Silent Brain Infarction Research Articles

Visceral adiposity index is associated with silent brain infarct in a healthy population

Visceral adiposity index (VAI) has been associated with various cardio-metabolic diseases; however, there is limited information about its association with cerebrovascular diseases. In this study, we evaluated the relationship between VAI and silent brain infarct (SBI). We evaluated a consecutive series of healthy volunteers over the age of 40 between January 2006 and December 2013. SBI was defined as an asymptomatic, well-defined lesion with a diameter ≥ 3 mm with the same signal characteristics as the cerebrospinal fluid. VAI was calculated using sex-specific equations as described in previous studies. A total of 2596 subjects were evaluated, and SBI was found in 218 (8%) participants. In multivariable analysis, VAI (adjusted odds ratio [aOR] = 1.30; 95% confidence interval [CI] 1.03–1.66; P = 0.030) remained a significant predictor of SBI after adjustment for confounders. The close relationship between VAI and SBI was prominent only in females (aOR = 1.44; 95% CI 1.00–2.07; P = 0.048). In the evaluation between VAI and the burden of SBI, VAI showed a positive dose–response relationship with the number of SBI lesions (P for trend = 0.037). High VAI was associated with a higher prevalence and burden of SBI in a neurologically healthy population.

Silent brain infarcts and white matter lesions in patients with asymptomatic carotid stenosis.

The association of carotid atherosclerosis with silent brain infarcts (SBIs) and white matter lesions (WMLs) currently remains unknown. This study aims to compare SBIs, deep white matter lesions (DWMLs), and periventricular white matter lesions (PWMLs) in ipsilateral and contralateral hemispheres to internal carotid artery (ICA) stenosis, and investigate their association with stenosis grade in patients with asymptomatic ≥ 50% unilateral extracranial ICA stenosis. Patients without previous history of stroke and/or transient ischemic attack who had ≥ 50% stenosis in unilateral ICA on carotid color Doppler ultrasound were enrolled in the study. Patient demographics, vascular risk factors and ICA stenosis grades; number, location, and size of SBIs, DWMLs, and PWMLs in ICA territory were evaluated in both hemispheres using magnetic resonance imaging of the brain. Of the 69 patients, 53 had 50-69% (76.8%) and 16 had ≥ 70% (23.2%) unilateral ICA stenosis. There was no statistically significant difference in SBIs between ipsilateral and contralateral hemispheres to ≥ 50% ICA stenosis. Comparison of ICA stenoses as 50-69% and ≥ 70% revealed a greater number of patients with SBI in ipsilateral hemisphere to ≥ 70% stenosis compared to contralateral (p = 0.025). The number of SBIs was also higher in ipsilateral hemisphere to ≥ 70% stenosis compared to contralateral (p = 0.022). While DWMLs and PWMLs did not differ between hemispheres, frequency of Fazekas grade1 DWMLs was lower in ipsilateral hemisphere to either 50-69% or ≥ 70% ICA stenosis compared to contralateral (p = 0.035 and p = 0.025, respectively). Results of the present study indicate that stenosis grade may be relevant in the association between asymptomatic carotid stenosis and SBIs, and ≥ 70% stenosis may pose a risk of SBI development.

Prevalence and Risk Factors of Silent Brain Infarction in Patients with Aortic Stenosis

