Publications by authors named "Ralph L Sacco"

604 Publications

Predictors of Development of Atrial Fibrillation in Patients With Embolic Stroke Of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial.

Circulation 2021 Oct 15. Epub 2021 Oct 15.

Duke Clinical Research Institute, Durham, NC.

A proportion of patients with embolic stroke of undetermined source (ESUS) have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke due to underlying AF. The RE-SPECT ESUS trial provides an opportunity to assess predictors for developing AF and associated recurrent stroke. RE-SPECT ESUS was a randomized, controlled trial (564 sites, 42 countries) assessing dabigatran versus aspirin for the prevention of recurrent stroke in patients with ESUS. Of 5390 patients enrolled and followed for a median of 19 months, 403 (7.5%) were found to develop AF reported as an adverse event or using cardiac monitoring per standard clinical care. Univariable and multivariable regression analyses were performed to define predictors of AF. In the multivariable model, older age (odds ratio [OR] for 10-year increase 1.99 [1.78-2.23]; P<0.001), hypertension (1.36 [1.03-1.79]; P=0.0304), diabetes (OR 0.74 [0.56-0.96]; P=0.022), and body mass index (OR for 5-unit increase 1.29 [1.16-1.43]; P<0.001) were independent predictors of AF during the study. In a sensitivity analysis restricted to 1117 patients with baseline N-terminal prohormone of brain natriuretic peptide (NT-proBNP) measurements, only older age and higher NT-proBNP were significant independent predictors of AF. Performances of several published predictive models were assessed, including the HAVOC and CHA2DS2-VASc scores, and higher scores were associated with higher rates of developing AF. Besides age as the most important variable, several other factors, including hypertension, higher body mass index, and lack of diabetes, are independent predictors of AF after ESUS. When baseline NT-proBNP was available, only older age and elevation of this biomarker were predictive of subsequent AF. Understanding who is at higher risk of developing AF will assist in identifying patients who may benefit from more intense, long-term cardiac monitoring.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055176DOI Listing
October 2021

Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke.

Stroke 2021 Oct 14:STROKEAHA121034124. Epub 2021 Oct 14.

Massachusetts General Hospital/Harvard Medical School, Boston (L.H.S.).

Background And Purpose: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized.

Methods: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0-5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines-Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes.

Results: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations.

Conclusions: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.
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http://dx.doi.org/10.1161/STROKEAHA.121.034124DOI Listing
October 2021

Withdrawal of Life-Sustaining Treatment Mediates Mortality in Patients With Intracerebral Hemorrhage With Impaired Consciousness.

Stroke 2021 Sep 29:STROKEAHA121035233. Epub 2021 Sep 29.

Department of Neurology, University of Miami, FL (A.A., A.J.B., N.A., E.M.-L., C.M.G., D.S., E.S., M.K., A.M., S.K., J.G.R., K.O., R.L.S., T.R.).

Background And Purpose: Impaired level of consciousness (LOC) on presentation at hospital admission in patients with intracerebral hemorrhage (ICH) may affect outcomes and the decision to withhold or withdraw life-sustaining treatment (WOLST).

Methods: Patients with ICH were included across 121 Florida hospitals participating in the Florida Stroke Registry from 2010 to 2019. We studied the effect of LOC on presentation on in-hospital mortality (primary outcome), WOLST, ambulation status on discharge, hospital length of stay, and discharge disposition.

Results: Among 37 613 cases with ICH (mean age 71, 46% women, 61% White, 20% Black, 15% Hispanic), 12 272 (33%) had impaired LOC at onset. Compared with cases with preserved LOC, patients with impaired LOC were older (72 versus 70 years), more women (49% versus 45%), more likely to have aphasia (38% versus 16%), had greater ICH score (3 versus 1), greater risk of WOLST (41% versus 18%), and had an increased in-hospital mortality (32% versus 12%). In the multivariable-logistic regression with generalized estimating equations accounting for basic demographics, comorbidities, ICH severity, hospital size and teaching status, impaired LOC was associated with greater mortality (odds ratio, 3.7 [95% CI, 3.1-4.3], <0.0001) and less likely discharged home or to rehab (odds ratio, 0.3 [95% CI, 0.3-0.4], <0.0001). WOLST significantly mediated the effect of impaired LOC on mortality (mediation effect, 190 [95% CI, 152-229], <0.0001). Early WOLST (<2 days) occurred among 51% of patients. A reduction in early WOLST was observed in patients with impaired LOC after the 2015 American Heart Association/American Stroke Association ICH guidelines recommending aggressive treatment and against early do-not-resuscitate.

