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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. [ABSTRACT FROM AUTHOR]

Background Disease-related gait dysfunction causes extensive disability for persons with Parkinson's disease (PD), with no effective therapies currently available. The potassium channel blocker dalfampridine has been used in multiple neurological conditions and improves walking in persons with multiple sclerosis. Objectives We aimed to evaluate the effect of dalfampridine extended release (D-ER) 10 mg tablets twice daily on different domains of walking in participants with PD. Methods Twenty-two participants with PD and gait dysfunction were randomized to receive D-ER 10 mg twice daily or placebo for 4 weeks in a crossover design with a 2-week washout period. The primary outcomes were change in the gait velocity and stride length. Results At 4 weeks, gait velocity was not significantly different between D-ER (0.89 m/s ± 0.33) and placebo (0.93 m/s ± 0.27) conditions. The stride length was also similar between conditions: 0.96 m ± 0.38 for D-ER versus 1.06 m ± 0.33 for placebo. D-ER was generally well tolerated with the most frequent side effects being dizziness, nausea and balance problems. Conclusions D-ER is well tolerated in PD patients, however it did not show significant benefit for gait impairment. [ABSTRACT FROM AUTHOR]

Background Alcohol consumption may interfere with absorption, distribution, metabolism, and excretion of medications and increase risk of adverse drug reactions (ADR). Studies report increasing prescription medication use over time, with many U.S. drinkers using alcohol-interactive medication. This study identified trends in incidence of U.S. emergency department (ED) visits for ADR with alcohol involvement (ADR-A), compared characteristics and disposition between ADR-A visits and ADR visits without alcohol involvement (ADR-NA), and examined frequency of implicated medications in such visits for 2005 to 2011. Methods ADR visits were identified through the Drug Abuse Warning Network, a national surveillance system monitoring drug-related ED visits. Analysis accounted for sampling design effects and sampling weights. Estimates are presented for totals (ages 12+), age group, and/or sex. Trends were assessed by joinpoint log-linear regression. Differences between ADR-A and ADR-NA visits were compared using two-tailed Rao-Scott chi-square tests. Results From 2005 to 2011, incidence of ADR-A visits increased for males and females ages 21 to 34 and females ages 55+. An average of 25,303 ADR-A visits ages 12+ occurred annually. Compared with ADR-NA visits, ADR-A visits were more likely to involve males, patients ages 21 to 54, and 2+ implicated drugs. Alcohol involvement increased odds of more serious outcomes from ADR visits. Central nervous system (CNS) agents were the most common medications in ADR-A visits (59.1%), with nearly half being analgesics (mainly opioid). About 13.8% of ADR-A visits involved psychotherapeutic agents, including antidepressants. Besides CNS and psychotherapeutic agents, ADR-A visits involved a higher percentage of genitourinary-tract agents (mainly for impotence) than ADR-NA visits. Sex and age variations were observed with certain implicated medications. Conclusions ED visits for alcohol-drug interactions can be prevented by avoiding alcohol when taking alcohol-interactive medications. Our results underscore the need for healthcare professionals to routinely ask patients about alcohol consumption and warn of ADR risks before prescribing and dispensing alcohol-interactive medications. [ABSTRACT FROM AUTHOR]

Background Sirtuins and uncoupling proteins have been implicated in cardiovascular diseases by controlling oxidative stress. Aims We sought to investigate the association of sirtuins and uncoupling proteins single nucleotide polymorphisms with total carotid plaque area and morphology measured by ultrasonographic gray scale median. Methods We analyzed 1356 stroke-free subjects (60% women, mean age = 68 ± 9 years) from the Northern Manhattan Study. Multiple linear regression models were used to evaluate the association of 85 single nucleotide polymorphisms in 11 sirtuins/uncoupling protein genes with total plaque area and gray scale median after controlling for demographics, vascular risk factors (RFs), and population stratification. We investigated effect modifications of these relationship by gender and RFs and performed stratified analysis if the interaction effect had P < 0·005. Results Among individuals with present plaque (55%), the mean total plaque area was 20·3 ± 20·8 mm² and gray scale median 90 ± 29. After adjustment, SIRT6 rs107251 was significantly associated with total plaque area (β = 0·30 per copy of T allele increase, Bonferroni-corrected P = 0·005). T allele carriers of rs1430583 in UCP1 showed a decreased gray scale median in women but not in men. The minor allele carriers of rs4980329 and rs12363280 in SIRT3 had higher gray scale median in men but not in women. Variants in UCP3 gene were significantly associated with higher mean gray scale median in individuals with dyslipidemia. Conclusion Our findings suggest that polymorphisms in SIRT6/UCP1 genes may be important for increased carotid plaque burden and echodensity, but translation of these findings to an individual risk of cerebrovascular events needs further investigation. Significant associations of rs1430583 in women, rs12363280 in men, and rs1685354 in those with dyslipidemia also deserve further investigations. [ABSTRACT FROM AUTHOR]

Background : There is an established sex-difference in carotid artery intima-media thickness (cIMT), a recognized marker of subclinical atherosclerosis. However, the genetic underpinnings of sex-differences in gene-IMT associations are largely unknown. Methods : With a multistage design using 731,037 single nucleotide polymorphisms (SNP), a genome wide interaction study was performed in a discovery sample of 931 unrelated Hispanics, followed by replication in 153 non-Hispanic whites and 257 non-Hispanic blacks. Assuming an additive genetic model, we tested for sex–SNP interactions on cIMT using regression analysis. Results : We did not identify any genome-wide significant SNPs but identified 14 loci with suggestive significance. Specifically, SNP-by-sex interaction was found for rs7616559 within LEKR1 gene (P = 3.5E-06 in Hispanic discovery sample, P = 0.018 in White, and P = 1.3E-06 in combined analysis) and for rs2081015 located within GALNT10 gene (P = 4.5E-06 in Hispanic discovery sample, P = 0.042 in Blacks, and P = 5.3E-07 in combined analysis). For rs7616559 within LEKR1 , men had greater cIMT than women in G allele carriers (beta ± SE: 0.044 ± 0.007, P = 4.2E-09 in AG carriers; beta ± SE: 0.064 ± 0.007, P = 6.2E-05 in GG carriers). For rs2081015 within GALNT10 , men had greater cIMT than women in C allele carriers (beta ± SE: 0.022 ± 0.007, P = 0.002 in CT carriers; beta ± SE: 0.051 ± 0.008, P = 3.1E-10 in CC carriers). Conclusions : Our genome-wide interaction analysis reveals multiple loci that may modulate sex difference in cIMT. Of them, genetic variants on LEKR1 and GALNT10 genes have been associated with control of adiposity and weight. Given the consistent findings across different-ethnic groups, further studies are warranted to perform investigations of functional genetic variants in these regions. [ABSTRACT FROM AUTHOR]