Introduction: Silent brain infarction (SBI) is an independent risk factor for subsequent symptomatic stroke in the general population. Although aortic stenosis (AS) is also known to be associated with an increased risk of future symptomatic stroke, little is known regarding the prevalence and risk factors for SBI in patients with AS. Methods: The study population comprised 83 patients with severe AS with no history of stroke or transient ischemic attack and paralysis or sensory impairment (mean age 75 ± 7 years). All patients underwent brain magnetic resonance imaging to screen for SBI and multidetector-row computed tomography to quantify the aortic valve calcification (AVC) volume. Comprehensive transthoracic and transesophageal echocardiography were performed to evaluate left atrial (LA) abnormalities, such as LA enlargement, spontaneous echo contrast, or abnormal LA appendage emptying velocity (<20 cm/s), and complex plaques in the aortic arch. Results: SBI was detected in 38 patients (46%). Multiple logistic regression analysis indicated that CHA₂DS₂-VASc score and estimated glomerular filtration rate (eGFR) were independently associated with SBI (p < 0.05), whereas LA abnormalities and AVC volume were not. When patients were divided into 4 groups according to CHA₂DS₂-VASc score and eGFR, the group with a higher CHA₂DS₂-VASc score (≥4) and a lower eGFR (<60 mL/min/1.73 m²) had a greater risk of SBI than the other groups (p < 0.05). Conclusion: These findings indicate that AS is associated with a high prevalence of SBI, and that the CHA₂DS₂-VASc score and eGFR are useful for risk stratification.

Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Artery Stenosis: Design and Rationale of a Randomized Phase II Clinical Trial.

Patients with stroke or transient ischemic attacks (TIAs) and internal carotid artery stenosis harbor an increased risk of recurrent stroke especially within 2 weeks after the first event. In addition, the revascularization procedure itself (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) is associated with both clinically apparent and silent brain infarctions, mainly caused by the embolic nature of the ruptured carotid plaque. The glycoprotein VI (GPVI) fusion protein Revacept is a highly specific antithrombotic drug without direct inhibition of systemic platelet function that might reduce periprocedural distal embolization from the vulnerable ruptured plaque located at the internal carotid artery. By shielding collagen at the site of vascular injury, Revacept inhibits plaque-mediated platelet adhesion and aggregation, while not directly affecting systemic hemostasis. In this phase II study, 158 patients with symptomatic carotid artery stenosis with recent TIA or stroke were randomized to receive a single dose of either Revacept (40 or 120 mg) or placebo. All patients were on standard secondary preventive therapy (statins and platelet inhibition) and underwent CEA, CAS, or best medical therapy according to current guidelines. The efficacy of Revacept was evaluated by exploratory assessment of new diffusion-weighted imaging lesions on magnetic resonance imaging after the revascularization procedure; a combination of cardiovascular events (ischemic and hemorrhagic stroke, TIA, myocardial infarction, or coronary intervention) and bleeding complications served to assess clinically critical patients' outcome and safety. This exploratory phase II randomized, double-blind clinical trial provides valuable insights on the safety, tolerability, and efficacy of Revacept in patients with symptomatic carotid artery stenosis.

Brain imaging biomarkers of carotid artery disease.

Extracranial carotid artery atherosclerotic disease is a major contributor to ischemic stroke. Carotid atherosclerotic disease can present with a spectrum of findings ranging from mild carotid intima-media thickness to high-risk vulnerable carotid plaque features and carotid stenosis. Before leading to clinically overt stroke or transient ischemic attack, there may be other markers of downstream ischemia secondary to carotid atherosclerotic disease. In this review article, we will review some of the imaging findings that may be seen downstream to carotid artery disease on various imaging modalities, including hemodynamic and perfusional abnormalities which may be seen on CT, MR, or using other advanced imaging techniques, white matter hyperintensities on brain imaging, silent or covert brain infarctions, cerebral microbleeds, and regional and generalized cerebral volume loss. Many of these imaging findings are seen routinely on brain magnetic resonance imaging in patients without overt clinical symptoms. Despite frequently being asymptomatic, many of these imaging findings are also strongly associated with increased risk of future stroke, cognitive impairment, and even mortality. We will review the existing evidence underpinning the associations between these frequently encountered imaging findings and carotid artery atherosclerotic disease. Future validation of these imaging findings could lead to them being powerful biomarkers of cerebrovascular health.