Conclusions: In this large multicenter stroke registry, a third of ICH cases presented with impaired LOC. Impaired LOC was associated with greater in-hospital mortality and worse disposition at discharge, largely influenced by early decision to withhold or WOLST.
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http://dx.doi.org/10.1161/STROKEAHA.121.035233DOI Listing
September 2021

Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke.

Front Neurol 2021 10;12:700616. Epub 2021 Sep 10.

Centogene AG, Rostock, Germany.

To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), < 0.01, respectively]. The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.
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http://dx.doi.org/10.3389/fneur.2021.700616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461233PMC
September 2021

Pre-Statistical Considerations for Harmonization of Cognitive Instruments: Harmonization of ARIC, CARDIA, CHS, FHS, MESA, and NOMAS.

J Alzheimers Dis 2021 ;83(4):1803-1813

Cognitive Health Services Research Program, University of Michigan Medical School, Ann Arbor, MI, USA.

Background: Meta-analyses of individuals' cognitive data are increasing to investigate the biomedical, lifestyle, and sociocultural factors that influence cognitive decline and dementia risk. Pre-statistical harmonization of cognitive instruments is a critical methodological step for accurate cognitive data harmonization, yet specific approaches for this process are unclear.

Objective: To describe pre-statistical harmonization of cognitive instruments for an individual-level meta-analysis in the blood pressure and cognition (BP COG) study.

Methods: We identified cognitive instruments from six cohorts (the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study) and conducted an extensive review of each item's administration and scoring procedures, and score distributions.

Results: We included 153 cognitive instrument items from 34 instruments across the six cohorts. Of these items, 42%were common across ≥2 cohorts. 86%of common items showed differences across cohorts. We found administration, scoring, and coding differences for seemingly equivalent items. These differences corresponded to variability across cohorts in score distributions and ranges. We performed data augmentation to adjust for differences.

Conclusion: Cross-cohort administration, scoring, and procedural differences for cognitive instruments are frequent and need to be assessed to address potential impact on meta-analyses and cognitive data interpretation. Detecting and accounting for these differences is critical for accurate attributions of cognitive health across cohort studies.
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http://dx.doi.org/10.3233/JAD-210459DOI Listing
January 2021

Development of an Equity, Diversity, Inclusion, and Anti-racism Pledge as the Foundation for Action in an Academic Department of Neurology.

Neurology 2021 Aug 18. Epub 2021 Aug 18.

University of Miami-Miller School of Medicine, Department of Neurology, Miami.

Racial inequities as illustrated by the health disparities in COVID19 infections and deaths, the recent killings of Black men and women by law enforcement, and the widening socioeconomic inequality and have brought systemic racism into a national conversation. These unprecedented times may have deleterious consequences, increasing stress, and trauma for many members of the neurology workforce. The Equity, Diversity, Inclusion and Anti-Racism Committee within our Department of Neurology provides infrastructure and guidance to foster a culture of belonging and addresses the well-being of faculty, staff, and trainees. Here, we present the creation and implementation of our Equity, Diversity, Inclusion, and Anti-Racism (EDIA) Pledge which was central to our committee's response to these unprecedented times. We outline the process of developing this unique EDIA Pledge and provide a roadmap for approaching these important topics through a CME Neurology Grand Rounds aimed at fostering a diverse, inclusive, equitable and antiracist work environment. Through the lived experiences of 4 faculty members, we identify the impact of bias and microaggressions, and encourage allyship and personal development for cultural intelligence. We hope these efforts will inspire Neurology departments and other academic institutions across the globe to make a similar pledge.
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http://dx.doi.org/10.1212/WNL.0000000000012674DOI Listing
August 2021

Determinants and Outcomes of Asymptomatic Intracranial Atherosclerotic Stenosis.

J Am Coll Cardiol 2021 Aug;78(6):562-571

Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, New York, USA.

