Silent Brain Infarction Research Articles

Performance assessment of an electrostatic filter-diverter stent cerebrovascular protection device. Is it possible not to use anticoagulants in atrial fibrilation elderly patients?

Stroke is the second leading cause of death worldwide. Nearly two-thirds of strokes are produced by cardioembolisms, and half of cardioembolic strokes are triggered by Atrial Fibrillation (AF), the most common type of arrhythmia. A more recent cause of cardioembolisms is Transcatheter Aortic Valve Replacements (TAVRs), which may onset post-procedural adverse events such as stroke and Silent Brain Infarcts (SBIs), for which no definitive treatment exists, and which will only get worse as TAVRs are implanted in younger and lower risk patients. It is well known that some specific characteristics of elderly patients may lower the safety and efficacy of anticoagulation therapy, making it a real urgency to find alternative therapies. We propose a device consisting of a strut structure placed at the base of the treated artery to model the potential risk of cerebral embolisms caused by dislodged debris of varying sizes. This work analyzes a design based on a patented medical device, intended to block cardioembolisms from entering the cerebrovascular system, with a particular focus on AF, and potentially TAVR patients. The study has been carried out in two stages. Both of them based on computational fluid dynamics (CFD) coupled with Lagrangian particle tracking method. The first stage of the work evaluates a variety of strut thicknesses and inter-strut spacings, contrasting with the device-free baseline geometry. The analysis is carried out by imposing flowrate waveforms characteristic of both healthy and AF patients. Boundary conditions are calibrated to reproduce physiological flowrates and pressures in a patient's aortic arch. In the second stage, the optimal geometric design from the first stage was employed, with the addition of lateral struts to prevent the filtration of particles and electronegatively charged strut surfaces, studying the effect of electrical forces on the clots if they are considered charged. Flowrate boundary conditions were used to emulate both healthy and AF conditions. Results from numerical simulations coming form the first stage indicate that the device blocks particles of sizes larger than the inter-strut spacing. It was found that lateral strut space had the highest impact on efficacy. Based on the results of the second stage, deploying the electronegatively charged device in all three aortic arch arteries, the number of particles entering these arteries was reduced on average by 62.6% and 51.2%, for the healthy and diseased models respectively, matching or surpassing current oral anticoagulant efficacy. In conclusion, the device demonstrated a two-fold mechanism for filtering emboli: while the smallest particles are deflected by electrostatic repulsion, avoiding microembolisms, which could lead to cognitive impairment, the largest ones are mechanically filtered since they cannot fit in between the struts, effectively blocking the full range of particle sizes analyzed in this study. The device presented in this manuscript offers an anticoagulant-free method to prevent stroke and SBIs, imperative given the growing population of AF and elderly patients.

Rationale and design of a randomized clinical trial evaluating the efficacy of mechanical neuroprotection in reducing the risk of silent brain infarcts associated with percutaneous left atrial appendage closure: study protocol for a LAAC-SBI trial

BackgroundLeft atrial appendage closure (LAAC) procedures prevent cardioembolic stroke in patients with atrial fibrillation who have contraindications to oral anticoagulant medications. However, these procedures carry certain risks of peri-procedural complications. One such complication is silent brain infarcts (SBI), which can lead to cognitive impairment and mood disturbances. The implementation of mechanical neuroprotection systems during LAAC procedures may reduce the risk of SBI and associated cognitive and mood disorders.MethodsThe LAAC-SBI trial is a prospective, multicenter, randomized, and double-blind interventional study. The study aims to enroll a total of 240 patients, with 120 patients allocated to each group. The study group will evaluate the use of the Sentinel CPS during LAAC, while the control group will undergo LAAC procedures without the Sentinel CPS. The primary endpoint of the study is the number of new SBIs or stroke foci detected by diffusion-weighted magnetic resonance imaging (DW MRI). Secondary endpoints include deterioration of cognitive function, development of dementia syndrome, and occurrence of depressive disorders. These endpoints will be assessed using questionnaire tools such as the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), Controlled Oral Word Association Test (COWAT), and Hospital Anxiety and Depression Scale (HADS). The observational period for patients in the study is 2 years.DiscussionIf the study demonstrates a favorable outcome with reduced incidence of SBI and improved cognitive and mood outcomes in patients receiving cerebral protection devices during LAAC, it will have significant implications for clinical management standards. This would support the use of neuroprotection devices not only for LAAC but also in procedures such as atrial fibrillation ablation or transcatheter mitral valve interventions, where the risk of embolic events and subsequent brain injury may also be present.Trial registrationClinicalTrials.gov NCT05369195. Registration on 11.05.2022.

