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BackgroundHispanic/Latino sexual and gender minorities (SGM) are the fastest growing ethnic group of SGM in the United States. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among Hispanics/Latinos. SGM inequities in CVD risk have been identified as early as young adulthood, and minority stress has been identified as a potential mediator. Yet, the small number of ethnic or racial minority participants in SGM studies have precluded the examination of the intersections of sexual orientation, gender identity, and race and ethnicity. ObjectiveMinority stress models conceptualize relationships between stressors in minority groups and health outcomes. In this study, we will (1) examine the influence of sexual orientation and gender identity on CVD risk among all Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants at visit 3 (2021-2024; N~9300); (2) model pathways from sexual orientation and gender identity to CVD risk through stigma, discrimination, and stress in a 1:2 matched subcohort of SGM and non-SGM participants at visit 3 (n~1680); and (3) examine the influence of resilience factors on sexual orientation or gender identity and CVD risk relationships among subcohort participants at visit 3 (n~1680). MethodsThis study will leverage existing data from the parent HCHS/SOL study (collected since 2008) while collecting new data on sexual orientation, gender identity, stigma, discrimination, stress, coping, social support, and CVD risk. Data analysis will follow the SGM minority stress model, which states that excess stigma against SGM populations leads to minority stress that increases CVD risk. In this model, coping and social support serve as resilience factors that can mitigate the impact of minority stress on CVD risk. Cross-sectional and longitudinal regression models as well as structural equation models will be used to test these relationships. ResultsThis study was funded by the National Heart, Lung, and Blood Institute in March 2020. Recruitment is scheduled to begin in the first quarter of 2021 and continue through 2024. ConclusionsUnderstanding the influence of stigma-induced stress on CVD risk among Hispanic/Latino SGM has significant implications for the development of culturally specific CVD risk reduction strategies. Study findings will be used to build on identified Hispanic/Latino cultural strengths to inform adaptation and testing of family and community acceptance interventions. International Registered Report Identifier (IRRID)PRR1-10.2196/28997

Background and objectivesTo investigate the associations between self-reported visual functioning (VF) and hearing functioning with cognition in the Hispanic/Latino population.Research design and methodsWe utilized data from the Miami Ocular Study of Latinos ancillary study to Hispanic Community Health Study/Study of Latinos with 1,056 participants aged 45 and older. The outcomes were cognitive performances assessed by the Digit Symbol Substitution Test (DSST), Word Fluency, Brief-Spanish English Verbal Learning Test-recall (B-SEVLT recall), words recalled over 3 trials, and the Six-Item Screener. VF was measured by National Eye Institute Visual Function Questionnaire (NEI-VFQ), and hearing function was measured by Hearing Handicap Inventory Screening Questionnaire for Adults and Elderly (HHIA/E-S). Multiple regressions were performed for each cognitive outcome while controlling for covariates and complex sampling design.ResultsNEI-VFQ was associated with 3 of the 5 cognitive outcomes. A 4-point NEI-VFQ score difference was associated with a 0.56-point difference in DSST (standard error [SE] = 0.27, p

BackgroundHypertension can have deleterious effects on cognitive function; however, few studies have examined its effects on cognition among Hispanics/Latinos.ObjectiveTo assess associations between hypertension status with 1) change in cognitive performance, and 2) having mild cognitive impairment (MCI) among diverse Hispanics/Latinos.MethodsThis population-based, prospective cohort, multisite study included Hispanic/Latino adults aged 45 to 72 years in enrolled in the Hispanic Community Health Study/Study of Latinos at Visit 1 (2008-2011; mean age of 63.40±8.24 years), and the Study of Latinos-Investigation of Neurocognitive Aging at Visit 2 (2016-2018), with a mean follow-up duration of 7 years (n = 6,173). Hypertension status was assessed at both visits: normotension (no hypertension), incident hypertension (only at Visit 2), and persistent hypertension (at both visits). We examined change in cognitive performance and having MCI (only assessed at Visit 2) relative to hypertension status and adjusted for demographics and cardiovascular disease risk factors.ResultsCompared to normotension, persistent hypertension was associated with significantly increased decline in verbal fluency (β= -0.08; CI = [-0.16;-0.01]; p