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors.

Objectives: This study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification.

Methods: Stroke-free participants in the NOMAS (Northern Manhattan Study) trial, prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: <50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period.

Results: The included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS).

Conclusions: ICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health.
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http://dx.doi.org/10.1016/j.jacc.2021.05.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352282PMC
August 2021

MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes.

Front Neurosci 2021 12;15:691244. Epub 2021 Jul 12.

Department of Neurology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO, United States.

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).

Results: Radiomic features were predictive of WMH burden ( = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected -values < 0.001, -value = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.

Conclusion: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients' brain health.
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http://dx.doi.org/10.3389/fnins.2021.691244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312571PMC
July 2021

Immune markers are associated with cognitive performance in a multiethnic cohort: The Northern Manhattan Study.

Brain Behav Immun 2021 10 25;97:186-192. Epub 2021 Jul 25.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

Objective: To determine whether immune protein panels add significant information to correlates of cognition.

Background: Immune mechanisms in vascular cognitive aging are incompletely characterized.

Design/methods: A subsample of the prospective Northern Manhattan Study underwent detailed neuropsychological testing. Cognitive scores were converted into Z-scores and categorized into four domains (memory, language, processing speed, and executive function) based on factor analysis. Blood samples were analyzed using a 60-plex immunoassay. We used least absolute shrinkage and selection operator (LASSO) procedures to select markers and their interactions independently associated with cognitive scores. Linear regression models assessed cross-sectional associations of known correlates of cognition with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers.

Results: Among 1179 participants (mean age 70 ± 8.9 years, 60% women, 68% Hispanic), inclusion of LASSO-selected immune markers improved model fit above age, education, and other risk factors (p for likelihood ratio test < 0.005 for all domains). C-C Motif Chemokine Ligand 11 (CCL 11, eotaxin), C-X-C Motif Chemokine Ligand 9 (CXCL9), hepatocyte growth factor (HGF), and serpin E1 (plasminogen activator inhibitor-1) were associated with each of the domains and with overall cognitive function. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 was associated with an effect equivalent to aging three years; for memory, HGF had twice the effect of aging.

Conclusions: Immune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to validate these findings and determine optimal treatment targets.
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http://dx.doi.org/10.1016/j.bbi.2021.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453105PMC
October 2021

Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke.

Stroke 2021 Oct 26;52(10):3258-3265. Epub 2021 Jul 26.

Julius Center for Health Sciences and Primary Care (N.A.H., A.A., J.P.G.), University Medical Center Utrecht, Utrecht University, the Netherlands.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.031755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478107PMC
October 2021

Launching a New Collaborative Journal: Stroke: Vascular and Interventional Neurology.

Stroke 2021 Jul 28;52(7):2200-2202. Epub 2021 Jun 28.

Department of Neurology, Miller School of Medicine, University of Miami, FL (R.L.S.).

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http://dx.doi.org/10.1161/STROKEAHA.121.035500DOI Listing
July 2021

Systemic Arterial Correlates of Cervical Carotid Artery Tortuosity : The Northern Manhattan Study.

Clin Neuroradiol 2021 Jun 16. Epub 2021 Jun 16.

Department of Neurology, Columbia University, New York, NY, USA.

Introduction: The association between cervical internal carotid artery (cICA) tortuosity and atherosclerosis is a matter of debate. Additionally, some genetic syndromes characterized by connective tissue remodeling are associated with arterial tortuosity, raising the possibility that cICA tortuosity may not only be atherosclerotic. In this study, we hypothesized that cICA tortuosity is not associated with imaging biomarkers of atherosclerosis.

Methods: The Northern Manhattan Study (NOMAS) was a prospective, multiethnic cohort of stroke-free individuals who underwent brain MRA, carotid ultrasound and transthoracic echocardiogram from 2003-2008. The cICA tortuosity was scored in each carotid as 0 = no tortuosity, 1 = tortuosity <90°, 2 = tortuosity ≥90°. A summary cICA tortuosity score (possible range 0-4) was created by adding up the tortuosity score from each carotid. Participants were assessed for atherosclerotic markers by using B‑mode carotid sonography and transthoracic echocardiography.