Screening for cognitive impairment in adults with sickle cell disease: a systematic review and meta-analysis

Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can have devastating consequences on quality of life, employment, and social functioning. Early recognition of neurovascular disease is a prerequisite for the timely optimization of medical care and to connect patients to adaptive resources. While cognitive impairment has been well described in children, currently available data are limited in adults. As a result, guidance on the optimal cognitive screening strategies in adults is scarce. We conducted a systematic review to identify the different screening tools that have been evaluated in SCD. A meta-analysis was performed to estimate the prevalence of suspected cognitive impairment in this population. In this qualitative synthesis, we present 8 studies that evaluated 6 different screening tools. Patient characteristics that impacted on cognitive screening performance included age, education level, and a prior history of stroke. We report a pooled prevalence of 38% [14-62%] of suspected cognitive impairment. We discuss the relative benefits and limitations of the different screening tools to help clinicians select an adapted approach tailored to their specific patients’ needs. Further studies are needed to establish and validate cognitive screening strategies in patients with diverse cultural and educational backgrounds.

Epidemiology and Risk Factors for Stroke in Chronic Kidney Disease: A Narrative Review.

Patients with chronic kidney disease (CKD) have a higher risk ofboth ischemic and hemorrhagic stroke. This association appears to be partly independent from the higher prevalence of established risk factors for stroke in patients with CKD, including hypertension and atrial fibrillation. In the present review we aim to discuss the impact of CKD on the risk of stroke and stroke-related consequences, and explore the pathophysiology underpinning the increased risk of stroke in patients with CKD. We cover the clinical association between renal dysfunction and cerebrovascular disease including stroke, silent brain infarct, cerebral small vessel disease, microbleeds, and white matter hyperintensity, and discuss the underlying mechanisms.

Biomarker, Imaging, and Clinical Factors Associated With Overt and Covert Stroke in Patients With Atrial Fibrillation.

Atrial fibrillation is a major risk factor for stroke and silent brain infarcts. We studied whether a multimodal approach offers additional insights to the CHA2DS2-VASc score in predicting stroke or new brain infarcts on magnetic resonance imaging (MRI) over a 2-year follow-up. Swiss-AF is a prospective, multicenter cohort study of patients with known atrial fibrillation. We included patients with available brain MRI both at enrollment and 2 years later. The dates of the baseline and follow-up visits ranged from March 2014 to November 2020. The primary outcome was assessed 2 years after baseline and was defined as a composite of clinically identified stroke or any new brain infarct on the 2-year MRI. We compared a multivariable logistic regression model including prespecified clinical, biomarker, and baseline MRI variables to the CHA2DS2-VASc score. We included 1232 patients, 89.8% of them taking oral anticoagulants. The primary outcome occurred in 78 patients (6.3%). The following baseline variables were included in the final multivariate model and were significantly associated with the primary outcome: white matter lesion volume in milliliters (adjusted odds ratio [aOR], 1.91 [95% CI, 1.45-2.56]), NT-proBNP (N-terminal pro-B-type natriuretic peptide; aOR, 1.75 [95% CI, 1.20-2.63]), GDF-15 (growth differentiation factor-15; aOR, 1.68 [95% CI, 1.11-2.53]), serum creatinine (aOR, 1.50 [95% CI, 1.02-2.22]), IL (interleukin)-6 (aOR, 1.37 [95% CI, 1.00-1.86]), and hFABP (heart-type fatty acid-binding protein; aOR, 0.48 [95% CI, 0.31-0.73]). Overall performance and discrimination of the new model was superior to that of the CHA2DS2-VASc score (C statistic, 0.82 [95% CI, 0.77-0.87] versus 0.64 [95% CI, 0.58-0.70]). In patients with atrial fibrillation, a model incorporating white matter lesion volume on baseline MRI and selected blood markers yielded new insights on residual stroke risk despite a high proportion of patients on oral anticoagulants. This may be relevant to develop further preventive measures.