ObjectivesDerive latent profiles of accelerometry-measured moderate-vigorous physical activity (MVPA) for Hispanic/Latino adults, examine associations between latent MVPA profiles and neurocognition, and describe profiles via self-reported MVPA.MethodsComplex survey design methods were applied to cross-sectional data from 7,672 adults ages 45-74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011). MVPA was measured via hip-worn accelerometers. Latent profile analysis was applied to derive latent MVPA profiles (minutes/day of week). Neurocognition was assessed with the Brief-Spanish English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, Controlled Oral Word Association Test (word fluency), and Digit Symbol Substitution (DSS) test. All tests were z-scored, and a global neurocognition score was generated by averaging across scores. Survey linear regression models were used to examine associations between latent MVPA profiles and neurocognitive measures. Self-reported MVPA domains were estimated (occupational, transportation, and recreational) for each latent profile.ResultsFour latent MVPA profiles from the overall adult target population (18-74 years) were derived and putatively labeled: No MVPA, low, moderate, and high. Only the high MVPA profile (compared to moderate) was associated with lower global neurocognition. Sensitivity analyses using latent MVPA profiles with only participants aged 45-74 years showed similar profiles, but no associations between latent MVPA profiles and neurocognition. The occupational MVPA domain led in all latent MVPA profiles.DiscussionWe found no consistent evidence to link accelerometry-measured MVPA profiles to neurocognitive function. Research to better characterize the role of high occupational MVPA in relation to neurocognition among Hispanic/Latino adults are needed.

BackgroundIdentifying Obstructive Sleep Apnea (OSA) phenotypes among middle-aged and older Hispanics/Latinos can facilitate personalized care, better inform treatment decisions, and could lead to improved clinical outcomes.MethodsWe focused on middle-aged and older adults (ages ≥45-74 years at baseline) with an apnea-hypopnea index (AHI) ≥5 from the HCHS/SOL (2008-2011) (unweighted n = 3,545). We used latent class analyses (LCA) to identify empirical and clinically meaningful OSA phenotypes. Sleep variables included AHI, percent sleep time SpO2

Study objectivesRecent work on US Whites from clinical samples used obstructive sleep apnea (OSA) symptoms to generate phenotypes for individuals with moderate-severe OSA which suggested 3 to 5 symptom classes. However, it is unknown whether similar classes generalize to diverse Hispanics/Latino adults. Therefore, we sought to fill this gap by empirically deriving sleep phenotypes among a large sample of diverse Hispanics/Latinos.MethodsWe used data from The Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011), a prospective cohort study designed using a multisite multistage probability sample of adults 18-74 years old. The subpopulation of interest included participants with moderate-severe OSA symptoms (≥15 respiratory event index (REI) events per hour; n = 1,605). We performed latent class analysis for complex survey data using 15 common OSA symptoms (e.g. Epworth Sleepiness Scale) and 4 comorbidities to identify phenotype classes.ResultsAverage age was 52.4 ± 13.9 years and 34.0% were female. Mean REI was 33.8 ± 22.5 events per hour. Fit statistics and clinical significance suggested that a three-class solution provided the best fit to the data. The three phenotypes were: (1) Minimally Symptomatic (47.7%), (2) Excessive sleepiness (37.1%), and (3) Disturbed Sleep (15.2%). Sensitivity models were consistent with the main proposed solution.ConclusionsDerived sleep phenotypes among diverse Hispanic/Latinos were consistent with recent findings from the Sleep Apnea Global Interdisciplinary Consortium, but we found notable differences in class prevalence relative to Whites. Further research is needed to link derived sleep phenotypes to health comorbidities in diverse populations.

