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The benefit of using antiplatelet monotherapy in acute ischemic stroke and secondary stroke prevention is well established. In the last few years, several large randomized trials showed that the use of short-term dual antiplatelet therapy in particular stroke subtypes may reduce the risk of recurrent ischemic events. The aim of this article is to provide a critical analysis of the current evidence and recommendations for the use of antiplatelet agents for stroke prevention.Long-term therapy with aspirin, clopidogrel, or aspirin plus extended-release dipyridamole is recommended for secondary stroke prevention in patients with noncardioembolic ischemic stroke. Short-term dual antiplatelet therapy with aspirin and clopidogrel is superior to antiplatelet monotherapy in secondary stroke prevention when used in patients with mild noncardioembolic stroke or high-risk transient ischemic attack. Dual therapy, however, is associated with an increased risk of major bleeding, particularly when the treatment is extended for greater than 30 days. Similarly, aspirin plus ticagrelor is superior to aspirin monotherapy for the prevention of recurrent ischemic stroke, although this combination is associated with a higher risk of hemorrhagic complications when compared to other dual antiplatelet regimens. Among patients who carry CYP2C19 genetic polymorphisms associated with a slow bioactivation of clopidogrel, short-term treatment with aspirin plus ticagrelor is superior to aspirin plus clopidogrel for the reduction of recurrent stroke; however, the use of ticagrelor is associated with a higher risk of any bleeding. In patients with symptomatic intracranial stenosis, aggressive medical management in addition to dual antiplatelet therapy up to 90 days is recommended. Antiplatelet therapy has an essential role in the management of ischemic stroke. The specific antiplatelet regimen should be individualized based on the stroke characteristics, time from symptom onset, and patient-specific predisposition to develop hemorrhagic complications.

ObjectiveGenome-wide association studies have identified1q22as a susceptibility locus for cerebral small vessel diseases (CSVDs), including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study we performed targeted high-depth sequencing of1q22in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown.Methods95,000 base pairs spanning1q22, includingSEMA4A, SLC25A44andPMF1/PMF1-BGLAPwere sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and RIFT analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, ChIP-Seq and ChIA-PET databases. Multivariable Mendelian randomization (MVMR) assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at1q22could be causally related to ICH risk.ResultsCommon and rare variant analyses prioritized variants inSEMA4A5’-UTR andPMF1intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that1q22is spatially organized in a single chromatin loop and that the genes therein belong to the same Topologically Associating Domain. ChIP-Seq and ChIA-PET data analysis highlighted the presence of long-range interactions between theSEMA4A-promoter andPMF1-enhancer regions prioritized by association testing. MVMR analyses demonstrated thatPMF1overexpression could be causally related to non-lobar ICH risk.InterpretationAltered promoter-enhancer interactions leading toPMF1overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at1q22, offering a potential new target for prevention of ICH and CSVD.

BackgroundSleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults.MethodsWe used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of Latinos. The primary model adjusted for age, sex, study centre, and measures of genetic ancestry. Associations are highlighted if their p-value

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body’s first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Background and Purpose: We investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack. Methods: Sociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression. Results: The analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia. Conclusions: Hispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02060344.

Fingolimod, an oral therapy for MS, decreases expression of membrane S1P1 receptors on CD4CD8, CD28, CD4, and CD69 expression on peripheral blood mononuclear cells was measured with flow cytometry. In vitro concanavalin A (ConA) activation of T cells, including CD8Fifty-nine patients with MS, 35 therapy-naive (16 clinically stable; 19 exacerbating) and 24 fingolimod-treated (19 clinically stable; 5 exacerbating), and 26 matched healthy controls (HCs) were compared. In therapy-naive patients, the CD8Fingolimod therapy markedly increases the percentage of CD8

The present review discusses the neurological complications associated with myocarditis of different etiologies.Myocarditis can be idiopathic or caused by different conditions, including toxins, infections, or inflammatory diseases. Clinical findings are variable and range from mild self-limited shortness of breath or chest pain to hemodynamic instability which may result in cardiogenic shock and death. Several neurologic manifestations can be seen in association with myocarditis. Tissue remodeling, fibrosis, and myocyte dysfunction can result in heart failure and arrhythmias leading to intracardiac thrombus formation and cardioembolism. In addition, peripheral neuropathies, status epilepticus, or myasthenia gravis have been reported in association with specific types of myocarditis. Multiple studies suggest the increasing risk of neurologic complications in patients with myocarditis. Neurologists should maintain a high suspicion of myocarditis in cases presenting with both cardiovascular and neurological dysfunction without a clear etiology.

Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin encephalopathy and progress to kernicterus spectrum disorder, a chronic condition characterized by hearing loss, extrapyramidal dysfunction, ophthalmoplegia, and enamel hypoplasia. Epidemiological data show that the implementation of universal pre-discharge bilirubin screening programs has reduced the rates of hyperbilirubinemia-associated complications. However, acute bilirubin encephalopathy and kernicterus spectrum disorder are still particularly common in low- and middle-income countries.The understanding of the genetic and biochemical processes that increase the susceptibility of defined anatomical areas of the central nervous system to the deleterious effects of bilirubin may facilitate the development of effective treatments for acute bilirubin encephalopathy and kernicterus spectrum disorder. Scoring systems are available for the diagnosis and severity grading of these conditions. The treatment of hyperbilirubinemia in newborns relies on the use of phototherapy and exchange transfusion. However, novel therapeutic options including deep brain stimulation, brain-computer interface, and stem cell transplantation may alleviate the heavy disease burden associated with kernicterus spectrum disorder. Despite improved screening and treatment options, the prevalence of acute bilirubin encephalopathy and kernicterus spectrum disorder remains elevated in low- and middle-income countries. The continued presence and associated long-term disability of these conditions warrant further research to improve their prevention and management.

This scientific statement describes a path to optimizing care for patients who experience an in-hospital stroke. Although these patients are in a monitored environment, their evaluation and treatment are often delayed compared with patients presenting to the emergency department, contributing to higher rates of morbidity and mortality. Reducing delays and optimizing treatment for patients with in-hospital stroke could improve outcomes. This scientific statement calls for the development of hospital systems of care and targeted quality improvement for in-hospital stroke. We propose 5 core elements to optimize in-hospital stroke care: 1. Deliver stroke training to all hospital staff, including how to activate in-hospital stroke alerts. 2. Create rapid response teams with dedicated stroke training and immediate access to neurological expertise. 3. Standardize the evaluation of patients with potential in-hospital stroke with physical assessment and imaging. 4. Address barriers to treatment potentially, including interfacility transfer to advanced stroke treatment. 5. Establish an in-hospital stroke quality oversight program delivering data-driven performance feedback and driving targeted quality improvement efforts. Additional research is needed to better understand how to reduce the incidence, morbidity, and mortality of in-hospital stroke.

Objective: There is a high prevalence of progressive cognitive impairment in intracerebral hemorrhage (ICH) survivors. We sought to identify gene expression changes, in association with long-term neurodegeneration, among patients 12-24 months post-ICH. Methods: The Recovery and Outcomes from StrokE (ROSE) study prospectively recruits patients with spontaneous, supratentorial ICH, collecting baseline peripheral blood samples and MRI with diffusion tract imaging (DTI). The Recovery of StrokE-Longitudinal Assessment with Neuroimaging (ROSE-LAWN) study performs long term follow-up at 12-24 months on cases enrolled in ROSE. We report on the first five cases enrolled in the ROSE-LAWN study from December 2020 to March 2021. Controls were matched to an overall ICH population by age, sex, and race. RNA-sequencing, aligned to human genome assembly GRCh38, was tested for differential gene expression. Canonical pathway enrichment and network analyses were computed for differentially expressed genes using Ingenuity Pathway Analysis, STRING and MCODE. Results: RNA-seq analysis of 5 ICH cases [male, 80%; median age, 61 (45 - 73); black, 40%; ICH volume, 14.88cc ± 13.07] and 13 controls [male, 54%; median age, 74 (69 - 79); black, 15%] identified 554 differentially expressed genes (genomic control adjusted p < 0.01), of which 24 met the false discovery rate correction for multiple comparisons (FDR < 0.05). The most significant difference was observed in hypoxia up-regulated 1 ( HYOU1), a heat shock protein related gene (p = 2.64E-11). Pathway analysis identified enrichment of dopamine and serotonin receptor signaling (p = 8.74E-03, 2.23E-02), cell cycle regulation (p = 1.75E-02) and agranulocyte adhesion pathways (p = 2.18E-02). Comparison of baseline and follow-up MRI DTI demonstrated extensive cortical tract degeneration, beyond the initial injury. Conclusion: These results provide novel evidence of significant gene expression changes occurring years after the initial ICH. Despite resolution of the ICH, persistent inflammation may correlate with progressive neurodegeneration and subsequent cognitive impairment in ICH survivors. Future studies with greater sample sizes are supported by this work.

