Abstract P67: Role of Genetic Variants in Predicting Cognitive Outcomes Following Small Vessel Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Wayneho Kam ◽  
Larry B Goldstein ◽  
Alec McConnell ◽  
Hussein Al-Khalidi ◽  
Ellen Bennett ◽  
...  

Background: About 20% of patients with small vessel ischemic stroke (SVS) have cognitive impairment; however, the role of genetic factors in predicting cognitive outcomes following SVS has not been fully explored. APOE and ABCC9 have been associated with Alzheimer’s disease and hippocampal sclerosis respectively and play an important role in the neurovascular unit. We evaluated whether allelic variants in these genes influence cognitive outcomes following SVS. Methods: We conducted a retrospective analysis of a prospective cohort of patients enrolled in the ASA-Bugher Small Vessel Intracranial Disease Whole Genome Association Studies. Patients with SVS were categorized by APOE (presence or absence of ε4 allele) and ABCC9 SNP rs704180 (presence or absence of A allele) status. The primary outcomes were total score on the short form of the MoCA, which assesses global cognition, and time to complete Trails B, which is a measure of executive function that can be affected by stroke. Linear regression analyses were performed using the genetic exposures of interest, adjusting for age, education, sex, race/ethnicity, NIHSS score, burden of white matter disease (WMD; using the CHS validated score 0-9), and time between stroke and the cognitive assessment. Results: The sample included 145 patients who had SVS and available APOE and ABCC9 data. Among this cohort, 51.4% were men and 27.6% African American. The median age of the study participants was 63.4 years, the median years of education was 12, the median NIHSS was 2, and the median WMD burden score was 2. The mean time between stroke and the cognitive assessment was 75 days. The APOE ε4 allele was present in 35.0% and ABCC9 A allele in 74.8%. The presence of APOE ε4 allele was not associated with post-stroke MoCA scores (p=0.31) or Trails B (p=0.86). ABCC9 A allele was also not associated with post-stroke MoCA scores (p=0.34) or Trails B (p=0.31). Older age, higher NIHSS score, and greater burden of WMD were independently associated with longer times to complete Trails B (p<0.0001), but not with the MoCA score. Conclusion: Following SVS, several patient characteristics, including age, stroke severity, and WMD burden, rather than their APOE and ABCC9 allelic statuses, were associated with post-stroke measures of executive function.

2021 ◽  
pp. 1-11
Author(s):  
Pi-Shan Sung ◽  
Kang-Po Lee ◽  
Po-Yu Lin ◽  
Hui-Chen Su ◽  
Rwei-Ling Yu ◽  
...  

Background: Differences exist regarding post-stroke cognitive outcomes. Objective: The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories. Methods: We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes. Results: A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p <  0.001, respectively), but tended to be worse in patients with higher SVD burden and HA. The GBTM model grouped patients into low, intermediate, and high performance (LP, IP, and HP) after stroke. A higher SVD burden, rather than HA and initial stroke severity and location, independently predicted a higher odds of poor post-stroke cognitive trajectory (being in the LP group) after stroke (adjusted odds ratio 2.74, 95%CI 1.09–6.86). Conclusion: In patients with first-ever mild stroke, cognitive improvement over time was evident. The detrimental impact of the SVD burden may outweigh the effect of HA or acute stroke insult on the post-stroke cognitive trajectory during the 1-year follow-up.


Author(s):  
Dwi Retno Hastani ◽  
Aldy S. Rambe ◽  
Kiki M. Iqbal

Background: ASCO Phenotype classification is a new classification of stroke based on phenotypic system. ASCO classification can evaluate the etiology of ischemic stroke comprehensively to characterize patients using different grade of evidence for the subtype of ischemic stroke. ASCO classification can predict post ischemic stroke cognitive decline. This Study purpose to evaluate the association between ASCO classification with the executive function in post ischemic stroke patients.Methods: This cross sectional study followed by 28 post ischemic stroke patients (men 16, women 12) over 3 months. Mean age 52.82±8.66. Cognitive function was assessed by Montreal Cognitive Assessment Indonesia (MoCA INA).Results: There were 17 patients with grade 1 atherosclerosis (ASCO A1), ten patients with grade 1 small vessel disease (ASCO S1), one patient with grade 1 cardioembolism (ASCO C1) in post ischemic stroke. Grade 1 atherosclerosis (ASCO A1) was significantly associated with executive function decline (p=0.002), naming decline (p=0.05), abstraction decline (p=0.001), memory decline (p=0.002) and orientation decline (p=0.016)). Grade 1 small vessel disease (ASCO S1) was significantly associated with executive function decline (p=0.001) and memory decline (p = 0.001) and abstraction (p=0.001). Grade 1 cardioembolism 1 (ASCO C1) was not significantly associated with cognitive decline.Conclusions: There was significant association between ASCO classification with the executive function of Montreal Cognitive Assestment Indonesia (MoCA INA) in post ischemic stroke patients.