A cross-sectional study on metabolic similarities and differences between inpatients with schizophrenia and those with mood disorders

BackgroundOne of the main causes of death in psychiatric patients is cardiovascular diseases which are closely related with lifestyle-related diseases. Psychiatric disorders include schizophrenia and mood disorders, whose symptoms and treatment medicines are different, suggesting that they might have different metabolic disorders. Thus, we studied the differences of lifestyle-related diseases between schizophrenia and mood disorders in Japan.MethodsThis cross-sectional study was performed from 2015 to 2017. Study participants were 189 Japanese hospitalized patients (144 schizophrenia group, 45 mood disorders group) in the department of psychiatry at Kohnodai hospital. We examined physical disorders, metabolic status of glucose and lipid, estimated glomerular filtration rate (eGFR) and brain magnetic resonance imaging. We compared these data between schizophrenia and mood disorders groups using analysis of covariance or logistic regression analysis. In comparisons between inpatients with schizophrenia or mood disorders group and the standard, we quoted ‘The National Health and Nutrition Survey in Japan 2015’ by Ministry of Health, Labor and Welfare as the standard.ResultseGFR and prevalence of smoking were significantly lower in patients with mood disorder group than those with schizophrenia group by adjustment for age. In comparisons between patients with schizophrenia group or mood disorders group and each standard, the ratio of silent brain infarction (SBI) and cerebral infarction were significantly high in both groups. Schizophrenia group showed significantly higher prevalence of diabetes, low high-density lipoprotein (HDL) cholesterolemia, metabolic syndrome and smoking than the standard. Mood disorders group had significantly high prevalence of low HDL-cholesterolemia compared with the standard. Fasting blood glucose and HbA1c were significantly higher in schizophrenia group and female mood disorders group than the standard. Female mood disorders group had significantly decreased eGFR with increased ratio of eGFR < 60 ml/min than the standard.ConclusionsParticipants of both groups had increased ratio of SBI and cerebral infarction, accompanied with glucose and lipid disorders. Compared with schizophrenia group, mood disorders group showed significantly low eGFR and prevalence of smoking.

Homocysteinemia is Associated with the Presence of Microbleeds in Cognitively Impaired Patients

Background & ObjectiveHomocysteine is possibly associated with cerebral small vessel diseases such as leukoaraiosis, silent brain infarction and cerebral microbleeds, which are in turn associated with cognitive dysfunction. We aimed to examine the relationships between cerebral microbleeds (CMBs) and plasma total homocysteine (tHcy) level, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cognitive function. MethodsA total of 819 patients with memory disturbance who visited a dementia clinic consecutively were included in this study. We retrospectively collected demographic, clinical and laboratory data including tHcy level, MTHFR C677T polymorphism and Mini-Mental State Examination (MMSE). All patients underwent brain MRI including fluid attenuated inversion recovery (FLAIR) image and T2*-weighed gradient-echo (GRE) image. Logistic regression analysis was performed to test the association between risk factors and the presence of microbleeds. ResultsOne hundred and sixty-one (19.7%) patients had CMBs, of whom 88 (54.7%) had CMBs in the lobar region. CMBs were more common in older hypertensive male patients with hyperhomocysteinemia. In multivariable analysis, plasma tHcy remained an independent predictor of the presence of CMBs after adjusting other confounders (OR: 1.035, 95% CI: 1.009-1.062, p = 0.009). Higher plasma tHcy level was also associated with number of CMBs, TT MTHFR genotype, and lower MMSE scores. ConclusionsElevated plasma tHcy level is related to high prevalence of CMBs and cognitive dysfunction. Lowering plasma tHcy could be helpful in cognitively impaired patients who have CMBs or the MTHFR TT genotype.

Acute retinal arterial ischaemia: silent brain infarcts prevalence and short-term recurrence.