Background The majority of Americans consume alcoholic beverages. Alcohol interacts negatively with numerous commonly prescribed medications. Yet, on a population level, little is known about use of alcohol-interactive ( AI) prescription medications among drinkers. The purpose of our study was to determine the prevalence of AI prescription medication use among current drinkers in the U.S. population. Methods Data were from the National Health and Nutrition Examination Survey ( NHANES 1999 to 2010); 26,657 adults aged ≥20 years had data on past year alcohol consumption and past month prescription medication use. Analyses were adjusted for covariates: age, race/ethnicity, education, marital status, and smoking. Statistical procedures accounted for survey stratification, clustering, and nonresponse. Analyses were weighted to be nationally representative. Results The unadjusted total prevalence of AI medication use was 42.8% (95% confidence interval [ CI] 41.5 to 44.0). Among current drinkers, adjusted prevalence was 41.5% ( CI 40.3 to 42.7). Among participants aged ≥65 total prevalence of AI medication use was 78.6% ( CI 77.3 to 79.9) and adjusted prevalence among current drinkers was 77.8% ( CI 75.7 to 79.7). The AI medications most commonly used by current drinkers were cardiovascular agents, central nervous system agents, and metabolic agents. Conclusions Our results suggest that there could be substantial simultaneous exposure to alcohol and AI prescription medications in the U.S. population. Given the adverse health risks of combining alcohol with AI prescription medications, future efforts are needed to collect data to determine actual simultaneous prevalence. [ABSTRACT FROM AUTHOR]

Objective: The authors compared the effectiveness of fluoxetine and desipramine treatment in a prospective double-blind pharmacogenetics study in first-generation Mexican Americans and examined the role of whole-exome functional gene variations in the patients' antidepressant response.Method: A total of 232 Mexican Americans who met DSM-IV criteria for major depressive disorder were randomly assigned to receive 8 weeks of double-blind treatment with desipramine (50-200 mg/day) or fluoxetine (10-40 mg/day) after a 1-week placebo lead-in period. Outcome measures included the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale, and the Beck Depression Inventory. At week 8, whole-exome genotyping data were obtained for 36 participants who remitted and 29 who did not respond to treatment.Results: Compared with desipramine treatment, fluoxetine treatment was associated with a greater reduction in HAM-D score, higher response and remission rates, shorter time to response and remission, and lower incidences of anticholinergic and cardiovascular side effects. Pharmacogenetics analysis showed that exm-rs1321744 achieved exome-wide significance for treatment remission. This variant is located in a brain methylated DNA immunoprecipitation sequencing site, which suggests that it may be involved in epigenetic regulation of neuronal gene expression. This and two other common gene variants provided a highly accurate cross-validated predictive model for treatment remission of major depression (receiver operating characteristic integral=0.95).Conclusions: Compared with desipramine, fluoxetine treatment showed a more rapid reduction of HAM-D score and a lower incidence of side effects in a population comprising primarily first-generation Mexican Americans with major depression. This study's pharmacogenetics approach strongly implicates the role of functional variants in antidepressant treatment response. [ABSTRACT FROM AUTHOR]

Self-reports of long or short sleep durations have indicated an association with cardiovascular morbidity and mortality, but there are limited data evaluating their association with white matter hyperintensity volume ( WMHV), a marker of cerebral small vessel disease. We conducted a cross-sectional analysis of self-reported sleep duration to test for a correlation with white matter hyperintensities, measured by quantitative magnetic resonance imaging ( MRI), in the Northern Manhattan Study. We used multivariable linear regression models to assess associations between both short (<6 h) and long (≥9 h) sleep durations and log-transformed WMHV, adjusting for demographic, behavioural and vascular risk factors. A total of 1244 participants, mean age 70 ± 9 years, 61% women and 68% Hispanics were analysed with magnetic resonance brain imaging and self-reported sleep duration. Short sleep was reported by 23% ( n = 293) and long sleep by 10% ( n = 121) of the sample. Long sleep ( β = 0.178; P = 0.035), but not short sleep ( β = −0.053; P = 0.357), was associated with greater log- WMHV in fully adjusted models. We observed an interaction between sleep duration, diabetes mellitus and log- WMHV ( P = 0.07). In fully adjusted models, stratified analysis showed that long sleep duration was associated with greater WMHV only in those with diabetes ( β = 0.78; P = 0.0314), but not in those without diabetes ( β = 0.022; P = 0.2), whereas short sleep was not associated with white matter hyperintensities in those with or without diabetes. In conclusion, long sleep duration was associated with a greater burden of white matter lesions in this stroke-free urban sample. The association was seen mainly among those with diabetes mellitus. [ABSTRACT FROM AUTHOR]

Knowledge of cardiovascular health (CVH) status of a given population is mandatory to reduce the burden of vascular diseases in the region. We compared CVH of two distinct populations having similar ethnic backgrounds to understand the role of lifestyle and environment on their CVH, and to provide insights in the planning of cost-effective health strategies. CVH status was compared in two Hispanic populations living in Northern Manhattan and Atahualpa (rural coastal Ecuador) using the health metrics proposed by the American Heart Association. Both studies used similar definitions of CVH and similar inclusion criteria for participating subjects (age ≥40 years, cardiovascular disease-free status, and living at their respective localities for ≥3 months). The studied populations consisted of 1,617 Caribbean Hispanics living in Northern Manhattan (mean age 66 ± 9 years), and 616 Atahualpa residents (mean age 59 ± 13 years). Atahualpa residents had significantly better metrics than Caribbean Hispanics, with the exception of fasting glucose levels. Likewise, the odds for having 5-7 ideal metrics were also better in Atahualpa residents, irrespective of age. CVH is better in Atahualpa residents than in Caribbean Hispanics living in Northern Manhattan. These differences are likely related to a healthier lifestyle in a rural setting and provide insights for setting cardiovascular prevention priorities. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Carotid plaque is a marker of subclinical atherosclerosis with a genetic component. The aim of this follow-up fine mapping study was to identify candidate genes for carotid plaque within four linkage regions. Methods: We successfully genotyped 3712 single nucleotide polymorphisms (SNPs) under the four linkage regions that were previously identified in 100 extended Dominican families. Family-based association tests were performed to investigate their associations with carotid plaque. Promising SNPs were evaluated in an independent population-based subcohort (N =941, 384 Dominicans) from the Northern Manhattan Study (NOMAS). Results: In the family study, evidence for association (p <0.0005) was found regarding several genes (NAV2, EFCAB11/TDP1, AGBL1, PTPN9, LINGO1 and LOC730118), with the strongest association at rs4143999 near EFCAB11/TDP1 (p =0.00001 for carotid presence and 0.00003 for plaque area, multiple testing corrected p ≤0.02). The association in AGBL1 and PTPN9 was mainly driven by the families with linkage evidence (p =0.00008–0.00001 and 0.76–0.32, respectively, in the families with and without linkage evidence). However, these associations explained only a small portion of the observed linkage. In NOMAS, replication (p <0.05 in the whole NOMAS subcohort and p <0.10 in the smaller Dominican subcohort) was found for SNPs within/near EFCAB11, NAV2, AGBL1 and other genes. Conclusion: This follow-up study has identified multiple candidate genes for carotid plaque in the Dominican population. Many of these genes have been implicated in neurodegenerative and cardiovascular diseases. Further studies with in-depth re-sequencing are needed to uncover both rare and common functional variants that contribute to the susceptibility to atherosclerosis. [Copyright &y& Elsevier]

