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1.
J Alzheimers Dis ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33646162

RESUMO

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.

2.
JAMA Netw Open ; 4(2): e210169, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630089

RESUMO

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.

3.
J Stroke Cerebrovasc Dis ; 30(3): 105586, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33412397

RESUMO

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.

4.
Stroke ; 52(3): 1065-1068, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33504190

RESUMO

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 (P 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.

6.
J Hypertens ; 39(1): 46-52, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33031165

RESUMO

OBJECTIVES: Recently, more sophisticated blood pressure (BP) measurements, such as central and ambulatory BP (ABP), have proven to be stronger predictors of future cardiovascular disease than conventional office BP. Their predictive value for atrial fibrillation development is not established. We investigated the prognostic impact for incident atrial fibrillation of office, central and ambulatory BP measurements in a predominantly older population-based cohort. METHODS: Of 1004 participants in the Cardiovascular Abnormalities and Brain Lesions (CABL) study, 769 in sinus rhythm with no history of atrial fibrillation or stroke (mean age 70.5 years) underwent ABP and arterial wave reflection analysis for central BP determination. Fine and Gray's proportional subdistribution hazards models were used to assess the association of BP parameters with incident atrial fibrillation. RESULTS: During 9.5 years, atrial fibrillation occurred in 83 participants. No office BP variable showed a significant association with incident atrial fibrillation. Central SBP and central pulse pressure were marginally associated with incident atrial fibrillation in multivariate analysis. Among ABP variables, 24-h SBP [adjusted hazard ratio per 10 mmHg, 1.24; 95% confidence interval (CI) 1.07--1.44; P = 0.004], daytime SBP (adjusted hazard ratio per 10 mmHg, 1.21; 95% CI 1.04--1.40; P = 0.011) and night-time SBP (adjusted hazard ratio per 10 mmHg, 1.22; 95% CI 1.07--1.39; P = 0.002) were significantly associated with incident atrial fibillation. CONCLUSION: In a predominantly older, stroke-free community-based cohort, ABP was a better independent predictor of incident atrial fibrillation than central BP, whereas office BP was inadequate for this purpose.

8.
Stroke ; 52(1): 5-7, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33349020
9.
J Alzheimers Dis ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33164939

RESUMO

BACKGROUND: Mid-life obesity is associated with cognitive impairment, though the relationship for late-life obesity is equivocal, and may depend on the anthropometric measure. OBJECTIVE: We examined the relationship between adiposity and cognition across age categories, cognitive domains, and by measures of obesity in a multi-ethnic population-based cohort. METHODS: The study included 1,179 Northern Manhattan Study participants with obesity measures at baseline (44% overweight, 30% obese), an initial neuropsychological assessment conducted within 7 years (mean age = 70), and a second cognitive assessment conducted on average 6 years later. Z-scores were derived for cognitive domains (episodic and semantic memory, executive function, processing speed) and averaged to calculate global cognition. Body mass index (BMI) and waist:hip ratio (WHR) were examined in relation to cognitive performance and change over time, stratified by age, using linear regression models adjusting for vascular risk factors. RESULTS: Among those age<65 years at baseline, greater WHR was associated with worse global cognitive performance at initial assessment and directly associated with decline in performance between assessments. The association with initial performance was strongest for non-Hispanic Whites (beta = -0.155/standard deviation, p = 0.04), followed by non-Hispanic Black/African Americans (beta = -0.079/standard deviation, p = 0.07), and Hispanics (beta = -0.055/standard deviation, p = 0.03). The associations were most apparent for the domains of processing speed and executive function. There was no association for BMI among those <65 years. Among those age ≥65, there was no association for BMI or WHR with cognitive performance at initial assessment nor decline over time. CONCLUSION: Our results support the detrimental effect of mid-life rather than later life obesity, particularly abdominal adiposity, on cognitive impairment and decline.

10.
Stroke ; 51(11): 3392-3405, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33104468

RESUMO

Numerous epidemiological studies have demonstrated stroke disparities across race and ethnic groups. The goal of the NOMAS (Northern Manhattan Study) was to evaluate race and ethnic differences in stroke within a community with 3 different race-ethnic groups. Starting as a population-based incidence and case-control study, the study evolved into a cohort study. Results from NOMAS have demonstrated differences in stroke incidence, subtypes, risk factors, and outcomes. Disparities in ideal cardiovascular health can help explain many differences in stroke incidence and call for tailored risk factor modification through innovative portals to shift more diverse subjects to ideal cardiovascular health. The results of NOMAS and multiple other studies have provided foundational data to support interventions. Conceptual models to address health disparities have called for moving from detecting disparities in disease incidence, to determining the underlying causes of disparities and developing interventions, and then to testing interventions in human populations. Further actions to address race and ethnic stroke disparities are needed including innovative risk factor interventions, stroke awareness campaigns, quality improvement programs, workforce diversification, and accelerating policy changes.

13.
Neurol Genet ; 6(4): e462, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32754642

RESUMO

Objective: We investigated whether APOE ϵ4 is an effect modifier of the association between infectious burden (IB) and poor cognition in a multiethnic cohort, the Northern Manhattan Study. Methods: IB was assessed by a quantitative weighted index of exposure to common pathogens associated with vascular risk, infectious burden index (IBI), and by serology for individual infections. Cognition was assessed by completion of the Mini-Mental State Examination at baseline and a full neuropsychological test battery after a median follow-up of approximately 6 years. Adjusted linear and logistic regressions estimated the association between IBI and cognition, with a term included for the interaction between APOE ϵ4 and IBI. Results: Among those with full neuropsychological test results (n = 569), there were interactions between IBI and APOE ϵ4 (p = 0.07) and herpes simplex virus 1 (HSV-1) and APOE ϵ4 (p = 0.02) for processing speed. IBI was associated with slower processing speed among non-ϵ4 carriers (ß = -0.08 per SD change in IBI, 95% confidence interval [CI] -0.16 to -0.01), but not among APOE ϵ4 carriers (ß = 0.06 per SD change in IBI, 95% CI -0.08 to 0.19). HSV-1 positivity was associated with slower processing speed among non-ϵ4 carriers (ß = -0.24, 95% CI -0.45 to -0.03), but not among APOE ϵ4 carriers (ß = 0.27, 95% CI -0.09 to 0.64). Conclusions: Potential effect modification by the APOE ϵ4 allele on the relationship of infection, and particularly viral infection, to cognitive processing speed warrants further investigation.

14.
Stroke ; 51(9): 2761-2769, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32811377

RESUMO

BACKGROUND AND PURPOSE: Carotid plaque is a heritable trait and a strong predictor of vascular events. Several loci have been identified for carotid plaque, however, studies in minority populations are lacking. Within a multi-ethnic cohort, we have identified individuals with extreme total carotid plaque area (TCPA), that is, higher or lower TCPA than expected based on traditional vascular risk factors (age, sex, smoking, diabetes mellitus, hypertension, etc). We hypothesized that these individuals are enriched with genetic variants accounting for the plaque burden that cannot be explained by traditional vascular risk factors. Herein, we sought to identify the genetic basis for TCPA using the multi-ethnic cohort. METHODS: Three hundred forty participants (170 from each extreme group) from 3 race/ethnic groups (53% Hispanic, 29% non-Hispanic Black, and 18% non-Hispanic White) were genotyped using a genome-wide single-nucleotide polymorphism (SNP) array and imputed using 1000Genome data. SNP-based analyses using logistic regression and gene-based analyses using VEGAS2 were performed within each race/ethnic group and then meta-analyzed. Genes with P<0.001 were included in an overrepresentation enrichment pathway analysis using WebGestalt. Promising findings were tested for association with ischemic stroke using the MEGASTROKE Consortium data set. RESULTS: No SNP or gene reached genome-wide significance. In the pathway analysis, GO:0050913 (sensory perception of bitter taste) gene set was significantly enriched (P=4.5×10-6, false discovery rate=0.04), which was confirmed in MEGASTROKE (P=0.01). Within the GO:0050913 gene set, 3 genes were associated with extreme TCPA in our study (P<0.001): TAS2R20, TAS2R50, and ITPR3. In TAS2R50, rs1376251 is the top SNP and has been associated with myocardial infarction by others. In ITPR3, a SNP with high regulatory potential (rs3818527, RegulomeScore=1f), and ITPR3 itself were among the top SNP-based and gene-based results and showed consistent evidence for association in all ethnic groups (P<0.05). CONCLUSIONS: Extreme TCPA analysis identified new candidate genes for carotid plaque in understudied populations.


Assuntos
Doenças das Artérias Carótidas/genética , Placa Aterosclerótica/genética , Paladar/genética , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/fisiopatologia , Dieta , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Hispano-Americanos , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Fenótipo , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Estados Unidos/epidemiologia
15.
Brain Imaging Behav ; 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32740887

RESUMO

High dimensional neuroimaging datasets and machine learning have been used to estimate and predict domain-specific cognition, but comparisons with simpler models composed of easy-to-measure variables are limited. Regularization methods in particular may help identify regions-of-interest related to domain-specific cognition. Using data from the Northern Manhattan Study, a cohort study of mostly Hispanic older adults, we compared three models estimating domain-specific cognitive performance: sociodemographics and APOE ε4 allele status (basic model), the basic model and MRI markers, and a model with only MRI markers. We used several machine learning methods to fit our regression models: elastic net, support vector regression, random forest, and principal components regression. Model performance was assessed with the RMSE, MAE, and R2 statistics using 5-fold cross-validation. To assess whether prediction models with imaging biomarkers were more predictive than prediction models built with randomly generated biomarkers, we refit the elastic net models using 1000 datasets with random biomarkers and compared the distribution of the RMSE and R2 in models using these random biomarkers to the RMSE and R2 from observed models. Basic models explained ~ 31-38% of the variance in domain-specific cognition. Addition of MRI markers did not improve estimation. However, elastic net models with only MRI markers performed significantly better than random MRI markers (one-sided P < .05) and yielded regions-of-interest consistent with previous literature and others not previously explored. Therefore, structural brain MRI markers may be more useful for etiological than predictive modeling.

17.
Front Neurol ; 11: 577, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670186

RESUMO

Background: Magnetic resonance imaging (MRI) serves as a cornerstone in defining stroke phenotype and etiological subtype through examination of ischemic stroke lesion appearance and is therefore an essential tool in linking genetic traits and stroke. Building on baseline MRI examinations from the centralized and structured radiological assessments of ischemic stroke patients in the Stroke Genetics Network, the results of the MRI-Genetics Interface Exploration (MRI-GENIE) study are described in this work. Methods: The MRI-GENIE study included patients with symptoms caused by ischemic stroke (N = 3,301) from 12 international centers. We established and used a structured reporting protocol for all assessments. Two neuroradiologists, using a blinded evaluation protocol, independently reviewed the baseline diffusion-weighted images (DWIs) and magnetic resonance angiography images to determine acute lesion and vascular occlusion characteristics. Results: In this systematic multicenter radiological analysis of clinical MRI from 3,301 acute ischemic stroke patients according to a structured prespecified protocol, we identified that anterior circulation infarcts were most prevalent (67.4%), that infarcts in the middle cerebral artery (MCA) territory were the most common, and that the majority of large artery occlusions 0 to 48 h from ictus were in the MCA territory. Multiple acute lesions in one or several vascular territories were common (11%). Of 2,238 patients with unilateral DWI lesions, 52.6% had left-sided infarct lateralization (P = 0.013 for χ2 test). Conclusions: This large-scale analysis of a multicenter MRI-based cohort of AIS patients presents a unique imaging framework facilitating the relationship between imaging and genetics for advancing the knowledge of genetic traits linked to ischemic stroke.

18.
Stroke ; 51(7): 1919-1920, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32517583
19.
J Neurol Sci ; 416: 116981, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32592869

RESUMO

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been associated with greater cerebral white matter hyperintensity (WMH) volume and microbleeds. The adiponutrin (PNPLA3) rs738409 G variant, a robust NAFLD susceptibility variant, has been variably associated with carotid atherosclerosis. We hypothesized that this variant is associated with WMH volume, microbleeds, covert brain infarction (CBI), and small perivascular spaces. METHODS: We performed a cross-sectional analysis of the Northern Manhattan Study-MRI Substudy. The associations between the rs738409 G variant allele and outcomes were assessed using linear regression for WMH volume, logistic regression for microbleeds and CBI, and Poisson regression for small perivascular spaces. Models were adjusted for age, sex, principal components, diabetes, and body mass index. RESULTS: We included 1063 Northern Manhattan Study participants who had brain MRI and genotype data available (mean age 70 ± 9 years, 61% women). The G allele frequency was 24%. The prevalence of any microbleeds and CBI were 8% and 18%, respectively. The median WMH volume and small perivascular space count score were 7.7 mL and 6, respectively. GG homozygosity, but not heterozygosity, was associated with WMH volume (ß = 0.27; 95% CI, 0.03, 0.51) compared to non-carriers. Having at least one G allele was associated with the presence of microbleeds (Odds ratio, 1.78; 95% CI, 1.02, 3.12); the association was attenuated in other models. No associations were observed for CBI and small perivascular spaces. CONCLUSION: The PNPLA3 rs738409 G allele was associated with greater WMH volume, and inconsistent associations with microbleeds were seen.

20.
Neurology ; 95(1): e79-e88, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32493718

RESUMO

OBJECTIVE: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). METHODS: For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool-based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes. RESULTS: Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18-14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001). CONCLUSION: In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.


Assuntos
Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Aprendizado Profundo , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
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