The purpose was to evaluate, in a consecutive series of patients with isolated acute retinal ischaemia, the proportion of patients with acute silent brain infarcts (SBIs) on diffusion-weighted imaging (DWI) and to assess risk of recurrence within 3months. In all, 103 consecutive patients with isolated acute retinal ischaemia (central retinal artery occlusion, branch retinal artery occlusion or transient monocular vision loss) were included between January 2015 and December 2016. They all had cerebral magnetic resonance imaging including DWI as well as a standardized aetiological workup and 3months of follow-up. The presence of DWI-positive cerebral lesions was recorded. Main clinical and radiological characteristics between DWI-positive and DWI-negative patients were compared. Of the 103 patients (including 42 transient monocular vision loss), 20 (19.5%) had SBIs on DWI, which were ipsilateral to the acute retinal ischaemia in 30% and involved different and/or multiple vascular territories in 70% of cases. Ipsilateral carotid stenosis and occlusion were respectively identified in 17 and eight patients whereas cardioaortic embolism was found in 19 patients. Overall, patients with and without acute SBIs were comparable. The topography of SBIs was related to the aetiology of the acute retinal ischaemia. At 3 months of follow-up, one patient suffered from ischaemic stroke and five had recurrent retinal ischaemia. Irrespective of the baseline characteristics of the patients, SBIs are present in about 20% of patients with isolated acute retinal ischaemia and may be of interest in the aetiological workup. Overall risk of recurrence is low, favoured by rapid aetiological workup and appropriate treatment.

Silent brain infarction after minimally invasive cardiac surgery with retrograde perfusion.

There is no report on silent brain infarction (SBI) after minimally invasive cardiac surgery (MICS) with retrograde perfusion. Thus, the current study aimed to investigate the incidence of SBI after MICS using magnetic resonance imaging (MRI). This study included 174 patients who underwent MICS with retrograde perfusion between July 2014 and July 2018. Preoperative computed tomography (CT) angiography was routinely performed and vascular pathology was evaluated for patient selection. Postoperative MRI was performed to investigate the occurrence of SBI. Out of the total 174 patients, 26 (14.9%) presented with SBI. A total of 61 SBI lesions were found in the 26 patients; of these, 34 (56%) SBI lesions were in the right hemisphere and 27 (44%) in the left hemisphere. SBIs were primarily observed in the posterior cerebral artery territory. Multivariate analysis revealed aortic stenosis to be the only risk factor of SBI. Retrograde perfusion via femoral cannulation may not increase the incidence of SBI in selected MICS patients based on preoperative CT findings.

Predictors and Consequences of Silent Brain Infarction in Patients with Asymptomatic Carotid Stenosis

AimSilent brain infarction (SBI) is associated with an increased risk of stroke in patients with asymptomatic carotid stenosis (ACS), and is therefore one of the criteria for performing carotid endarterectomy (CEA). Despite an extensive literature, this issue is still a matter of debate. Aim of the present work was to evaluate incidence and predictors of SBI in patients undergoing CEA for ACS, and to investigate its possible impact on CEA outcome. MethodsAll patients submitted to CEA in a single academic center from 2005 to 2019 were prospectively inserted into a specific database. The presence of SBI was evaluated by preoperative computed tomography (CT), considering exclusively infarctions in the carotid territories from an athero-embolic source. Preoperative characteristics were investigated as possible risk factor for SBI at the uni- and multivariate analysis. The impact of SBI on stroke occurrence after CEA was also evaluated. ResultsIn the designated period, over a total of 1288 ACS considered and submitted to CEA, 105 (8.2%) were associated with SBI. Male sex, hypertension, dyslipidaemia, smoking, contralateral carotid occlusion and severity of carotid stenosis were associated with SBI at the univariate analysis; preoperative statin therapy showed to be a protective factor. At the multivariate analysis, contralateral carotid occlusion and severity of stenosis were independently associated with SBI (OR: 3.16, 95%CI 1.62–6.18, P=.001; OR: 1.04, 95%CI 1.01–1.07, P=.004, respectively), with statin therapy confirmed as a protective factor (OR: 0.60, 95%CI: 0.40–0.92, P=.002). Overall post-CEA stroke rate was 0.9%, with a higher post-operative risk independently predicted by the presence of SBI (OR:4.23, 95%CI: 1.40–12.73, P=.01). ConclusionSBI is present in 8% of patients with ACS, and is significantly associated with contralateral carotid occlusion and severity of the carotid stenosis. Statin therapy reduces the occurrence of this phenomenon. The presence of SBI should be carefully considered in indication to CEA since it significantly increases the surgical risk

Incidence and Risk Factors for Silent Brain Infarction After On-Pump Cardiac Surgery: A Meta-analysis and Meta-regression of 29 Prospective Cohort Studies.

