein levels also differed in the univariate analysis. In the logistic regression analysis, the NLR was an independent risk factor associated with the patients with PSCI after adjustment for potential confounders (OR = 1.67, 95%CI: 1.21–2.29, P = 0.002). The nomogram based on patient sex, age, NIHSS score, and NLR had good predictive power with an AUC of 0.807. In the validation group, the AUC was 0.816.ConclusionAn increased NLR at admission is associated with PSCI, and the model built with NLR as one of the predictors can increase prognostic information for the early detection of PSCI.

Development and validation of a clinical model (DREAM-LDL) for post-stroke cognitive impairment at 6 months

Introduction: This multicenter, retrospective study assessed the prevalence of post-stroke cognitive impairment (PSCI) 6 months after acute ischemic stroke (AIS) and its risk factors to build a bedside early predictive model for PSCI using the Montreal Cognitive Assessment (MoCA).Methods: Records of consecutive patients with AIS treated at 4 stroke centers in Shanghai had MoCA assessments within 2 weeks after AIS onset and 6 months later were reviewed. Prevalence of PSCI (MoCA<22) was calculated and risk factors were identified by multivariate logistic regression analysis. The modeling and validation and identified risk factors were included in a predictive model using multivariate regression.Results: There were 383 patients included and prevalence of PSCI 6 months after AIS was 34.2%, significantly lower than prevalence of patients with acute cognitive impairment (49.6%). Aging, less education, higher glucose level and severe stroke were PSCI risk factors, while level of low-density lipoprotein cholesterol (LDL-C) had a paradox effect on the risk of PSCI. 40.0% of the patients with cognitive impairment at acute phase reverted to normal, and patients with LDL-C 1.8-2.5 mmol/L were more likely to revert. The predictive model we built, DREAM-LDL (Diabetes [fasting blood glucose level], Rating [NIHSS], level of Education, Age, baseline MoCA and LDL-C level), had an AUROC of 0.93 for predicting PSCI at 6 months.Conclusion: PSCI was common among AIS patients 6 months after AIS. We provided a practical tool to predict PSCI based on MoCA and risk factors present during acute phase of AIS.

Carotid Atherosclerotic Calcification Characteristics Relate to Post-stroke Cognitive Impairment

Background: Together with cerebral small vessel disease (CSVD), large vessel atherosclerosis is considered to be an equally important risk factor in the progression of vascular cognitive impairment. This article aims to investigate whether carotid atherosclerotic calcification is associated with the increased risk of post-stroke cognitive impairment (PSCI).Methods: A total of 128 patients (mean age: 62.1 ± 12.2 years, 37 women) suffering from ischemic stroke underwent brain/neck computer tomography angiography examination. The presence and characteristic of carotid calcification (size, number and location) were analyzed on computer tomography angiography. White matter hyperintensity (WMH) was assessed using Fazekas scales. PSCI was diagnosed based on a battery of neuropsychological assessments implemented 6−12 months after stroke.Results: Among 128 patients, 26 developed post-stroke dementia and 96 had carotid calcification. Logistic regression found carotid calcification (odds ratio [OR] = 7.15, 95% confidence interval [CI]: 1.07–47.69) and carotid artery stenosis (OR = 6.42, 95% CI: 1.03–40.15) both significantly increased the risk for post-stroke dementia. Moreover, multiple, thick/mixed, and surface calcifications exhibited an increasing trend in PSCI (Ptrend = 0.004, 0.016, 0.045, respectively). The prediction model for post-stroke dementia including carotid calcification (area under curve = 0.67), WMH (area under curve = 0.67) and other covariates yielded an area under curve (AUC) of 0.90 (95% CI: 0.82–0.99).Conclusion: Our findings demonstrated that the quantity and location of carotid calcifications were independent indicators for PSCI. The significant role of large vessel atherosclerosis in PSCI should be concerned in future study.