Background and purposeThere is limited literature on the prevalence of incidental brain MRI findings in the Hispanic/Latino population, despite their increased prevalence of vascular disease and undertreatment of chronic conditions. The purpose of our study was to determine the prevalence of clinically relevant incidental findings on brain MRI examinations obtained as a part of the Study of Latinos-Investigation of NeuroCognitive Aging MRI (SOL-INCA-MRI) study.MethodsBrain MRI examinations were obtained on 1389 participants in the SOL-INCA-MRI study, a cross-sectional ancillary study of the Hispanic Community Health Study, Study of Latinos, which is a longitudinal, community-based study. Study design of SOL-INCA-MRI involves imaging cognitively normal and participants with mild cognitive impairment. Brain MRI findings were categorized as Level 1 (normal), Level 1.5 (findings of unclear medical significance), Level 2 (potential medical concern), or Level 3 (medically urgent). This article focuses on Level 2 and Level 3 findings.ResultsThe average age of the sample was 60.8 years (+/- 10.3 years), 66.1% were females. Level 2 and 3 findings were identified in 117 participants, (8.4%), of which 109 (7.8%) were recommended for medical follow-up (Level 2), and 8 (0.6%) were recommended for immediate medical attention (Level 3). Brain MRI findings consisted of chronic infarction in 33 (2.4%), vascular abnormality in 27 (1.9%), intracranial mass in 20 (1.4%), other intracranial findings in 28 (2.0%), and skull base/extracranial findings in 26 (1.9%) patients.ConclusionIncidental findings of clinical relevance were common among SOL-INCA-MRI participants, but rarely required urgent medical intervention.

Chronic stress has a deleterious effect on prefrontal lobe functioning. Empirical evidence suggests elevated vagal tone, indexed by elevated heart rate variability (HRV), mitigates the effect of mental stress on frontal lobe function. Here, the mitigating effect of HRV on stress-related decrements in cognitive performance is assessed based on information processing speed (DSST), word fluency and verbal learning task performance. Artifact free electrocardiogram (ECG) data was analyzed from 1420 Hispanic/Latino adults from the Sociocultural Ancillary of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). A 12-lead ECG was used to collect short-term recordings of the root mean square of successive differences in all normal R-peak to R-peak intervals (RMSSD) and the change between adjacent beats and the standard deviation of those intervals (SDNN) as indices of total HRV. As predicted, an interaction emerged for HRV and stress on the task presumed to require the greatest prefrontal lobe involvement, i.e., the DSST. After accounting for sociodemographic factors, chronic stress was associated with better DSST performance amongst individuals at higher quartile of SDNN, but not RMSSD. The paradoxical effect for greater stress exposure on DSST performance may in part be explained by increased speed of information processing and decision making often reported in high-stress cohorts. The nature of this interaction highlights the importance of examining the relationship between stress and cognition across a spectrum of vagal tone.

Background and purposeWe investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack.MethodsSociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression.ResultsThe analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia.ConclusionsHispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060344.

IntroductionEpisodic learning and memory performance are crucial components of cognitive assessment. To meet the needs of a diverse Hispanic/Latino population, we aimed to provide normative data on the Brief Spanish-English Verbal Learning Test (B-SEVLT).MethodsThe target population for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) included individuals 45+ years old from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds. Average age was 56.5 years ± 9.92, 54.5% were female, and mean education was 11.0 years ± 5.6 (unweighted n = 9309). Participants were administered the B-SEVLT in their preferred language (Spanish or English). Hispanic/Latino background adjusted B-SEVLT scores and percentile cut-points were created using survey-adjusted regression models.ResultsHigher educational attainment, younger age, and being female were associated with higher learning and memory performance. Hispanic/Latino background groups differed in B-SEVLT performance.DiscussionRepresentative learning and memory norms for Hispanic/Latinos of diverse backgrounds will improve cognitive assessment and accuracy of neurocognitive disorder diagnosis.

BackgroundThe relationships between obesity and cognitive decline in aging are mixed and understudied among Hispanics/Latinos.ObjectiveTo understand associations between central obesity, cognitive aging, and the role of concomitant cardiometabolic abnormalities among Hispanics/Latinos.MethodsParticipants included 6,377 diverse Hispanics/Latinos enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation for Neurocognitive Aging (SOL-INCA). Participants were 45 years and older at the first cognitive testing session (Visit 1). Cognitive outcomes (z-score units) included global composite and domain specific (learning, memory, executive functioning, processing speed) measures at a second visit (SOL-INCA, on average, 7 years later), and 7-year change. We used survey linear regression to examine associations between central obesity (waist circumference≥88 cm and≥102 cm for women and men, respectively) and cognition. We also tested whether the relationships between obesity and cognition differed by cardiometabolic status (indication of/treatment for 2 + of the following: high triglycerides, hypertension, hyperglycemia, low high-density lipoprotein cholesterol).ResultsCentral obesity was largely unassociated with cognitive outcomes, adjusting for covariates. However, among individuals with central obesity, cardiometabolic abnormality was linked to poorer cognitive function at SOL-INCA (ΔGlobalCognition =-0.165, p

Following publication of the original paper [1], an error was reported in the third paragraph in the section "Analysis of GMB composition and its correlates" (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.