Fasting plasma glucose is a multigenic trait related to both diabetes and obesity. We performed a genome scan for quantitative fasting plasma glucose levels in 320 families (1,514 subjects), segregating extreme obesity and normal weight using 382 autosomal microsatellite markers. We found significant linkages on 18q22-23 using family regression (logarithm of odds [LOD] 3.67, P = 0.00002, D18S1371 at 116 cM) and variance components (LOD 4.48, P < 0.00001) methods. Evidence for linkage remained strong when restricted to European Americans (260 families, 1,258 individuals). After an additional 60 families were added, the linkage signal strengthened (LOD 6.59). The result on 18q22-23 remained significant, even after controlling for both BMI and diabetes status. We also found suggestive linkages on chromosomes 2 (LOD 1.58, 216 cM) and 7 (LOD 1.78, 163 cM). Our results suggest that there is a quantitative trait locus in chromosome region 18q22-23 that influences fasting glucose levels and may play a role in the pathogenesis of type 2 diabetes. The strength of the serum glucose results after controlling for BMI suggests that this putative gene does not influence glucose levels merely through an effect on obesity. [ABSTRACT FROM AUTHOR]

Obesity is a growing health problem in the U.S. As a complex trait, obesity involves multiple genes and gene-gene and gene-environment interactions that contribute to its pathogenesis. Here we report significant linkage from a scan of a large sample segregating extreme obesity and normal weight. We have used 382 microsatellite markers in 1,297 individuals from 260 European-American families. We conducted nonparametric linkage (NPL) analyses for dichotomous BMI (using BMI >/=27, >/=30, >/=35, and >/=40 kg/m(2)) using Genehunter. We also analyzed quantitative traits (BMI, percentage of fat, and waist circumference) by the family regression method using Merlin_regress. We found evidence for linkage on chromosome 12 (125 cM, D12S2070, logarithm of odds [LOD] 3.79, P = 0.00001 for percentage of fat; LOD 2.98, P = 0.0001 for BMI; and LOD 2.86, P = 0.00014 for waist circumference) by family regression analyses. Adding three additional markers to the intervals flanking the chromosome 12 peak yielded an LOD score of 4.08 (P = 0.00001) for percentage of fat at 116 cM and LOD scores of 3.57 (P = 0.00003) and 3.05 (P = 0.00009) for BMI and waist circumference, respectively, at 125 cM. We also obtained other suggestive linkages on chromosomes 2, 3, 7, 8, 9, 12, 13, and 21. Our results suggest multiple loci that could influence obesity, particularly a locus in chromosome region 12q23-24. [ABSTRACT FROM AUTHOR]

• WSGSA can study heat transfer in the medium of soot aggregates. • WSGSA coupled with WSGG can study heat transfer in gas and soot aggregates mixture. • Effect of soot radiation cannot be ignored even with small volume faction. Soot, a product of insufficient combustion, is usually in the form of aggregate. The multi-scattering of soot fractal aggregates has been proved to play an important role in studying the soot radiative properties, which is rarely considered in predicting the radiative heat transfer in combustion flame. In the present study, based on the Rayleigh-Debey-Gans-Fractal-Aggregate (RDG-FA) theory, a model, named Weighted Sum of Gray Soot fractal Aggregates (WSGSA), used to calculate the radiative properties of nongray soot fractal aggregates in gas-soot mixture is developed by combining the features of full-spectrum k-distribution (FSK) model and Weighted-Sum-of-Gray-Gases (WSGG) model. Four gray soot fractal aggregates obtained from reordering in the form of the k-distribution at Gauss-Legendre integral points are selected to represent the nongray soot fractal aggregate, while corresponding weighting factors are obtained by fitting the radiation data obtained by the line-by-line (LBL) model with soot radiation data. Then, the WSGSA model is systematically validated by studying the radiative heat transfer properties in a one-dimensional plane-parallel slab system only with soot aggregates. The maximum relative discrepancies of emittance under different temperatures and different path lengths are less than 12%, while the maximum relative discrepancies of radiative heat source term and radiative heat flux are both less than 11% with path length less than 3 m. Moreover, combined with the WSGG model, the performance of the WSGSA model is further validated by predicting the radiative heat transfer properties in the mixture consisted of gases and soot aggregates, and acceptable results are also obtained. All the results reveal that the developed model can be applied to predict the radiative heat transfer in the mixture containing gases and soot aggregates, even in the case of significant changes in temperature and species concentration. [ABSTRACT FROM AUTHOR]

The unsteady-state laser, i.e. time-domain (TD) and frequency-domain (FD) lasers, and the steady-state (SS) laser are employed as the measurement lasers to reconstruct the geometrical characteristic parameters of soot fractal aggregates, i.e. the root mean square radius R g and fractal dimension D f. The direct problems are solved by the finite volume method and Rayleigh-Debye-Gans fractal aggregate method, while an improved artificial bee colony algorithm is used as the inverse problem algorithm. The sensitivity analysis is employed to study the effective sampling region of the TD and FD laser measurement signals, and the results show that the time-resolved signals selected within [L, 0.5L + ct p ] for the TD laser and the dimensionless frequency selected within [0.5, 5] for the FD laser are conducive to improving the retrieval accuracy. Then, the geometrical characteristic parameters of soot fractal aggregates are retrieved by using different measurement lasers, and the results reveal that the retrieval accuracy can be ensured by using the TD laser measurement technique. Moreover, the retrieval accuracy and robustness of R g are better than those of D f. All the studies in the present manuscript supply an application plat of the laser measurement techniques in reconstructing the geometrical characteristic parameters of soot fractal aggregates. [ABSTRACT FROM AUTHOR]

Aging affects all organs. Arteries, in particular, are among the most affected. Vascular aging (VA) is defined as age-associated changes in function and structure of vessels. Classical VA phenotypes are carotid intima-media thickness (IMT), carotid plaque (CP), and arterial stiffness (STIFF). Individuals have different predisposition to these VA phenotypes and their associated risk of cardiovascular events. Some develop an early vascular aging (EVA), and others are protected and identified as having supernormal vascular aging (SUPERNOVA). The mechanisms leading to these phenotypes are not well understood. In the Northern Manhattan Study (NOMAS), we found genetic variants in the 7 Sirtuins (SIRT) and 5 Uncoupling Proteins (UCP) to be differently associated with risk to developing VA phenotypes. In this article, we review the results of genetic-epidemiology studies to better understand which of the single nucleotide polymorphisms (SNPs) in SIRT and UCP are responsible for both EVA and SUPERNOVA. [Display omitted] • Vascular aging (VA) is an age-associated changes in function and structure of vessels. • Individuals have different predisposition to VA phenotypes. • Some individuals develop an early vascular aging (EVA). • Some individuals are protected and identified as having supernormal vascular aging (SUPERNOVA). • Single nucleotide polymorphisms in SIRT and UCP are responsible for both EVA and SUPERNOVA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Four SNPs in LINC01362 are associated with executive function in a diverse cohort. • The SNPs are associated with color trails test form 2, odd-man-out subtests 2 and 4. • Identified SNPs influence expression of TTLL7 and PRKACB in several brain regions. Executive function is a cognitive domain with sizable heritability representing higher-order cognitive abilities. Genome-wide association studies (GWAS) of executive function are sparse, particularly in populations underrepresented in medical research. We performed a GWAS on a composite measure of executive function that included measures of mental flexibility and reasoning using data from the Northern Manhattan Study, a racially and ethnically diverse cohort (N = 1077, 69% Hispanic, 17% non-Hispanic Black and 14% non-Hispanic White). Four SNPs located in the long intergenic non-protein coding RNA 1362 gene, LINC01362 , on chromosome 1p31.1, were significantly associated with the composite measure of executive function in this cohort (top SNP rs2788328, ß = 0.22, p = 3.1 × 10-10). The associated SNPs have been shown to influence expression of the tubulin tyrosine ligase like 7 gene, TTLL7 and the protein kinase CAMP-activated catalytic subunit beta gene, PRKACB, in several regions of the brain involved in executive function. Together, these findings present new insight into the genetic underpinnings of executive function in an understudied population. [ABSTRACT FROM AUTHOR]

Background: Perivascular spaces (PVS) are fluid-filled compartments surrounding small intracerebral vessels that transport fluid and clear waste.Objective: We examined associations between PVS count, vascular and neurodegenerative risk factors, and cognitive status among the predominantly Hispanic participants of the FL-VIP Study of Alzheimer's Disease Risk.Methods: Using brain MRI (n = 228), we counted PVS in single axial image through the basal ganglia (BG) and centrum semiovale (CSO). PVS per region were scored as 0 (none), 1 (<10), 2 (11-20), 3 (21-40), and 4 (>40). Generalized linear models examined PVS associations with vascular risk factors and a composite vascular comorbidity risk (VASCom) score.Results: Our sample (mean age 72±8 years, 61% women, 60% Hispanic, mean education 15±4 years, 33% APOE4 carriers) was 59% hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. PVS scores ranged from 0-4 in the BG (mean 1.3±0.7) and CSO (mean 1.2±0.9), and 0-7 combined (mean 2.5±1.4). In multivariable regression models, BG PVS was associated with age (β= 0.03/year, p < 0.0001), Hispanic ethnicity (β= 0.29, p = 0.01), education (β= 0.04/year, p = 0.04), and coronary bypass surgery (β= 0.93, p = 0.02). CSO PVS only associated with age (β= 0.03/year, p < 0.01). APOE4 and amyloid-β were not associated with PVS.Conclusion: BG PVS may be a marker of subclinical cerebrovascular disease. Further research is needed to validate associations and identify mechanisms linking BG PVS and cerebrovascular disease markers. PVS may be a marker of neurodegeneration despite our negative preliminary findings and more research is warranted. The association between BG PVS and Hispanic ethnicity also requires further investigation. [ABSTRACT FROM AUTHOR]

Objectives To determine whether infectious burden ( IB) is associated with worse performance and decline on a battery of neuropsychological tests. Design Prospective cohort study (Northern Manhattan Study ( NOMAS)). Setting Community. Participants A subsample of 588 stroke-free NOMAS participants with IB and cognitive data (mean age 71 ± 8, 62% female, 14% white, 16% black, 70% Hispanic) and 419 with repeat cognitive testing. Measurements Samples used for IB data were collected at baseline. Two waves of neurocognitive assessments occurred during follow-up. Participants underwent a neuropsychological battery and had repeated testing (mean time span 6 ± 2 years). Using factor analysis-derived domain-specific Z scores for language, memory, executive function, and processing speed, associations between a quantitative stroke risk-weighted IB index ( IBI), based on five common infections ( Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, herpes simplex viruses 1 and 2), and cognitive performance and decline in each domain was examined. Results Adjusting for demographic characteristics, socioeconomic status, crystallized cognitive abilities, and vascular risk factors, the IBI was inversely associated with executive function at baseline (beta = −0.10, P = .01) but not with baseline language, memory, or processing speed performance in adjusted analyses. The IBI was associated with cognitive decline in the memory domain, adjusting for demographic and vascular risk factors ( P = .02). Conclusion A quantitative stroke risk-weighted measure of IB explained variability in baseline executive function performance and associated with decline in memory. Past exposure to common infections may contribute to vascular cognitive impairment and warrants further study. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a clustering of vascular risk factors and is associated with increased risk of cardiovascular disease. Less is known about the relationship between MetS and cognition. We examined component vascular risk factors of MetS as correlates of different cognitive domains. The Northern Manhattan Study (NOMAS) includes 1290 stroke-free participants from a largely Hispanic multi-ethnic urban community. We used structural equation modeling (SEM) to model latent variables of MetS, assessed at baseline and an average of 10 years later, at which time participants also underwent a full cognitive battery. The two four-factor models, of the metabolic syndrome (blood pressure, lipid levels, obesity, and fasting glucose) and of cognition (language, executive function, psychomotor, and memory), were each well supported (CFI=0.97 and CFI=0.95, respectively). When the two models were combined, the correlation between metabolic syndrome and cognition was −.31. Among the metabolic syndrome components, only blood pressure uniquely predicted all four cognitive domains. After adjusting for age, gender, race/ethnicity, education, smoking, alcohol, and risk factor treatment variables, blood pressure remained a significant correlate of all domains except memory. In this stroke-free race/ethnically diverse community-based cohort, MetS was associated with cognitive function suggesting that MetS and its components may be important predictors of cognitive outcomes. After adjusting for sociodemographic and vascular risk factors, blood pressure was the strongest correlate of cognitive performance. Findings suggest MetS, and in particular blood pressure, may represent markers of vascular or neurodegenerative damage in aging populations. (JINS, 2014, 20, 1–10) [ABSTRACT FROM AUTHOR]

Stroke subtypes have been reported to differ by race and ethnic subgroups and have not been adequately explained. We aim to evaluate if the prevalence of vascular risk factors accounts for differences observed in stroke subtypes by race/ethnicity. Patients with acute stroke were prospectively enrolled in the Miami Stroke Registry. Patients' demographic, clinical and radiological characteristics were systematically collected. Stroke subtypes were ascertained using TOAST criteria. The sample was divided into Non-Hispanic Whites (NHW), Hispanics, African Americans (AA), and Non-Hispanic Black Caribbean (NHBC). Univariable and multivariable logistic regression analyses were performed to assess differences among groups. Among 473 stroke patients (mean age 64 ± 14 years; 63.7 % were men) of which 52.9 % were Hispanic, 22.6 % were AA, 13.5 % NHBC and 11.0 % were NHW. Large artery atherosclerosis was more prevalent in NHBC (OR 1.74, 95 % CI 1.02-2.97) than in the other groups. Adjusting for covariates rendered the association not significant (OR 1.71, 95 % CI 0.93-3.16). Cardioembolism was more frequent in Hispanics (OR 1.94, 95 % CI 1.28-2.96) and NHW (OR 2.66, 95 % CI 1.42-4.96) as compared to NHBC and AA combined. Adjusting for covariates, the association was no longer significant for Hispanics but was further strengthened for NHW (OR 3.02, 95 % CI 1.42-6.42). Our results suggest that the vascular risk factors prevalence among different racial and ethnic groups partially explains disparities found in the prevalence of some stroke subtypes. Addressing health disparities remains an important public health aspect of stroke prevention. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Genetic variation in coagulation and fibrinolysis may affect the development of subclinical atherosclerosis modifying the risk of stroke and cardiovascular disease. However, data on the relationship between subclinical atherosclerosis and genes involved in the coagulation system are sparse. The objective of this study is to examine the association between single nucleotide polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque phenotypes. Methods: From the Genetic Determinants of Subclinical Carotid Disease Study, 287 Dominicans were examined for carotid plaque presence, thickness, and surface irregularity by high-resolution B-mode carotid ultrasound. Logistic regression was used to test for association between 101 SNPs in 23 coagulation system genes and plaque phenotypes while controlling for age, sex, smoking, hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions between genes were examined. A follow-up of SNPs in moderate to high (r2 >0.25) linkage disequilibrium (LD) with those implicated in the discovery analysis (p≤0.01) was performed in an independent sample of 301 Dominicans. Results: The prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean age (65±8 discovery; 65±9 follow-up) of the participants was similar in both datasets. Two genes (vWF and THBS1) were associated (p≤0.01) with plaque size and surface irregularity. In follow-up, 5 SNPs in vWF were associated (p≤0.05) with plaque size. SERPINE1 was an additional gene of interest in the haplotype and interaction analyses. Conclusions: Variation in the vWF, THBS1, and SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic plaque. [Copyright &y& Elsevier]

Carotid plaque is a subclinical measure of atherosclerosis. We have previously shown measures of carotid plaque to be heritable in a sample of 100 Dominican families and found evidence for linkage and association of common variants (CVs) on 7q36, 11p15, 14q32 and 15q23 with plaque presence. Our current study aimed to refine these regions further and identify rare variants (RVs) influencing plaque presence. Therefore, we performed targeted sequencing of the one LOD unit down region on 7q36, 11p15, 14q32 and 15q23 in 12 Dominican families with evidence for linkage to plaque presence. Gene-based RV analyses were performed using the Sequence Association Test for familial data (F-SKAT) under two filtering algorithms; 1. all exonic RVs and 2. non-synonymous RVs. Replication analyses were performed using a sample of 22 Dominican families and 556 unrelated Dominicans with Exome Array data. To identify additional non-synonymous RVs influencing plaque, we looked for co-segregation of RVs with plaque in each of the sequenced families. Our most strongly associated gene with evidence for replication was AMPD3 which showed suggestive association with plaque presence in the sequenced families (exonic RV p = 0.003, nonsynonymous RV p = 0.005) and replication families (exonic RV p = 0.04, nonsynonymous RV p = 0.02). Examination of the sequenced family pedigrees revealed two missense variants on chromosome 11 which co-segregated with plaque presence in one of our families; rs61751342 (located in DENND2B), and rs61760882 (located in RNF141). The rs61751342 missense variant is an eQTL for SCUBE2 in the atrial appendage. Notably, SCUBE2 encodes a protein which interacts with vascular endothelial growth factor (VEGF) receptor 2 to regulate VEGF-induced angiogenesis, thus providing biologic plausibility for this gene in atherosclerosis. In conclusion, using targeted sequencing of previously-identified linkage regions, we have identified suggestive evidence for the role of RVs in carotid plaque pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Neighborhood greenness (vegetative presence) has been linked to multiple health outcomes, but its relationship to Alzheimer's disease (AD) and non-Alzheimer's (non-AD) dementia has been less studied.Objective: This study examines the relationship of greenness to both AD and non-AD dementia in a population-based sample of Medicare beneficiaries.Methods: Participants were 249,405 US Medicare beneficiaries aged > 65 years living in Miami-Dade County, FL, from 2010 to 2011. Multi-level analyses examined the relationship of greenness, assessed by mean Census block level Normalized Difference Vegetation Index (NDVI), to odds of each of AD, Alzheimer's disease and related dementias (ADRD), and non-AD dementia, respectively. Covariates included age, gender, race/ethnicity, number of comorbid health conditions, and neighborhood income.Results: Higher greenness was associated with reduced risk of AD, ADRD, and non-AD dementia, respectively, adjusting for individual and neighborhood sociodemographics. Compared to the lowest greenness tertile, the highest greenness tertile was associated with reduced odds of AD by 20%(odds ratio, 0.80; 95%CI, 0.75-0.85), ADRD by 18%(odds ratio, 0.82; 95%CI, 0.77-0.86), and non-AD dementia by 11%(odds ratio, 0.89; 95%CI, 0.82-0.96). After further adjusting for number of comorbidities, compared to the lowest greenness tertile, the highest greenness tertile was associated with reduced odds of AD (OR, 0.94; 95%CI, 0.88-1.00) and ADRD (OR, 0.93; 95%CI, 0.88-0.99), but not non-AD dementia (OR, 1.01; 95%CI, 0.93-1.08).Conclusion: High neighborhood greenness may be associated with lower odds of AD and ADRD. Environmental improvements, such as increasing neighborhood vegetation, may be a strategy to reduce risk for AD and possibly other dementias. [ABSTRACT FROM AUTHOR]

Background: Modifiable vascular risk factors (VRF) have been implicated in cognitive impairment.Objective: We compared the prediction of cognitive performance between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score, a validated tool to estimate dementia risk using VRF, and the Northern Manhattan Study (NOMAS) global vascular risk score (GVRS), created to predict vascular events.Methods: The CAIDE and GVRS scores were calculated based on baseline VRF among 1,290 stroke-free participants in the prospective population-based NOMAS MRI cohort (mean age 64±8 years, 60% women; 66% Hispanic, 17% Black, 15% White; 46% completed high school). Domain-specific Z-scores were derived for episodic and semantic memory, executive function, and processing speed, and averaged to calculate global cognition.Results: The CAIDE score was associated with worse global cognition at initial assessment (Beta per SD = -0.347, p < 0.0001), and with greater decline over time (Beta per SD = -0.033, p = 0.02). These associations were largely due to age and education, and the association with cognitive decline was not significant after adjusting for age, sex, and education. The GVRS was inversely associated with global cognition at initial testing (Beta per SD = -0.247, p < 0.0001) and greater decline over time (Beta per SD = -0.127, p < 0.0001), which persisted after adjusting for sociodemographics. The associations for both scores with initial cognitive performance were driven by executive function and processing speed, and the GVRS was associated with decline in episodic memory and processing speed.Conclusions: The GVRS was a stronger predictor of cognitive decline than the CAIDE in a multi-ethnic urban cohort. The inclusion of glucose and smoking in the GVRS, which are absent in CAIDE, likely explains the better performance of the GVRS. [ABSTRACT FROM AUTHOR]

Introduction: We report the prevalence of abnormal tandem gait (TG) in patients with idiopathic Parkinson disease (PD) and its association with symptoms of subjective unsteadiness, falls, freezing of gait, and cognitive impairment.Methods: We assessed subjective balance impairment, fall history, antero-posterior postural instability, and TG in PD patients (Hoehn and Yahr (HY) stage 0-4). We recorded the age, sex, current medications, HY stage, Schwab and England (S&E) scale score, and MOCA score for each patient. Logistic regression was used to evaluate age-adjusted associations between TG and other demographic and clinical factors.Results: A total of 102 patients with PD were assessed. Of those, 63.5% of HY 2 patients and 100% of HY 2.5 and 3 patients had a TG abnormality. The presence of TG abnormality was associated with subjective imbalance, falls, freezing of gait, S&E < 80, and MOCA score <24 after adjustment for age.Conclusions: TG abnormality is common in PD, precedes the development of antero-posterior postural instability, is associated with cognitive impairment, and may predict fall risk. A longitudinal study will help determine if TG is a predictor of impending progression from HY 2 to HY 3. [ABSTRACT FROM AUTHOR]

Background: A detailed analysis of the tomographic thickness of intraretinal layers may provide more information on neurodegeneration in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD).Objective: The goal was to analyze tomographic thickness patterns of intraretinal layers in patients with AD andMCI.Method: Forty-nine patients (25 AD and 24 MCI) and 21 cognitively normal (CN) controls were imaged using ultra-high-resolution optical coherence tomography to obtain volumetric data centered on the fovea. The segmented intraretinal layers were retinal nerve fiber layer (RNFL), ganglion cell- inner plexiform layer (GCIPL), inner nuclear layer (INL), outer nuclear layer (ONL), outer plexiform layer (OPL), and retinal photoreceptor (PR), in addition to the total retinal thickness(TRT).Results: The thickness differences were negative (thinning) mainly in TRT, RNFL, and GCIPL in both AD and MCI groups in comparison to CN, while the thickness differences were positive (thickening) mainly in ONL and PR in AD. GCIPL of AD and MCI was thinner in superior, nasal superior, and temporal superior quadrants, compared to CN (p < 0.05). GCIPL of the inner superior, inner nasal superior, inner temporal superior, and outer nasal superior sectors was significantly thinner in AD than CN (p < 0.05). GCIPL of the outer superior, inner temporal superior, outer nasal, and temporal superior sectors was significantly thinner in MCI than CN (p < 0.05).Conclusion: Focal thinning of the GCIPL was visualized and quantified by detailed partitions in AD and MCI, which provides specific information about neurodegeneration in MCI and AD. [ABSTRACT FROM AUTHOR]

Objectives: To test the hypothesis that brain arterial diameters are associated with cognitive performance, particularly in arteries supplying domain-specific territories. Methods: Stroke-free participants in the Northern Manhattan Study were invited to have a brain MRI from 2003–2008. The luminal diameters of 13 intracranial arterial segments were obtained using time-of-flight magnetic resonance angiogram (MRA), and then averaged and normalized into a global score and region-specific arterial diameters. Z-Scores for executive function, semantic memory, episodic memory and processing speed were obtained at MRI and during follow-up. Adjusted generalized additive models were used to assess for associations. Results: Among the 1034 participants with neurocognitive testing and brain MRI, there were non-linear relationships between left anterior (ACA) and middle cerebral artery (MCA) diameter and semantic memory Z-scores (χ2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores (χ2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd neuropsychological testing, on average 5.0±0.4 years after their MRI, semantic memory change was associated non-linearly with the left PCA/Pcomm mean diameter (χ2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (χ2=8.43; DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants with the larger brain arterial diameters had more consistently lower Z-scores and greater decline than the rest of the participants. Conclusions: Brain arterial diameters may have downstream effects in brain function presenting as poorer cognition. Identifying the mechanisms and the directionality of such interactions may increase the understanding of the vascular contribution to cognitive impairment and dementia. (JINS, 2018, 24, 335–346) [ABSTRACT FROM AUTHOR]

Objectives: Although disparities in stroke care and outcomes have been well documented nationally, state-based registries to monitor acute stroke care in Florida (FL) and Puerto Rico (PR) have not been established. The FL-PR Collaboration to Reduce Stroke Disparities (CReSD) was developed to evaluate race-ethnicity and regional disparities in stroke care performance. The objective of this study was to assess and compare hospital characteristics within a large quality improvement registry to identify characteristics associated with better outcomes for acute ischemic stroke care.Methods: Trained personnel from 78 FL-PR CReSD hospitals (69 FL, 9 PR) completed a 50-item survey assessing institutional characteristics across seven domains: acute stroke care resource availability, emergency medical services integration, stroke center certification, data collection and use, quality improvement processes, FL-PR CReSD recruitment incentives, and hospital infrastructure.Results: The rate of survey completion was 100%. Differences were observed both within FL and between FL and PR. Years participating in Get With The Guidelines-Stroke (8.9 ± 2.6 years FL vs 4.8 ± 2.4 years PR, P < 0.0001) and proportion of hospitals with any stroke center certification (94.2% FL vs 11.1% PR, P < 0.0001) showed the largest variations. Smaller hospital size, fewer years in Get With The Guidelines-Stroke, and lack of stroke center designation and acute stroke care practice implementation may contribute to poorer outcomes.Conclusions: Results from our survey indicated variability in hospital- and system-level characteristics in stroke care across hospitals in Florida and Puerto Rico. Identification of these variations, which may explain potential disparities, can help clinicians understand gaps in stroke care and outcomes and targeted interventions to reduce identified disparities can be implemented. [ABSTRACT FROM AUTHOR]

Background: We sought to determine the association between cigarette smoking and carotid plaque ultrasound morphology in a multiethnic cohort. Methods: We analyzed 1,743 stroke-free participants (mean age 65.5 ± 8.9 years; 60% women; 18% white, 63% Hispanic, 19% black; 14% current and 38% former smokers, 48% never smoked) from the Northern Manhattan Study using an ultrasound index of plaque echodensity, the Gray-Scale Median (GSM). Echolucent plaque (low GSM) represents soft plaque and echodense (high GSM) more calcified plaque. The mean GSM weighted by plaque area for each plaque was calculated for those with multiple plaques. Quintiles of GSM were compared to no plaque. Multinomial logistic regression models were used to assess associations of cigarette smoking with GSM, adjusting for demographics and vascular risk factors. Results: Among subjects with carotid plaque (58%), the mean GSM scores for quintiles 1-5 were 48, 72, 90, 105, and 128, respectively. Current smokers had over a two fold increased risk of having GSM in quintile 1 (odds ratio (OR) = 2.17; 95% confidence interval (CI), 1.34-3.52), quintile 2 (OR = 2.33; 95% CI, 1.42-3.83), quintile 4 (OR = 2.05; 95% CI, 1.19-3.51), and quintile 5 (OR = 2.13; 95% CI, 1.27-3.56) but not in quintile 3 (OR = 1.18; 95% CI, 0.67-2.10) as compared to never smokers in fully adjusted models. Former smokers had increased risk in quintile 2 (OR = 1.46; 95% CI, 1.00-2.12), quintile 3 (OR = 1.56; 95% CI, 1.09-2.24), quintile 4 (OR = 1.66; 95% CI, 1.13-2.42), and quintile 5 (OR = 1.73; 95% CI, 1.19-2.51), but not in quintile 1 (OR = 1.05; 95% CI, 0.72-1.55). Conclusions: A nonlinear, V-shaped-like relationship between current cigarette smoking and plaque echodensity was observed. Former smokers were at the highest risk for plaques in high GSM quintiles. Thus, current smokers were more likely to have either soft or calcified plaques and former smokers were at greater risk of having only echodense plaques when compared to those who have never smoked. Further research is needed to determine if plaque morphology mediates an association between smoking and clinical vascular events. [ABSTRACT FROM AUTHOR]

Objective Carotid intima-media thickness (cIMT) and carotid plaque (CP) are proposed biomarkers of subclinical atherosclerosis associated with stroke risk. Whether cIMT and CP are distinct phenotypes or single traits at different stages of atherosclerotic development is unclear. We explored the relationship between these markers in the population-based Northern Manhattan Study. Methods We used high-resolution ultrasound and validated imaging protocols to study the cross-sectional (N = 1788 stroke-free participants) and prospective relationship (N = 768 with follow-up scan; mean years between examinations = 3.5) between CP and cIMT measured in plaque-free areas. Results The mean age was 66 ± 9 (40% male, 19% black, 17% white, 61% Hispanic). The mean baseline cIMT was 0.92 ± 0.09 mm, 0.94 ± 0.09 mm among the 58% with prevalent plaque, 0.90 ± 0.08 mm among the 42% without prevalent plaque (p < 0.0001). Each 0.1 mm increase in baseline cIMT was associated with a 1.72-fold increased odds of plaque presence (95%CI = 1.50–1.97), increased plaque thickness (effect on the median = 0.46 mm, p < 0.0001), and increased plaque area (effect on the median = 3.45 mm 2 , p < 0.0001), adjusting for demographics and vascular risk factors. Elevated baseline cIMT was associated with an increased risk of new plaque in any location at follow-up, but after adjusting for demographics and vascular risk factors this association was no longer present. No association was observed in carotid segment-specific analyses. Conclusion Increased cIMT was associated with baseline prevalent plaque but did not predict incident plaque independent of other vascular risk factors. This finding suggests that increased cIMT is not an independent predictor of plaque development although these atherosclerotic phenotypes often coexist and share some common vascular determinants. [ABSTRACT FROM AUTHOR]

Background Recent cohort studies suggested that serum levels of soluble Receptor for Advanced Glycation End-products (sRAGE) are associated with the risk of cardiovascular disease. We hypothesized that sRAGE levels are associated with subclinical atherosclerosis in a racially and ethnically diverse population. Methods and results 828 stroke-free participants from the Northern Manhattan Study (mean age 71.1 ± 8.7yrs; 64% Hispanic, 19% black, and 17% white) underwent high-resolution carotid B-mode ultrasound to measure carotid plaque (present in 62% of subjects) and intima-media thickness (IMT) (mean Total = 0.96 ± 0.10 mm). Serum sRAGE was measured by ELISA and associations tested between sRAGE with IMT and plaque presence. Soluble RAGE levels were not associated with plaque presence or IMT after adjusting for sociodemographic, vascular risk factors and medication use. Stratification by race-ethnicity did not reveal any associations with carotid IMT or plaque. Conclusion In the present study, sRAGE levels were not associated with carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective The objective of this cross-sectional analysis was to investigate the relation between two major high-density lipoprotein cholesterol (HDL-C) subfractions (HDL2-C and HDL3-C) and carotid plaque in a population based cohort. Methods We evaluated 988 stroke-free participants (mean age 66 ± 8 years; 40% men; 66% Hispanic and 34% Non-Hispanic) with available data on HDL subfractions using precipitation method and carotid plaque area and thickness assessed by a high-resolution 2D ultrasound. The associations between HDL-C subfractions and plaque measurements were analyzed by quantile regression. Results Plaque was present in 56% of the study population. Among those with plaque, the mean ± SD plaque area was 19.40 ± 20.46 mm² and thickness 2.30 ± 4.45 mm. The mean ± SD total HDL-C was 46 ± 14 mg/dl, HDL2-C 14 ± 8 mg/dl, and HDL3-C 32 ± 8 mg/dl. After adjusting for demographics and vascular risk factors, there was an inverse association between HDL3-C and plaque area (per mg/dl: beta = −0.26 at the 75th percentile, p = 0.001 and beta = −0.32 at the 90th percentile, p = 0.02). A positive association was observed between HDL2-C and plaque thickness (per mg/dl; beta = 0.02 at the 90% percentile, p = 0.003). HDL-C was associated with plaque area (per mg/dl: beta = −0.18 at the 90th percentile, p = 0.01), but only among Hispanics. Conclusion In our cohort we observed an inverse association between HDL3-C and plaque area and a positive association between HDL2-C and plaque thickness. HDL-C subfractions may have different contributions to the risk of vascular disease. More studies are needed to fully elucidate HDL-C anti-atherosclerotic functions in order to improve HDL-based treatments in prevention of vascular disease and stroke. [ABSTRACT FROM AUTHOR]