Author(s):  
Elisabeth Kliem ◽  
Elise Gjestad ◽  
Truls Ryum ◽  
Alexander Olsen ◽  
Bente Thommessen ◽  
...  

Abstract Objective: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. Method: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 – Revised (SCL-90-R). Results: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3–7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). Conclusion: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Mackenzie Steck ◽  
Omar Saeed ◽  
Balaji Krishnaiah ◽  
Samarth Shah ◽  
Jaclyn Stoffel ◽  
...  

Presentation Objective: Does glycemic variability worsen Modified Rankin Score (mRS) following ischemic stroke in patients treated with thrombolytics (tPA)? Background/Purpose: Acute hyperglycemia and strict glucose control have been identified as predictors of hemorrhage, increased length of stay and hypoglycemia following ischemic stroke. However, the role of glucose variability in patients with ischemic stroke treated with tPA is largely unknown. The aim of this study was to evaluate the role of glycemic variability on discharge outcomes in patients treated with tPA for ischemic stroke. Methodology: A retrospective review of adults with ischemic stroke who received tPA was completed. Patients hospitalized for at least 48 hours with image-confirmed ischemic stroke and symptom onset within 4.5 hours of presentation were included. Glycemic variability was measured using the J-index calculation and groups were defined as patients with normal or abnormal J-indices. Logistic regression models were developed to determine odds ratios for defined outcomes including NIHSS score, mRS and disposition at discharge. Statistical significance was a p-value of <0.05. Results: Of the 229 patients included, 132 (58%) had a normal J-index (4.7 – 23.6). In the univariate analysis, abnormal J-index was associated with higher rates of hypertension (94% vs 73%), type 2 diabetes mellitus (74% vs 12%), chronic kidney disease (34% vs 11%), higher initial blood glucose values (220 ±172 vs 111 ±20) and HbA1c, and worse outcomes in terms of NIHSS score, mRS and disposition at discharge. In the multivariate analysis, patients with an abnormal J-index had higher odds of unfavorable outcomes in terms of discharge mRS (OR 2.1; 95% CI 1.0 – 4.3, p=0.045) and hemorrhagic transformation (OR 4.1; 95% CI 1.7 – 10.2, p=0.002). There was no difference in discharge disposition (OR 1.4; 95% CI 0.7 – 3.0 p=0.4). Conclusion: Glycemic variability, following ischemic stroke, may result in unfavorable patient outcomes in patients treated with tPA. Additional studies are needed to determine the appropriate glucose management strategy.


Author(s):  
Shail S Thanki ◽  
Elliot Pressman ◽  
Shail S Thanki ◽  
John D Mayfield ◽  
Maximilian J Rabil ◽  
...  

Introduction : Acute ischemic stroke (AIS) is a leading cause of disability internationally. Most therapies focus on intra‐arterial treatment to improve post‐stroke deficits and neurologic status. However, if a relationship between venous anatomy and post‐stroke deficits or infarct size can be shown, then venous augmentation strategies represent a possibility for future interventions as an adjunct to intra‐arterial treatment. Methods : We retrospectively reviewed all ischemic infarcts at our institution that underwent thrombectomy from January 2018 – October 2020. From these, we selected cases that were demonstrated as M1 occlusions on intra‐procedural angiogram and those who had a CT Head obtained within six hours of the patient’s last known normal (LKN). Patients without a CT Head or CT Angiogram of their head were excluded. Using axial and sagittal reconstructed views of 0.9mm slices, cross‐sectional area measurements were taken of the superior sagittal sinus 1cm above the Torcula, in three locations of the ipsilateral and contralateral transverse sinus, in three locations of the ipsilateral and contralateral sigmoid sinus, and of the ipsilateral and contralateral internal jugular vein (IJV) at the external surface of the skull. For the transverse and sigmoid sinuses, the three measurements were averaged together. These measurements were then compared against patient’s Alberta Stroke Program Early CT Score (ASPECTS). Results : 77 patients were identified in the study period. Average ASPECTS was 8.9, ranging from 5–10. There were three patients included with ASPECTS < 6. Average ipsilateral transverse sinus area was 34.4mm ± 3.34, average ipsilateral sigmoid sinus area was 32.8mm ± 2.74, average ipsilateral IJV area was 46.9 mm ± 5.00. Correlation tests to identify relationships between venous sinus area and ASPECTS was unremarkable (ipsilateral transverse sinus p = 0.574, ipsilateral sigmoid sinus p = 0.548, ipsilateral IJV p = 0.798). When assessed as a ratio of ipsilateral venous sinus area to contralateral sinus area to assess correlation with ASPECTS, results were unremarkable (transverse sinus p = 0.891, sigmoid sinus p = 0.292, IJV p = 0.499). Conclusions : Venous sinus size was not found to be predictive or associated with predominantly favorable ASPECTS for strokes found within six hours. We believe this may be due to our cohort lacking significant numbers of patients with low ASPECTS, yielding a false negative result. We are currently expanding this project to include a comparable number of patients with ASPECTS < 6 to determine the role of venous collateral system in infarct progression.


