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Sex and gender, as biological and social factors, significantly influence health outcomes. Among the biological factors, sex differences in vascular physiology may be one specific mechanism contributing to the observed differences in clinical presentation, response to treatment, and clinical outcomes in several vascular disorders. This review focuses on the cerebrovascular bed and summarizes the existing literature on sex differences in cerebrovascular hemodynamics to highlight the knowledge deficit that exists in this domain. The available evidence is used to generate mechanistically plausible and testable hypotheses to underscore the unmet need in understandingsex-specificmechanisms as targets for more effective therapeutic and preventive strategies. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial dysfunction, both in the brain and systemic circulation. Impairments in memory and cognition have been associated with cardiovascular diseases, but little is known about their relationships to abnormal cerebral endothelial function.Methods: We studied the cross-sectional association between sVCAM-1 and markers of cerebrovascular hemodynamics and cognitive function in 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. Cognitive function was assessed using the Hopkins Verbal Learning Memory Test and Trail Making Tests (TMTs) A and B. Global cognitive impairment was defined as Mini-Mental State Examination (MMSE) score less than 24. sVCAM-1 was measured by ELISA assay. Beat-to-beat blood flow velocity (BFV) and cerebrovascular resistance (CVR = mean arterial pressure / BFV) in the middle cerebral artery were assessed at rest by transcranial Doppler ultrasound.Results: sVCAM-1 concentrations were higher among participants with an MMSE score <24 versus ≥24 (1,201±417 vs 1,122±494ng/mL). In regression models adjusted for sociodemographic characteristics and health conditions, increasing levels of sVCAM-1 were linearly associated with higher resting CVR (p = .006) and lower performance on the Hopkins Verbal Learning Memory (immediate recall and delayed recall) and adjusted TMT B tests (p < .05). Higher levels of sVCAM-1 were also associated with global cognitive impairment on the MMSE (odds ratio = 3.9; 95% confidence interval: 1.4-10.9; p = .011).Conclusions: In this cohort of elderly participants, we observed a cross-sectional association between elevated sVCAM-1 levels and both cognitive impairment and increased cerebrovascular resistance. Longitudinal studies are needed to determine whether elevated sVCAM-1 is a cause or consequence of cerebrovascular damage. [ABSTRACT FROM AUTHOR]

Background: Establishing biological aging markers that predict cognitive performance may aid early identification of individuals at risk for accelerated cognitive decline and promote the development of interventions to preserve optimal cognitive function across the lifespan. We investigated two distinct classes of biological aging markers, 1) epigenetic aging, an emerging class of blood‐derived DNA methylation markers that aggregate aging‐related DNA methylation information; and 2) Spatial Patterns of Abnormality for Recognition of Brain Aging (SPARE‐BA), a composite magnetic resonance imaging (MRI) index of brain aging. Method: We evaluated the cross‐sectional and prospective associations between both classes of aging markers and cognitive performance across a 15‐year follow‐up in the biracial CARDIA cohort of approximately 1,000 middle‐aged adults, using multiple linear regression and logistic regression. We compared the diagnostic performance of both aging markers using receiver operating characteristic (ROC) curve analysis. Result: We found that accelerated epigenetic aging and brain aging were both cross‐sectionally and prospectively associated with worse cognitive outcomes. Specifically, every 5‐year faster epigenetic/brain aging is on average associated with 9.7% standard deviation (SD) higher in Stroop Test score, 7.7% SD lower in Rey Auditory Verbal Learning Test score, and 10.3% SD lower in Digital Symbol Substitution Test (all false‐discovery‐rate‐adjusted p <0.05). ROC analysis showed that a combined model with both epigenetic aging and brain aging markers optimized discriminability of individuals with lower cognitive performance 5 to 10 years later (area under the ROC curve: 0.70; 95% confident interval: 0.63‐0.77, Figure). Epigenetic and brain aging markers were weakly correlated with one another (Person's r =0.17) and not statistically significant. Conclusion: Our results showcase the significance of novel biological aging markers for cognitive health. Accelerated epigenetic aging and brain aging may capture distinct facets of biological aging and may jointly serve as early indicators of future cognitive decline and inform early interventions to prevent or delay cognitive impairment. [ABSTRACT FROM AUTHOR]

Objectives: Excess dietary salt and chronic kidney disease (CKD) are acknowledged stroke risk factors. The development of small vessel disease, similarly affecting the cerebral and renal microvasculatures, may be an important mechanistic link underlying this interaction. Therefore, we aimed to evaluate if the dietary salt intake and markers of CKD (estimated glomerular filtration rate, albuminuria) relate to transcranial Doppler (TCD) markers of cerebral small vessel disease (CSVD) in hypertensive patients.Materials and Methods: Fifty-six hypertensive patients (57% with diabetes) underwent TCD monitoring in the middle (MCA) and posterior (PCA) cerebral arteries for evaluating neurovascular coupling (NVC), dynamic cerebral autoregulation (dCA), and vasoreactivity to carbon dioxide (VRCO2). We investigated the relation between renal parameters and TCD studies using Pearson's correlation coefficient and linear regression analyses.Results: There were no associations between dCA, VRCO2, NVC, and renal function tests. However, there was a negative association between the daily salt intake and the natural frequency during visual stimulation (r2=0.101, ß=-0.340, p=0.035), indicative of increased rigidity of the cerebral resistance vessels that react to cognitive activation.Conclusions: In this cross-sectional study, we found an association between excess dietary salt consumption and CSVD in hypertensive patients. Future research is needed to evaluate whether the natural frequency could be an early, non-invasive, surrogate marker for microvascular dysfunction in hypertension. [ABSTRACT FROM AUTHOR]

Homocysteine is a sulfur-containing amino acid that is involved in one-carbon metabolism. Hyperhomocysteinemia is a common phenomenon among elderly people. There is growing evidence of an association between hyperhomocysteinemia and geriatric multisystem problems, including coronary artery disease, stroke, peripheral vascular disease, cognitive impairment, dementia, depression, osteoporotic fractures, and functional decline. The proposed mechanisms of the association include angiotoxicity, neurotoxicity, and inhibition of collagen cross-linking. A homocysteine-lowering strategy may prevent or slow the development of these age-related problems. Vitamin supplementation and folic acid fortification of grain foods have been shown to decrease plasma homocysteine concentrations. More research is needed to investigate whether lifelong homocysteine lowering can prevent the development of late-life morbidity. [ABSTRACT FROM AUTHOR]

Background. Little is known about what specific cognitive functions are affected by elevated blood pressure (BP) and how orthostatic BP change is related to cognitive impairment. The aim of this study was to determine the effect of BP and its postural change on cognitive functions in otherwise healthy elders. Methods. In 70 healthy persons (mean age, 72 ± 4 years), supine systolic BP (SBP) was assessed 3 times using a sphygmomanometer, and the average values were obtained for the analysis. After 1, 3, and 5 minutes of standing, 3 BP measurements were obtained and the orthostatic SBP changes were determined by subtracting these values from the supine average. Neuropsychological tests were administered to assess short-term and long-term verbal and visual memory, visuospatial skills, and frontal-executive functions. Participants were considered impaired in the specific cognitive performance if their scores fell below the 25th percentile of the study population. Multiple logistic regression models were used to evaluate the relation of SBP and the magnitude of orthostatic SBP decline to risk for impairment in each of the cognitive tests. Results. Controlling for potential confounders, each 10 mmHg increase in supine SBP was associated with a 2.31- fold increase (95% confidence interval, 1.14 to 4.66) in risk for impairment in psychomotor speed and set shifting as measured using the Trailmaking Part-B test. There was no significant association between cognitive functions and orthostatic SBP decline at 1, 3, and 5 minutes of standing. Conclusion. Elevation of BP is associated with a selective impairment in executive function in otherwise healthy community-dwelling elders. [ABSTRACT FROM AUTHOR]

Objective: To report six consecutive patients with confirmed coronavirus disease-2019 (COVID-19) who underwent Transcranial Doppler (TCD) ultrasonography evaluation for cerebral microemboli in the setting of suspected or confirmed acute ischemic stroke.Methods: Patient data were obtained from medical records from Northwestern Memorial Hospital, Chicago, IL between May and June 2020. All patients with confirmed COVID-19 who underwent clinical TCD ultrasonography for microemboli detection were included.Results: A total of eight TCD studies were performed in six patients with COVID-19 (4 men and 2 women, median age 65±5), four with confirmed ischemic stroke and two with refractory encephalopathy. Microemboli were detected in three male patients, two patients had suffered a confirmed ischemic stroke and one who developed prolonged encephalopathy. Microemboli of varying intensity were identified in multiple vascular territories in two patients, and microemboli persisted despite therapeutic anticoagulation in a third patient. Of the three patients without evidence of microemboli on TCD ultrasonography, two patients had suffered a confirmed ischemic stroke, while one remained with refractory encephalopathy.Conclusions: TCD ultrasonography for microemboli detection identified three patients with confirmed COVID-19 with evidence of cerebral arterial microemboli, including one who was therapeutically anticoagulated. TCD ultrasonography provides a non-invasive method for evaluating cerebral microemboli in patients with COVID-19 and may be useful in assessing response to treatment in cases with suspected or confirmed disorders of hypercoagulability. Further studies investigating the prevalence of cerebral microemboli and associated risk factors are needed to characterize their pathogenic mechanism and guide therapeutic interventions in hospitalized COVID-19 patients. [ABSTRACT FROM AUTHOR]

Objectives: COVID-19 disproportionately affects older adults and individuals with cardiovascular co-morbidities. This report presents fifteen patients who had COVID-19 respiratory illness followed by cerebrovascular events.Materials and Methods: A call by the Iranian Neurological Association gathered cases across the country who developed neurological symptoms attributed to hemorrhagic or ischemic stroke after a definite or probable Covid-19 respiratory illness. Definite cases were those with a typical respiratory illness, positive nasopharyngeal Covid-19 PCR test, and chest CT consistent with Covid-19 infection. Probable cases were defined by a typical respiratory illness, history of contacts with a Covid-19 case, and chest CT characteristic for Covid-19 infection.Results: Fifteen patients (12 men and 3 women) with an age range of 38 to 93 years old (median: 65 years old) were included. Fourteen patients had a first-ever acute ischemic stroke and one patient had a subarachnoid hemorrhage. Eleven patients (73%) had previous cardiovascular comorbidities. The median time between respiratory symptoms and neurological symptoms was seven days (range 1-16 days). Stroke severity in two patients was mild (NIHSS ≤ 6), in six patients moderate (NIHSS: 7-12), and in seven patients severe (NIHSS ≥13). One patient received intravenous tissue plasminogen activator ( IV-tPA) with improved neurological symptoms. Six out of 15 patients (40%) died. All but one of those who survived had significant disability assessed by a modified ranking scale >2. The majority of patients in this case series had vascular risk factors and their stroke was associated with severe disability and death.Conclusion: This report highlights the need for further investigation of the links between Covid-19 and cerebrovascular events. [ABSTRACT FROM AUTHOR]

Background: Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone. Methods: We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Results: Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003). Conclusions: Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.

Background: Falls are the sixth leading cause of death in elderly people in the U.S. Despite progress in understanding risk factors for falls, many suspected risk factors have not been adequately studied. Putative risk factors for falls such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot disorders are poorly understood, in part because they pose measurement challenges, particularly for large observational studies. Methods: The MOBILIZE Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. Using a door-to-door population-based recruitment, we have enrolled 765 persons aged 70 and older. The baseline assessment was conducted in 2 segments: a 3-hour home interview followed within 4 weeks by a 3-hour clinic examination. Measures included pain, cerebral hemodynamics, and foot disorders as well as established fall risk factors. For the falls follow-up, participants return fall calendar postcards to the research center at the end of each month. Reports of falls are followed-up with a telephone interview to assess circumstances and consequences of each fall. A second assessment is performed 18 months following baseline. Results: Of the 2382 who met all eligibility criteria at the door, 1616 (67.8%) agreed to participate and were referred to the research center for further screening. The primary reason for ineligibility was inability to communicate in English. Results from the first 600 participants showed that participants are largely representative of seniors in the Boston area in terms of age, sex, race and Hispanic ethnicity. The average age of study participants was 77.9 years (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and 17% black. Many participants (39%) reported having fallen at least once in the year before baseline. Conclusion: Our results demonstrate the feasibility of conducting comprehensive assessments, including rigorous physiologic measurements, in a diverse population of older adults to study non-traditional risk factors for falls and disability. The MBS will provide an important new data resource for examining novel risk factors for falls and mobility problems in the older population.

Objective: To report the very early magnetic resonance imaging features of eclampsia. Design: Case report. Setting: Inpatient neurology service. Patient: A 35-year-old woman who developed late postpartum eclampsia with cerebral edema, caudate hemorrhage, and ischemic strokes. Main Outcome Measure: Very early magnetic resonance imaging features. Results: Magnetic resonance imaging with gadolinium showed posterior sulcal hyperintensity and leptomeningeal enhancement preceding the development of posterior reversible encephalopathy syndrome, hemorrhage, and ischemic strokes by days. Conclusion: Magnetic resonance imaging with gadolinium shows early characteristic findings that precede the more classic clinical presentation of eclampsia. [ABSTRACT FROM AUTHOR]