Results: Of 558 participants 178 (31.9%) had any cervical ICA tortuosity (tortuosity score >0). The cICA tortuosity score was higher in women and was associated with diastolic and systolic blood pressures and height (all P < 0.05). In models adjusted for demographics and risk factors, only the association with diastolic blood pressure remained significant (β = 0.002, P = 0.02). Similarly, cICA tortuosity was associated with larger aortic root diameter (B = 1.03 ± 0.36, P = 0.004) but not with other markers of carotid or aortic atherosclerosis.

Conclusion: Cervical ICA tortuosity is associated with a higher diastolic blood pressure and larger aortic root diameter but not with other measures of atherosclerosis. Determining the risks of vascular events associated with this non-atherosclerotic phenotype may help for a better risk stratification for individuals with cICA tortuosity.
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http://dx.doi.org/10.1007/s00062-021-01044-yDOI Listing
June 2021

Gut permeability and cognitive decline: A pilot investigation in the Northern Manhattan Study.

Brain Behav Immun Health 2021 Mar 29;12. Epub 2021 Jan 29.

Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: Gut microbiota may impact cognitive function and decline, though data are limited. This pilot study examines the associations between gut dysbiosis products, plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14), with cognitive decline and immune molecule activation among 40 participants in the longitudinal population-based Northern Manhattan Study.

Methods: We selected stroke- and dementia-free participants at baseline with high activation levels of core components of the immune signaling pathways underlying microbiota metabolite-cognitive associations (IL-1, IL-17, TNF). Participants were followed with up to three complete neuropsychological assessments, at least 5 years apart.

Results: Elevated sCD14 was associated with high levels of IL-1 pathway activation (p < 0.05), whereas in samples where only those molecules within the IL-17 and TNF pathways were increased, LPS and sCD14 levels were not elevated. LPS was associated with decline in global cognitive performance over 2-3 assessments (adjusted β = -0.023 per SD per year, 95% CI:-0.036, -0.010). The association between sCD14 and cognitive decline was marginal (adjusted β = -0.018 per SD per year, 95% CI:-0.040, 0.004).

Conclusions: These preliminary data support the hypothesis that gut dysbiosis leads to systemic and neuro-inflammation, and subsequently cognitive decline. Further large targeted and untargeted gut microbiota-derived metabolomic studies are needed.
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http://dx.doi.org/10.1016/j.bbih.2021.100214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186438PMC
March 2021

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns.

Nat Commun 2021 06 2;12(1):3289. Epub 2021 Jun 2.

Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, MO, USA.

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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http://dx.doi.org/10.1038/s41467-021-23492-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172535PMC
June 2021

Systolic Blood Pressure and Cognition in the Elderly: The Northern Manhattan Study.

J Alzheimers Dis 2021 ;82(2):689-699

Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.

Background: Increasing evidence suggests that hypertension is a risk factor for cognitive impairment and dementia. The relationship between blood pressure and cognition in a racially and ethnically diverse population remains unclear.

Objective: To study association of blood pressure with cognition cross-sectionally and longitudinally in the elderly.

Methods: Participants are stroke-free individuals from the racially and ethnically diverse Northern Manhattan Study (NOMAS) (n = 1215). General linear models are constructed to examine blood pressure in relation to cognition cross-sectionally and longitudinally at a five-year follow-up.

Results: We found a cross-sectional association of systolic blood pressure (SBP) with word fluency/semantic memory, executive function, and processing speed/visual motor integration (VMI) function. This association was independent of demographics, vascular risk factors, white matter hyperintensity volume (WMHV), and carotid intima-media thickness (cIMT). The cross-sectional association of SBP with processing speed/VMI and executive function was attenuated after adjusting anti-hypertension medications in the models. Baseline SBP was associated with the change of processing speed/VMI function after adjusting vascular risk factors, WMHV, and cIMT at a 5-year follow-up. This longitudinal association was not found after adjusting anti-hypertension medications in the models. Further analyses revealed that individuals with category SBP from < 120 mmHg to≥140 mmHg had a linear decline in processing speed/VMI function at a 5-year follow-up.

