Search

AimsHeart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort.Methods and resultsTwo-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>-14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47-4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51-8.43; P = 0.004) but not other subtypes.ConclusionLV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain-heart interaction and may help improve stroke primary prevention strategies.

Background/objectivesChronic kidney disease (CKD) is associated with frailty. Fibroblast growth factor 23 (FGF23) is elevated in CKD and associated with frailty among non-CKD older adults and individuals with human immunodeficiency virus. Whether FGF23 is associated with frailty and falls in CKD is unknown.DesignCross-sectional and longitudinal observational study.SettingSystolic Blood Pressure Intervention Trial (SPRINT), a randomized trial evaluating standard (systolic blood pressure [SBP]

BackgroundMeta-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.ObjectiveTo describe pre-statistical harmonization of cognitive instruments for an individual-level meta-analysis in the blood pressure and cognition (BP COG) study.MethodsWe 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.ResultsWe 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.ConclusionCross-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.

BackgroundVariability 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.ObjectiveEstimate 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.MethodsCases 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).ResultsThere 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.ConclusionIn 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.

Cognitive function such as reasoning, attention, memory, and language is strongly correlated with brain aging. Compared to non-Hispanic whites, Hispanics/Latinos have a higher risk of cognitive impairment and dementia. The genetic determinants of cognitive function have not been widely explored in this diverse and admixed population. We conducted a genome-wide association analysis of cognitive function in up to 7600 middle aged and older Hispanics/Latinos (mean = 55 years) from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Four cognitive measures were examined: the Brief Spanish English Verbal Learning Test (B-SEVLT), the Word Fluency Test (WFT), the Digit Symbol Substitution Test (DSST), the Six-Item Screener (SIS). Four novel loci were identified: one for B-SEVLT at 4p14, two for WFT at 3p14.1 and 6p21.32, and one for DSST at 10p13. These loci implicate genes highly expressed in brain and previously connected to neurological diseases (UBE2K, FRMD4B, the HLA gene complex). By applying tissue-specific gene expression prediction models to our genotype data, additional genes highly expressed in brain showed suggestive associations with cognitive measures possibly indicating novel biological mechanisms, including IFT122 in the hippocampus for SIS, SNX31 in the basal ganglia for B-SEVLT, RPS6KB2 in the frontal cortex for WFT, and CSPG5 in the hypothalamus for DSST. These findings provide new information about the genetic determinants of cognitive function in this unique population. In addition, we derived a measure of general cognitive function based on these cognitive tests and generated genome-wide association summary results, providing a resource to the research community for comparison, replication, and meta-analysis in future genetic studies in Hispanics/Latinos.

Background and purposePeriventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.MethodsParticipants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC.ResultsIn the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype.ConclusionsOur study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

Elevated blood pressure (BP) level is one of the most consistently identified risk factors for silent brain disease. BP values obtained at the proximal segment of the aorta (central BP) are more directly involved than brachial BP in the pathogenesis of cardiovascular disease. However, the association between central BP and silent cerebrovascular disease has not been clearly established. Participants in the CABL (Cardiovascular Abnormalities and Brain Lesions) study (n=993; mean age, 71.7±9.3 years; 37.9% men) underwent 2-dimensional echocardiography, arterial wave reflection analysis for determination of central BPs, and brain magnetic resonance imaging. Central BPs were calculated from the radial pulse waveform. Subclinical silent cerebrovascular disease was defined as silent brain infarction and white matter hyperintensity volume. Both brachial (P=0.014) and central pulse pressure (P=0.026) were independently associated with silent brain infarctions after adjustment for clinical variables, but not adjusting for each other. None of the brachial BP values was associated with upper quartile of white matter hyperintensity volume in multivariable analysis. Both central systolic BP (P