Background: Life’s Simple 7 (LS7) include not smoking, having a healthy diet pattern, adequate physical activity, healthy body weight, and healthy blood pressure, cholesterol, and blood glucose. Better cardiovascular health metrics, measured by increasing LS7 scores, was associated with improved cognitive function. Purpose: Investigate the effect of LS7 on brain imaging outcomes in Hispanics/Latinos participating of the SOL-INCA sub-study. Methods: Hispanics/Latinos adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) who participated in the SOL - Investigation of Neurocognitive Aging Magnetic Resonance Imaging (SOL-INCA MRI) ancillary study underwent 3T brain MR imaging. LS7 scores and brain volumes were calculated. Volumes of interest included total brain, total and regional grey matter (frontal, temporal, parietal, and occipital), total white matter, total CSF, lateral ventricle, and white matter hyperintensity (WMH). WMH values were log-transformed. All MRI volumes were residualized for total cranial volume prior to analysis. The influence of LS7 scores on MRI outcomes was investigated using linear regression analysis adjusted by baseline characteristics. These included sex, height, immigrant status and years of residence in the US, age at MRI scan, Hispanic/Latino background, level of education, household income, insurance status, and language preference. Results: A total of 1,534 participants (males 33%) were included in the study. The average age (mean±SD) was 60±10 and the average LS7 score 7±2. In the adjusted model, increasing LS7 scores were associated with larger cerebral white (β=1.40; p≤0.001) and frontal grey volumes (β=0.33; p≤0.001) as well as smaller CSF (β=-1.26; p≤0.001) and WMH volumes (β=-0.01; p≤0.001). The association of higher LS7 scores and better brain MR outcomes was observed in both males and females. Conclusions: Higher LS7 scores are associated with improved biomarkers of brain health. Further studies are necessary to determine if the anatomic changes observed correlate with cognitive performance.

Marijuana is perceived as a harmless drug, and its recreational use has gained popularity among young individuals. The concentration of active ingredients in recreational formulations has gradually increased over time, and high-potency illicit cannabinomimetics have become available. Thus, the consumption of cannabis in the general population is rising. Data from preclinical models demonstrate that cannabinoid receptors are expressed in high density in areas involved in cognition and behavior, particularly during periods of active neurodevelopment and maturation. In addition, growing evidence highlights the role of endogenous cannabinoid pathways in the regulation of neurotransmitter release, synaptic plasticity, and neurodevelopment. In animal models, exogenous cannabinoids disrupt these important processes and lead to cognitive and behavioral abnormalities. These data correlate with the higher risk of cognitive impairment reported in some observational studies done in humans. It is unclear whether the effect of cannabis on cognition reverts after abstinence. However, this evidence, along with the increased risk of stroke reported in marijuana users, raises concerns about its potential long-term effects on cognitive function. This scientific statement reviews the safety of cannabis use from the perspective of brain health, describes mechanistically how cannabis may cause cognitive dysfunction, and advocates for a more informed health care worker and consumer about the potential for cannabis to adversely affect the brain.

OBJECTIVEThe utility of ICP monitoring and its benefit with respect to outcomes after ICH is unknown. The aim of this study was to compare intracerebral hemorrhage (ICH) outcomes in patients who underwent intracranial pressure (ICP) monitoring to those who were managed by care-guided imaging and/or clinical examination alone.METHODSThis was a retrospective analysis of data from the Ethnic/Racial variations of Intracerebral Hemorrhage (ERICH) study between 2010 and 2015. ICH patients who underwent ICP monitoring were propensity-score matched, in a 1:1 ratio, to those who did not undergo ICP monitoring. The primary outcome was 90-day mortality. Secondary outcomes were in-hospital mortality, hyperosmolar therapy use, ICH evacuation, length of hospital stay, and 90-day modified Rankin Scale (mRS) score, excellent outcome (mRS score 0–1), good outcome (mRS score 0–2), Barthel Index, and health-related quality of life (HRQoL; measured by EQ-5D and EQ-5D visual analog scale [VAS] scores). A secondary analysis for patients without intraventricular hemorrhage was performed.RESULTSThe ICP and no ICP monitoring cohorts comprised 566 and 2434 patients, respectively. The matched cohorts comprised 420 patients each. The 90-day and in-hospital mortality rates were similar between the matched cohorts. Shift analysis of 90-day mRS favored no ICP monitoring (p < 0.001). The rates of excellent (p < 0.001) and good (p < 0.001) outcome, Barthel Index (p < 0.001), EQ-5D score (p = 0.026), and EQ-5D VAS score (p = 0.004) at 90 days were lower in the matched ICP monitoring cohort. Rates of mannitol use (p < 0.001), hypertonic saline use (p < 0.001), ICH evacuation (p < 0.001), and infection (p = 0.001) were higher, and length of hospital stay (p < 0.001) was longer in the matched ICP monitoring cohort. In the secondary analysis, the matched cohorts comprised 111 patients each. ICP monitoring had a lower rate of 90-day mortality (p = 0.041). Shift analysis of 90-day mRS, Barthel Index, and HRQoL metrics were comparable between the matched cohorts.CONCLUSIONSThe findings of this study do not support the routine utilization of ICP monitoring in patients with ICH.

