Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities. METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts. RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13. DISCUSSION: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies. HIGHLIGHTS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

Outcomes Among Mexican American and Non-Hispanic White Informal Stroke Caregivers.

BACKGROUND: Informal home care is prevalent among Mexican American stroke survivors, but data on the impact on caregivers are not available. The aim was to assess ethnic differences in informal stroke caregiving and caregiver outcomes at 90 days poststroke. METHODS: Informal caregivers were recruited from the population-based Brain Attack Surveillance in Corpus Christi Project (2019-2023), conducted in a bi-ethnic community in Texas. Caregivers of community-dwelling stroke survivors who were not cognitively impaired and not employed by a formal caregiving agency were interviewed. Interviews included sociodemographics, dyad characteristics, Modified Caregiver Strain Index (range 0-26, higher more positive), Positive Aspects of Caregiving scale (range, 5-45, higher more), Patient Health Questionnaire-8 (range, 0-30, higher worse), and PROMIS (Patient-Reported Outcomes Measurement Information System)-10 physical (range, 16.2-67.7, higher better) and mental health (range, 21.2-67.6, higher better) summary scores. Stroke survivor data was from interviews and medical records. Propensity score methods were used to balance caregiver and patient factors among Mexican American and Non-Hispanic White caregivers by fitting a model with ethnicity of caregiver as the outcome and predictors being caregiver sociodemographics, patient-caregiver dyad characteristics, and patient sociodemographics and functional disability. Propensity scores were included as a covariate in regression models, considering the association between ethnicity and outcomes. RESULTS: Mexican American caregivers were younger, more likely female, and more likely a child of the stroke survivor than Non-Hispanic White caregivers. Mexican American caregiver ethnicity was associated with less caregiver strain (ß, -1.87 [95% CI, -3.51 to -0.22]) and depressive symptoms (ß, -2.02 [95% CI, -3.41 to -0.64]) and more favorable mental health (ß, 4.90 [95% CI, 2.49-7.31]) and positive aspects of caregiving (ß, 3.29 [95% CI, 1.35-5.23]) but not associated with physical health. CONCLUSIONS: Understanding the mechanisms behind more favorable caregiver outcomes in Mexican American people may aid in the design of culturally sensitive interventions to improve both caregiver and stroke survivor outcomes, potentially across all race and ethnic groups.

Adverse childhood experiences and adult disease: Examining mediating pathways in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

OBJECTIVES: Adverse childhood experiences (ACEs) have been linked to adulthood chronic diseases, but there is little research examining the mechanisms underlying this association. We tested pathways from ACEs to adult disease mediated via risk factors of depression, smoking, and body mass index. METHOD: Prospective data from adults 18 to 74 years old from the Hispanic Community Health Study/Study of Latinos and Sociocultural Ancillary Study were used. Retrospectively reported ACEs and hypothesized mediators were measured at Visit 1 (2008-2011). Outcomes of disease prevalence were assessed at Visit 2, approximately 6 years later. The analytic sample includes 5,230 Hispanic/Latino participants with ACE data. Statistical mediation was examined using structural equation modeling on cardiometabolic and pulmonary disease prevalence and reported probit regression coefficients with 95% confidence intervals (CIs). RESULTS: We found a significant association between ACEs and the prevalence of asthma/chronic obstructive pulmonary disorder (standardized ß = .07, 95% CI [0.02, 0.12]). In the mediational model, the direct association was nonsignificant (ß = .02, 95% CI [-0.04, 0.07]) but was mediated by depressive symptoms (ß = .03, 95% CI [0.02, 0.04]). There were no associations between ACEs and the prevalence of diabetes and self-reported coronary heart disease or cerebrovascular disease. However, a small indirect effect was identified via depressive symptoms and coronary heart disease (ß = .02, 95% CI [0.01, 0.03]). CONCLUSION: In this diverse Hispanic/Latino sample, depressive symptoms were found to be a pathway linking ACEs to self-reported cardiopulmonary diseases, although the effects were of small magnitude. Future work should replicate pathways, confirm the magnitude of effects, and examine cultural moderators that may dampen expected associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Polycystic Ovary Syndrome, Metabolic Syndrome, and Inflammation in the Hispanic Community Health Study/Study of Latinos.