The article presents the Vascular Accreditation, Location & Utilization Evaluation (VALUE) Study on the accreditation status and geographic distribution of vascular testing facilities among Medicare beneficiaries in the U.S. The study uses data sets from the U.S. Centers for Medicare & Medicaid Services (CMS) and the Intersocietal Accreditation Commission (IAC), geographic information system (GIS), and descriptive analysis. Results show that IAC accredited facilities are low and vary by region.

Intra-arterial (IA) delivery of mesenchymal stem cells (MSCs) for acute ischemic stroke is attractive for clinical translation. However, studies using rat model of stroke have demonstrated that IA MSCs delivery can decrease middle cerebral artery (MCA) flow, which may limit its clinical translation. The goal of this study is to identify a dose of IA MSCs (maximum tolerated dose; MTD) that does not compromise MCA flow and evaluate its efficacy and optimal timing in a rat model of reversible middle cerebral artery occlusion (rMCAo). We sought to determine if there is a difference in efficacy of acute (1 h) versus sub-acute (24 h) IA MSCs treatment after rMCAo. Adult female Sprague-Dawley rats underwent rMCAo (90 min) and an hour later a single dose of MSCs (at de-escalating doses 1×106, 5×105, 2×105, 1×105 and 5×104) was given using IA route. MSCs were suspended in phosphate buffered saline (PBS) and PBS alone was used for control experiments. We measured the percent change in mean laser Doppler flow signal over the ipsilateral MCA in de-escalating doses groups to determine MTD. The results demonstrated that the lowering of IA MSC dose to 1×105 and below did not compromise MCA flow and hence an IA MSC dose of 1×105 considered as MTD. Subsequently, 1 h and 24 h after rMCAo, rats were treated with IA MSCs or PBS. The 24 h delivery of IA MSCs significantly improved neurodeficit score and reduced the mean infarct volume at one month as compared to control, but not the 1 h delivery. Overall, this study suggests that the IA delivery of MSCs can be performed safely and efficaciously at the MTD of 1×105 delivered at 24 hours in rodent model of stroke. [ABSTRACT FROM AUTHOR]

Background: Evidence of the relationship of cardiovascular health (CVH), defined by the American Heart Association, and specific cardiovascular outcomes is lacking, particularly among Hispanics. This study sought to evaluate the relationship between the number of ideal CVH metrics and cardiovascular risk, overall and by event subtype, in a multiethnic community-based prospective cohort.Methods and Results: A total of 2981 subjects (mean age, 69±10 years; 54% Caribbean Hispanic, 25% black, 21% white) free of myocardial infarction and stroke at baseline in the Northern Manhattan Study were prospectively followed up (median follow-up, 11 years). The relationship between the number of ideal CVH metrics and the risk of cardiovascular disease, including myocardial infarction, stroke, and vascular death, was investigated. Overall, a strong gradient relationship was observed between the adjusted hazard ratios for cardiovascular disease and the number of ideal CVH metrics: 0.73 (95% confidence interval, 0.60-0.89), 0.61 (95% confidence interval, 0.50-0.76), 0.49 (95% confidence interval, 0.38-0.63), and 0.41 (95% confidence interval, 0.26-0.63) for those having 2, 3, 4, and 5 to 6 ideal CVH metrics, respectively, compared with those having 0 to 1 ideal CVH metrics (P for trend <0.0001). Similar graded relationships were found between the number of ideal CVH metrics and the adjusted incidence rate for each specific outcome and among whites, blacks, and Caribbean Hispanics.Conclusions: Our findings demonstrated a steep gradient relationship between ideal CVH and individual cardiovascular disease end points, including stroke, that was similar for whites, blacks, and Caribbean Hispanics. This evidence supports the application of the AHA ideal cardiovascular health metrics for cardiovascular disease risk assessment and health promotion for all Americans regardless of race-ethnic background. [ABSTRACT FROM AUTHOR]

Abstract: Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E2) and inhibits E2-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E2-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-d-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E2 in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E2-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation. [Copyright &y& Elsevier]

Abstract: Objective: Race/ethnic differences in carotid arterial function and structure exist among those with cerebrovascular disease, but whether differences persist among healthy populations is unknown. Our objective was to investigate differences in carotid artery diameter and stiffness between race/ethnic groups, and examine whether these race/ethnic differences were age-dependent. Methods: Carotid diameters were assessed by B-mode ultrasound among 1536 participants from the Northern Manhattan Study (NOMAS), and carotid stiffness metrics were calculated. We used multivariable linear regression models to determine the relationship between race/ethnicity and both carotid arterial stiffness and carotid diastolic diameter. Results: Mean participant age was 70±9 years (Hispanics=68±8, blacks=72±9, and whites=74±9, p <0.0001). Mean DDIAM was 6.2±1.0mm (Hispanics=6.2±0.9mm, blacks=6.3±1.0mm, and whites=6.3±1.0mm, p <0.005) and mean STIFF was 8.7±6.3 (Hispanics=8.5±5.7, blacks=9.2±6.2 and whites=8.9±6.9, p <0.02). In a model that adjusted for sociodemographics and vascular risk factors including hypertension, diabetes, dislipidemia, renal function, physical acticity and a history of known coronary artery diseases; age was positively associated with greater DDIAM in Hispanics (p <0.0001) but not among blacks or whites. Older age was associated with greater stiffness among Hispanics (p <0.0001) and blacks (p <0.003), but not among whites. Conclusions: We found race/ethnic differences in the association between age and arterial stiffness and diameter, including age-dependent arterial dilation observed in Hispanics that was not observed among blacks or whites. [Copyright &y& Elsevier]