Stroke is a leading cause of death and disability worldwide. Inflammation and microvascular dysfunction have been associated with brain injury and long-term disability after both ischemic and hemorrhagic stroke. Recent studies have suggested a potential role of extracellular vesicles (EVs) as a link underlying these pathogenic processes. EVs are cell-derived particles enveloped by a lipid bilayer, containing proteins, lipids, and nucleic acids. From a functional standpoint, EVs can facilitate intercellular communication, including across the blood-brain barrier (BBB). Recent advances in EV research have shown a preferential release of EVs from specific cell types in the context of stroke, some of which were associated with increased neuroinflammation, microvascular dysfunction, and neuronal cytotoxicity while others offered a degree of neuroprotection. However, one historic challenge in the studies of EVs in stroke is the lack of consistent definitions and methods to analyze EVs, only recently updated in the MISEV2018 guidelines. Given limitations and complexity in the treatment of stroke, particularly delivery of therapeutics across the BBB, increasing attention has been paid towards manipulating EVs as one vehicle that can permit targeted therapeutic delivery to the central nervous system. These discoveries point towards a future where a better understanding of EVs will advance our knowledge of stroke-associated mechanisms of cerebral and systemic injury and contribute to the development of novel treatments. Here, we review the role that EVs play in ischemic and hemorrhagic stroke.

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for 5% of strokes but results in significant morbidity and mortality. In addition to systemic inflammation, up to half of patients develop cardiac injury; however, the relationship between systemic inflammation and cardiac injury after aSAH is unknown. We investigated changes in leukocyte counts in relation to cardiac dysfunction MATERIALS AND METHODS: We reviewed the records of consecutive patients with SAH at our large academic medical referral center. The inclusion criteria were aSAH and available cardiac troponin I (cTnI) levels within 48 h of admission. The primary outcome was cardiac injury, defined as cTnI ≥0.04 ng/mL (lab reference range 0.01-0.03 ng/mL). We compared baseline characteristics, including serum leukocyte counts and performed univariable and multivariable logistic regression analysis to determine whether changes in leukocyte subpopulations predict cardiac injury.Of 288 SAH patients, 250 met inclusion criteria. Of these, 116 (46.4%) had elevated cTnI. In univariable analysis, total leukocyte count (p 0.001), absolute neutrophil count (ANC, p 0.001), and absolute monocyte count (p = 0.013), were associated with elevated cTnI. in multivariable analysis, total leukocyte count (OR=1.079, p = 0.037) and ANC (OR=1.081, p = 0.044) remained predictors of elevated cTnI. Adjusted ANC distinguishes between aSAH patients with normal and elevated TnI (area under the curve=0.766, p 0.001) with specificity of 89.2%.Elevated total leukocytes and ANC are independently associated with cardiac injury in aSAH. Systemic inflammatory responses after aSAH may play a role in cardiac dysfunction, warranting additional studies to further characterize how cardiac inflammation after aSAH drives subsequent morbidity and mortality.

Recurrent stroke after ischemic stroke (IS) or high-risk transient ischemic attack (TIA) increases morbidity and mortality. Secondary stroke prevention strategies include modification of behavioral and vascular risk factors and antithrombotic use, including single or dual antiplatelet therapy (DAPT). In this review, we focus on DAPT indications, combinations, and treatment duration. Studies showed that for patients with mild to moderate non-cardioembolic strokes or those with symptomatic intracranial or mild extracranial stenosis (≤ 30% diameter reduction), short-term DAPT (21–90 days) with aspirin plus clopidogrel, compared with mono-antiplatelet therapy (MAPT), decreases recurrent stroke risk without significantly increasing major bleeding risk. The combination of aspirin plus extended release dipyridamole or cilostazol may confer decrease of risk for recurrent stroke with long-term use, at the expense of increasing major bleeding risk. Treatment with aspirin plus ticagrelor for a short time period is superior to aspirin monotherapy for decreasing risk for recurrent stroke, but significantly increases the risk for major bleeding. Short-term DAPT with aspirin plus clopidogrel, compared with MAPT, decreases risk for recurrent stroke without increasing major bleeding risk. Short-term DAPT with aspirin plus ticagrelor also reduces risk for recurrent stroke, but with a significant increase in the risk of major bleeding, compared with MAPT. Direct comparisons among different DAPT regimens are currently underway.

Key Points Question Does the prevalence and burden of risk factors for lobar and nonlobar intracerebral hemorrhage (ICH) differ among Black, Hispanic, and White populations? Findings In this case-control study of 3000 cases of ICH among Black, Hispanic, and White patients, the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E, were associated with lobar ICH in White but not Black and Hispanic patients; hypertension was a risk factor for both lobar and nonlobar ICH in all groups; and the mean age for ICH among Black and Hispanic patients was more than 10 years younger than that of their White counterparts. Black and Hispanic patients had a higher attributable risk percentage for treated or untreated hypertension and lack of health insurance than White patients. Meaning These findings suggest that potentially modifiable risk factors and social determinants of health are important contributors to the disproportionate ICH burden experienced by Black and Hispanic populations., This case-control study examines the prevalence, odds, and population attributable risk for established and novel risk factors for intracerebral hemorrhage, stratified by intracerebral hemorrhage location and racial/ethnic group., Importance Black and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations. Objective To examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group. Design, Setting, and Participants The Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020. Main Outcomes and Measures Case and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location. Results There were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals. Conclusions and Relevance This study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.