ObjectiveTo examine associations between measures of obesity in middle to early-old age with later-life MRI markers of brain aging.MethodsWe analyzed data from the Northern Manhattan MRI Sub-Study (n = 1,289). Our exposures of interest were body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and plasma adiponectin levels. Our outcomes of interest were total cerebral volume (TCV), cortical thickness, white matter hyperintensity volume (WMHV), and subclinical brain infarcts (SBI). Using multivariable linear and logistic regression models adjusted for sociodemographics, health behaviors, and vascular risk factors, we estimated β coefficients (or odds ratios) and 95% confidence intervals (CIs) and tested interactions with age, sex, and race/ethnicity.ResultsOn average at baseline, participants were aged 64 years and had 10 years of education; 60% were women and 66% were Caribbean Hispanic. The mean (SD) time lag between baseline and MRI was 6 (3) years. Greater BMI and WC were significantly associated with thinner cortices (BMI β [95% CI] -0.089 [-0.153, -0.025], WC β [95% CI] -0.103 [-0.169, -0.037]) in fully adjusted models. Similarly, compared to those with BMI

Objectives:To examine the association between diabetes and cognitive function within U.S. Hispanics/Latinos of Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American background. Method: This cross-sectional study included 9,609 men and women (mean age = 56.5 years), who are members of the Hispanic Community Health Study/Study of Latinos. We classified participants as having diabetes, prediabetes, or normal glucose regulation. Participants underwent a neurocognitive battery consisting of tests of verbal fluency, delayed recall, and processing speed. Analyses were stratified by Hispanic/Latino subgroup. Results: From fully adjusted linear regression models, compared with having normal glucose regulation, having diabetes was associated with worse processing speed among Cubans (β = -1.99; 95% CI [confidence interval] = [-3.80, -0.19]) and Mexicans (β = -2.26; 95% CI = [-4.02, -0.51]). Compared with having normal glucose regulation, having prediabetes or diabetes was associated with worse delayed recall only among Mexicans (prediabetes: β = -0.34; 95% CI = [-0.63, -0.05] and diabetes: β = -0.41; 95% CI = [-0.79, -0.04]). No associations with verbal fluency. Discussion: The relationship between diabetes and cognitive function varied across Hispanic/Latino subgroup.

AimsAlthough ambulatory blood pressure (BP) is a better predictor of cardiovascular outcomes than office BP, its association with subclinical cerebrovascular disease is not clarified. We investigated the associations of office and ambulatory BP values with subclinical cerebrovascular disease in a population based, predominantly elderly cohort without prior stroke.Methods and resultsEight hundred and twenty-eight participants underwent 24-h ambulatory BP monitoring (ABPM), 2D echocardiography and brain magnetic resonance imaging in the Cardiac Abnormalities and Brain Lesion (CABL) study. Daytime, night-time, and 24-h BPs, nocturnal dipping pattern, morning surge (MS), and 24-h variability were assessed. Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV). The association of BP measures with the presence of SBI and upper quartile of log-WMHV (log-WMHV4) was analysed. SBIs were detected in 111 patients (13.4%). Mean log-WMHV was -0.99 ± 0.94. In multivariable analysis, only night-time systolic BP (SBP) was significantly associated with SBI [odds ratio (OR) 1.15 per 10 mmHg, P = 0.042], independent of cardiovascular risk factors, and pertinent echocardiographic parameters. Although daytime, night-time, 24-h BPs, and non-dipping pattern were all significantly associated with log-WMHV4 (all P

ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

In the above article, Fig. 1 was repeated and the correct Fig. 2 was omitted. Please find below the correct Fig. 2. The Publisher apologises for this error. [Figure presented]