Silent brain infarction (SBI) happens at a considerable rate after on-pump cardiac surgery. Though termed silent, SBI is related to unfavorable clinical outcomes including higher incidence of future stroke and neurocognitive impairment in the general population. The risk factors of SBI have not been fully identified in both individual studies and several meta-analyses addressing the topic. In this meta-analysis, we aimed to conduct meta-regression analysis for the first time to explore risk factors for SBI after on-pump cardiac surgery. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Medline, Embase, Central, Web of Science, and Wiley databases were searched for relevant studies. Preoperative patient baseline characteristics and intraoperative surgical parameters were extracted from included studies. For meta-regression, a P value of less than 0.1 was considered statistically significant in both univariable and multivariable analyses. Twenty-nine studies with 1478 patients were included in this meta-analysis. The summarized SBI rate after on-pump cardiac surgery was 37% (95% CI 0.27-0.47, P < 0.0001). Heterogeneity between studies was significant (I2 = 94.9%, P < 0.0001). In multivariable meta-regression, we found that age (coefficient 0.014, 95% CI 0.001-0.029, P = 0.043), diabetes (coefficient 0.006, 95% CI - 0.001 to 0.013, P = 0.075), and proportion of CABG (coefficient - 0.001, 95% CI - 0.003 to 0.0003, P = 0.096) were significantly associated with SBI incidence. From the meta-regression, we concluded that advanced age and diabetes were related to increased SBI incidence after on-pump cardiac surgery, while CABG procedure alone was associated with less SBI onset. Studies with more accurate diagnoses of SBI are required to add more conclusive evidence to the field.

Results of Carotid Endarterectomy in Patients With Asymptomatic Carotid Artery Stenosis With or Without Criteria for Surgery on the Basis of the Recent European Guidelines

The objective was to retrospectively compare perioperative outcomes of carotid endarterectomy (CEA) performed for >60% asymptomatic stenosis in patients with or without preoperative clinical and imaging features suggesting the need for intervention on the basis of the 2018 European Society of Cardiology-European Society for Vascular Surgery guidelines. From January 2008 to December 2018, there were 2501 consecutive CEAs performed in a single academic institution. Data concerning these interventions were prospectively collected in a dedicated database. A retrospective analysis of the database was performed, and 1956 interventions performed in asymptomatic patients were found. Those patients were divided in two subgroups: patients not candidates for intervention on the basis of the 2018 European Society of Cardiology-European Society for Vascular Surgery guidelines (life expectancy <5 years, predominantly hyperechoic plaques on preoperative duplex ultrasound, absence of silent brain infarction at preoperative computed tomography scan; 876 interventions, group 1) and patients fulfilling the suggested indications (1080 interventions, group 2). The two groups were compared in terms of clinical, anatomic, and surgical characteristics and perioperative (<30 days) outcomes with the χ2 test. There were no differences between the two groups in terms of demographics, risk factors, and comorbidities and preoperative features, except for the cited characteristics. Intraoperative features were also similar in the two groups, with >85% of the interventions performed under clinical monitoring of the neurologic status and about 95% of polyurethane patch angioplasty closures in both groups. Shunt insertion rate was significantly higher in group 1 (19.7%) than in group 2 (16%; P = .03). Perioperative mortality was 0.3% in group 1 (three patients) and 0.3% in group 2 (three cases; P = .7). At 30 days, there were seven neurologic events in group 1 (0.8%) and eight events in group 2 (0.7%; P = .8), of which six and five were strokes, respectively. Thirty-day stroke and death rates were 1% in group 1 and 0.75% in group 2 (P = .5). There were no differences between the two groups in terms of neck hematoma requiring surgical revision, cranial nerve injuries, and perioperative myocardial infarction. Patients in group 1 more frequently experienced a perioperative atrial fibrillation (13 cases [1.4%]) than patients in group 2 (5 cases [0.4%]; P = .02). CEA performed in patients who should not undergo intervention on the basis of the recent guidelines provided excellent perioperative results, similar to those of patients inside the suggested indications. A long-term comparison is necessary.