BACKGROUND Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm. METHODS We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm. RESULTS A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P

Background and purpose There is limited literature on the prevalence of incidental brain MRI findings in the Hispanic/Latino population, despite their increased prevalence of vascular disease and undertreatment of chronic conditions. The purpose of our study was to determine the prevalence of clinically relevant incidental findings on brain MRI examinations obtained as a part of the Study of Latinos-Investigation of NeuroCognitive Aging MRI (SOL-INCA-MRI) study. Methods Brain MRI examinations were obtained on 1389 participants in the SOL-INCA-MRI study, a cross-sectional ancillary study of the Hispanic Community Health Study, Study of Latinos, which is a longitudinal, community-based study. Study design of SOL-INCA-MRI involves imaging cognitively normal and participants with mild cognitive impairment. Brain MRI findings were categorized as Level 1 (normal), Level 1.5 (findings of unclear medical significance), Level 2 (potential medical concern), or Level 3 (medically urgent). This article focuses on Level 2 and Level 3 findings. Results The average age of the sample was 60.8 years (+/- 10.3 years), 66.1% were females. Level 2 and 3 findings were identified in 117 participants, (8.4%), of which 109 (7.8%) were recommended for medical follow-up (Level 2), and 8 (0.6%) were recommended for immediate medical attention (Level 3). Brain MRI findings consisted of chronic infarction in 33 (2.4%), vascular abnormality in 27 (1.9%), intracranial mass in 20 (1.4%), other intracranial findings in 28 (2.0%), and skull base/extracranial findings in 26 (1.9%) patients. Conclusion Incidental findings of clinical relevance were common among SOL-INCA-MRI participants, but rarely required urgent medical intervention.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) interacts with the low-density lipoprotein (LDL) receptor and, by enhancing its degradation, has a pivotal role in the regulation of cholesterol homeostasis. Two fully humanized monoclonal antibodies targeting PCSK9, evolocumab and alirocumab, are available for clinical use. PCSK9 inhibitors reduce LDL-C 30% more than ezetimibe and 60% more than placebo when added to statins. This reduction in LDL-C is accompanied by a decrease in the risk of major cardiovascular and cerebrovascular events. However, questions have been raised in relation to the cost-effectiveness of these medications. In this article, we review the clinical evidence on the use of PCSK9 inhibitors in lowering LDL-C and their effect on cerebrovascular health.

IntroductionCurrent guidelines recommend blood pressure (BP) lowering in patients after acute intracerebral haemorrhage (ICH) without guidance on initial choice of antihypertensive class. This study sought to determine if initial antihypertensive class differentially effects acute BP lowering in a large multiethnic ICH cohort.MethodsSubjects enrolled in the Ethnic/Racial Variations in ICH study between August 2010 and August 2017 with elevated admission BP and who received labetalol, nicardipine or hydralazine monotherapy as initial antihypertensive were analysed. Primary outcomes were systolic and diastolic BP changes from baseline to first BP measurement after initial antihypertensive treatment. Secondary outcomes included haematoma expansion (HE), hospital length of stay (LOS) and modified Rankin Score (mRS) up to 12 months after ICH. Exploratory outcomes assessed effects of race/ethnicity. Linear and logistic regression analyses, adjusted for relevant covariates, were performed to determine associations of antihypertensive class with outcomes.ResultsIn total, 1156 cases were used in analyses. Antihypertensive class was associated with diastolic BP change (p=0.003), but not systolic BP change (p=0.419). Initial dosing with nicardipine lowered acute diastolic BP than labetalol (least square mean difference (labetalol-nicardipine)=5.47 (2.37, 8.57), pConclusionIn this large acute ICH cohort, initial antihypertensive class was associated with acute diastolic, but not systolic, BP-lowering suggesting differential effects of antihypertensive agents.Trial registration numberNCT01202864.

Background: Dual antiplatelet treatment (DAPT) with aspirin plus clopidogrel for a limited time is recommended after minor noncardioembolic stroke. Methods: We performed a meta-analysis of all major studies that compared the efficacy and safety of DAPT versus monotherapy for the secondary prevention of recurrent stroke or transient ischemic attack. The primary outcomes were stroke and the composite of stroke, transient ischemic attack, acute coronary syndrome, and death from any cause. The safety outcome was major hemorrhage. Relative risk (RR) and 95% CIs were calculated. Heterogeneity was assessed by I 2 and Cochrane Q statistics. Results: The analysis included 27 358 patients, the quality of evidence was moderate to low, and the heterogeneity for all the comparisons was low ( I 2 ≤25%). Compared with monotherapy, DAPT reduced the risk of recurrent stroke (RR, 0.71 [95% CI, 0.63–0.81]) and composite outcome (RR, 0.76 [95% CI, 0.69–0.83]) but increased the risk of major bleeding (RR, 2.17 [95% CI, 1.45–3.25]). In the subgroup analysis, ≤30 days of DAPT increased the risk of hemorrhage relative to monotherapy (RR, 1.94 [95% CI, 1.08–3.52]). In the sensitivity analysis, the risk for hemorrhage with ≤30 days of DAPT after excluding the combination of aspirin plus ticagrelor was comparable to monotherapy (RR, 1.42 [95% CI, 0.77–2.60]). However, the risk for stroke recurrence and composite outcomes in the subgroup and sensitivity analyses remain decreased compared with monotherapy. Conclusions: DAPT decreases the risk of recurrent stroke and composite events compared with monotherapy. DAPT increases the risk of major hemorrhage, except if the treatment is limited to 30 days and does not include the combination of aspirin plus ticagrelor.