CONTEXT: Polycystic Ovary Syndrome (PCOS) is a multifaceted endocrine disorder with reproductive and metabolic dysregulation. PCOS has been associated with inflammation and Metabolic Syndrome (MetS); however, the moderating effects of inflammation as measured by C-reactive protein (CRP) and menopause on the PCOS-MetS association have not been studied in Hispanic/Latinas with PCOS who have a higher metabolic burden. OBJECTIVE: We studied the cross-sectional association between PCOS and (i) MetS in 7316 females of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), (ii) subcomponents of MetS including impaired fasting glucose (IFG) and elevated triglycerides (TGL), and (iii) effect modification by menopausal status and CRP. DESIGN: HCHS/SOL is a multicenter, longitudinal, and observational study of US Hispanic/Latinos. Our study sample included females from Visit 2 with self-reported PCOS and MetS (ages 23-82 years). RESULTS: PCOS (prevalence=18.8%) was significantly associated with MetS prevalence (OR=1.41[95% confidence interval: 1.13-1.76]), IFG and TGL (OR=1.42[1.18-1.72], OR=1.48[1.20-1.83] respectively). We observed effect modification by menopausal status (ORpre=1.46, pint=0.02; ORpost=1.34, pint=0.06) and CRP (ORelevated=1.41, pint=0.04; ORnormal=1.26, pint=0.16) on the PCOS-MetS association. We also observed a super-additive interaction between CRP and PCOS, adjusting for which resulted in an attenuated effect of PCOS on MetS (OR=1.29[0.93-1.78]). CONCLUSIONS: Hispanic/Latino females with PCOS had higher odds of MetS, IFG, and elevated TGL, than their peers without PCOS. Interaction analyses revealed that the odds of MetS are higher among PCOS females who have pre-menopausal status or high inflammation. Interventions in Hispanic/Latinas should target these outcomes for effective management of the disease.

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Physical Activity, Cardiovascular Status, Mortality, and Prediabetes in Hispanic and Non-Hispanic Adults.

Importance: Data are limited on the association of physical activity (PA) with incident cardiovascular disease (CVD) and mortality in prediabetes, especially in racial and ethnic minority groups, including Hispanic and Latino populations. Objective: To determine the association of PA with incident CVD and mortality by prediabetes status among Hispanic or Latino and non-Hispanic adults. Design, Setting, and Participants: This cohort study included data from 2 cohorts of adults with prediabetes or normoglycemia who were free of CVD at baseline visit: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from baseline examination through 2017, with median (IQR) follow-up of 7.8 (7.2-8.5) years, and the Framingham Heart Study (FHS) with non-Hispanic participants from index examination through 2019, with median (IQR) follow-up of 9.6 (8.1-10.7) years. Analyses were conducted between September 1, 2022, and January 10, 2024. Exposure: The primary exposure was baseline accelerometry-measured moderate to vigorous PA, insufficient vs sufficient to meet 2018 Physical Activity Guidelines for Americans (PAG) in both cohorts; additional accelerometer-measured exposures in HCHS/SOL were steps per day, sedentary behavior, and counts per min. Main Outcomes and Measures: The outcome was a composite of incident CVD or all-cause mortality, whichever came first. Results: This cohort study included 13 223 participants: from HCHS/SOL, there were 9456 adults (all self-identified Hispanic or Latino ethnicity; survey-adjusted mean [SD] age, 38.3 [13.9] years, unweighted counts 5673 (60.0%) female; 4882 [51.6%] with normoglycemia; 4574 [48.4%] with prediabetes), and from FHS there were 3767 adults (3623 [96.2%] non-Hispanic and 140 [3.7%] Hispanic or Latino ethnicity, with 4 [0.1%] participants missing ethnicity; mean [SD] age, 54.2 [13.6] years; 2128 (56.5%) female; 2739 [72.7%] with normoglycemia; 1028 [27.3%] with prediabetes). Not meeting PAG was associated with higher risk of the composite outcome among participants with normoglycemia (vs PAG met; hazard ratio [HR], 1.85 [95% CI, 1.12-3.06]), but not among participants with prediabetes (HR, 1.07 [95% CI, 0.72-1.58]). For HCHS/SOL, no statistically significant association was found between the composite outcome and other PA metrics, although estimated HRs tended to be higher for lower activity in the normoglycemia group but not for the prediabetes group (eg, for steps less than vs at least 7000 per day, the HR was 1.58 [95% CI, 0.85-2.93] for normoglycemia vs 1.08 [95% CI 0.67-1.74] for prediabetes). While there was also no association in HCHS/SOL between the composite outcome and sedentary behavior, results were similar in the prediabetes group (HR per 30 minutes per day of sedentary behavior, 1.05 [95% CI 0.99-1.12]) and in the normoglycemia group (HR, 1.07 [95% CI 0.98-1.16]). Conclusions and Relevance: In this cohort study of US Hispanic or Latino and non-Hispanic adults, lower moderate to vigorous PA levels were associated with CVD or mortality among participants with normoglycemia but not participants with prediabetes. Adults with prediabetes may benefit from reducing sedentary behavior and improving multiple lifestyle factors beyond improving moderate to vigorous PA alone.

Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: Results From a Pragmatic Cluster Randomized Controlled Trial.

OBJECTIVE: This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health). RESEARCH DESIGN AND METHODS: A total of 600 adults with type 2 diabetes who met one or more of the following criteria in the last 90 days were enrolled: HbA1c ≥8% and/or LDL cholesterol ≥100 mg/dL and/or systolic blood pressure (SBP) ≥140 mmHg. Participants at MAC clinics received in-person and telephone self-management support from a specially trained MA health coach for 12 months. Electronic medical records were used to examine clinical outcomes in the overall sample. Behavioral and psychosocial outcomes were evaluated in a subsample (n = 300). RESULTS: All clinical outcomes improved significantly over 1 year in the overall sample (P < 0.001). The reduction in HbA1c was significantly greater in the MAC versus UC group (unstandardized Binteraction = -0.06; P = 0.002). A significant time by group by site interaction also showed that MAC resulted in greater improvements in LDL cholesterol than UC at Neighborhood Healthcare relative to Scripps Health (Binteraction = -1.78 vs. 1.49; P < 0.05). No other statistically significant effects were observed. CONCLUSIONS: This was the first large-scale pragmatic RCT supporting the real-world effectiveness of MAC for type 2 diabetes in U.S. primary care settings. Findings suggest that this team-based approach may be particularly effective in improving diabetes outcomes in FQHC settings.

Associations of Anxiety Symptoms With 6-Year Blood Pressure Changes and Incident Hypertension: Results From the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Despite the high burden of anxiety and hypertension in Hispanic/Latino adults, little is known about their association in this population. PURPOSE: To examine the associations of anxiety symptoms with 6-year changes in blood pressure (BP) and incident hypertension in Hispanic/Latino adults. METHODS: We examined data from a probability sample of 10,881 Hispanic/Latino persons aged 18-74 who attended visits 1 (V1; 2008-2011) and 2 (V2; 2014-2017) of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective cohort study. Anxiety symptoms were assessed at V1 using the 10-item Spielberger Trait Anxiety Scale (M = 17.1; Range = 10-40) and dichotomized using a cut-point of 20, the highest quartile in this cohort. BP was measured at both visits using a standardized protocol. RESULTS: Adults with elevated anxiety symptoms had a 1.02 mm Hg greater increase in systolic (p = .02) and a 0.75 mm Hg greater increase in diastolic BP (p = .02) over 6.1 years than those with lower symptoms, after adjusting for sociodemographic and clinical covariates. These associations differed by sex. Elevated anxiety was associated with a greater increase in systolic and diastolic BP in men only. Among persons without hypertension at V1 (N = 7,412), those with elevated anxiety symptoms at V1 had a 22% higher incidence of hypertension (p = .02) 6.1 years later. CONCLUSIONS: Our findings underscore the importance of screening for and treating elevated anxiety symptoms to help prevent hypertension. Further research on the role of sex and underlying mechanisms is warranted.