Strategic infarct locations for post-stroke cognitive impairment: a pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts

Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute ischaemic stroke and use this information to develop a prediction model. In this large-scale multicohort lesion-symptom mapping study, we pooled and harmonised individual patient data from 12 cohorts through the Meta-analyses on Strategic Lesion Locations for Vascular Cognitive Impairment using Lesion-Symptom Mapping (Meta VCI Map) consortium. The identified cohorts (as of Jan 1, 2019) comprised patients with acute symptomatic infarcts on CT or MRI (with available infarct segmentations) and a cognitive assessment up to 15 months after acute ischaemic stroke onset. PSCI was defined as performance lower than the fifth percentile of local normative data, on at least one cognitive domain on a multidomain neuropsychological assessment or on the Montreal Cognitive Assessment. Voxel-based lesion-symptom mapping (VLSM) was used to calculate voxel-wise odds ratios (ORs) for PSCI that were mapped onto a three-dimensional brain template to visualise PSCI risk per location. For the prediction model of PSCI risk, a location impact score on a 5-point scale was derived from the VLSM results on the basis of the mean voxel-wise coefficient (ln[OR]) within each patient's infarct. We did combined internal-external validation by leave-one-cohort-out cross-validation for all 12 cohorts using logistic regression. Predictive performance of a univariable model with only the location impact score was compared with a multivariable model with addition of other clinical PSCI predictors (age, sex, education, time interval between stroke onset and cognitive assessment, history of stroke, and total infarct volume). Testing of visual ratings was done by three clinicians, and accuracy, inter-rater reliability, and intra-rater reliability were assessed with Cohen's weighted kappa. In our sample of 2950 patients (mean age 66·8 years [SD 11·6]; 1157 [39·2%] women), 1286 (43·6%) had PSCI. We achieved high lesion coverage of the brain in our analyses (86·9%). Infarcts in the left frontotemporal lobes, left thalamus, and right parietal lobe were strongly associated with PSCI (after false discovery rate correction, q<0·01; voxel-wise ORs >20). On cross-validation, the location impact score showed good correspondence, based on visual assessment of goodness of fit, between predicted and observed risk of PSCI across cohorts after adjusting for cohort-specific PSCI occurrence. Cross-validations showed that the location impact score by itself had similar performance to the combined model with other PSCI predictors, while allowing for easy visual assessment. Therefore the univariable model with only the location impact score was selected as the final model. Correspondence between visual ratings and actual location impact score (Cohen's weighted kappa: range 0·88-0·92), inter-rater agreement (0·85-0·87), and intra-rater agreement (for a single rater, 0·95) were all high. To the best of our knowledge, this study provides the first comprehensive map of strategic infarct locations associated with risk of PSCI. A location impact score was derived from this map that robustly predicted PSCI across cohorts. Furthermore, we developed a quick and reliable visual rating scale that might in the future be applied by clinicians to identify individual patients at risk of PSCI. The Netherlands Organisation for Health Research and Development.

Severity of Small Vessel Disease Biomarkers Reduces the Magnitude of Cognitive Recovery after Ischemic Stroke

Objective: The objective of this study was to evaluate the impact of radiological biomarkers suggestive of cerebral small vessel disease (SVD) on the evolution of cognitive performances after an ischemic stroke (IS). Methods: We studied patients with a supratentorial IS recruited consecutively to a prospective monocentric longitudinal study. A cognitive assessment was performed at baseline, 3 months, and 1 year and was based on a Montreal Cognitive Assessment, an Isaacs set test of verbal fluency (IST), and a Zazzo’s cancellation task (ZCT) for the evaluation of attentional functions and processing speed. The following cerebral SVD biomarkers were detected on a 3-T brain MRI performed at baseline: white matter hyperintensities (WMHs), deep and lobar microbleeds, enlarged perivascular spaces in basal ganglia and centrum semiovale, previous small deep infarcts, and cortical superficial siderosis (cSS). Generalized linear mixed models were used to evaluate the relationship between these biomarkers and changes in cognitive performances. Results: A total of 199 patients (65 ± 13 years, 68% male) were analyzed. Overall, the cognitive performances improved, more significantly in the first 3 months. Severe WMH was identified in 34% of the patients, and focal cSS in 3.5%. Patients with severe WMH and focal cSS had overall worse cognitive performances. Those with severe WMH had less improvement over time for IST (β = −0.16, p = 0.02) and the number of errors to ZCT (β = 0.19, p = 0.02), while those with focal cSS had less improvement over time for ZCT completion time (β = 0.14, p = 0.01) and number of errors (β = 0.17, p = 0.008), regardless of IS volume and location, gray matter volume, demographic confounders, and clinical and cardiovascular risk factors. Conclusion: The severity of SVD biomarkers, encompassing WMH and cSS, seems to reduce the magnitude of cognitive recovery after an IS. The detection of such SVD biomarkers early after stroke might help to identify patients with a cognitive vulnerability and a higher risk of poststroke cognitive impairment.