In the last few years, the attitude toward marijuana in many parts of the world has shifted from illicit to legalized for medical use and to decriminalized. In parallel, there has been a gradual increase in the consumption of this product in the general population, particularly among adolescents and young adults. Marijuana is generally perceived as a harmless drug. However, data obtained in observational studies and preclinical models have established associations between cannabis use and cardiovascular events. In addition, there is emerging evidence linking marijuana use to cerebrovascular complications. Here we provide a critical review of the literature with special emphasis on the association of cannabinoids with stroke and the possible pathogenic mechanisms involved. Ischemic and hemorrhagic stroke have been described in association with cannabis use, particularly in young individuals. Cerebral infarction remains the most commonly reported stroke subtype seen in marijuana users. Several pathogenic mechanisms have been proposed to explain this association, including multifocal intracranial stenosis, reversible cerebral vasoconstriction syndrome, and coexisting vascular risk factors. Cannabis use is increasingly recognized in young individuals presenting with acute stroke. Our understanding of the pathogenic mechanisms associated with cannabis use and stroke is limited but rapidly evolving. Healthcare providers should educate patients about the potential cardiovascular and cerebrovascular complications related to marijuana or cannabinoids use.

Background Children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are typically asymptomatic but contagious. The authors investigated the positivity rate of asymptomatic SARS-CoV-2 infection in pediatric dental patients. Methods The authors reviewed consecutive charts of children younger than 18 years scheduled for elective dental procedures from April 1, 2020, through August 1, 2020. All patients were screened for signs and symptoms of SARS-CoV-2 infection. Asymptomatic patients scheduled for dental procedures underwent polymerase chain reaction (PCR) testing for SARS-CoV-2. Sociodemographic characteristics were abstracted, and positivity rates were calculated. Variables for patients who were SARS-CoV-2 positive and SARS-CoV-2 negative were compared using Fisher exact and Mann-Whitney U tests. Results The sample size was 921. The median age was 6 years, and 50.9% were boys. The overall SARS-CoV-2 positivity rate was 2.3%. Age, insurance status, medical history, and dental diagnosis were comparable in patients who were SARS-CoV-2 positive and SARS-CoV-2 negative. Positivity rates were statistically higher for Hispanic or Latinx patients than other groups (P = .038). Conclusions Although the yield of testing was low, the systematic evaluation of asymptomatic pediatric dental cases via PCR resulted in the identification of SARS-CoV-2 carriers who could have been infectious. In this study, Hispanics or Latinx had a higher positivity rate than other demographic groups. Practical Implications PCR testing for SARS-CoV-2 of asymptomatic patients in pediatric dentistry adds value to the use of screening questionnaires for the identification of infected people who could be contagious.

Aneurysmal subarachnoid hemorrhage has a high mortality rate and, for those who survive this devastating injury, can lead to lifelong impairment. Clinical trials have demonstrated that cerebral vasospasm of larger extraparenchymal vessels is not the sole contributor to neurological outcome. Recently, the focus of intense investigation has turned to mechanisms of early brain injury that may play a larger role in outcome, including neuroinflammation and microvascular dysfunction. Extravasated blood after aneurysm rupture results in a robust inflammatory response characterized by activation of microglia, upregulation of cellular adhesion molecules, recruitment of peripheral immune cells, as well as impaired neurovascular coupling, disruption of the blood-brain barrier, and imbalances in endogenous vasodilators and vasoconstrictors. Each of these phenomena is either directly or indirectly associated with neuronal death and brain injury. Here, we review recent studies investigating these various mechanisms in experimental models of subarachnoid hemorrhage with special emphasis on neuroinflammation and its effect on microvascular dysfunction. We discuss the various therapeutic targets that have risen from these mechanistic studies and suggest the utility of a multi-targeted approach to preventing delayed injury and improving outcome after subarachnoid hemorrhage.