Cerebrovascular Disease and Cognition in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) affects both brain structure and function. Patients with CKD have a higher risk of both ischemic and hemorrhagic strokes. Age, prior disease history, hypertension, diabetes, atrial fibrillation, smoking, diet, obesity, and sedimentary lifestyle are most common risk factors. Renal-specific pathophysiologic derangements, such as oxidative stress, chronic inflammation, endothelial dysfunction, vascular calcification, anemia, gut dysbiosis, and uremic toxins are important mediators. Dialysis initiation constitutes the highest stroke risk period. CKD significantly worsens stroke outcomes. It is essential to understand the risks and benefits of established stroke therapeutics in patients with CKD, especially in those on dialysis. Subclinical cerebrovascular disease, such as of silent brain infarction, white matter lesions, cerebral microbleeds, and cerebral atrophy are more prevalent with declining renal function. This may lead to functional brain damage manifesting as cognitive impairment. Cognitive dysfunction has been linked to poor compliance with medications, and is associated with greater morbidity and mortality. Thus, understanding the interaction between renal impairment and brain is important in to minimize the risk of neurologic injury in patients with CKD. This article reviews the link between chronic kidney disease and brain abnormalities associated with CKD in detail.

No association between migraine frequency, white matter lesions and silent brain infarctions: a study in a series of women with chronic migraine.

It has been suggested that silent infarctions (SIs) and hyperintense white matter lesions (WMLs) are related to migraine frequency. We studied their prevalence and anatomical distribution in patients with chronic migraine (CM). A total of 96 women with CM [mean age 43 (range 16-65)years] and 29 women with episodic migraine (EM) [mean age 36 (range 16-58)years] underwent 1.5-T magnetic resonance imaging following the CAMERA protocol. The number, size and location of SIs and deep WMLs were recorded and a modified Fazekas scale was applied to assess periventricular WMLs. White matter lesions were found in 59 (61.5%) women with CM and 17 (58.6%) women with EM (odds ratio, 1.13; 95% confidence intervals, 0.48-2.62; P=0.784). The majority (63% CM and 71% EM) were small deep WMLs. Exclusive periventricular WMLs were exceptional. Of the 739 WMLs seen in patients with CM, 734 (99.3%) were hemispheric and mostly frontal (81%). Posterior fossa WMLs were seen in only five (5.2%) women with CM (always in the pons) and two (6.9%) women with EM. Age >45years was the only vascular risk factor associated with a higher WML number (median: 0<45years and 3>45years; P=0.004). We found seven SIs in six women with CM (6.3%). As compared with the expected prevalence at this age, this study confirms that the prevalence of WMLs, in most cases small, deep and frontal, was increased in CM and EM. However, our results do not support an association of WMLs or SIs with a higher frequency of attacks, but with the presence of vascular risk factors and mainly age >45years.

Prevalence and risk factors of silent brain infarcts in patients with AF detected by 3T-MRI.

Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause of SBI. The aim of this study is to determine the prevalence of and risk factors for SBI in patients with AF and low-to-moderate embolic risk according to CHADS2 and CHA2DS2VASc score. Patients with a history of AF based on medical records who scored 0-1 in the CHADS2 score were selected from the Seville urban area using the Andalusian electronic healthcare database (DIRAYA). Demographic and clinical data were collected and a 3T brain MRI was performed on patients older than 50years and with absence of neurological symptoms. 66 of the initial 443 patients (14.9%) and 41 of the 349 patients with low risk according to CHA2DS2VASc score (11.7%) presented at least 1 SBI. After adjusted multivariable analysis, an older age (OR 3.84, 95% CI 1.07-13.76) and left atrial (LA) enlargement (OR 3.13, 95% CI 1.15-8.55) were associated with SBI in the whole cohort, while only LA enlargement was associated with SBI in the low-risk cohort (OR 3.19, 95% CI 1.33-7.63). LA enlargement on echocardiogram was associated with SBI in patients with AF and low or moderate embolic risk according to CHADS2 and in the low-risk population according to CHA2DS2VASc. Although further studies are needed, a neuroimaging screening might be justified in these patients to guide medical therapies to improve stroke prevention.

High triglyceride-glucose index is associated with subclinical cerebral small vessel disease in a healthy population: a cross-sectional study

BackgroundThe triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases. However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD). In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH).MethodsWe assessed health check-up participants aged 40–79 years from 2006 to 2013. The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD. SBI was measured for both prevalence and burden. The WMH volume was quantitatively rated using a computer-assisted semi-automated technique.ResultsA total of 2615 participants were evaluated (median age: 56 years, male sex: 53%). In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06–1.81). Further quantitative analyses showed a positive dose–response relationship between the TyG index and SBI burden (P for trend = 0.006). In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (β = 0.084; 95% CI = 0.013 to 0.154). Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR.ConclusionsA high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population. This marker of IR could be a convenient and useful predictor of cSVD.

Atrial Fibrillation and Cognitive Impairment: An Associated Burden or Burden by Association?

Growing evidence suggests that atrial fibrillation (AF), in addition to its thromboembolic risk, is a risk factor for cognitive impairment (CI) via several pathways and mechanisms, further contributing to morbidity/mortality. Prior stroke is a contributor to CI, but AF is also associated with CI independently from prior stroke. Silent brain infarctions, microemboli and microbleeds, brain atrophy, cerebral hypoperfusion from widely fluctuating ventricular rates, altered hemostatic function, vascular oxidative stress, and inflammation may all exacerbate CI, particularly in patients with persistent/permanent rather than paroxysmal AF and with increased duration/burden of the arrhythmia. Brain magnetic resonance imaging is an important screening tool in eliciting and monitoring vascular and nonvascular lesions contributing to CI. Evidence is also emerging about the role of genetics in CI development. Anticoagulation and rhythm/rate control strategies may protect against CI preventing or slowing its progression or conversion to dementia, particularly at the early stages when CI may still be a treatable condition. Importantly, AF and CI share many common risk factors. Thus, screening for these 2 conditions and searching for and managing modifiable risk factors and potentially reversible causes for both AF and CI remains an important step toward prevention or amelioration of the impact incurred by these 2 conditions.

Assessment of the impact of EHR heterogeneity for clinical research through a case study of silent brain infarction

BackgroundThe rapid adoption of electronic health records (EHRs) holds great promise for advancing medicine through practice-based knowledge discovery. However, the validity of EHR-based clinical research is questionable due to poor research reproducibility caused by the heterogeneity and complexity of healthcare institutions and EHR systems, the cross-disciplinary nature of the research team, and the lack of standard processes and best practices for conducting EHR-based clinical research.MethodWe developed a data abstraction framework to standardize the process for multi-site EHR-based clinical studies aiming to enhance research reproducibility. The framework was implemented for a multi-site EHR-based research project, the ESPRESSO project, with the goal to identify individuals with silent brain infarctions (SBI) at Tufts Medical Center (TMC) and Mayo Clinic. The heterogeneity of healthcare institutions, EHR systems, documentation, and process variation in case identification was assessed quantitatively and qualitatively.ResultWe discovered a significant variation in the patient populations, neuroimaging reporting, EHR systems, and abstraction processes across the two sites. The prevalence of SBI for patients over age 50 for TMC and Mayo is 7.4 and 12.5% respectively. There is a variation regarding neuroimaging reporting where TMC are lengthy, standardized and descriptive while Mayo’s reports are short and definitive with more textual variations. Furthermore, differences in the EHR system, technology infrastructure, and data collection process were identified.ConclusionThe implementation of the framework identified the institutional and process variations and the heterogeneity of EHRs across the sites participating in the case study. The experiment demonstrates the necessity to have a standardized process for data abstraction when conducting EHR-based clinical studies.