Serum Retinoic Acid Level and The Risk of Poststroke Cognitive Impairment in Ischemic Stroke Patients

Background: Retinoic acid (RA), an active metabolite of vitamin A, possesses enormous protective effects on vascular systems. It may also be positively related to good functional outcome after ischemic stroke. However, whether circulating RA concentration is associated with poststroke cognitive impairment (PSCI) remains unclear. This study aimed to detect the association between RA level and PSCI among patients with first-ever acute ischemic stroke. Methods: Two hundred and 61 consecutive patients were prospectively recruited during March 2018 and March 2019. Serum RA concentration was measured at admission for all patients. We also performed cognitive function examination using the Montreal Cognitive Assessment (MoCA) at admission and at every follow-up visit. Patients with MoCA score less than 26 were identified as developing PSCI. Results: The median serum RA level was 2.0 ng/mL (interquartile range, 1.1-3.2 ng/mL) after admission. Patients diagnosed as PSCI at admission, 1-month and 3-month were 53 (20.3%), 91 (34.6%), and 141 (54.0%), respectively. Univariate analysis showed that reduced RA level was correlated with PSCI at 3-month (P = .003), but not at admission (P = .416) and 1-month poststroke (P = .117). After adjusting for all potential confounders, the odds ratio for the lowest tertile of RA, compared with the highest tertile, was 1.97 (95% confidence interval, 1.01-3.83, P = .046) for PSCI at 3 months. Furthermore, multiple-adjusted spline regression model further confirmed the dose-response relationships between RA level and 3-month PSCI (P < .001). Conclusions: Decreasing serum RA level might be associated with 3-month PSCI in ischemic stroke patients.

Multiple biomarkers covering several pathways improve predictive ability for cognitive impairment among ischemic stroke patients with elevated blood pressure

Background and aimsWe aimed to evaluate the ability of multiple novel biomarkers representing several pathophysiological pathways to improve risk prediction of post-stroke cognitive impairment. MethodsWe conducted a prospective multicenter study in 638 ischemic stroke patients with elevated blood pressure based on a random subsample from China Antihypertensive Trial in Acute Ischemic Stroke and measured 12 circulating biomarkers in these participants. Cognitive impairment was assessed at 3 months after stroke with definitions of Mini-Mental State Examination (MMSE) score <27 or Montreal Cognitive Assessment (MoCA) score <25. ResultsAccording to MMSE score, 1 SD increase of rheumatoid factor (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.02–1.46), matrix metalloproteinase-9 (OR 1.47, 95% CI 1.22–1.77) and total homocysteine (OR 1.22, 95% CI 1.01–1.49) after log transformation was significantly associated with the risk of post-stroke cognitive impairment. The ORs associated with their simultaneously high levels were 4.89 (95% CI, 2.31–10.35; ptrend<0.001) and 3.09 (95% CI, 1.60–5.98; ptrend<0.001) for cognitive impairment and the severity of cognitive impairment, respectively. Adding these 3 biomarkers to conventional model significantly improved the risk prediction of cognitive impairment (C statistic 0.729 vs. 0.688, p = 0.004; net reclassification improvement = 33.67%, p < 0.001; integrated discrimination index = 4.61%; p < 0.001). Similar significant findings were observed when cognitive impairment was defined by MoCA score. ConclusionsCombination of rheumatoid factor, matrix metalloproteinase-9 and total homocysteine can improve the risk prediction of cognitive impairment among ischemic stroke patients with elevated blood pressure. Further studies are warranted to validate our findings and explore their roles as potential therapeutic targets.

Serum Rheumatoid Factor Levels at Acute Phase of Ischemic Stroke are Associated with Poststroke Cognitive Impairment

Background: The effect of serum rheumatoid factor (RF) on poststroke cognitive impairment remains unknown. We aimed to investigate the association of serum RF in the acute phase with cognitive impairment at 3 months after ischemic stroke onset. Methods: Our study was based on a random sample from the China Antihypertensive Trial in Acute Ischemic Stroke, a total of 582 patients from 7 of 26 participating sites of the trial with serum RF levels were included in this analysis. Cognitive impairment was defined as Mini-Mental State Examination less than 27 or Montreal Cognitive Assessment less than 25. Results: According to Mini-Mental State Examination score, the multivariate-adjusted odds ratio and 95% confidence interval of cognitive impairment for the highest tertile of serum RF was 1.79 (1.08-2.99) compared with the lowest tertile. Each standard deviation increase of log-transformed RF was associated with 33% (95% confidence interval: 7%-66%) increased risk of cognitive impairment, and a linear association between serum RF and risk of poststroke cognitive impairment was observed (P for linearity < .01). Adding log-transformed RF to a model containing conventional risk factors improved the predictive power for poststroke cognitive impairment (net reclassification improvement: 26.21%, P < .01; integrated discrimination index: 1.24%, P = .02). Similar significant findings were observed when cognitive function was defined by Montreal Cognitive Assessment score. Conclusions: Elevated serum RF levels in the acute phase were independently associated with 3-month cognitive impairment among ischemic stroke patients. Further studies are needed to replicate our findings and to clarify the potential mechanisms.

Effects of Blood Pressure in the Early Phase of Ischemic Stroke and Stroke Subtype on Poststroke Cognitive Impairment.

Blood pressure (BP) control in the early phase of stroke is controversial to reduce the risk of poststroke cognitive impairment (PSCI). This study was to investigate the impact of BP levels in the early phase of ischemic stroke and stroke subtype on PSCI. Seven hundred and ninety-six patients with acute ischemic stroke were included. Cognitive function was assessed after stroke onset using the Montreal Cognitive Assessment. Patients were divided into quintiles according to systolic BP and diastolic BP levels in the early phase. Subtype analyses were according to Trial of ORG 10172 in Acute Stroke Treatment classification (infarct cause) and Oxfordshire Community Stroke Project classification (infarct location). After adjusting for multiple variables, the quintiles with the lowest systolic BP (Q1, 102-127 mm Hg) and with the highest systolic BP (Q5, 171-215 mm Hg) were associated with increased PSCI risk (odds ratio, 1.83; 95% confidence interval, 1.64-2.28; P=0.007 in Q1; odds ratio, 2.32; 95% confidence interval, 1.74-2.90; P<0.001 in Q5) at 3 months as compared with the middle quintile (Q3, 143-158 mm Hg). Similar association was found in diastolic BP quintiles. The analysis of cerebral infarction subtype demonstrated that both large artery atherosclerosis and total anterior circulation infarct were associated with increased risk of PSCI at 3 months after adjusting for multiple variables (large artery atherosclerosis: odds ratio, 1.42; 95% confidence interval, 1.06-1.90; P=0.031; total anterior circulation infarct: odds ratio, 1.68; 95% confidence interval, 1.32-2.15; P=0.001). Lower or higher BP in the early phase of ischemic stroke was correlated with increased PSCI risk at 3 months. Maintaining systolic/diastolic BP in the levels of 143 to 158/93 to 102 mm Hg might be beneficial to reduce the occurrence of PSCI. Moreover, large artery atherosclerosis subtype and total anterior circulation infarct subtype were correlated with increased PSCI risk at 3 months. URL: https://www.chictr.org. Unique identifier: ChiCTR-TRC-14004804.

Prediabetes is associated with post-stroke cognitive impairment in ischaemic stroke patients

AimDiabetes mellitus is associated with post-stroke cognitive impairment. To the best of our knowledge, no study has explored the relationship between prediabetes and post-stroke cognitive impairment. The purpose of this study is to explore the association between prediabetes and cognitive impairment in ischaemic stroke patients at 1 month. MethodsTwo hundred one acute ischaemic stroke patients were consecutively recruited within the first 24 h after admission and were followed up for 1 month. Patients were divided into a diabetes mellitus group, prediabetes group and non-diabetes mellitus group by fasting glucose levels, 2-h postprandial blood glucose levels and glycosylated haemoglobin levels at admission. Cognitive function was evaluated by the Mini-Mental State Examination at 1 month after stroke. ResultsThe prediabetes group had a higher risk of post-stroke cognitive impairment than the non-diabetes group (35.7% vs. 18.1%, χ2 = 4.252, P = .039). In logistical analyses, prediabetes was associated with post-stroke cognitive impairment after adjusting for potential confounding factors (odds ratio 3.062, 95% confidence interval 1.130–8.299, P = .028). ConclusionsOur findings show that prediabetes is associated with post-stroke cognitive impairment and may predict its development at 1 month post-stroke.