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.

ObjectiveHispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos.Research design and methodsThe Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes.ResultsPrevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (βGC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models.ConclusionsDiabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.

BackgroundCardiovascular disease is linked to cognitive decline and disorders (e.g., dementia). The evidence is based largely on older non-Latino White cohorts.ObjectiveExamine the association between global vascular risk and cognitive function among Hispanics/Latinos in the United States.MethodsWe used data from a large sample of stroke- and cardiovascular disease-free, middle-aged and older Hispanics/Latinos with diverse backgrounds (n=7,650) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We compared associations between two measures of cardiovascular risk (CVR), the Framingham Cardiovascular Risk Score (FCRS) and the multiethnic Global Vascular Risk Score (GVRS), and cognitive performance using measures of global and domain specific cognitive function, and tested for modification by sex and age.ResultsHigher FCRS and GVRS were associated with lower global cognition and higher probability of low mental status, after covariates adjustment. Both CVR indices were associated with lower performances in learning and memory, verbal fluency, and psychomotor speed. Higher GVRS presented stronger associations with lower cognitive function compared to the FCRS. Women and younger age (45-64 years) exhibited more pronounced associations between higher CVR and worse cognition, particularly so with the GVRS.DiscussionCVR is also a risk for compromised cognitive function and evident in middle-age among Hispanics/Latinos. The multiethnic GVRS, tailored to specific risks based on racial/ethnic background, is feasible to use in primary care settings and can provide important insight on cognitive risk. Even modest shifts in population toward cardiovascular health in the high-risk Hispanic/Latino population can have important positive impacts on healthy cognitive aging.

BackgroundAmong older adults, poorer cognitive functioning has been associated with impairments in instrumental activities of daily living (IADLs). However, IADL impairments among older Hispanics/Latinos is poorly understood.ObjectiveTo characterize the relationships between cognition and risk for IADL impairment among diverse Hispanics/Latinos.MethodsParticipants included 6,292 community-dwelling adults from the Study of Latinos - Investigation of Neurocognitive Aging, an ancillary study of 45+ year-olds in the Hispanic Community Health Study/Study of Latinos. Cognitive data (learning, memory, executive functioning, processing speed, and a Global cognitive composite) were collected at Visit 1. IADL functioning was self-reported 7 years later, and treated as a categorical (i.e., risk) and continuous (i.e., degree) measures of impairment. Survey two-part models (mixture of logit and generalized linear model with Gaussian distribution) and ordered logistic regression tested the associations of cognitive performance (individual tests and composite z-score) with IADL impairment. Additionally, we investigated the moderating role of age, sex, and Hispanic/Latino background on the association between cognition and IADL impairment.ResultsAcross all cognitive measures, poorer performance was associated with higher odds of IADL impairment 7 years later. Associations were generally stronger for the oldest group (70+ years) relative to the youngest group (50-59 years). Sex and Hispanic/Latino background did not modify the associations. Across the full sample, lower scores on learning, memory, and the Global cognitive composite were also associated with higher degree of IADL impairment.ConclusionAcross diverse Hispanics/Latinos, cognitive health is an important predictor of everyday functioning 7 years later, especially in older adulthood.

BackgroundHispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.ResultsAmplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.ConclusionsOur analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

Hispanics/Latinos are the largest ethnic/racial group in the United States and at high risk for Alzheimer's disease and related dementia (ADRD). Yet, ADRD among diverse Latinos is poorly understood and disparately understudied or unstudied compared to other ethnic/racial groups that leave the nation ill-prepared for major demographic shifts that lay ahead in coming decades. The primary purpose of this Perspectives article was to provide a new research framework for advancing Latino ADRD knowledge, encompassing the unique sociocultural, cardiometabolic, and genomic aspects of Latino health, aging, and ADRD. In addition, we describe some of the research challenges to progress in Latino ADRD research. Finally, we present the Study of Latinos - Investigation of Neurocognitive Aging (SOL-INCA) as an example of implementing this new framework for advancing Latino ADRD research.

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50-86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging-Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.