ObjectiveWe examined whether greater depressive symptoms were associated with domain-specific cognitive performance, change in cognition, and MRI markers of brain atrophy and subclinical cerebrovascular disease in a diverse sample of older adults from the Northern Manhattan Study.MethodsData were analyzed from the Northern Manhattan Study, a prospective cohort study of mostly Caribbean Hispanic, stroke-free, older adults. A total of 1,111 participants had baseline measures of depressive symptoms, measured as the Center of Epidemiological Studies-Depression Scale, MRI markers, and cognitive function. A Center of Epidemiological Studies-Depression score ≥16 was considered indicative of greater depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations of interest.ResultsAt baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographic, vascular risk factor, behavioral, and antidepressive medication variables (β [95% confidence interval] = -0.21 [-0.33 to -0.10], p = 0.0003). Greater depressive symptoms were also associated with smaller cerebral parenchymal fraction (β [95% confidence interval] = -0.56 [-1.05 to -0.07], p = 0.02) and increased odds of subclinical brain infarcts (odds ratio [95% confidence interval] = 1.55 [1.00-2.42], p = 0.05), after adjustment for sociodemographic, behavioral, and vascular risk factor variables. Greater depressive symptoms were not significantly associated with white matter hyperintensity volume, hippocampal volume, or change in cognition over an average of 5 years. Results were unchanged when stabilized inverse probability weights were applied to address selective attrition during the study period.ConclusionsIn this sample of mostly Caribbean Hispanic, stroke-free, older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts.

Background and aimsThe Ankle-Brachial index (ABI) is a well-accepted measure of peripheral artery disease (arterial stenosis and stiffness) and has been shown to be associated with cognitive function and disorders; however, these associations have not been examined in Hispanics/Latinos. Therefore, we sought to examine relationships between ABI and cognitive function among diverse middle-age and older Hispanics/Latinos.MethodsWe used cross-sectional data on n = 7991 participants aged 45-74 years, without stroke or coronary heart disease, from the Hispanic Community Health Study/Study of Latinos. Our primary outcome, global cognition (GC), was a continuous composite score of four cognitive domains (verbal learning and memory, verbal fluency, executive function, and mental status). Secondary outcomes were the individual tests representing these domains. The ABI was analyzed continuously and categorically with standard clinical cut-points. We tested associations using generalized survey regression models incrementally adjusting for confounding factors. Age, sex, hypertension, diabetes, and dyslipidemia moderations were examined through interactions with the primary exposure.ResultsIn age, sex, and education adjusted models, continuous ABI had an inverse u-shape association with worse GC. We found similar associations with measures of verbal learning and memory, verbal fluency, executive function, but not with low mental status. The associations were attenuated, but not completely explained, by accounting for the confounders and not modified by age, sex, education, and vascular disease risks.ConclusionsIn addition to being a robust indicator of arterial compromise, our study suggests that abnormal ABI readings may also be useful for early signaling of subtle cognitive deficits.

Background and purposeAlthough increased heart rate (HR) is a predictor of cardiovascular events and mortality, its possible association with subclinical cerebrovascular disease, which is prevalent in the elderly, has not been evaluated. This study aimed to investigate the association of daytime, nighttime, 24-hour HR, and HR variability with subclinical cerebrovascular disease in an elderly cohort without history of stroke.MethodsThe study cohort consisted of 680 participants (mean age, 73±7 years; 42% men) in sinus rhythm who underwent 24-hour ambulatory blood pressure and HR monitoring, 2-dimensional echocardiography, and brain magnetic resonance imaging as part of the CABL study (Cardiac Abnormalities and Brain Lesion). Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume (WMHV). The relationship of HR measures with the presence of silent brain infarct and upper quartile of log WMHV (log WMHV4) was analyzed.ResultsPresence of silent brain infarct was detected in 93 participants (13.7%); mean log WMHV was -0.92±0.93 (median, -1.05; min, -5.88; max, 1.74). Multivariate analysis showed that only nighttime HR (adjusted odds ratio, 1.29 per 10 bpm; 95% confidence interval, 1.03-1.61; P=0.026) was significantly associated with log WMHV4, independent of traditional cardiovascular risk factors, ambulatory systolic blood pressure, and echocardiographic parameters. No similar association was observed for daytime HR and HR variability. There was no significant association between all HR measures and silent brain infarct.ConclusionsIn a predominantly elderly cohort, elevated nighttime HR was associated with WMHV, suggesting an independent role of HR in subclinical cerebrovascular disease.

