BACKGROUND: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.

BACKGROUND: Despite the high burden of anxiety and hypertension in Hispanic/Latino adults, little is known about their association in this population.
OBJECTIVE: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: Thyroid-related hormones act to regulate metabolic pathways and blood pressure (BP). However, the relationship of TSH and peripheral thyroid hormones and the role of the hypothalamic-pituitary-thyroid axis on hypertension development is not fully understood. We assessed sex-specific associations of thyroid-related hormones with BP and hypertension in Hispanic/Latino adults followed for 6 years.
UNASSIGNED: We studied 1789 adults, ages 45 to 74, free of diabetes at baseline from a subcohort of the Hispanic Community Health Study/Study of Latinos. We assessed TSH, free T4 (FT4), T3, and various indicators of thyroid axis. Using multivariable linear and Poisson regression adjusted for survey design and confounding variables, we estimated a priori sex-specific associations of thyroid-related hormones with changes in BP and hypertension development.
UNASSIGNED: In men and women, TSH and TSH/FT4 ratios were associated with changes in diastolic BP and T3 with changes in pulse pressure and the development of hypertension from prehypertension. In men, a 1-SD increase in TSH [incident rate ratio (IRR) = 1.42; 95% confidence interval (CI): 1.15, 1.75] and TSH/FT4 ratio (IRR = 1.20; 95% CI: 1.07, 1.35) were positively associated with the development of hypertension from prehypertension while the TSH/FT4 ratio (IRR = 0.85; 95% CI: .72, 1.00) was protective in women. We observed sex-specific differences in associations of the T3/FT4 ratio and indices of pituitary sensitivity to thyroid hormones with changes in pulse pressure and hypertension development.
UNASSIGNED: Thyroid-related hormones are associated with sex-specific changes in BP and hypertension among Hispanic/Latino adults consistent with selected studies conducted in other populations. Mechanisms underlying associations of pituitary sensitivity to thyroid hormones with BP and hypertension development warrant further study.

OBJECTIVE: 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.
CONCLUSIONS: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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%).
UNASSIGNED: 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.
UNASSIGNED: 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.

BACKGROUND: Optimal glycemic management after diabetes onset remains a challenge in Hispanic/Latino adults with type 2 diabetes (T2D), often resulting in poor health outcomes and higher rates of diabetes-related complications. The aim of this study was to examine and compare demographic and clinical characteristics, glycemic outcomes, health care resource utilization (HCRU), and costs among injection-naïve Hispanic/Latino adults with T2D initiating dulaglutide or basal insulin.
METHODS: This retrospective, observational study used administrative claims data from the Optum Research Database. Hispanic/Latino adults with T2D were assigned to dulaglutide or basal insulin cohorts on the basis of pharmacy claims and were propensity-score matched on demographic and baseline characteristics. Measures of glycemic management included 12 month follow-up glycated hemoglobin (HbA1c) and change in HbA1c from baseline. Follow-up all-cause and diabetes-related HCRU and costs, including costs per 1% change in HbA1c, were compared between cohorts.
RESULTS: The final propensity-score matched sample included 2872 patients: 1436 patients in each cohort. Mean (SD) reduction in HbA1c from baseline to 12 month follow-up was greater in the dulaglutide cohort compared with the basal insulin cohort [-1.40% (1.88) versus -0.92% (2.07); p < 0.001]. The dulaglutide cohort had significantly lower proportions of patients with ≥ 1 all-cause and diabetes-related outpatient visits, emergency room visits, and inpatient stays compared with the basal insulin cohort (p < 0.05). The dulaglutide cohort had significantly lower all-cause total costs per 1% HbA1c reduction than the basal insulin cohort ($13,768 versus $19,128; p < 0.001). Diabetes-related costs per 1% reduction were numerically lower for the dulaglutide cohort, but the difference was not statistically significant ($9737 versus $11,403; p = 0.081).
CONCLUSIONS: Dulaglutide demonstrated better glycemic outcomes and lower all-cause costs per 1% HbA1c reduction among Hispanic/Latino adults compared with those initiating basal insulin. Our real-world findings in the Hispanic/Latino population were consistent with results obtained from the overall population and confirm the glycemic benefits of dulaglutide observed in clinical settings.

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 23–80 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.

Hispanic/Latino individuals are less likely to receive optimal treatment for chronic kidney disease than non-Hispanic whites. This may be particularly detrimental for women of reproductive age as chronic kidney disease increases risk for infertility, menstrual irregularities, and pregnancy loss. While these maternal outcomes have been associated with advanced chronic kidney disease, their occurrence in early chronic kidney disease is unclear.
Using baseline (2008-2011) and second study visit (2014-2017) data from the Hispanic Community Health Study/Study of Latinos, we retrospectively assessed the prevalence of chronic kidney disease as well as the association between chronic kidney disease and self-reported infertility, cessation of menses, hysterectomy, and nonviable pregnancy loss (experienced at less than 24 weeks gestation) in women of reproductive age (18-45 years).
Multivariable survey logistic regression analyses determined the unadjusted and multivariable-adjusted prevalence odds ratios with 95% confidence intervals between chronic kidney disease and the separate outcomes.
Among 2589 Hispanic/Latino women included (mean age = 31.4 years), 4.6% were considered to have chronic kidney disease. In adjusted analyses, women with chronic kidney disease did not have a significantly increased odds of infertility (odds ratio = 1.02, 95% confidence interval = 0.42-2.49), cessation of menses (odds ratio = 1.25, 95% confidence interval = 0.52-3.04), or hysterectomy (odds ratio = 1.17, 95% confidence interval = 0.61-2.25) compared to those without chronic kidney disease. In those with chronic kidney disease, the adjusted odds of a nonviable pregnancy loss occurring after baseline visit were increased (odds ratio = 2.11, 95% confidence interval = 0.63-7.02) but not statistically significance.
The presence of early stage chronic kidney disease did not confer a significant risk of infertility, cessation of menses, or nonviable pregnancy loss.
The Hispanic Community Health Study/Study of Latinos is a population-based study of over 16,000 Hispanic/Latino individuals throughout the United States. Within this cohort, we assessed the prevalence of chronic kidney disease in women of reproductive age (18–45 years old) and the associations between kidney disease and infertility, cessation of menses, and nonviable pregnancy loss (loss occurring before the 24th week of pregnancy). We found that kidney disease affected 1 in 20 women of reproductive age and those with kidney disease were more likely to have obesity, diabetes, and hypertension. Compared to those without kidney disease, the presence of kidney disease did not increase risk of infertility, cessation of menses, or nonviable pregnancy loss.

We assess how immigrant parent legal status shapes children\'s physical and mental health. Using the Hispanic Community Health Study of Latino Youth-a multi-site dataset-we evaluated mean differences in multiple physical and mental health indicators and parents\' and children\'s stress and resilience by parents\' (primarily mothers\') legal status (N = 1177). We estimated regression models of two overall child health outcomes-allostatic load and any internalized disorder. Average allostatic load was 28% higher (0.36 standard deviations) and average prevalence of any internalizing disorder was 16% points greater for children of foreign-born unauthorized versus US-born parents. Higher levels of socioeconomic and acculturative stress contributed to children of foreign-born unauthorized parents\' heightened health risk, while resilience factors-parental health and familial support-protected their health. Children with unauthorized immigrant parents experience both negative physical and mental health outcomes that can have potential long-term costs.