ObjectiveWe aimed to identify hemoglobin A1c (HbA1c)-associated genetic variants and examine their implications for glycemic status evaluated by HbA1c in U.S. Hispanics/Latinos with diverse genetic ancestries.Research design and methodsWe conducted a genome-wide association study (GWAS) of HbA1c in 9,636 U.S. Hispanics/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos, followed by a replication among 4,729 U.S. Hispanics/Latinos from three independent studies.ResultsOur GWAS and replication analyses showed 10 previously known and novel loci associated with HbA1c at genome-wide significance levels (P < 5.0 × 10-8). In particular, two African ancestry-specific variants, HBB-rs334 and G6PD-rs1050828, which are causal mutations for sickle cell disease and G6PD deficiency, respectively, had ∼10 times larger effect sizes on HbA1c levels (β = -0.31% [-3.4 mmol/mol]) and -0.35% [-3.8 mmol/mol] per minor allele, respectively) compared with other HbA1c-associated variants (0.03-0.04% [0.3-0.4 mmol/mol] per allele). A novel Amerindian ancestry-specific variant, HBM-rs145546625, was associated with HbA1c and hematologic traits but not with fasting glucose. The prevalence of hyperglycemia (prediabetes and diabetes) defined using fasting glucose or oral glucose tolerance test 2-h glucose was similar between carriers of HBB-rs334 or G6PD-rs1050828 HbA1c-lowering alleles and noncarriers, whereas the prevalence of hyperglycemia defined using HbA1c was significantly lower in carriers than in noncarriers (12.2% vs. 28.4%, P < 0.001). After recalibration of the HbA1c level taking HBB-rs334 and G6PD-rs1050828 into account, the prevalence of hyperglycemia in carriers was similar to noncarriers (31.3% vs. 28.4%, P = 0.28).ConclusionsThis study in U.S. Hispanics/Latinos found several ancestry-specific alleles associated with HbA1c through erythrocyte-related rather than glycemic-related pathways. The potential influences of these nonglycemic-related variants need to be considered when the HbA1c test is performed.

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.

AimsInsulin resistance (IR) adversely impacts memory and executive functioning in non-Hispanic whites without diabetes. Less is known in Hispanics/Latinos, despite the fact that Hispanics/Latinos have higher rates of insulin resistance than non-Hispanic whites. We investigated the association between IR and cognition and its variation by age.MethodsData from 5987 participants 45-74 years old without diabetes from the Hispanic Community Health Study/Study of Latinos. IR was considered continuously using homeostasis model assessment for insulin resistance (HOMA-IR) and also dichotomized based on clinically relevant thresholds for hyperinsulinemia (fasting insulin > 84.73 pmol/L or HOMA-IR > 2.6) and sample-based norms (75th percentile of fasting insulin or HOMA-IR). Cognitive testing included the Brief Spanish English Verbal Learning Test (B-SEVLT), Verbal Fluency, and Digit Symbol Substitution.ResultsThere was 90% overlap in participant categorization comparing clinically relevant and sample-based thresholds. In separate fully-adjusted linear regression models, age modified the association between HOMA-IR and Digit Symbol Substitution (p = 0.02); advancing age combined with higher HOMA-IR levels resulted in higher scores. Age also modified the association between clinically relevant hyperinsulinemia and B-SEVLT recall (p = 0.03); with increasing age came worse performance for individuals with hyperinsulinemia.ConclusionThe relationship of IR with cognition in Hispanics/Latinos without diabetes may reflect an age- and test-dependent state.

Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, Cuban, and Dominican). We estimated the SNP-diabetes association in the six groups and in the combined sample. We found that the risk alleles occur in two non-reference haplotypes in HCHS/SOL, as in the SIGMA Mexicans. The haplotype frequencies were very similar between SIGMA Mexicans and the HCHS/SOL Mainland groups, but different in the Caribbean groups. The SLC16A11 sequence variants were significantly associated with risk for diabetes in the Mexican origin group (P = 0.025), replicating the SIGMA findings. However, these variants were not significantly associated with diabetes in a combined analysis of all groups, although the power to detect such effects was 85% (assuming homogeneity of effects among the groups). Additional analyses performed separately in each of the five non-Mexican origin groups were not significant. We also analyzed (1) exclusion of young controls and, (2) SNP by BMI interactions, but neither was significant in the HCHS/SOL data. The previously reported effects of SLC16A11 variants on diabetes in Mexican samples was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. Lack of replication in the HCHS/SOL non-Mexicans, and in the entire HCHS/SOL sample combined may represent underlying genetic heterogeneity. These results indicate a need for future genetic research to consider heterogeneity of the Hispanic/Latino population in the assessment of disease risk, but add to the evidence suggesting SLC16A11 as a potential therapeutic target for type 2 diabetes.