Post-stroke cognitive impairment: epidemiology, mechanisms and management.

Post-stroke cognitive impairment occurs frequently in the patients with stroke. The prevalence of post-stroke cognitive impairment ranges from 20% to 80%, which varies for the difference between the countries, the races, and the diagnostic criteria. The risk of post-stroke cognitive impairment is related to both the demographic factors like age, education and occupation and vascular factors. The underlying mechanisms of post-stroke cognitive impairment are not known in detail. However, the neuroanatomical lesions caused by the stroke on strategic areas such as the hippocampus and the white matter lesions (WMLs), the cerebral microbleeds (CMBs) due to the small cerebrovascular diseases and the mixed AD with stroke, alone or in combination, contribute to the pathogenesis of post-stroke cognitive impairment. The treatment of post-stroke cognitive impairment may benefit not only from the anti-dementia drugs, but also the manage measures on cerebrovascular diseases. In this review, we will describe the epidemiological features and the mechanisms of post-stroke cognitive impairment, and discuss the promising management strategies for these patients.

RtPA in acute stroke patients with history of cognitive impairment

A solid body of evidence has accumulated over the past 20 years confirming the critical role of cerebrovascular disease in Alzheimer disease (AD) and other dementias of the aged.1–6 Most recently, data from the National Alzheimer's Coordinating Center7 demonstrated the presence of vascular pathology in 79.9% of 4,629 brains from patients with neuropathologically confirmed AD. Lesions included atherosclerosis in the circle of Willis, arteriosclerotic leukoencephalopathy, arteriolosclerosis, large infarcts, lacunes, multiple microinfarcts, and hemorrhages. Notably, cerebral amyloid angiopathy was present in less than half of the brains (40.8%). Given the absence of an effective treatment to halt the progression of AD, the current emphasis is on dementia prevention by appropriate treatment of vascular risk factors for stroke.8,9 Once stroke occurs, optimal treatment of the acute ictus with prompt restoration of flow in the occluded vessels improves the cognitive outcome. In contrast, stroke complications such as aspiration pneumonia, hypoxemia, seizures, hypotension, or cardiac arrhythmias increase the risk of poststroke cognitive impairment 4-fold.10

Frequency and Determinants of Poststroke Cognitive Impairment at Three and Twelve Months in Chile

Background: A higher risk of poststroke cognitive impairment (CI) has been reported in Hispanics in a US cohort but has not been systematically studied in Latin America. Objectives: Our purpose was to investigate the frequencies and determinants of poststroke CI in the hispano-mestizo population of Santiago, Chile. Methods: A prospective study of hospitalized patients aged >60 years admitted with an ischemic or hemorrhagic stroke was conducted. The cognitive status was determined at 3 and 12 months after the stroke by informant questionnaires, neuropsychological testing and clinical diagnosis. Cardiovascular risk factors, brain imaging and stroke features were analyzed using regression models to establish determinants for poststroke CI. Results: A total of 164 patients (mean age = 72 ± 7.5 years) were recruited. Out of 122 patients (74%) evaluated at 3 months, 81 (66%) had CI. Out of 101 patients (62%) evaluated at 12 months, 39 (39%) had CI no dementia, and 22 (22%) were demented. The new-onset dementia frequency at 1 year was 16%. Independent determinants for dementia were higher functional impairment at hospital egress (OR = 4.0), left-hemisphere large-vessel infarction (OR = 6.9) and a larger amount of white matter changes (OR = 1.3). Conclusions: In this first study on poststroke CI in Latin America, the frequencies and determinants of poststroke CI were similar to those in other cohorts of different ethnic origin.