ObjectiveTo investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population.MethodsUsing 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genome-wide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln(WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians.ResultsFrom the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1 × 10-5) and 5 genes from the gene-based analysis with p < 1 × 10-3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p < 0.05) in the African American sample. Four SNPs with p < 1 × 10-5 were shown to affect binding of SPI1 using RegulomeDB.ConclusionsThis GWAS of 2 community-based Hispanic cohorts revealed several novel WMH-associated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants.

BackgroundThe effects of white matter hyperintensity volume and subclinical brain infarcts on the risk of incident stroke, its ischemic subtypes, and mortality require further study in diverse samples.Methods and resultsStroke-free participants in the Northern Manhattan Study underwent magnetic resonance imaging (N=1287; mean age 71±9 years, 60% women, 15% non-Hispanic white, 17% non-Hispanic black, 68% Hispanic) and were followed for a median of 8 years (interquartile range: 6-9 years). Cox models estimated proportional hazards of incident stroke of all types, ischemic stroke (and its subtypes), and mortality and stratified by race/ethnicity. In total 72 participants (6%) had incident strokes and 244 died (19%). In fully adjusted models, those with larger white matter hyperintensity volume had greater risk of all stroke types (hazard ratio [HR]: 1.4; 95% CI, 1.1-1.9), ischemic stroke (HR: 1.3; 95% CI, 1.0-1.8), and cryptogenic stroke (HR: 2.2; 95% CI, 1.1-4.4). White and black but not Hispanic participants had increased stroke risk (P

ObjectiveSince arterial stiffness is a functional measure of arterial compliance and may be an important marker of cerebrovascular disease, we examined the association of carotid artery stiffness with white matter hyperintensity volume (WMHV) in a cross-sectional study of 1,166 stroke-free participants.MethodsCarotid beta stiffness index (STIFF) was assessed by M-mode ultrasound of the common carotid artery and calculated as the ratio of natural log of the difference between systolic and diastolic blood pressure over STRAIN, a ratio of the difference between carotid systolic and diastolic diameter (DD) divided by DD. WMHV was measured by fluid-attenuated inversion recovery MRI. The associations of STIFF, DD, and STRAIN with WMHV were examined using linear regression after adjusting for sociodemographic, lifestyle, and vascular risk factors.ResultsIn a fully adjusted model, larger carotid DD was significantly associated with greater log-WMHV (β = 0.09, p = 0.001). STIFF and STRAIN were not significantly associated with WMHV. In adjusted analyses stratified by race-ethnicity, STRAIN (β = -1.78, p = 0.002) and DD (β = 0.11, p = 0.001) were both associated with greater log-WMHV among Hispanic participants, but not among black or white participants.ConclusionsLarge carotid artery diameters are associated with greater burden of white matter hyperintensity (WMH) in this multiethnic population. The association between increased diameters, decreased STRAIN, and greater WMH burden is more pronounced among Hispanics. These associations suggest a potential important pathophysiologic role of extracranial large artery remodeling in the burden of WMH.

BackgroundWalking speed is associated with functional status and all-cause mortality. Yet the relationship between walking speed and stroke, also a leading cause of disability, remains poorly understood, especially in older Latino adults who suffer from a significant burden of stroke.MethodsA total of 1,486 stroke-free participants from the Sacramento Area Latino Study on Aging, aged 60 and older at baseline in 1998-1999, were followed annually through 2010. Participants reported their usual walking speed outdoors which was classified into slow, medium, or fast. We also assessed timed tandem walk ability (unable or eight or more errors vs less than eight errors). We ascertained three incident stroke endpoints: total stroke, nonfatal stroke, and fatal stroke. Using Cox proportional hazards models, we estimated hazard ratios (HRs) for stroke at different walking speed and timed tandem walk categories.ResultsOver an average of 6 years of follow-up (SD = 2.8), the incidence rate of total strokes was 23.2/1,000 person-years for slow walkers compared to 15.6/1,000 person-years for medium walkers, and 7.6/1,000 person-years for fast walkers. In Cox models adjusted for sociodemographics, cardiovascular risk, cognition and functional status, and self-rated health, the hazard of total stroke was 31% lower for medium walkers (HR: 0.69, 95% confidence interval [CI]: 0.47, 1.02) and 56% lower for fast walkers (HR: 0.44, 95% CI: 0.24, 0.82) compared with slow walkers. We found similar associations with timed tandem walk ability (fully adjusted HR: 0.66, 95% CI: 0.45, 0.98).ConclusionsOur findings suggest perceived walking speed captures more than self-rated health alone and is a strong risk factor for stroke risk in Latino older adults.