Introduction:Higher cognitive stimulation (CS) is associated with improved cognition. Sources of CS among Hispanics/Latinos are understudied. Methods:In the Hispanic Community Health Study/Study of Latinos 2008 to 2011 (n = 9438), we used finite mixture models to generate latent CS profiles, and multivariate linear regressions to examine associations with cognition in Hispanic/Latino adults (45-74 years). CS included education, occupation, social network, and acculturation. Cognitive measures included the Six-Item Screener, Brief-Spanish English Verbal Learning Test Sum and Recall, Controlled Oral Word Association Test, Digit Symbol Substitution, and Global Cognition. Results:Two CS profiles emerged, and were labeled "typical" and "enhanced." The enhanced CS profile (22%) had more family connections, bicultural engagements, skilled/professional occupations, education, and higher cognitive scores. Discussion:An enhanced CS profile emerged from contextual and culturally relevant factors, and was associated with higher cognitive scores across all measures. This provides initial evidence on how factors coalesce to shape cognitive protection in Hispanics/Latinos.

ObjectiveHispanics/Latinos have the highest risks for metabolic syndrome (MetS) in the U.S. and are also at increased risk for Alzheimer disease. In this study, we examined associations among neurocognitive function, MetS, and inflammation among diverse middle-aged and older Hispanics/Latinos.Research design and methodsCross-sectional data (2008-2011) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were analyzed to examine associations between neurocognition and MetS among diverse Hispanics/Latinos (N = 9,136; aged 45-74 years).ResultsMetS status was associated with lower global neurocognition, mental status, verbal learning and memory, verbal fluency, and executive function. Age significantly modified the associations between MetS and learning and memory measures. Significant associations between MetS and neurocognition were observed among middle-aged Hispanics/Latinos, and all associations remained robust to additional covariates adjustment.ConclusionsWe found that MetS was associated with lower neurocognitive function, particularly in midlife. Our findings support and extend current hypotheses that midlife may be a particularly vulnerable developmental period for unhealthy neurocognitive aging.

BackgroundCurrent evidence suggests that periodontal disease (PD) is associated with a significant increased risk of atherosclerotic cardiovascular disease (CVD) independent of known confounders. PD is a chronic oral disease with significant variation in prevalence demonstrated among Hispanic/Latino subgroups. The purpose of this study was to investigate the associations between PD and CVD risk and variations with sex, age, and Hispanic/Latino background.MethodsThe sample included 7379 participants aged 30 to 74 years, from the Hispanic Community Health Study/Study of Latinos (2008 to 2011). We assessed CVD risk by the Framingham 10-year general CVD risk score (FGRS). PD severity classification was based on calibrated measurements of gingival recession and probing depth. Multivariable sequential linear models for complex sample design assessed FGRS by PD severity, Hispanic/Latino background, and covariates.ResultsThe prevalence of moderate and severe PD combined was 46%. For women and men with severe PD, the combined prevalence of moderate and high CVD risk was 44% and 85%, respectively. The FGRS observed for women (5.1% [95% CI: 4.1%, 6.0%], p

OBJECTIVE: To study the associations of comprehensive measures of cardiac structure and function with multidimensional neurocognitive measures. PATIENTS AND METHODS: The Echocardiographic Study of Latinos is a population-based cohort of Hispanic/Latino adults older than 45 years enrolled from October 1, 2011, through June 30, 2014. Neurocognitive measures included Word Fluency (WF), Brief-Spanish English Verbal Learning Test (B-SEVLT), and Digit Symbol Substitution Test. The B-SEVLT included B-SEVLT-recall and B-SEVLT-sum. Echocardiographic measures included cardiac structure, systolic and diastolic function, and myocardial strain. Multivariable regression models were fit using survey statistics and sampling probabilities. RESULTS: A total of 1794 participants (mean age, 56±0.5 years; 56% women) were included in the analysis. In the adjusted model, higher left ventricular mass index was associated with lower B-SEVLT-sum and Digit Symbol Substitution Test scores. Left ventricular systolic dysfunction was associated with lower WF scores. Abnormal left ventricular geometry was associated with lower B-SEVLT-sum scores. Higher relative wall thickness was associated with B-SEVLT-recall and B-SEVLT-sum scores. Mitral annular relaxation velocities were associated with lower B-SEVLT-recall, B-SEVLT-sum, and WF scores. Higher mitral inflow to annular early diastolic velocity ratio was associated with lower B-SEVLT-recall and B-SEVLT-sum scores. Diastolic dysfunction was associated with lower B-SEVLT-sum scores. Finally, lower global longitudinal strain was associated with lower WF scores. CONCLUSION: Alterations in cardiac structure, systolic and diastolic function, and myocardial strain were associated with worse neurocognitive function. Further study is needed to determine the mechanisms (ie, impairment of cerebral flow and silent brain infarctions) mediating these heart-brain associations.

