Genetic aspects of aspirin resistance in patients with cerebrovascular pathology

2021 ◽  
Author(s):  
А.А. Корнилова ◽  
М.М. Танашян ◽  
А.А. Раскуражев ◽  
А.А. Шабалина ◽  
Е.В. Ройтман
Keyword(s):  
Cognitive Assessment ◽  
Aspirin Resistance ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
In Vitro Test ◽  
Laboratory Assessment ◽  
Compliance To Treatment ◽  
Cox 1 ◽  
Sensitive Group

Введение. Цереброваскулярные заболевания (ЦВЗ) и нарушения мозгового кровообращения (НМК) остаются одной из основных причин смерти во всем мире. Доказана генетическая составляющая возникновения НМК, генетические полиморфизмы могут изменять ответ на фармакологические агенты. Ацетилсалициловая кислота (АСК) — «золотой стандарт» антиагрегантного лечения ЦВЗ. С начала XXI века в мировой науке накопились факты о недостаточном эффекте АСК, в связи с чем возник термин аспиринорезистентность. Цель исследования: оценка вклада гемореологических и генетических факторов в возникновение феномена аспиринорезистентности у пациентов с ЦВЗ. Материалы и методы. В настоящее проспективное рандомизированное контролируемое наблюдательное исследование были включены 186 пациентов с ЦВЗ в возрасте 45–75 лет. Все пациенты получали 75 мг АСК ежедневно. Наряду с комплексным клиническим обследованием, оценкой когнитивного статуса и приверженности к лечению, проводилась лабораторная оценка функции тромбоцитов, развернутый биохимический анализ крови, идентификация полиморфизмов A842G гена циклооксигеназы 1-го типа (ЦОГ-1) (rs 10306114), С50Т ЦОГ-1 (rs3842787) и А1676G ЦОГ-1 (rs1330344). Статистическая обработка выполнена с использованием программ IBM SPSS Statistics. Результаты. Выявлена положительная взаимосвязь между уровнем агрегации тромбоцитов (АТ) с аденозиндифосфатом (АТ-АДФ) и адреналином и (АТ-адр) и пробой АСК in vitro (r = 0,722 и r = 0,689; р < 0,001). Обнаружена отрицательная взаимосвязь между АТ-АДФ и баллом по Монреальской шкале оценки когнитивных функций (англ. Montreal Cognitive Assessment, MoCA) и приверженностью к лечению (r = –0,845; p = 0,001). На основании анализа АТ все обследованные были подразделены на АСК-нечувствительных (группа 1, n = 100) и АСК-чувствительных (группа 2, n = 86). В группе АСК-нечувствительных наблюдалось больше пациентов, несущих хотя бы один аллель G полиморфизма гена ЦОГ-1 rs1330344 по сравнению с пациентами в группе ACK-чувствительных (60,4% против 47,7%; p < 0,01). Наличие rs1330344 часто ассоциировано с сахарным диабетом 2-го типа (отношение шансов = 3,749; 95% доверительный интервал = 1,937–7,254; p = 0,001). Полиморфизм ЦОГ-1 C50T (rs3842787) по данным логистической регрессии связан с АТ-Адр (r = 0,845; р < 0,001). Заключение. Среди причин аспиринорезистентности у пациентов с ЦВЗ следует учитывать генетические аспекты. Background. Cerebrovascular disease (CVD) and stroke remain one of the leading causes of death worldwide. The genetic component of stroke has been proven; genetic polymorphisms can alter the response to pharmacological agents. Acetylsalicylic acid (ASA) is the “gold standard” for antiplatelet treatment of CVD. Since the beginning of the XXI century, the world science has accumulated facts about the insufficient effect of ASA, so the term aspirin resistance appeared. Objectives: to assess hemorheological and genetic factors to the occurrence of the phenomenon of aspirin resistance in patients with CVD. Patients/Methods. This prospective randomized controlled observational study included 186 patients with CVD, aged 45–75 years. All patients received 75 mg ASA daily. Clinical examination, assessment of cognitive status and compliance to treatment, a laboratory assessment of platelet function, a detailed biochemical blood test, identifi cation of A842G polymorphisms of type 1 cyclooxygenase (COX-1) gene (rs 10306114), C50T COX-1 (rs3842787) and A1676G COX-1 (rs3842787) and A1676G COX-1 (rs1330344) were performed. Statistics was carried out using the IBM SPSS Statistics software. Results. The positive correlation was found between platelet aggregation (РА) with adenosine diphosphate (РА-ADP) and adrenaline (РА-Аdr) and an in vitro test with ASA (r = 0.722 and r = 0.689; p < 0.001). A negative correlation was found between РА-ADP and the Montreal Cognitive Assessment (MoCA) score for compliance to treatment (r = –0,845; p = 0,001). Based on the analysis of PA, all examined patients were divided into ASA-insensitive (group 1, n = 100) and ASA-sensitive (group 2, n = 86). In the ASA-insensitive group, there were more patients carrying at least one G allele of the COX-1 gene rs1330344 polymorphism compared with patients in the ACK-sensitive group (60.4% versus 47.7%; p < 0.01). The presence of rs1330344 is often associated with type 2 diabetes mellitus (OR = 3.749; 95% СI = 1.937–7.254; p = 0.001). C50T polymorphism of COX-1 (rs3842787) according to logistic regression is associated with AT-Adr (r = 0.845; p < 0.001). Conclusions. Genetic aspects should be considered among the causes of aspirin resistance in patients with CVD.

scholarly journals Concurrent validity of the short version of Montreal Cognitive Assessment (MoCA) for patients with stroke

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yali Feng ◽  
Jiaqi Zhang ◽  
Yi Zhou ◽  
Bo Chen ◽  
Ying Yin
Keyword(s):  
Neurological Disorders ◽  
Cognitive Assessment ◽  
Concurrent Validity ◽  
Operating Characteristic ◽  
Cognitive Impairments ◽  
Characteristic Curve ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
Short Version ◽  
External Criterion

AbstractThe aim of the present study was to examine the concurrent validity of 2 Chinese versions of the short version of the Montreal Cognitive Assessment (MoCA) in patients with stroke, i.e., MoCA 5-minute protocol and National Institute for Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) 5-minute Protocol. A total of 54 patients and 27 healthy controls were enrolled in this study. In this study, the Neurobehavioural Cognitive Status Examination (NCSE) was used as an external criterion of cognitive impairment. We found that the 5-min protocol did not differ from the MoCA in differentiating patients with cognitive impairments from those without (area under the receiver operating characteristic curve, AUC, of 0.948 for the MoCA 5-min protocol v.s. 0.984 for MoCA, P = 0.097). These three assessments demonstrated equal performance in differentiating patients with stroke from controls. The Chinese version of the MoCA 5-min protocol can be used as a valid screening for patients with stroke.

scholarly journals Psychometric Properties of the Persian Montreal Cognitive Assessment in Mild Cognitive Impairment and Alzheimer Disease

2021 ◽  
pp. 51-57
Author(s):  
Vahid Rashedi ◽  
Mahshid Foroughan ◽  
Negin Chehrehnegar
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Alzheimer Disease ◽  
Psychometric Properties ◽  
Cognitive Assessment ◽  
Screening Test ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
Cutoff Score ◽  
Persian Version

Introduction: The Montreal Cognitive Assessment (MoCA) is a cognitive screening test widely used in clinical practice and suited for the detection of Mild Cognitive Impairment (MCI). The aims were to evaluate the psychometric properties of the Persian MoCA as a screening test for mild cognitive dysfunction in Iranian older adults and to assess its accuracy as a screening test for MCI and mild Alzheimer disease (AD). Method: One hundred twenty elderly with a mean age of 73.52 ± 7.46 years participated in this study. Twenty-one subjects had mild AD (MMSE score ≤21), 40 had MCI, and 59 were cognitively healthy controls. All the participants were administered the Mini-Mental State Examination (MMSE) to evaluate their general cognitive status. Also, a battery of comprehensive neuropsychological assessments was administered. Results: The mean score on the Persian version of the MoCA and the MMSE were 19.32 and 25.62 for MCI and 13.71 and 22.14 for AD patients, respectively. Using an optimal cutoff score of 22 the MoCA test detected 86% of MCI subjects, whereas the MMSE with a cutoff score of 26 detected 72% of MCI subjects. In AD patients with a cutoff score of 20, the MoCA had a sensitivity of 94% whereas the MMSE detected 61%. The specificity of the MoCA was 70% and 90% for MCI and AD, respectively. Discussion: The results of this study show that the Persian version of the MoCA is a reliable screening tool for detection of MCI and early stage AD. The MoCA is more sensitive than the MMSE in screening for cognitive impairment, proving it to be superior to MMSE in detecting MCI and mild AD.

scholarly journals Detecting Subtle Cognitive Impairment in Multiple Sclerosis with the Montreal Cognitive Assessment

2020 ◽  
Vol 47 (5) ◽  
pp. 620-626 ◽  
Author(s):  
Kim Charest ◽  
Alexandra Tremblay ◽  
Roxane Langlois ◽  
Élaine Roger ◽  
Pierre Duquette ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Cognitive Assessment ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
Rapid Screening ◽  
Cognitive Complaints ◽  
Subjective Complaints ◽  
Subjective Cognitive Complaints

ABSTRACT:Background:Although cognitive deficits are frequent in multiple sclerosis (MS), screening for them with tools such as the Montreal Cognitive Assessment (MoCA) test is usually not performed unless there is a subjective complaint. The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) is among the instruments most commonly used to assess self-reported subjective complaints in MS. Nonetheless, it does not always accurately reflect cognitive status; many patients with cognitive deficits thus fail to receive appropriate referral for detailed neuropsychological evaluation. The objective of this study was to examine the validity of the MoCA test to detect the presence of objective cognitive deficits among patients with MS without subjective complaints using the Minimal Assessment of Cognitive Function in MS (MACFIMS) as the gold standard.Methods:The sample included 98 patients who were recruited from a university hospital MS clinic. The MSNQ was used to select patients without subjective cognitive complaints who also completed the MACFIMS, MoCA test and MSQOL-54.Results:23.5% of patients without subjective cognitive complaints had evidence of objective cognitive impairment on the MACFIMS (z score < -1.5 on two or more tests). The MoCA had a sensitivity of 87% and a specificity of 68% for detecting objective cognitive impairment in this patient population using a cut-off score of 27.Conclusion:A significant proportion of patients without self-reported cognitive impairment do have evidence of cognitive deficits on more exhaustive cognitive assessment. The MoCA is a rapid screening test that could be used to target patients for whom a more detailed neuropsychological assessment would be recommended.

Cyclooxygenase-1 haplotype C50T/A-842G does not affect platelet response to aspirin

2009 ◽  
Vol 101 (04) ◽  
pp. 687-690 ◽  
Author(s):  
Caterina Pettinella ◽  
Mario Romano ◽  
Liborio Stuppia ◽  
Francesca Santilli ◽  
Rossella Liani ◽  
...  
Keyword(s):  
Low Dose ◽  
Ex Vivo ◽  
Aspirin Resistance ◽  
Platelet Response ◽  
Dose Aspirin ◽  
Cyclooxygenase 1 ◽  
Low Dose Aspirin ◽  
Induced Aggregation ◽  
Cox 1

SummaryCOX-1 polymorphism C50T, in complete linkage disequilibrium with the other polymorphism A-842G, has been depicted as a determinant of pharmacological response to aspirin treatment. Whether these polymorphisms exert an effect on response to aspirin both in vitro and ex vivo is still controversial. We geno-typed a population of 148 healthy individuals for the C50T/A-842G haplotype. Thirty of them underwent low-dose aspirin (100 mg daily) treatment for four weeks and were followed up for seven days after withdrawal. In this subgroup, we evaluated the thromboxane-dependence of biochemical and functional indexes used to monitor the antiplatelet effect of low-dose aspirin. Among the 148 subjects studied, 10 were heterozygous for the C50T/A-842G haplotype (6.7%) and only one was homozygous for the 50T/-842G haplotype (0.67%). In the group on low-dose aspirin, serum thromboxane (TX) B2 as well as urinary 11-dehydro-TXB2 and arachidonic acid (AA)-induced aggregation were similarly suppressed in carriers and non-carriers of the 50T/-842G haplotype, with an increase until basal levels of all the parameters within seven days after withdrawal. We found no relationship between the 50T/-842G haplotype and the so-called phenomenon of aspirin resistance. Platelet cyclooxygenase activity, as reflected by serum TXB2, was uniformly and persistently suppressed by low-dose aspirin in both carriers and non carriers of these polymorphisms.

scholarly journals Comparative assessment of Montreal Cognitive Assessment (MOCA) and Minimental State Examination (MMSE) in apolipoprotein E (APOE) ɛ4 allele carriers in epilepsy

2016 ◽  
Vol 03 (01) ◽  
pp. 007-011 ◽  
Author(s):  
Amirthalingam Palanisamy ◽  
Natham Rajendran ◽  
Mukundhu Narmadha ◽  
Ruckmani Ganesvaran
Keyword(s):  
Cognitive Impairment ◽  
Apolipoprotein E ◽  
Cognitive Assessment ◽  
High Sensitivity ◽  
Educational Status ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
Normal Cognitive Function ◽  
E4 Allele ◽  
State Examination

AbstractBackground/Aim Mini mental state examination (MMSE) is a widely accepted tool till date to investigate cognitive status; however, its sensitivity is questioned by few studies. Alternately, Montreal cognitive assessment (MOCA) is considered more effective with high sensitivity to assess cognitive status than MMSE. The usefulness of MOCA is well established in assessing cognitive status in patients in various disorders. Apolipoprotein E (APOE) ɛ4 allele is identified as one of the risk factors associated with cognitive impairment on MMSE; however, the usefulness of MOCA on the association between APOE ɛ4 allele and cognitive impairment is not clearly established and hence the present study.Methods This prospective study recruited 123 subjects diagnosed as tonic-clonic seizures in the study site during the study period.Results Gender and educational status showed normal cognitive function on MMSE but showed cognitive impairment on MOCA. Among epilepsy patients, all APOE ɛ4 carriers showed mild to severe cognitive impairment on MOCA but differences in cognitive status were observed in this population as well as in APOE ɛ4 non-carriers on MMSE.Conclusion Thus, the present study demonstrates the sensitivity of MOCA over MMSE in detecting cognitive impairment in epilepsy.

Abstract 2640: Montreal Cognitive Assessment as a Short and Valuable Cognitive Evaluation in Acute Stroke

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
ANNA POGGESI ◽  
MARCO PASI ◽  
EMILIA SALVADORI ◽  
DOMENICO INZITARI ◽  
Leonardo PANTONI
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Acute Stroke ◽  
Acute Phase ◽  
Cognitive Assessment ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
Independent Effect ◽  
Stroke Patients

Background: Stroke patients are at high risk of developing dementia, but no agreement exists on what instrument should be used in the acute stroke phase to detect patients at higher risk of cognitive decline. Our aims were to investigate: 1) the feasibility and applicability of the Montreal Cognitive Assessment (MoCA) test in the acute phase of stroke; 2) the predictive value of MoCA on the diagnosis of cognitive impairment. Methods: Consecutive stroke patients (ischemic or hemorrhagic) admitted to our Stroke Unit were evaluated with MoCA between 5-9 days after stroke. Pre-morbid functional and cognitive status were assessed by a structured interview to caregivers. Neuroimaging information was collected regarding index and pre-existing lesions (number and site of lesions, leukoaraiosis, atrophy). Clinical and neuropsychological follow-up was scheduled after 6 months. Results: From December 2009 to December 2010, out of 208 patients with stroke, 138 (66%) were enrolled [mean age 69.1+/-15.0; males 62%; mean NIHSS score 5.7+/-7.7]. Non-enrolment was mostly due to unfitting of the time window inclusion criteria. MoCA was applicable to 114/138 (83%) of enrolled patients and the mean score was 17.9+/-7.2. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR(95% CI)=1.4(1.2-1.7) for each point] and left sided lesions [OR(95% CI)=13.3(1.8-97.9)]. After 6 months, 73 patients (53%) have been re-assessed: 40 had cognitive impairment (6 dementia, 34 MCI), while the remaining 33 did not show any cognitive impairment. Using logistic regression model, considering clinical variables such as age, gender, years of schooling, NIHSS, and pre-morbid cognitive status, MoCA was the only predictor of cognitive decline [OR(95% CI)=1.4(1.2-1.6) for each test point]. When adding neuroimaging features to the model, the independent effect of MoCA was only slightly attenuated [OR(95% CI)=1.4(1.1-1.7)]. The other independent predictor of cognitive decline turned out to be leukoaraiosis severity [OR(95%CI)=0.4(0.2-0.9) for each point of the van Swieten scale]. Conclusions: Our preliminary results indicate that the MoCA is feasible and applicable in the acute phase of stroke. Moreover, MoCA seems to have a predictive effect on the diagnosis of cognitive decline at 6-month follow-up, making it a good candidate for cognitive screening in stroke setting.

Abstract TP412: Predicting Pharmacokinetic versus Pharmacodynamic Aspirin Resistance in Patients

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Erica S Westphal ◽  
Michelle M Rainka ◽  
Michelle Amsler ◽  
Traci Aladeen ◽  
Caitlin Snyder ◽  
...  
Keyword(s):  
Aspirin Resistance ◽  
Secondary Prophylaxis ◽  
In Vitro Test ◽  
Reasonable Accuracy ◽  
Platelet Response ◽  
Clinical Tool ◽  
Patient Will ◽  
Vitro Test ◽  
Higher Doses

20%-40% of patients being treated with aspirin for secondary prophylaxis of stroke or myocardial infarction may derive no antiplatelet effects. Early identification of patients as pharmacokinetically or pharmacodynamically resistant to aspirin has the potential to become an invaluable clinical tool, reducing delays to optimal treatment, cardiovascular events, and healthcare costs. This study tested the capability of an assay that was previously developed in healthy volunteers, to differentiate between these two types of resistance in patients. Patients who needed aspirin treatment in the course of normal medical care were included. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to a maximum 325 mg daily occurred every 10-14 days based on the results of whole blood impedance aggregation testing to the agonists, collagen (1 ug/mL, 5 ug/mL) and arachidonate (0.5 mM). The in vitro test was conducted in triplicate by performing the same aggregometry test on blood samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Resistance was defined as a response to collagen 1 ug/mL >10 ohms, and/or response to arachidonate >6 ohms, and/or the ratio of collagen 1 to 5 ug/mL >0.5. Patients were excluded if they had any disorders affecting platelet function, an abnormal CBC, alcohol use within 24 hours of a test, NSAID use, or had any conditions that would affect absorption. Of the 36 patients included who were compliant with their 81 mg aspirin regimen based on pill count, 16 were found to be resistant to 81 mg of aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten actually remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose of aspirin while six actually did. No statistical difference was found between predicted aspirin response and actual aspirin response (p=0.61). Sensitivity was 83% and specificity was 80%. In conclusion, results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin therapy necessitating an alternative antiplatelet regimen. Larger, multi-site studies are inevitably needed.

Influence of Previous-Year Physical Activity on the Cognition of Older COPD Patients During Exacerbation

2020 ◽  
Vol 17 (5) ◽  
pp. 519-524
Author(s):  
Irene Torres-Sánchez ◽  
Araceli Ortiz-Rubio ◽  
Irene Cabrera-Martos ◽  
María Granados-Santiago ◽  
Isabel López-Torres ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Assessment ◽  
Health Impact ◽  
Cognitive Status ◽  
Activity Level ◽  
Montreal Cognitive Assessment ◽  
Chronic Obstructive ◽  
Copd Exacerbation ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Background: Growing evidence demonstrates the negative health impact of physical inactivity. Our aim was to examine the influence of previous-year physical activity (PA) on the cognition of chronic obstructive pulmonary disease (COPD) patients during exacerbation. Methods: Observational study. One hundred and fifty-one patients with COPD exacerbation were recruited over a period of 3 years and divided in 2 groups according to their previous activity level. Sociodemographic, anthropometric, and clinical variables were collected. Our main outcome measures were previous-year PA level, measured using the Modified Baecke Physical Activity Questionnaire and cognitive status measured using the Montreal Cognitive Assessment. Results: The cognitive variables that exhibited significant differences (P < .05) according to PA level were the visuoconstructional skills subscore, attention subscore, language subscore, orientation subscore, and Montreal Cognitive Assessment total score, with worse results in the sedentary group. Based on the relationships between total scores, the Baecke score was positively correlated with the Montreal Cognitive Assessment total score (r = .457). Conclusions: The cognitive status of COPD patients during an exacerbation is related to previous-year PA level. Previous-year PA level should be taken into consideration when patients with a COPD exacerbation are evaluated.

Montreal cognitive assessment for evaluating cognitive impairment in Huntington’s disease: a systematic review

CNS Spectrums ◽  
2020 ◽  
pp. 1-19
Author(s):  
Elena Cecilia Rosca ◽  
Mihaela Simu
Keyword(s):  
Cognitive Impairment ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Assessment ◽  
Cognitive Status ◽  
Montreal Cognitive Assessment ◽  
Cutoff Score ◽  
Index Test ◽  
Cross Sectional ◽  
Cross Sectional Studies

Abstract Objective This study aims to systematically review evidence of the accuracy of the Montreal Cognitive Assessment (MoCA) for evaluating the presence of cognitive impairment in patients with Huntington’s disease (HD) and to outline the quality and quantity of research evidence available about the use of the MoCA in this population. Methods We conducted a systematic literature review, searching four databases from inception until April 2020. Results We identified 26 studies that met the inclusion criteria: two case–control studies comparing the MoCA to a battery of tests, three studies comparing MoCA to Mini-Mental State Examination, two studies estimating the prevalence of cognitive impairment in individuals with HD and 19 studies or clinical trials in which the MoCA was used as an instrument for the cognitive assessment of participants with HD. We found no cross-sectional studies in which participants received the index test (MoCA) and a reference standard diagnostic assessment composed of an extensive neuropsychological battery. The publication period ranged from 2010 to 2020. Conclusions In patients with HD, the MoCA provides information about disturbances in general cognitive function. Even if the MoCA demonstrated good sensitivity and specificity when used at the recommended threshold score of 26, further cross-sectional studies are required to examine the optimum cutoff score for detecting cognitive impairments in patients with HD. Moreover, more studies are necessary to determine whether the MoCA adequately assesses cognitive status in individuals with HD.

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