BackgroundAlthough abnormal left ventricular geometric patterns have prognostic value for morbidity and mortality, their possible association with silent cerebrovascular disease has not been extensively evaluated.MethodsWe examined 665 participants in the CABL study who underwent transthoracic echocardiography and brain magnetic resonance imaging. Participants were divided into 4 geometric patterns: normal geometry (n=397), concentric remodeling (n=89), eccentric hypertrophy (n=126), and concentric hypertrophy (n=53). Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV; expressed as log-transformed percentage of the total cranial volume).ResultsSilent brain infarcts were observed in 94 participants (14%). Mean log-WMHV was -0.97±0.93. Concentric hypertrophy carried the greatest risk for both SBI (adjusted odds ratio [OR] 3.39, P

BackgroundBrain magnetic resonance imaging (MRI) allows researchers to observe structural pathology that may predict cognitive decline. Some populations are less accessible through traditional in-person visits, and may be under-represented in the literature.MethodsWe examined white matter hyperintensity volume (WMHV) and cerebral parenchymal fraction (CPF) as predictors of cognitive decline measured by a modified Telephone Interview for Cognitive Status (TICS-m) in the Northern Manhattan Stroke Study, a racially and ethnically diverse cohort study. Participants were stroke-free, above 50 years old, and had no contraindications to MRI. A total of 1143 participants had MRI and TICS-m data available [mean age 70 (SD=9), 61% women, 66% Hispanic, 17% Black, 15% white].ResultsThose in the third and fourth quartiles of WMHV had significantly greater decline in TICS-m over time as compared with those in the first quartile (Q3: -0.17 points/year, Q4: -0.30 points/year). Those in the bottom 2 quartiles of CPF had significantly greater decline in TICS-m than those in the top quartile (Q1: -0.3 points/year, Q2: -0.2 points/year). Apolipoprotein E (APOE) e4 allele carriers had greater cognitive decline per unit of CPF. Those with greater CPF preserve TICS-m performance better despite greater WMHV.ConclusionsTelephone cognitive assessments can detect decline due to white matter lesions and smaller brain volumes.

Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

INTRODUCTION: Arterial stiffness is linked to age‐related cognitive dysfunction. Estimated pulse wave velocity (ePWV) is associated with cerebrovascular disease. We sought to determine whether ePWV was associated with cognition in a multiethnic population. METHODS: We included 1257 participants enrolled in a Northern Manhattan Study magnetic resonance imaging MRI‐cognitive study (mean age 64 ± 8 years, 61% women, 67% Hispanic, 18% non‐Hispanic Black, 15% non‐Hispanic white) and analyzed cognitive performance at two time points, at enrollment and on an average 5.0 ± 0.6 years later. ePWV was calculated using baseline age and blood pressure. Cognition and cognitive change scores were regressed on ePWV in multivariable linear regression models. RESULTS: In adjusted models, ePWV (mean 11 ± 2 m/s) was significantly associated with cognition (b = −0.100, 95% CI, −0.120, −0.080) and cognitive change over time (b = −0.063, 95% CI, −0.082, −0.045). Effect modification by race and sex was found. DISCUSSION: In this multiethnic population, the associations of ePWV with cognitive performance underline the role of vascular stiffness in age‐related cognitive decline. Highlights: ePWV is a modest but independent predictor of cognitive function and cognitive decline among older individuals.After adjustment, the ePWV measure was inversely associated with performance and decline in global cognition, processing speed, episodic memory, executive function, and semantic memory.After adjustment, modification of the association between ePWV and change in episodic memory and executive function by race and ethnicity was suggested by a significant interaction term.The association between ePWV and episodic memory decline was stronger in females. [ABSTRACT FROM AUTHOR]