Higher urine albumin-to-creatinine ratio (UACR) has been associated with cardiac dysfunction in the general population. We assessed the association of UACR with cardiac structure and function in the Echocardiographic Study of Latinos (Echo-SOL), an ancillary study of the Hispanic Community Health Study/Study of Latinos across 4 US sites. Echo-SOL participants underwent standard 2-dimensional echocardiography, including speckle-tracking strain analysis. UACR was categorized as normal and high-normal (based on the midpoint of values below microalbuminuria), microalbuminuria (≥17 mg/g for men; ≥25 mg/g for women), and macroalbuminuria (≥250 mg/g; ≥355 mg/g). Simultaneous assessments were made of left ventricular (LV) mass index and hypertrophy and measures of LV systolic and diastolic dysfunction. We assessed the association of UACR with subclinical cardiac measures, adjusting for sociodemographic and cardiometabolic factors. Among 1,815 participants (median age 54, women 65%), 42% had normal UACR, 43% high-normal UACR, 13% microalbuminuria, and 2% macroalbuminuria. Prevalence of LV hypertrophy was 13%, LV systolic dysfunction (ejection fraction

Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (>12 000 participants) and also assessed the generalization of previously known loci to this population. We then evaluated whether iron-associated variants were associated with diabetes and glycemic traits. We found evidence for a novel association between TIBC and a variant near the gene for protein phosphatase 1, regulatory subunit 3B (PPP1R3B; rs4841132, β = -0.116, P = 7.44 × 10-8). The effect strengthened when iron deficient individuals were excluded (β = -0.121, P = 4.78 × 10-9). Ten of sixteen variants previously associated with iron traits generalized to HCHS/SOL, including variants at the transferrin (TF), hemochromatosis (HFE), fatty acid desaturase 2 (FADS2)/myelin regulatory factor (MYRF), transmembrane protease, serine 6 (TMPRSS6), transferrin receptor (TFR2), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ABO blood group (ABO), and GRB2 associated binding protein 3 (GAB3) loci. In examining iron variant associations with glucose homeostasis, an iron-raising variant of TMPRSS6 was associated with lower HbA1c levels (P = 8.66 × 10-10). This association was attenuated upon adjustment for iron measures. In contrast, the iron-raising allele of PPP1R3B was associated with higher levels of fasting glucose (P = 7.70 × 10-7) and fasting insulin (P = 4.79 × 10-6), but these associations were not attenuated upon adjustment for TIBC-so iron is not likely a mediator. These results provide new genetic information on iron traits and their connection with glucose homeostasis.

Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in U.S. Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2,499 T2D case subjects and 5,247 control subjects from six Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance levels. Conditional analysis on known index single nucleotide polymorphisms (SNPs) indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (odds ratio 1.49 [95% CI 1.27-1.75]). This association was consistent across Hispanic/Latino background groups and replicated in the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium. Among 80 previously known index SNPs at T2D loci, 66 SNPs showed consistency with the reported direction of associations and 14 SNPs significantly generalized to the HCHS/SOL. A genetic risk score based on these 80 index SNPs was significantly associated with T2D (odds ratio 1.07 [1.06-1.09] per risk allele), with a stronger effect observed in nonobese than in obese individuals. Our study identified a novel independent signal suggesting an African ancestry-specific allele at KCNQ1 for T2D. Associations between previously identified loci and T2D were generally shown in a large cohort of U.S. Hispanics/Latinos.