Decrease of Patients with Brain Infarction through Evaluation of Relative Risk Value of Brain Infarction by Measurement of Protein-Conjugated Acrolein, IL-6 and CRP in Plasma Together with Age

Background: The Relative Risk Value of Brain Infarction (RRVBI) estimated by measuring protein-conjugated acrolein (PC-Acro), interleukin-6 (IL-6) and C-reactive protein (CRP) in plasma together with age finds silent (small) brain infarction (SBI) with 84% sensitivity and specificity. The purpose of this study is to evaluate the effect of RRVBI estimation on the disease onset probability of brain infarction. Methods: The number of patients with brain infarction was evaluated among the workers belonging to a union of the similar business health insurance. Results: The number of disease onset patients with brain infarction gradually decreased after the adoption of RRVBI during 7 years evaluation. Finally, the number of disease onset patients with brain infarction decreased to less than 35% compared with the number before the adoption of RRVBI. Conclusion: Our results suggest that RRVBI contributes to maintenance of quality of life (QOL) for the elderly.

Reduced Cognitive Assessment Scores Among Individuals With Magnetic Resonance Imaging-Detected Vascular Brain Injury.

Background and Purpose- Little is known about the association between covert vascular brain injury and cognitive impairment in middle-aged populations. We investigated if scores on a cognitive screen were lower in individuals with higher cardiovascular risk, and those with covert vascular brain injury. Methods- Seven thousand five hundred forty-seven adults, aged 35 to 69 years, free of cardiovascular disease underwent a cognitive assessment using the Digital Symbol Substitution test and Montreal Cognitive Assessment, and magnetic resonance imaging (MRI) to detect covert vascular brain injury (high white matter hyperintensities, lacunar, and nonlacunar brain infarctions). Cardiovascular risk factors were quantified using the INTERHEART (A Global Study of Risk Factors for Acute Myocardial Infarction) risk score. Multivariable mixed models tested for independent determinants of reduced cognitive scores. The population attributable risk of risk factors and MRI vascular brain injury on low cognitive scores was calculated. Results- The mean age of participants was 58 (SD, 9) years; 55% were women. Montreal Cognitive Assessment and Digital Symbol Substitution test scores decreased significantly with increasing age (P<0.0001), INTERHEART risk score (P<0.0001), and among individuals with high white matter hyperintensities, nonlacunar brain infarction, and individuals with 3+ silent brain infarctions. Adjusted for age, sex, education, ethnicity covariates, Digital Symbol Substitution test was significantly lowered by 1.0 (95% CI, -1.3 to -0.7) point per 5-point cardiovascular risk score increase, 1.9 (95% CI, -3.2 to -0.6) per high white matter hyperintensities, 3.5 (95% CI, -6.4 to -0.7) per nonlacunar stroke, and 6.8 (95% CI, -11.5 to -2.2) when 3+ silent brain infarctions were present. No postsecondary education accounted for 15% (95% CI, 12-17), moderate and high levels of cardiovascular risk factors accounted for 19% (95% CI, 8-30), and MRI vascular brain injury accounted for 10% (95% CI, -3 to 22) of low test scores. Conclusions- Among a middle-aged community-dwelling population, scores on a cognitive screen were lower in individuals with higher cardiovascular risk factors or MRI vascular brain injury. Much of the population attributable risk of low cognitive scores can be attributed to lower educational attainment, higher cardiovascular risk factors, and MRI vascular brain injury.