2015 ◽  
Vol 7 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Ashley B. Petrone ◽  
Grant C. O’Connell ◽  
Michael D. Regier ◽  
Paul D. Chantler ◽  
James W. Simpkins ◽  
...  

Stroke ◽  
2019 ◽  
Vol 50 (7) ◽  
pp. 1805-1811 ◽  
Author(s):  
Susumu Kobayashi ◽  
Shingo Fukuma ◽  
Tatsuyoshi Ikenoue ◽  
Shunichi Fukuhara ◽  
Shotai Kobayashi ◽  
...  

Background and Purpose— In Japan, nearly half of ischemic stroke patients receive edaravone for acute treatment. The purpose of this study was to assess the effect of edaravone on neurological symptoms in patients with ischemic stroke stratified by stroke subtype. Methods— Study subjects were 61 048 patients aged 18 years or older who were hospitalized ≤14 days after onset of an acute ischemic stroke and were registered in the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between June 2001 and July 2013. Patients were stratified according to ischemic stroke subtype (large-artery atherosclerosis, cardioembolism, small-vessel occlusion, and cryptogenic/undetermined) and then divided into 2 groups (edaravone-treated and no edaravone). Neurological symptoms were evaluated using the National Institutes of Health Stroke Scale (NIHSS). The primary outcome was changed in neurological symptoms during the hospital stay (ΔNIHSS=NIHSS score at discharge−NIHSS score at admission). Data were analyzed using multivariate linear regression with inverse probability of treatment weighting after adjusting for the following confounding factors: age, gender, and systolic and diastolic blood pressure at the start of treatment, NIHSS score at admission, time from stroke onset to hospital admission, infarct size, comorbidities, concomitant medication, clinical department, history of smoking, alcohol consumption, and history of stroke. Results— After adjusting for potential confounders, the improvement in NIHSS score from admission to discharge was greater in the edaravone-treated group than in the no edaravone group for all ischemic stroke subtypes (mean [95% CI] difference in ΔNIHSS: −0.46 [−0.75 to −0.16] for large-artery atherosclerosis, −0.64 [−1.09 to −0.2] for cardioembolism, and −0.25 [−0.4 to −0.09] for small-vessel occlusion). Conclusions— For any ischemic stroke subtype, edaravone use (compared with no use) was associated with a greater improvement in neurological symptoms, although the difference was small (<1 point NIHSS) and of limited clinical significance.


2009 ◽  
Vol 25 (8) ◽  
pp. 833-842 ◽  
Author(s):  
Jørgen Wagle ◽  
Lasse Farner ◽  
Kjell Flekkøy ◽  
Torgeir B. Wyller ◽  
Leiv Sandvik ◽  
...  

Author(s):  
Anna Marseglia ◽  
Alexander Darin-Mattsson ◽  
Johan Skoog ◽  
Lina Rydén ◽  
Timothy Hadarsson-Bodin ◽  
...  

Abstract Background Individual conditions of metabolic syndrome (MetS) have been related to dementia, however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors. Methods Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least two factors [reduced HDL-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from ten neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein (APOE) genotype were ascertained by trained staff. Data were analyzed with linear regression models. Results Overall, 618 participants (55%) had MetS. In multi-adjusted linear regressions, MetS was related to poorer performance in attention/perceptual speed (β -0.14 [95% CI -0.25, -0.02]), executive function (β -0.12 [95% CI -0.23, -0.01]), and verbal fluency (β -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-ε4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone. Conclusions MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, APOE-ε4 allele, and comorbid cardiovascular disease influenced the observed associations.


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