This study investigated the relationship between anxiety symptoms and changes in blood pressure, as well as the incidence of hypertension among Hispanic/Latino adults over time. Using data from 10,881 Hispanic/Latino adults who participated in the Hispanic Community Health Study/Study of Latinos, we found that men, but not women, with elevated anxiety symptoms experienced a greater increase in both systolic and diastolic blood pressure over a 6-year period compared to those with lower symptoms. Additionally, among 7,412 participants who were free of hypertension at baseline, individuals with elevated anxiety symptoms developed hypertension at a higher rate after 6 years of follow-up compared to those with lower symptoms. These findings suggest that anxiety symptoms play a role in the development of hypertension among Hispanic/Latino adults, underscoring the importance of screening for and addressing elevated anxiety to potentially prevent hypertension.

Sleep-wake behaviors associated with cognitive performance in middle-aged participants of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVES: Many sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance. METHODS: The outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions. RESULTS: In individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with ∼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility. CONCLUSION: The strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition.

Cardiovascular disease risk exacerbates brain aging among Hispanic/Latino adults in the SOL-INCA-MRI Study.

Background: Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Methods: Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Results: Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. Conclusion: The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging.

Associations of Allostatic Load with Level of and Change in Cognitive Function Among Middle-Aged and Older Hispanic/Latino Adults: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. Methods: We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. Results: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. Conclusions: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.

Glycemic Control, Cognitive Aging, and Impairment Among Diverse Hispanic/Latino Individuals: Study of Latinos- Investigation of Neurocognitive Aging (Hispanic Community Health Study/Study of Latinos).

OBJECTIVE: Hispanic/Latino individuals in the U.S. have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanic/Latino individuals of diverse heritages. RESEARCH DESIGN AND METHODS: Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanic/Latino individuals aged 50 years and older (2016-2018). The primary outcomes were cognitive function, 7-year cognitive decline, and mild cognitive impairment (MCI). The primary glycemia exposure variables were measured from fasting blood samples collected at HCHS/SOL visit 1 (2008-2011). RESULTS: Visit 1 mean age was 56.5 years ± 8.2 SD, and the average glycosylated hemoglobin A1C (HbA1c) was 6.12% (43.5 ± 14.6 mmol/mol). After covariate adjustment, higher HbA1c was associated with accelerated 7-year global (b = -0.045; 95% CI -0.070; -0.021; in z score units) and executive cognitive decline and a higher prevalence of MCI (odds ratio 1.20; 95% CI 1.11; 1.29). CONCLUSIONS: Elevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanic/Latino individuals. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanic/Latino individuals of diverse heritages.

Association Between High-Sensitivity C-Reactive Protein and Metabolic Syndrome Among Hispanic/Latino Participants of the Hispanic Community Health Study/Study of Latinos.

Purpose: To determine whether high-sensitivity C-reactive protein (hsCRP) is associated with incident Metabolic Syndrome (MetS) among U.S. Hispanic/Latino adults. Patients and Methods: The Hispanic Community Health Study/Study of Latinos is a longitudinal observational cohort assessing cardiovascular health among diverse U.S. Hispanic/Latino adults. hsCRP was measured at visit 1 (2008-2011) and classified as low, moderate, or high, based on the Centers for Disease Control and Prevention and American Heart Association (CDC/AHA) guidelines. All MetS components [abdominal obesity, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and fasting glucose] were measured at visit 1 and visit 2 (2014-2017). MetS was defined as the presence of three or more components based on the 2005 definition from the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (modified NCEP ATP III). Participants free of MetS at visit 1 and with complete data on hsCRP and all MetS components were included (n = 6121 participants). We used Poisson regression analysis to determine whether hsCRP was associated with incident MetS after adjusting for demographic, behavioral, and clinical factors. All analyses accounted for the complex survey design of the study. Results: In fully adjusted models, moderate versus low hsCRP was associated with a 33% increased risk of MetS [incidence rate ratio (IRR): 1.33, 95% confidence interval (CI): 1.10-1.61], while high versus low hsCRP was associated with a 89% increased risk of MetS (IRR: 1.89, 95% CI: 1.58-2.25). Conclusions: Greater levels of hsCRP were associated with new onset of MetS in a diverse sample of U.S. Hispanic/Latino adults. Results suggest that hsCRP may be an independent risk factor for MetS.

A sociodemographic index identifies non-biological sex-related effects on insomnia in the Hispanic Community Health Study/Study of Latinos.

Background: Sex differences are related to both biological factors and the gendered environment. To untangle sex-related effects on health and disease it is important to model sex-related differences better. Methods: Data came from the baseline visit of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a longitudinal cohort study following 16,415 individuals recruited at baseline from four study sites: Bronx NY, Miami FL, San Diego CA, and Chicago IL. We applied LASSO penalized logistic regression of male versus female sex over sociodemographic, acculturation, and psychological factors jointly. Two "gendered indices", GISE and GIPSE, summarizing the sociodemographic environment (GISE, primary) and psychosocial and sociodemographic environment (GIPSE, secondary) associated with sex, were calculated by summing these variables, weighted by their regression coefficients. We examined the association of these indices with insomnia derived from self-reported symptoms assessed via the Women Health Initiative Insomnia Rating Scale (WHIIRS), a phenotype with strong sex differences, in sex-adjusted and sex-stratified analyses. All analyses were adjusted for age, Hispanic/Latino background, and study center. Results: The distribution of GISE and GIPSE differed by sex with higher values in male individuals, even when constructing and validating them on separate, independent, subsets of HCHS/SOL individuals. In an association model with insomnia, male sex was associated with lower likelihood of insomnia (odds ratio (OR)=0.60, 95% CI (0.53, 0.67)). Including GISE in the model, the association was slightly weaker (OR=0.63, 95% CI (0.56, 0.70)), and weaker when including instead GIPSE in the association model (OR=0.78, 95% CI (0.69, 0.88)). Higher values of GISE and of GIPSE, more common in male sex, were associated with lower likelihood of insomnia, in analyses adjusted for sex (per 1 standard deviation of the index, GISE OR= 0.92, 95% CI (0.87, 0.99), GIPSE OR=0.65, 95% CI (0.61, 0.70)). Conclusions: New measures such as GISE and GIPSE capture sex-related differences beyond binary sex and have the potential to better model and inform research studies of health. However, such indices do not account for gender identity and may not well capture the environment experienced by intersex and non-binary persons.

Normative data for the Digit Symbol Substitution for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

INTRODUCTION: Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS: The target population for the Study of Latinos-Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage-adjusted DSS scores, and percentile cut-points were created using survey-adjusted regression and quantile regression models. RESULTS: Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION: Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights: Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) This study is the first to develop norms for the DSS test across four regions of the United States.Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed.We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.

Characterizing cognitive profiles in diverse middle-aged and older Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL).

Introduction: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design. Methods: Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL-INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function. Results: Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average-to-high-average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average-to-low-average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low-average-to-mildly impaired across all cognitive/IADL tests (12.1%). Discussion: Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community-dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights: The present study characterized cognitive profiles among diverse middle-aged and older Hispanic/Latino adults.Latent profile analysis of neurocognitive test scores was the primary analysis conducted.The target population consists of middle-aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos - Investigation of Neurocognitive Aging.

Cumulative All-Cause Mortality in Diverse Hispanic/Latino Adults : A Prospective, Multicenter Cohort Study.

BACKGROUND: All-cause mortality among diverse Hispanic/Latino groups in the United States and factors underlying mortality differences have not been examined prospectively. OBJECTIVE: To describe cumulative all-cause mortality (and factors underlying differences) by Hispanic/Latino background, before and during the COVID-19 pandemic. DESIGN: Prospective, multicenter cohort study. SETTING: Hispanic Community Health Study/Study of Latinos. PARTICIPANTS: 15 568 adults aged 18 to 74 years at baseline (2008 to 2011) of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other backgrounds from the Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California. MEASUREMENTS: Sociodemographic, acculturation-related, lifestyle, and clinical factors were assessed at baseline, and vital status was ascertained through December 2021 (969 deaths; 173 444 person-years of follow-up). Marginally adjusted cumulative all-cause mortality risks (11-year before the pandemic and 2-year during the pandemic) were examined using progressively adjusted Cox regression. RESULTS: Before the pandemic, 11-year cumulative mortality risks adjusted for age and sex were higher in the Puerto Rican and Cuban groups (6.3% [95% CI, 5.2% to 7.6%] and 5.7% [CI, 5.0% to 6.6%], respectively) and lowest in the South American group (2.4% [CI, 1.7% to 3.5%]). Differences were attenuated with adjustment for lifestyle and clinical factors. During the pandemic, 2-year cumulative mortality risks adjusted for age and sex ranged from 1.1% (CI, 0.6% to 2.0%; South American) to 2.0% (CI, 1.4% to 3.0%; Central American); CIs overlapped across groups. With adjustment for lifestyle factors, 2-year cumulative mortality risks were highest in persons of Central American and Mexican backgrounds and lowest among those of Puerto Rican and Cuban backgrounds. LIMITATION: Lack of data on race and baseline citizenship status; correlation between Hispanic/Latino background and site. CONCLUSION: Differences in prepandemic mortality risks across Hispanic/Latino groups were explained by lifestyle and clinical factors. Mortality patterns changed during the pandemic, with higher risks in persons of Central American and Mexican backgrounds than in those of Puerto Rican and Cuban backgrounds. PRIMARY FUNDING SOURCE: National Institutes of Health.

Randomized trial of an integrated care intervention among Latino adults: Sustained effects on diabetes management.

We examined the 12-month maintenance effects of a previously successful integrated model of diabetes care at improving glycemic management and psychological well-being among Latino adults with type 2 diabetes (T2D). A randomized controlled trial (2015-19) compared an integrated care intervention (ICI) with usual care among 456 adults with T2D. The ICI included integrated medical and behavioral care and health education over 6 months. Assessments were completed at baseline, 3, 6, 9, and 12 months. Most participants were female (63.7%) with a mean age of 55.7 years. In multilevel models, significant Group × Time (quadratic) interaction effects were found for HbA1c [Bint = 0.10, 95% confidence interval (CI) 0.02, 0.17, P < .01] and anxiety symptoms (Bint = 0.20, 95% CI 0.05, 0.35, P < .009), but not depression symptoms (Bint = 0.15, 95% CI -0.01, 0.31, P < .07). Analyses of instantaneous rate of change in the ICI group showed significant decreases at 3 and 6 months for both HbAc1 (B = -0.31 at 3 months; B = -0.12 at 6 months) and anxiety symptoms (B = -0.92 at 3 months; B = -0.46 at 6 months), and no significant instantaneous changes at 9 or 12 months, suggesting that initial improvements were largely maintained. The usual care group showed a small decrease in anxiety symptoms at 6 months (B = -0.17), but no other significant changes at any time-point for anxiety or HbA1c (all Ps > .05). This culturally tailored integrated care model shows potential in producing and sustaining positive effects on clinical and psychological outcomes above standard care.

Our previous studies found that a culturally adapted, enhanced service (integrated care intervention) that we developed improved glycemic management and decreased depression and anxiety symptoms over the 6 months that the service was offered. In this study, we examined whether those improvements in diabetes management and depression and anxiety symptoms were maintained up to 6 months after the conclusion of the intervention. The integrated care intervention involved providing medical and behavioral healthcare on the same day and at the same location as well as health education for 6 months. The study participants were 456 Latino adults (aged 23­80 years) who had type 2 diabetes and were not taking insulin. Participants were randomly assigned to one of two groups: the integrated care intervention or usual care. In this study, we found that the improvements in glycemic management and in anxiety and depression symptoms previously shown were largely maintained. These findings suggest that culturally adapted health services that include both medical and behavioral care and health education programs may benefit Latino patients with type 2 diabetes.

Increasing HbA1c is associated with reduced CD8+ T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus.

Diabetes mellitus is on the rise globally and is a known susceptibility factor for severe influenza virus infections. However, the mechanisms by which diabetes increases the severity of an influenza virus infection are yet to be fully defined. Diabetes mellitus is hallmarked by high glucose concentrations in the blood. We hypothesized that these high glucose concentrations affect the functionality of CD8+ T cells, which play a key role eliminating virus-infected cells and have been shown to decrease influenza disease severity. To study the effect of hyperglycemia on CD8+ T cell function, we stimulated peripheral blood mononuclear cells (PBMCs) from donors with and without diabetes with influenza A virus, anti-CD3/anti-CD28-coated beads, PMA and ionomycin (PMA/I), or an influenza viral peptide pool. After stimulation, cells were assessed for functionality [as defined by expression of IFN-γ, TNF-α, macrophage inflammatory protein (MIP)-1ß, and lysosomal-associated membrane protein-1 (CD107a)] using flow cytometry. Our results showed that increasing HbA1c correlated with a reduction in TNF-α production by CD8+ T cells in response to influenza stimulation in a TCR-specific manner. This was not associated with any changes to CD8+ T cell subsets. We conclude that hyperglycemia impairs CD8+ T cell function to influenza virus infection, which may be linked with the increased risk of severe influenza in patients with diabetes.

General or Central Obesity and Mortality Among US Hispanic and Latino Adults.

Importance: The Hispanic and Latino population is the second largest ethnic group in the US, but associations of obesity parameters with mortality in this population remain unclear. Objective: To investigate the associations of general and central obesity with mortality among US Hispanic and Latino adults. Design, Setting, and Participants: The Hispanic Community Health Study/Study of Latinos is an ongoing, multicenter, population-based cohort study with a multistage probability sampling method performed in Hispanic and Latino adults aged 18 to 74 years with a baseline between January 1, 2008, and December 31, 2011. Active follow-up for this analyses extended from baseline through February 17, 2022. All analyses accounted for complex survey design (ie, stratification and clustering) and sampling weights to generate estimates representing the noninstitutionalized, 18- to 74-year-old Hispanic or Latino populations from selected communities. Exposures: Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), body fat percentage, waist circumference (WC), and waist to hip ratio (WHR). Main Outcome and Measure: Deaths were ascertained via death certificates, the National Death Index, and active follow-up. Results: Of 15 773 adults (mean [SE] age, 40.9 [0.3] years; 52.8% female), 686 deaths occurred during a median (IQR) follow-up of 10.0 (9.9-10.2) years. When adjusting for sociodemographic, lifestyle, and family history covariates, hazard ratios (HRs) for mortality were 1.55 (95% CI, 1.08-2.22) for a BMI of 35.0 or greater vs 18.5 to 24.9, 1.22 (95% CI, 0.92-1.64) for the highest vs lowest body fat percentage groups (defined according to sex-, age-, and Hispanic or Latino background-specific BMI distribution), 1.35 (95% CI, 0.98-1.85) for WC greater than 102 cm (men) or 88 cm (women) vs 94 cm (men) or 80 cm (women) or less, and 1.91 (95% CI, 1.28-2.86) for WHR of 0.90 (men) or 0.85 (women) or greater vs less than 0.90 (men) or 0.85 (women). Only WHR was associated with mortality with additional adjustment for major comorbidities (HR, 1.75; 95% CI, 1.17-2.62). The association of WHR with mortality was stronger among women compared with men (P = .03 for interaction), and the association between BMI and mortality was stronger among men (P = .02 for interaction). The positive association between severe obesity (BMI ≥ 35.0) and mortality was observed only among adults with WHR of 0.90 (men) or 0.85 (women) or greater but not among those with WHR below 0.90 (men) or 0.85 (women) (P = .005 for interaction) who had greater hip circumference. Conclusions and Relevance: In this cohort of US Hispanic and Latino adults, WHR was independently associated with higher all-cause mortality regardless of BMI and prevalent comorbidities. These findings suggest that prioritizing clinical screening and intervention for WHR in this population may be an important public health strategy, with sex-specific strategies potentially being needed.