Plasma Neurofilament Light Chain Is Elevated after Transcatheter Aortic Valve Implantation

Introduction: Transcatheter aortic valve implantation (TAVI) is associated with a high incidence of new silent brain infarcts (SBIs) on postprocedural neuroimaging. A venous blood sample reflecting neuronal damage following TAVI could help identify patients with potential SBIs. We aimed to investigate if a biochemical marker of neuronal injury, neurofilament light chain (NFL), is elevated after TAVI. Methods: In this observational study, NFL was measured in plasma from 31 patients before and after TAVI. Multivariable regression analysis was performed to investigate any effect of clinical- and procedure-related factors on differences in NFL levels before and after TAVI. Results: Samples were collected 41 (14–81) days before and 44 (35–59) days after TAVI, median (interquartile range). Median age was 81 (77–84) years, and 35% were female. No patient had any overt procedure-related neurological complications. The geometric mean (95% confidence interval) of the NFL concentration was 30 (25–36) pg/mL before TAVI and 48 (39–61) pg/mL, after TAVI, p <0.001. None of the included variables in the multiple linear regression model were statistically significantly associated with the difference in levels before and after TAVI. Conclusions: NFL levels in plasma were higher after TAVI as compared with levels before, with a mean increase of 60% (18 pg/mL). Further studies including neuroimaging and cognitive outcomes are needed to understand the potential value of measuring NFL in relation to TAVI.

1715-P: Osteopenic Obesity Is Associated with Small Vessel Disease in Old Adults—The Bunkyo Health Study

Obesity is one of the most important causes of metabolic disorders and cardiovascular events. Indeed, while the presence of cerebral small vessel disease (SVD) that includes silent brain infarcts, cerebral white matter lesions, and microhemorrhage increased the risk of stroke &amp;gt; 3-fold, and dementia &amp;gt; 2-fold, respectively, obesity has been identified as a risk factor for SVD. On the other hand, low bone mineral density (BMD), is also recognized as a risk factor for SVD. Whereas obesity is generally associated with high BMD, it has recently been reported that there is a special subtype of osteopenic obesity in which obesity and low BMD coexist. Thus, we hypothesized that this osteopenic obesity is at high risk for SVD. To test this hypothesis, we studied 1531 (641 male and 890 female) old adults aged 65 to 85 years without a history of stroke (Bunkyo Health Study). All subjects underwent dual-energy X-ray absorptiometry, brain MRI, and blood sampling, and they were classified into four groups according to the presence or absence of obesity and osteopenia (men) or osteoporosis (women) diagnosed by the BMD at the hip joint. The mean age of the subjects was 73.0 years. The prevalence of osteopenic obesity was 7.8% and 8.0% for men and women, respectively. While overall prevalence of SVD was 25% in men and 22% in women, the prevalence of SVD in osteopenic obesity was 46% and 42%, respectively. Logistic regression analysis revealed that odds ratio [95% CI] for SVD in control, obesity, osteopenia/osteoporosis and osteopenic obesity were 1.00, 1.203 [0.730-1.982], 0.970 [0.670-1.549] and 3.024 [1.560-5.861] in men and 1.00, 1.452 [0.818-2.575], 1.548 [1.012-2.368], 2.747 [1.489-5.069] in women, respectively. In conclusion, osteopenic obesity was independently associated with the presence of SVD in old adults without a history of stroke. Disclosure N.Ito: None. Y.Yoshizawa: None. H.Watada: Research Support; Boehringer Ingelheim Japan, Inc., Mitsubishi Tanabe Pharma Corporation, LifeScan Diabetes Institute, Eli Lilly Japan K.K., Sun Pharmaceutical Industries Ltd., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Merck Sharp &amp; Dohme Corp., Sanwa Kagaku Kenkyusho, Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Novo Nordisk, Abbott Japan Co., Ltd., Astellas Pharma Inc., Merck Sharp &amp; Dohme Corp., Kissei Pharmaceutical Co., Ltd., AstraZeneca, Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Eli Lilly Japan K.K. Y.Tamura: None. H.Kaga: None. Y.Someya: None. H.Tabata: None. S.Kakehi: None. M.Kiya: None. T.Tajima: None. H.Naito: None. Funding Strategic Research Foundation at Private Universities (S1411006); Ministry of Education, Culture, Sports, Science and Technology of Japan (18H03184); Mizuno Sports Promotion Foundation; Mitsui Life Social Welfare Foundation