Background Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). Objective To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. Methods Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. Results Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. Conclusion This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

In the last few years, the attitude toward marijuana in many parts of the world has shifted from illicit to legalized for medical use and to decriminalized. In parallel, there has been a gradual increase in the consumption of this product in the general population, particularly among adolescents and young adults. Marijuana is generally perceived as a harmless drug. However, data obtained in observational studies and preclinical models have established associations between cannabis use and cardiovascular events. In addition, there is emerging evidence linking marijuana use to cerebrovascular complications. Here we provide a critical review of the literature with special emphasis on the association of cannabinoids with stroke and the possible pathogenic mechanisms involved.Ischemic and hemorrhagic stroke have been described in association with cannabis use, particularly in young individuals. Cerebral infarction remains the most commonly reported stroke subtype seen in marijuana users. Several pathogenic mechanisms have been proposed to explain this association, including multifocal intracranial stenosis, reversible cerebral vasoconstriction syndrome, and coexisting vascular risk factors. Cannabis use is increasingly recognized in young individuals presenting with acute stroke. Our understanding of the pathogenic mechanisms associated with cannabis use and stroke is limited but rapidly evolving. Healthcare providers should educate patients about the potential cardiovascular and cerebrovascular complications related to marijuana or cannabinoids use.

Introduction: Up to 50% of subarachnoid hemorrhage (SAH) patients develop cardiac injury. The relationship between early systemic inflammation and cardiac injury after SAH is unknown. Here we examined changes in blood leukocyte counts and their relationship to cardiac dysfunction. Methods: We reviewed the medical records of 288 SAH patients admitted to our Comprehensive Stroke Center. Patients were dichotomized based on elevated (≥0.04ng/mL) or normal (70%) from echocardiogram data. We performed univariate and multivariate logistic regression to establish the relationship between blood leukocyte counts and cardiac injury. Results: Of 288 SAH patients, 241 had TnI levels performed at the time of admission and 119 (49.4%) of these had elevated TnI on admission. Patients with elevated TnI were significantly older, had higher grade SAH, abnormal EF, and were more likely to have hypertension and dyslipidemia. 10 (4.1%) had low EF while 58 (24.1%) had high EF on admission echocardiogram. In univariate analysis, total leukocyte count (p Conclusions: Blood total leukocyte count is an independent predictor of cardiac injury in SAH patients. This highlights the role of inflammation in mediating cardiac dysfunction after brain hemorrhage, and raises questions regarding the potential of anti-inflammatory therapy for cardioprotection in SAH.

Objective: Studies in subarachnoid hemorrhage (SAH) animal models are limited to early timepoints, after which the brain is extracted to confirm hemorrhage. For long-term studies, blood is resorbed by the time of euthanasia and thus alternative methods of confirming SAH are necessary. Here, we used in vivo MRI to determine the presence, extent, and location of blood in the endovascular perforation rat model of SAH. Methods: Animals were divided into two groups - SAH and sham controls (no perforation). Rats were imaged at 24 hours in a 9.4T MRI scanner. T2-weighted imaging (T2WI) was used to quantify and localize the volume and extension of blood. T2WI was performed with a fast spin echo sequence with TR/TE = 5000/60 ms, FOV = 40x40 mm 2 , 0.75 mm slice thickness, and no interslice gap. SAH was identified as hypointense signal at the skull base, a normally hyperintense region due to cerebrospinal fluid in the basal cisterns. Regions of interest were identified and segmented manually. Pixels were converted to areas, and the total hypointense volume (V hypo ) was computed by summing all areas. V hypo was normalized to total brain volume (TBV) for each animal. Ability to detect blood via MRI was compared to the gold standard of direct visualization of blood after brain extraction using receiver operating characteristic (ROC) curves. The location of blood was plotted along a standardized antero-posterior axis. 3D reconstructions were developed in 3D Slicer to visualize the spatial distribution of hemorrhage. Results: V hypo values were 1.6±1.4 mm 3 sham (n = 8) and 7.5±3.9 mm 3 for SAH (n = 10) [p=0.0003]. This difference persisted when V hypo was normalized to TBV (p=0.0005). There was no difference in the TBV between groups (p=0.1493). V hypo distinguished between SAH and sham animals (p=0.001, area under curve = 0.963). A cutoff of V hypo = 4.63 mm 3 corresponded to 100% specificity and 80% sensitivity for confirming SAH. The spatial distribution of bleeding varied along the antero-posterior axis within the subarachnoid space. Conclusions: We developed an in vivo MRI method for the quantification of SAH blood volume and location in rats. This will be used for future long-term studies to confirm and grade severity of SAH.

Introduction: Perihematomal Edema (PHE) is a neuroimaging biomarker of secondary brain injury in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). There are limited data on racial/ethnic differences in the development of PHE. This dearth of data is partially driven by the time-consuming process of manually segmenting PHE. Leveraging a validated automated pipeline for PHE segmentation, we evaluated whether race and ethnicity influence baseline PHE volume in patients with ICH. Methods: The Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study is a prospective, multicenter study of ICH that recruited 1,000 adult participants from each of three racial/ethnic groups (non-Hispanic White, non-Hispanic Black, and Hispanic). We applied a previously validated deep learning algorithm to automatically determine PHE volumes on baseline CTs in these study participants. Quality control procedures were used to include only sufficiently accurate PHE measurements. Linear regression was used to identify factors associated with log-transformed PHE volume and to identify differences across Ethnic/Racial groups. Results: Our imaging pipeline provided good quality baseline PHE measurements on 2,008 out of 3,000 ERICH study participants. After excluding infratentorial hemorrhages (273) and those with missing or null baseline ICH volume (49), 1,686 remained for analysis (median age 59 [IQR 51-71], 687 [41%] female sex). Median PHE volume was 12.0 (IQR 4.8-27.1) for whites, 11.9 (IQR 4.5-26.1) for Hispanics and 8.3 (IQR 3.0-19.2) for blacks. Compared to Blacks, Hispanics (beta 0.22; 95%CI 0.11-0.32; p Conclusion: Race and ethnicity influence the volume of baseline PHE. Further studies are needed to validate our results and investigate the biological underpinnings of this difference.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. We describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease, and investigate the role of sex on outcome. Methods: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers from Chicago metropolitan area. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. Results: The study included 83 patients. Median age was 64 years and the majority were Blacks (47%) followed by Hispanics (28%) and whites (16%). Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Higher proportions of male experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p=0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared to female, males had higher mortality (38% vs. 13%; p=0.02) and were less likely to be discharged home (12% vs. 33%; p=0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR=1.47, 95% CI=1.03-2.09) Conclusion: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

Approximately one-third of strokes are cryptogenic in origin. These patients have a higher prevalence of patent foramen ovale (PFO) compared to individuals with stroke of known origin. It has been proposed that some cryptogenic strokes (CSs) can be caused by paradoxical embolism across a PFO. PFOs can be treated medically with antithrombotic agents and percutaneously with occluder devices. Large randomized clinical trials have found transcatheter PFO closure to be superior to medical treatment for the prevention of recurrent stroke in young patients with CS. However, the superiority of PFO closure over medical treatment in unselected populations has not been demonstrated. In this chapter, we review the evidence supporting PFO closure and the selection of patients for such intervention.

Neurodegenerative dementias, such as Alzheimer's disease, and vascular cognitive impairment were once considered unrelated processes. Emerging evidence, however, shows that both conditions often coexist and that vascular risk factors in midlife predispose to the development of cognitive decline later in older adults. In addition, recent advanced in basic science research have elucidated key underpinnings of this association. In this chapter, we review the clinical and basic science data that explain the relationship between vascular risk factors, heart disease, and cognitive decline.

OBJECTIVES To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage. DESIGN Individual patient data meta-analysis of three studies of intracerebral hemorrhage. SETTING Two randomized clinical trials and one multiethnic observational study. PATIENTS Patients with spontaneous, nontraumatic intracerebral hemorrhage. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion. CONCLUSIONS Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.

Background A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified at the end of 2019. The disease caused by SARS-CoV-2 was named COVID-19. The main purpose of this review was to provide an overview of SARS-CoV-2. Methods The authors searched the MEDLINE database for clinical studies related to virus characteristics, pathogenesis, diagnosis, transmission mechanisms, and treatment options. Results As of January 27, 2021, the number of infected people and deaths associated with COVID-19 worldwide were approximately 100 million and 2 million, respectively. The manifestations of COVID-19 are variable, and the severity is affected by age and preexisting medical conditions. Children and adolescents are usually asymptomatic or have mild symptoms. Older adults, in comparison, may experience severe illness and have disproportionally elevated mortality. Among those who survive, some may experience enduring deficits. The viral load is particularly elevated in saliva and oropharynx, which constitute potential sources of infection. The diagnosis of the disease may be confounded by factors related to the replicating cycle of the virus, viral load, and sensitivity of the diagnostic method used. As of January 2021, COVID-19 has no cure but can be prevented. Its treatment is based on supportive care along with antiviral medications and monoclonal antibodies. In severe cases with multiorgan involvement, mechanical ventilation, dialysis, and hemodynamic support may be necessary. Conclusions COVID-19 is a transmittable disease with a variable course. A substantial number of patients, particularly children, remain asymptomatic. Important advances have been made in the development of new treatments. However, the mortality in vulnerable populations remains elevated. Practical Implications The elevated viral load in the oral cavity and pharynx suggests that oral health care professionals could get infected through occupational exposure. Providers should understand the variables that influence the yield of diagnostic studies because false-negative results can occur.

Neurodegenerative dementias, such as Alzheimer's disease, and vascular cognitive impairment were once considered unrelated processes. Emerging evidence, however, shows that both conditions often coexist and that vascular risk factors in midlife predispose to the development of cognitive decline later in older adults. In addition, recent advanced in basic science research have elucidated key underpinnings of this association. In this chapter, we review the clinical and basic science data that explain the relationship between vascular risk factors, heart disease, and cognitive decline.