Conclusion: We show that SBP is negatively associated with cognition cross-sectionally and longitudinally in the elderly. Anti-hypertension treatment eliminates the negative association of SBP with processing speed/VMI function longitudinally. Our findings support the treatment of stage 1 systolic hypertension in the elderly.
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http://dx.doi.org/10.3233/JAD-210252DOI Listing
September 2021

Prevalence and Clinical Correlates of Intracranial Dolichoectasia in Individuals With Ischemic Stroke.

Stroke 2021 Jul 13;52(7):2311-2318. Epub 2021 May 13.

Departments of Neurology (V.J.D.B., R.L.S., T.R., J.G.R.), University of Miami Miller School of Medicine, FL.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.032225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238812PMC
July 2021

Frequency of cardiac arrhythmias in older adults: Findings from the Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study.

Int J Cardiol 2021 08 6;337:64-70. Epub 2021 May 6.

Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States of America. Electronic address:

Background: Prolonged monitoring of cardiac rhythm has been used to screen for subclinical atrial fibrillation (AF); little is known about other arrhythmias in the general population, especially in the elderly, who are at higher risk of arrhythmias.

Methods: We evaluated the frequency of arrhythmias in the tri-ethnic (white, Black, Hispanic), community-based Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study using a patch-based recorder for up to 14 days in 527 participants free of AF, congestive heart failure (CHF) or history of stroke. Differences according to gender, age, ethnicity and presence of hypertension, diabetes and pertinent ECG and echocardiographic variables were examined.

Results: Mean age was 77.2 ± 6.8 years (37.2% men, 62.8% women). AF was present in 10 participants (1.9%), only 2 of them symptomatic. Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) episodes were observed in 84.4% and 25.0% but only 13.5% and 10.6% of participants reported symptoms, respectively. Severe bradycardia (<40 bpm) was present in 12.5%. Sinus pauses and high-degree atrioventricular blocks were infrequent (2.1% and 1.5%, respectively). Most arrhythmias were more frequent in participants > 75 years; ventricular arrhythmias and severe bradycardia were more common in men. Whites had significantly more episodes of AF than Hispanics, SVT than Blacks and VT ≥ 10 beats than Hispanics and Blacks. Hypertensives had more episodes of severe bradycardia. LV hypertrophy or LVEF <55% were associated with more frequent ventricular and supraventricular arrhythmias.

Conclusions: Prolonged cardiac rhythm monitoring revealed moderate frequency of AF, but higher than expected frequencies of AF-predisposing arrhythmias. Ventricular arrhythmias were relatively frequent, whereas severe bradyarrhythmias were infrequent.
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http://dx.doi.org/10.1016/j.ijcard.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243841PMC
August 2021

Association Between Intracerebral Hemorrhage and Subsequent Arterial Ischemic Events in Participants From 4 Population-Based Cohort Studies.

JAMA Neurol 2021 Jul;78(7):809-816

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Cornell Medicine, New York, New York.

Importance: Intracerebral hemorrhage and arterial ischemic disease share risk factors, to our knowledge, but the association between the 2 conditions remains unknown.

Objective: To evaluate whether intracerebral hemorrhage was associated with an increased risk of incident ischemic stroke and myocardial infarction.

Design, Setting, And Participants: An analysis was conducted of pooled longitudinal participant-level data from 4 population-based cohort studies in the United States: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Northern Manhattan Study (NOMAS), and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Patients were enrolled from 1987 to 2007, and the last available follow-up was December 31, 2018. Data were analyzed from September 1, 2019, to March 31, 2020.

Exposure: Intracerebral hemorrhage, as assessed by an adjudication committee based on predefined clinical and radiologic criteria.

Main Outcomes And Measures: The primary outcome was an arterial ischemic event, defined as a composite of ischemic stroke or myocardial infarction, centrally adjudicated within each study. Secondary outcomes were ischemic stroke and myocardial infarction. Participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction at their baseline study visit were excluded. Cox proportional hazards regression was used to examine the association between intracerebral hemorrhage and subsequent arterial ischemic events after adjustment for baseline age, sex, race/ethnicity, vascular comorbidities, and antithrombotic medications.

Results: Of 55 131 participants, 47 866 (27 639 women [57.7%]; mean [SD] age, 62.2 [10.2] years) were eligible for analysis. During a median follow-up of 12.7 years (interquartile range, 7.7-19.5 years), there were 318 intracerebral hemorrhages and 7648 arterial ischemic events. The incidence of an arterial ischemic event was 3.6 events per 100 person-years (95% CI, 2.7-5.0 events per 100 person-years) after intracerebral hemorrhage vs 1.1 events per 100 person-years (95% CI, 1.1-1.2 events per 100 person-years) among those without intracerebral hemorrhage. In adjusted models, intracerebral hemorrhage was associated with arterial ischemic events (hazard ratio [HR], 2.3; 95% CI, 1.7-3.1), ischemic stroke (HR, 3.1; 95% CI, 2.1-4.5), and myocardial infarction (HR, 1.9; 95% CI, 1.2-2.9). In sensitivity analyses, intracerebral hemorrhage was associated with arterial ischemic events when updating covariates in a time-varying manner (HR, 2.2; 95% CI, 1.6-3.0); when using incidence density matching (odds ratio, 2.3; 95% CI, 1.3-4.2); when including participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction (HR, 2.2; 95% CI, 1.6-2.9); and when using death as a competing risk (subdistribution HR, 1.6; 95% CI, 1.1-2.1).

Conclusions And Relevance: This study found that intracerebral hemorrhage was associated with an increased risk of ischemic stroke and myocardial infarction. These findings suggest that intracerebral hemorrhage may be a novel risk marker for arterial ischemic events.
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http://dx.doi.org/10.1001/jamaneurol.2021.0925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094038PMC
July 2021

Sex and Race-Ethnic Disparities in Door-to-CT Time in Acute Ischemic Stroke: The Florida Stroke Registry.

J Am Heart Assoc 2021 04 31;10(7):e017543. Epub 2021 Mar 31.

Department of Neurology University of Miami Miller School of Medicine Miami FL.

Background Less than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race-ethnic and sex differences in door-to-CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry). Methods and Results Data were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator-treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio [OR], 0.90; 95% CI, 0.87-0.93) and Black (OR, 0.88; CI, 0.84-0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01-1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activator-treated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77-0.94) whereas no significant differences were observed by race or ethnicity. Conclusions In the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race-ethnic disparities persist and require further efforts to improve performance and reduce these disparities.
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http://dx.doi.org/10.1161/JAHA.120.017543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174374PMC
April 2021

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

medRxiv 2021 Mar 20. Epub 2021 Mar 20.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.
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http://dx.doi.org/10.1101/2021.03.19.21253986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987050PMC
March 2021

Race/Ethnic Disparities in Mild Cognitive Impairment and Dementia: The Northern Manhattan Study.

J Alzheimers Dis 2021 ;80(3):1129-1138

Evelyn F McKnight Brain Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: Variability in dementia rates across racial and ethnic groups has been estimated at 60%. Studies suggest disparities in Caribbean Hispanic and Black populations, but community-based data are limited.

Objective: Estimate the prevalence of mild cognitive impairment (MCI) and dementia in the racially and ethnically diverse community-based Northern Manhattan Study cohort and examine sociodemographic, vascular risk factor, and brain imaging correlates.

Methods: Cases of MCI and dementia were adjudicated by a team of neuropsychologists and neurologists and prevalence was estimated across race/ethnic groups. Ordinal proportional odds models were used to estimate race/ethnic differences in the prevalence of MCI or dementia adjusting for sociodemographic variables (model 1), model 1 plus potentially modifiable vascular risk factors (model 2), and model 1 plus structural imaging markers of brain integrity (model 3).

Results: There were 989 participants with cognitive outcome determinations (mean age 69±9 years; 68% Hispanic, 16% Black, 14% White; 62% women; mean (±SD) follow-up five (±0.6) years). Hispanic and Black participants had greater likelihood of MCI (20%) and dementia (5%) than White participants accounting for age and education differences. Hispanic participants had greater odds of MCI or dementia than both White and Black participants adjusting for sociodemographic variables, vascular risk factors, and brain imaging factors. White matter hyperintensity burden was significantly associated with greater odds of MCI or dementia (OR = 1.3, 1.1 to 1.6), but there was no significant interaction by race/ethnicity.

Conclusion: In this diverse community-based cohort, cross-sectional data revealed significant race/ethnic disparities in the prevalence of MCI and dementia. Longer follow-up and incidence data are needed to further clarify these relationships.
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http://dx.doi.org/10.3233/JAD-201370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150441PMC
September 2021

Sex Differences in Cognitive Decline Among US Adults.

JAMA Netw Open 2021 02 1;4(2):e210169. Epub 2021 Feb 1.

Cognitive Health Services Research Program, Department of Internal Medicine, University of Michigan, Ann Arbor.

Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women.

Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.

Design, Setting, And Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.

Exposure: Sex.

Main Outcomes And Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.

Results: Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61).

Conclusions And Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907956PMC
February 2021

Academic Neurology Departments: Structure, Diversity, and Financial Pressures in 2019 vs 2002.

Neurology 2021 03 27;96(10):483-490. Epub 2021 Jan 27.

From the Department of Neurology (R.L.), University of Texas Health San Antonio, San Antonio, TX; American Academy of Neurology (T.O.), Minneapolis, MN; Department of Neurological Sciences (M.R.), University of Nebraska Medical Center, Omaha, ; and Departments of Neurology and Public Health Sciences (R.L.S.), Evelyn McKnight Brain Institute, Miami Clinical and Translational Science Institute, Miller School of Medicine, University of Miami, Miami, FL.

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http://dx.doi.org/10.1212/WNL.0000000000011538DOI Listing
March 2021

Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale: Results From RE-SPECT ESUS.

Stroke 2021 Mar 28;52(3):1065-1068. Epub 2021 Jan 28.

Department of Neurology, Miller School of Medicine, University of Miami, FL (R.L.S.).

Background And Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed.

Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS.

Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43-1.14]) for ischemic stroke.

Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120.
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http://dx.doi.org/10.1161/STROKEAHA.120.031237DOI Listing
March 2021

Adherence to Acute Care Measures Affects Mortality in Patients with Ischemic Stroke: The Florida Stroke Registry.

J Stroke Cerebrovasc Dis 2021 Mar 5;30(3):105586. Epub 2021 Jan 5.

Department of Neurology, University of Miami Miller School of Medicine, Miami, FL USA.

Objectives: How race/ethnic disparities in acute stroke care contribute to disparities in outcomes is not well-understood. We examined the relationship between acute stroke care measures with mortality within the first year and 30-day hospital readmission by race/ethnicity.

Materials And Methods: The study included fee-for-service Medicare beneficiaries age ≥65 with ischemic stroke in 2010-2013 treated at 66 hospitals in the Florida Stroke Registry. Stroke care metrics included intravenous Alteplase treatment, in-hospital antithrombotic therapy, DVT prophylaxis, discharge antithrombotic therapy, anticoagulation therapy, statin use, and smoking cessation counseling. We used mixed logistic models to assess the associations between stroke care and mortality (in-hospital, 30-day, 6-month, 1-year post-stroke) and hospital readmission by race/ethnicity, adjusting for demographics, stroke severity, and vascular risk factors.

Results: Among 14,100 ischemic stroke patients in the full study population (73% white, 11% Black, 15% Hispanic), mortality was 3% in-hospital, 12% at 30d, 21% at 6m, 26% at 1y, and 15% had a hospital readmission within 30 days. Patients who received antithrombotics early and at discharge had lower mortality at all time points, and the protective association for early antithrombotic use was strongest among whites. Eligible patients who received statin therapy at discharge had decreased 6m and 1y mortality, but specifically among minority groups. Statin therapy was associated with lower 30-day hospital readmission.

Conclusions: Acute stroke care measures, particularly antithrombotic use and statin therapy, were associated with reduced odds of long-term mortality. The benefits of these acute care measures were less likely among Hispanic patients. Results underscore the importance of optimizing acute stroke care for all patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880890PMC
March 2021

Achievements and New Initiatives for Stroke in 2021.

Authors:
Ralph L Sacco

Stroke 2021 01 22;52(1):5-7. Epub 2020 Dec 22.

Departments of Neurology and Public Health Sciences, Miami Clinical Translational Science Institute, Evelyn McKnight Brain Institute, Miller School of Medicine, University of Miami, FL.

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http://dx.doi.org/10.1161/STROKEAHA.120.033123DOI Listing
January 2021
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