Impacts of cerebral small vessel disease on global and domain‐specific cognition

AbstractBackgroundThe 2021 Alzheimer’s Association International Conference press release forecasted global dementia cases to triple by 2050, due to the major contribution of increases in vascular risk factors. The Global Vascular Risk Score (GVRS) was developed to predict vascular events using a point‐based index for risk factor variables, though has demonstrated to be a significant predictor of global and domain‐specific cognitive performance in a multi‐ethnic cohort (Rundek, T. et al. Global Vascular Risk Score and CAIDE Dementia Risk Score Predict Cognitive Function in the Northern Manhattan Study. J Alzheimers Dis 73, 1221‐1231 (2020)). However, more than half of the variance in global and domain‐specific cognitive performance is still unexplained by GVRS variables. We sought to explain additional variance in cognitive performance by addition of MRI biomarkers of cerebral small vessel disease to the GVRS model.MethodWe included 1290 subjects from the multiethnic Northern Manhattan Study population (age 64+/‐8 years, 40% women, 66% Hispanic, 17% non‐Hispanic Black, 15% non‐Hispanic White, education 10+/‐5 years). Multivariate linear regression models were employed to assess the added value of the cerebral small vessel disease MRI measures (white matter hyperintensity volume, silent brain infarcts, cerebral microbleeds, and perivascular spaces) beyond GVRS variables in explaining more variance in global and domain‐specific (episodic memory, executive function, semantic memory, and processing speed) cognitive performance. The explained variance (R2) of the GVRS model was compared to the proposed model with added imaging markers to determine their predictive performance. Statistical significance was determined using F‐statistic difference test between the models.ResultThe explained variance (R2) and F‐statistic for models of global and domain‐specific cognition are in the table. Addition of MRI measures significantly improved the model for global cognition (F(4, 1108) = 2.68, p &lt; 0.05) and domain‐specific cognitive performance models of episodic memory (F(4, 1096) = 3.34, p &lt; 0.01) and processing speed (F(4, 1096) = 2.40, p &lt; 0.05).ConclusionMRI measures of cerebral small vessel disease explain more variance in global cognition, episodic memory, and processing speed than GVRS factors alone. However, most of the variance in cognitive performance remains unexplained.

Impact of serum leptin and adiponectin levels on the development of brain infarcts in patients with mild cognitive impairment and Alzheimer’s disease

AbstractBackgroundThe adipokines leptin and adiponectin have been associated with the development of atherosclerosis and the risk of cerebral infarctions. According to pre‐clinical studies, however, they play a protective role against ischemic brain damage. In this study we analysed the relationship between serum leptin and adiponectin levels and the onset or progression of silent brain infarctions in a population of subjects with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).MethodAll data were extracted from the ADNI database. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographic and anamnestic data, neuropsychological test results, tau, phosphotau and amyloid levels in CSF and regional brain metabolism with FDG‐PET data were also extracted. The determination of the number of silent cerebral infarctions was performed on baseline brain MRI. The final population includes 566 subjects, with 58 normal controls, 396 MCI and 112 AD.ResultLeptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the three groups. Multivariate regression analysis in patients with cognitive impairment (MCI + AD, 508 subjects) showed that leptin levels were significantly associated with BMI, arterial hypertension and female sex. By stratifying the three diagnostic groups by the presence or absence of baseline infarctions, leptin levels were significantly higher in patients with AD and brain infarcts than in patients with AD without brain infarcts. However, multivariate logistic regression analysis at baseline for the presence or absence of brain infarcts did not confirm the predictive value of leptin. Multivariate longitudinal analysis did not attribute predictive value to serum leptin levels on the development of silent brain infarcts in this MCI and AD population.ConclusionThe evidence on the pathogenetic or protective role of adipokines on ischemic brain damage in the literature is mixed. In this population affected by MCI and AD, serum leptin and adiponectin levels are not associated with the development of brain infarctions; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population.

Effects of silent brain infarction on the hemorrhagic transformation and prognosis in patients with acute ischemic stroke after intravenous thrombolysis.

Silent brain infarction (SBI) is a special type of stroke with no definitive time of onset, which can be found on pre-thrombolysis imaging examination in some patients with acute ischemic stroke (AIS). However, the significance of SBI on intracranial hemorrhage transformation (HT) and clinical outcomes after intravenous thrombolysis therapy (IVT) is uncertain. We aimed to explore the effects of SBI on intracranial HT and the 3-month clinical outcome in patients with AIS after IVT. We consecutive collected patients who were diagnosed with ischemic stroke and received IVT from August 2016 to August 2022, and conducted a retrospective analysis in this study. The clinical and laboratory data were obtained from hospitalization data. Patients were divided into SBI and Non-SBI groups based on clinical and neuroimaging data. We use Cohen's Kappa to assess the interrater reliability between the two evaluators, and multivariate logistic regression analysis was used to further assess the association between SBI, HT and clinical outcomes at 3 months after IVT. Of the 541 patients, 231 (46.1%) had SBI, 49 (9.1%) had HT, 438 (81%) had favorable outcome, 361 (66.7%) had excellent outcome. There was no significant difference in the incidence of HT (8.2 vs. 9.7%, p = 0.560) and favorable outcome (78.4% vs. 82.9%, p = 0.183) between patients with SBI and Non-SBI. However, patients with SBI had a lower incidence of excellent outcome than the patients with Non-SBI (60.2% vs. 71.6%%, p = 0.005). After adjustment for major covariates, multivariate logistic regression analysis disclosed that SBI was independently associated with the increased risk of worse outcome (OR = 1.922, 95%CI: 1.229-3.006, p = 0.004). We found that SBI was no effect for HT after thrombolysis in ischemic stroke patients, and no effect on favorable functional outcome at 3 months. Nevertheless, SBI remained an independent risk factor for non-excellent functional outcomes at 3 months.

Estimated Pulse Wave Velocity Inversely Associates with Cognition in the Northern Manhattan Study (S8.002)

Estimated Pulse Wave Velocity Inversely Associates with Cognition in the Northern Manhattan Study (S8.002)

Analysis of clinical and imaging characteristics of patients with freezing of gait in cerebral small vessel disease (P11-5.004)

<h3>Objective:</h3> This study aims to study the clinical and imaging characteristics of patients with freeing of gait (FOG) in Cerebral small vessel disease (CSVD). <h3>Background:</h3> FOG is prevalent in Parkinson’s disease in those with severe gait disorders. However, little is known about vascular FOG in patients with CSVD. <h3>Design/Methods:</h3> The current study is a case-control study. Symptomatic CSVD patients were recruited. Patients with FOG (CSVD-FOG) and without FOG (CSVD-no-FOG) were categorized into two groups. The differences of clinical and imaging characteristics in these two groups were studied. <h3>Results:</h3> In 444 symptomatic CSVD patients with gait testing records, 24 were CSVD-FOG. 72 CSVD-no-FOG patients were matched according to age and sex. Prevalence of vascular risk factors including hypertension, diabetes mellitus, and hyperlipidemia were not significantly different between two groups. In CSVD-FOG groups, 83.3% were claimed about gait disorder, and had a higher percentage of urinary disorders and impaired cognitive functions compared with CSVD-no-FOG. Patients with apathy were not different between two groups. In assessing quantitative gait parameters, CSVD-FOG patients had slower gait speed, shorter gait stride and gait length, lower gait height and wider gait width. For CSVD imaging burdens, the CSVD-FOG had similar white matter hyperintensity burden with CSVD-no-FOT. However, CSVD-FOG had higher prevalence of silent brain infarction (SBI) and cerebral microbleeds (CMBs) in location of whiter matter and brain stem. <h3>Conclusions:</h3> CSVD-FOG patients had severe clinical symptoms of gait disorder, cognitive impairment and urinary problems, as well as higher imaging burdens of SBI and CMBs in whiter matter and brain stem. <b>Disclosure:</b> Dr. Su has nothing to disclose. Miss Mao has nothing to disclose. Jiangxia Zhang has nothing to disclose. Mr. Zhu has nothing to disclose. Fei Han has nothing to disclose. Ming Yao has nothing to disclose. Lixin Zhou has nothing to disclose. Jun Ni has nothing to disclose. Dr. Fan has nothing to disclose. Feng Tian has nothing to disclose. Yi-Cheng Zhu has nothing to disclose.

Silent brain infarcts after carotid or vertebrobasilar artery stenting.

Stenting is an important treatment for preventing stroke. However, the effect of vertebrobasilar stenting (VBS) might be limited because of relatively high periprocedural risks. Silent brain infarcts (SBIs) are known as a predictor for future stroke. Because of anatomical differences, factors for SBIs might be different between carotid artery stenting (CAS) and VBS. We compared the characteristics of SBIs between VBS and CAS. We included patients who underwent elective VBS or CAS. Diffusion-weighted imaging was performed pre- and post-procedure to detect new SBIs. Clinical variables, occurrence of SBIs, and procedure-related factors were compared between CAS and VBS. Moreover, we investigated predictors of SBIs in each group separately. Ninety-two (34.2%) out of 269 patients had SBIs. SBIs were more frequently observed in VBS (29 [56.6%] vs. 63 [28.9%], p<.001). The risk of SBIs outside the stent-inserted vascular territory was higher in VBS compared to CAS (14 [48.3%] vs. 8 [12.7%], p<.001). Larger-diameter stents (odds ratio: 1.28, 95% confidence interval: 1.06-1.54, p = .012) and prolonged procedure time (1.01, [1.00-1.03], p = .026) increased the risk of SBIs in CAS, whereas only age increased the risk of SBIs in VBS (1.08 [1.01-1.16], p = .036). Compared to CAS, VBS was associated with longer procedure time, more residual stenosis, and more SBIs, especially outside the stent-inserted vascular territory. The risk of SBIs after CAS was associated with stent size and procedural difficulty. Only age was associated with SBIs in VBS. The pathomechanism of SBIs after VBS and CAS may be different.

Association of Left Atrial Strain With Ischemic Stroke Risk in Older Adults

The risk of ischemic stroke is higher among patients with left atrial (LA) enlargement. Left atrial strain (LAε) and LA strain rate (LASR) may indicate LA dysfunction when LA volumes are still normal. The association of LAε with incident ischemic stroke in the general population is not well established. To investigate whether LAε and LASR are associated with new-onset ischemic stroke among older adults. The Cardiovascular Abnormalities and Brain Lesions study was conducted from September 29, 2005, to July 6, 2010, to investigate cardiovascular factors associated with subclinical cerebrovascular disease. A total of 806 participants in the Northern Manhattan Study who were aged 55 years or older without history of prior stroke or atrial fibrillation (AF) were included, and annual follow-up telephone interviews were completed May 22, 2022. Statistical analysis was performed from June through November 2022. Left atrial strain and LASR were assessed by speckle-tracking echocardiography. Global peak positive longitudinal LAε and positive longitudinal LASR during ventricular systole, global peak negative longitudinal LASR during early ventricular diastole, and global peak negative longitudinal LASR during LA contraction were measured. Brain magnetic resonance imaging was used to detect silent brain infarcts and white matter hyperintensities at baseline. Risk analysis with cause-specific Cox proportional hazards regression modeling was used to assess the association of positive longitudinal LAε and positive longitudinal LASR with incident ischemic stroke, adjusting for other stroke risk factors, including incident AF. The study included 806 participants (501 women [62.2%]) with a mean (SD) age of 71.0 (9.2) years; 119 participants (14.8%) were Black, 567 (70.3%) were Hispanic, and 105 (13.0%) were White. During a mean (SD) follow-up of 10.9 (3.7) years, new-onset ischemic stroke occurred in 53 participants (6.6%); incident AF was observed in 103 participants (12.8%). Compared with individuals who did not develop ischemic stroke, participants with ischemic stroke had lower positive longitudinal LAε and negative longitudinal LASR at baseline. In multivariable analysis, the lowest (ie, closest to zero) vs all other quintiles of positive longitudinal LAε (adjusted hazard ratio [HR], 3.12; 95% CI, 1.56-6.24) and negative longitudinal LASR during LA contraction (HR, 2.89; 95% CI, 1.44-5.80) were associated with incident ischemic stroke, independent of left ventricular global longitudinal strain and incident AF. Among participants with a normal LA size, the lowest vs all other quintiles of positive longitudinal LAε (HR, 4.64; 95% CI, 1.55-13.89) and negative longitudinal LASR during LA contraction (HR, 11.02; 95% CI 3.51-34.62) remained independently associated with incident ischemic stroke. This cohort study suggests that reduced positive longitudinal LAε and negative longitudinal LASR are independently associated with ischemic stroke in older adults. Assessment of LAε and LASR by speckle-tracking echocardiography may improve stroke risk stratification in elderly individuals.

Abstract WP170: Validation Of Magnetically Induced Physiological Response Assessment To Identify Patients Likely Harboring Silent Brain Infarcts

Background: Silent brain infarcts (SBIs) are among the most potent risk factors for future symptomatic stroke and vascular cognitive impairment, increasing the hazard ratio up to 3.3-fold. But high costs make MRI screening for SBIs in asymptomatic patients cost-ineffective. The AHA/ASA 2017 Scientific Statement on silent cerebrovascular disease calls for research to develop techniques to identify people at higher risk of SBIs who could go on to targeted neuroimaging and intensive prevention intervention. We performed a derivation and validation study of such a tool, a magnetically induced physiological response assessment of brain network integrity. Methods: Multicenter international study conducted at 5 sites (3 US, 2 OUS), assessing direct electrophysiological imaging (DELPHI) technology that records brain network magnetically induced physiological response. One site recruited the derivation cohort and 4 the validation cohort. Healthy subjects ages 50-75 with at least one vascular RF underwent multiple evaluations including computerized cognitive testing, MR assessment of SBIs, gray matter volume, white matter integrity, and brain network physiological function using DELPHI measures of connectivity. MRI findings, including SBIs, were assessed by 3 blinded independent neuroradiologists. Results: The derivation cohort enrolled 220 subjects and validation cohort 264 subjects. Across both groups, age was 61.5 (±7.1), 57% were female, and leading vascular risk factors were obesity/overweight in 67%, hypertension in 51%, and dyslipidemia in 45%. Silent brain infarcts were present in 10.8% of individuals, among whom 92% had 1-4 SBIs and 8% had ≥ 5 SBIs. The validation cohort was tested using the DELPHI thresholds established in the derivation cohort. In the validation cohort, DELPHI assessment discriminated SBI positive patients with AUC=0.70, sensitivity 82%, specificity 65%, p=0.001. Conclusion: Brain network physiology evaluation using the DELPHI technology detects silent brain infarcts with substantial accuracy in the outpatient office setting. This system is a safe and reliable means to identify older individuals likely harboring silent brain infarcts who could go on to targeted neuroimaging and intensified prevention treatment.

Mechanisms and Clinical Manifestations of Cognitive Decline in Atrial Fibrillation Patients: Potential Implications for Preventing Dementia.

Atrial fibrillation (AF) patients face an approximate 1.5-fold increased risk of cognitive decline compared with the general population. Among poststroke AF patients, the risk of cognitive decline is even higher with an estimated threefold increase. This article provides a narrative review on the current evidence and highlights gaps in knowledge and areas for future research. Although earlier studies hypothesized that the association between AF and cognitive decline is mainly a consequence of previous ischemic strokes, more recent evidence also suggests such an association in AF patients without a history of clinical stroke. Because AF and cognitive decline mainly occur among elderly individuals, it is not surprising that both entities share multiple risk factors. In addition to clinically overt ischemic strokes, silent brain infarcts and other brain injury are likely mechanisms for the increased risk of cognitive decline among AF patients. Oral anticoagulation for stroke prevention in AF patients with additional stroke risk factors is one of the only proven therapies to prevent brain injury. Whether a broader use of oral anticoagulation, or more intense anticoagulation in some patients are beneficial in this context needs to be addressed in future studies. Although direct studies are lacking, it is reasonable to recommend optimal treatment of comorbidities and risk factors for the prevention of cognitive decline and dementia.

Abstract 130: History Of Pregnancy Induced Hypertension Is Associated With Markers Of Cerebral Small Vessel Disease: The Northern Manhattan Study And Washington Heights-Hamilton Heights-Inwood Columbia Aging Project

Background: A history of pregnancy-induced hypertension (PIH) is associated with higher risk of developing cerebrovascular disease. Data are lacking on the relationship between PIH, chronic hypertension, and MRI markers of cerebral small vessel disease (CSVD) in older people. Methods: We recruited parous individuals without dementia from the Northern Manhattan Study and the Washington Heights-Inwood Washington Heights-Hamilton Heights-Inwood Columbia Aging Project, two long-running prospective cohort studies in New York City. Detailed obstetric and medical histories were obtained by interview. We defined history of PIH as self-report of at least one pregnancy complicated by gestational hypertension, preeclampsia or eclampsia. We categorized participants as having no hypertension, current hypertension without history of PIH, or current hypertension with history of PIH. Number and location of infarcts and white matter hyperintensity (WMH) volume was assessed by MRI. We used generalized linear models to compare imaging outcomes between groups, adjusting for demographics and cardiovascular risk factors. To account for the effects of early onset hypertension, we performed a sensitivity analysis in NOMAS participants only, adjusting for hypertension as a time varying covariate. Results: A total of 221 participants were interviewed (mean age 69 years [SD 7.5]; 22% white, 28% non-Hispanic Black, 48% Hispanic) of whom 128 (58%) had current hypertension without history of PIH, and 16 (7%) had current hypertension with history of PIH. Adjusting for covariates, hypertensive participants with a history of PIH had higher WMH volume, but no difference in deep silent brain infarcts (Table). Conclusions: In a multiethnic cohort of older parous individuals, those with hypertension and a history of PIH had the highest volume of WMH, suggesting a higher burden of CSVD.

Association of Body Shape Index with Cerebral Small Vessel Disease

Introduction: A body shape index (ABSI) is an anthropometric index designed to reflect the influence of visceral fat. ABSI has been previously associated with various atherosclerosis, metabolic diseases, and cardiovascular diseases; however, relatively few studies have been conducted on cerebrovascular disease. In this study, we evaluated the association between ABSI and cerebral small vessel disease (cSVD) in health check-up participants. Methods: We evaluated consecutive health check-up participants between January 2006 and December 2013. As subtypes of cSVD, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of silent brain infarct (SBI) and cerebral microbleed (CMB). ABSI was calculated according to the following formula: ABSI (m^11/6/kg^−2/3) = waist circumference (m)/(body mass index [kg/m²]^2/3 × height [m]^1/2). Results: A total of 3,219 health check-up participants were assessed (median age, 56 years; male sex, 54.0%). In the multivariable analysis, ABSI was significantly associated with WMH volume (β = 0.107, 95% confidence interval [CI] = 0.013–0.200), SBI (adjusted odds ratio [aOR] = 1.62, 95% CI = 1.14–2.31), and CMB (aOR = 1.64, 95% CI = 1.16–2.33) after adjusting for confounders (per 100 m^11/6/kg^−2/3). Furthermore, ABSI showed a dose-response relationship with the burden of each cSVD pathology. Conclusions: High ABSI was associated with a higher burden of cSVD in health check-up participants. As ABSI showed close associations with all subtypes of cSVD, visceral fat may be a common risk factor penetrating cSVD pathologies.

Nomogram for Prediction of Postoperative Delirium after Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease under General Anesthesia.

Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson's disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson's disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium. A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56-13.02, p < 0.01) was the most important risk factor; other independent predictors were orthostatic hypotension (OR 3.42, 95% CI 0.90-13.06, p=0.07), inhibitors of type-B monoamine oxidase (OR 3.07, 95% CI 1.17-8.04, p=0.02), preoperative MRI with silent brain ischemia or infarction (OR 2.36, 95% CI 0.90-6.14, p=0.08), Hamilton anxiety scale score (OR 2.12, 95% CI 1.28-3.50, p < 0.01), and apolipoprotein E level in plasma (OR 1.48, 95% CI 0.95-2.29, p=0.08). The area under the receiver operating characteristic curve (AUC) was 0.76 (95% CI 0.66-0.86). A nomogram was established and showed good calibration and clinical predictive capacity. After bootstrap for internal verification, the AUC was 0.74 (95% CI 0.66-0.83). This study provides evidence for the independent inducing factors of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. By predicting the development of delirium, our model may identify high-risk groups that can benefit from early or preventive intervention.

Assessment of silent brain injury in patients undergoing elective percutaneous coronary intervention due to chronic total occlusion

Objective: Silent brain infarcts (SBI) are thromboembolic complications associated with cardiac surgery, diagnostic angiography, and percutaneous interventions. Serum neuron-specific enolase (NSE) is the proven biomarker for measuring neuronal damage. This study aimed to evaluate the incidence of SBI, defined as elevated NSE after coronary chronic total occlusion (CTO) intervention and elective coronary stenting. Design: The study population consisted of two patient groups: the CTO group included consecutive patients with coronary CTO intervention, and the control group consisted of patients who underwent elective coronary intervention. NSE blood levels were measured before and 12–18 h after the procedure. NSE blood levels of >20 ng/mL were considered SBI. Results: A total of 108 patients were included in the study. Of these, 55 (50.9%) had SBI after the procedure. The SBI rate was 59.7% in the CTO group and 39.1% in the control group. Patients with SBI were more likely to have diabetes mellitus, hyperlipidemia, higher HbA1c, higher total stent length, and longer procedural time. Multivariate logistic regression analysis showed that CTO procedure (odds ratio [OR]: 3.129; 95% confidence interval [CI]: 1.246–7.858; p < 0.015) and diabetes mellitus (OR: 2.93; 95% CI: 1.185–7.291; p < 0.020) are independent predictors of SBI. Conclusion: Our data suggest that SBI occurs more frequently after CTO intervention than after non-CTO intervention. Intervention complexity and patient clinical characteristics may explain the increased incidence.