Background: Osteopontin (OPN) is a proinflammatory cytokine that has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that an increase in plasma OPN is a deleterious neuroinflammatory marker in people with dementia and cerebral small vessel disease (CSVD). Methods: A pilot study was conducted on participants in the Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD and chosen to be similar in age, sex, and education attainment: No dementia/No CSVD (n = 19), Dementia/No CSVD (n = 22), and Dementia + CSVD (n = 21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of the medical history. CSVD was indicated by silent brain infarcts, enlarged perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes (WMHV) on MRI. Multinomial logistic regression was used to examine the difference in OPN levels across groups, adjusting for key determinants of CSVD and neurodegeneration. Results: Plasma OPN levels were elevated in the Dementia+CSVD group (mean = 70.69 ± 39.00 ng/mL) but not in the Dementia/No CSVD group (mean = 45.46 ± 19.11 ng/mL) compared to the No Dementia/No CSVD group (mean = 36.43 ± 15.72 ng/mL). OPN was associated with Dementia+CSVD (Odds Ratio [OR] per ng/mL = 1.06, 95% CI 1.02–1.11) after adjusting for covariates, including brain volume. OPN was strongly correlated with WMHV (Spearman's rank correlation ρ = 0.46, p = 0.0001) but not with other components of CSVD. Conclusion: In this pilot, greater levels of plasma OPN were associated with dementia with evidence of CSVD. This link was predominately driven by the contribution of OPN to dementia through the burden of white matter lesions. [ABSTRACT FROM AUTHOR]

Background and purposeAortic arch plaque (AAP) is a risk factor for ischemic stroke, but its association with subclinical cerebrovascular disease is not established. We investigated the association between AAP and subclinical cerebrovascular disease in an elderly stroke-free community-based cohort.MethodsThe CABL study (Cardiovascular Abnormalities and Brain Lesions) was designed to investigate cardiovascular predictors of silent cerebrovascular disease in the elderly. AAPs were assessed by suprasternal transthoracic echocardiography in 954 participants. Silent brain infarcts and white matter hyperintensity volume (WMHV) were assessed by brain magnetic resonance imaging. The association of AAP thickness with silent brain infarcts and WMHV was evaluated by logistic regression analysis.ResultsMean age was 71.6±9.3 years; 63% were women. AAP was present in 658 (69%) subjects. Silent brain infarcts were detected in 138 participants (14.5%). In multivariate analysis adjusted for potential confounders, AAP thickness and large AAP (≥4 mm in thickness) were significantly associated with the upper quartile of WMHV (WMHV-Q4; odds ratio =1.17; 95% confidence interval, 1.04-1.32; P=0.009 and odds ratio =1.79; 95% confidence interval, 1.40-3.09; P=0.036, respectively), but not with silent brain infarcts (odds ratio =1.08; 95% confidence interval, 0.94-1.23; P=0.265 and odds ratio =1.46; 95% confidence interval, 0.77-2.77; P=0.251, respectively).ConclusionsAortic arch atherosclerosis was associated with WMHV in a stroke-free community-based elderly cohort. This association was stronger in subjects with large plaques and independent of cardiovascular risk factors. Aortic arch assessment by transthoracic echocardiography may help identify subjects at higher risk of subclinical cerebrovascular disease, who may benefit from aggressive stroke risk factors treatment.

ObjectiveWe investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population.MethodsWe quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates.ResultsMRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function.ConclusionsIn this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance.