Hispanic Community Health Study/Study Of Latinos Research Articles

Gut microbiota, blood metabolites, and left ventricular diastolic dysfunction in US Hispanics/Latinos

BackgroundLeft ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD.ResultsWe included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion involving tissue Doppler assessment and left atrial volume index measurements. Among 1996 participants, 916 (45.9%) had prevalent LVDD, and 212 out of 594 participants without LVDD at baseline developed incident LVDD over a median 4.3 years of follow-up. Using multivariable-adjusted analysis of compositions of microbiomes (ANCOM-II) method, we identified 7 out of 512 dominant gut bacterial species (prevalence > 20%) associated with prevalent LVDD (FDR-q < 0.1), with inverse associations being found for Intestinimonas_massiliensis, Clostridium_phoceensis, and Bacteroide_coprocola and positive associations for Gardnerella_vaginali, Acidaminococcus_fermentans, Pseudomonas_aeruginosa, and Necropsobacter_massiliensis. Using multivariable adjusted linear regression, 220 out of 669 circulating metabolites with detection rate > 75% were associated with the identified LVDD-related bacterial species (FDR-q < 0.1), with the majority being linked to Intestinimonas_massiliensis, Clostridium_phoceensis, and Acidaminococcus_fermentans. Furthermore, 46 of these bacteria-associated metabolites, mostly glycerophospholipids, secondary bile acids, and amino acids, were associated with prevalent LVDD (FDR-q < 0.1), 21 of which were associated with incident LVDD (relative risk ranging from 0.81 [p = 0.001, for guanidinoacetate] to 1.25 [p = 9 × 10−5, for 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)]). The inclusion of these 21 bacterial-related metabolites significantly improved the prediction of incident LVDD compared with a traditional risk factor model (the area under the receiver operating characteristic curve [AUC] = 0.73 vs 0.70, p = 0.001). Metabolite-based proxy association analyses revealed the inverse associations of Intestinimonas_massilliensis and Clostridium_phoceensis and the positive association of Acidaminococcus_fermentans with incident LVDD.ConclusionIn this study of US Hispanics/Latinos, we identified multiple gut bacteria and related metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity.E59jTaJp--U2oUtePgjZu8Video

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

Hispanics/Latinos in the United States 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 Hispanics/Latinos of diverse heritages. 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 Hispanics/Latinos age 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). 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 covariates 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). Elevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanics/Latinos. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanics/Latinos of diverse heritages.

Genetic subtypes of prediabetes, healthy lifestyle, and risk of type 2 diabetes.

Prediabetes is a heterogenous metabolic state with various risk for development of type 2 diabetes (T2D). In this study, we used genetic data on 7,227 US Hispanic/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and 400,149 non-Hispanic whites without diabetes from the UK Biobank (UKBB) to calculate five partitioned polygenetic risk scores (pPRSs) representing various pathways related to T2D. Consensus clustering was performed in participants with prediabetes in HCHS/SOL (n=3,677) and UKBB (n=16,284) separately, based on these pPRSs. Six clusters of individuals with prediabetes with distinctive patterns of pPRSs and corresponding metabolic traits were identified in the HCHS/SOL, five of which were confirmed in the UKBB. Although baseline glycemic traits were similar across clusters, individuals in Cluster 5 and Cluster 6 showed elevated risk of T2D during follow-up compared to Cluster 1 (RR=1.29 [95% CI 1.08-1.53] and1.34 [1.13-1.60], respectively). Inverse associations between a healthy lifestyle score and risk of T2D were observed across different clusters, with a suggestively stronger association observed in Cluster 5 compared to Cluster 1. Among individuals with healthy lifestyle, those in Cluster 5 had a similar risk of T2D compared to those in Cluster 1 (RR=1.03 [0.91-1.18]). This study identified genetic subtypes of prediabetes which differed in risk of progression to T2D and in benefits from healthy lifestyle.

Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.

Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes.

Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio, Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio, with T2D were attenuated after further adjustment for these microbial metabolites. Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.

Thyroid Hormones and Diabetes in Euthyroid Hispanic/Latino Adults of Diverse Backgrounds: HCHS/SOL.

Previous studies have demonstrated associations of endogenous thyroid hormones with diabetes; less is known about stages of diabetes development at which they are operative, mechanisms of associations, and the role of the hypothalamic-pituitary-thyroid axis. This study examined associations of thyroid hormones with incident prediabetes and diabetes and with changes in glycemic traits in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the largest cohort of Hispanic/Latino adults with diverse backgrounds in the United States. The study includes 592 postmenopausal euthyroid women and 868 euthyroid men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Baseline hormones included thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (T3), and indices calculated from thyroid hormones evaluating pituitary sensitivity to thyroid hormone. Transitions to diabetes and prediabetes, and changes in glycemic traits determined at the 6-year follow-up visit, were examined using multivariable Poisson and linear regressions. Among women, T3 (incident rate ratio [IRR] = 1.65; 95% CI, 1.22-2.24; P = .001) and TSH (IRR = 2.09; 95% CI, 1.01-4.33; P = .047) were positively, while FT4 (IRR = 0.59; 95% CI, 0.39-0.88; P = .011) was inversely, associated with transition from prediabetes to diabetes. Among men, the T3/FT4 ratio was positively associated with transition from normoglycemia to prediabetes but not from prediabetes to diabetes. Indices measuring sensitivity of the pituitary to thyroid hormone suggested increased sensitivity in men who transitioned from prediabetes to diabetes. Positive associations in women of T3 and TSH and inverse associations of FT4, as well as inverse associations of thyroid indices in men with transition from prediabetes to diabetes, but not from normoglycemia to diabetes, suggest decreased pituitary sensitivity to thyroid hormones in women and increased sensitivity in men later in the development of diabetes.

Metabolomic profiles of sleep-disordered breathing are associated with hypertension and diabetes mellitus development

Sleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we apply principal component analysis (PCA) to seven SDB-related measures. We estimate the associations of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint penalized regression analysis. The discovery analysis includes 3299 individuals, with validation in a separate dataset of 1522 individuals. Five metabolite associations with SDB PCs are discovered and replicated. SDB PC1, characterized by frequent respiratory events common in older and male adults, is associated with pregnanolone and progesterone-related sulfated metabolites. SDB PC2, characterized by short respiratory event length and self-reported restless sleep, enriched in young adults, is associated with sphingomyelins. Metabolite risk scores (MRSs), representing metabolite signatures associated with the two SDB PCs, are associated with 6-year incident hypertension and diabetes. These MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.

Abstract TMP102: Association of Lipoprotein(a) With Stroke and Cerebral Injury: Insights From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Investigation of Neurocognitive Aging-MRI (SOL-INCA MRI)

Introduction: Lipoprotein(a) [Lp(a)] is a known risk factor for cardiovascular disease; however, its association with cerebrovascular disease is not as well established. Methods: Data from HCHS/SOL, a population-based cohort of Hispanics/Latinos, was utilized. We included 16,039 participants with measured Lp(a) levels (nmol/L) and self-reported history of prevalent stroke or transient-ischemic attack (TIA) from Visit 1. Data from SOL-INCA MRI (ancillary study conducted after Visit 2) was utilized to identify a subset of 2,668 HCHS/SOL participants with brain MRI. Linear and logistic regression was used to study the association of Lp(a) with 1. Self-reported stroke or TIA; 2. Cerebral injury defined as self-reported stroke or TIA or evidence of a stroke on brain MRI; and 3. White matter hyperintensity (WMH) volume modeled as log (WMH/total cranial volume). Lp(a) was modeled as a continuous variable and as quintiles. Sampling weights and surveys methods were used to account for the complex HCHS/SOL design. Results: HCHS/SOL mean age ± SE was 41.1 ± 0.3 years, 52.0% female, and median (IQR) Lp(a) level 19.7 (7.3-60.6) nmol/L. SOL-INCA MRI mean age ± SE was 49.9 ± 0.4 years, 56.4% female, and median (IQR) Lp(a) level 21.7 (8.1-62.9). A ten nmol/L unit increase in Lp(a) was significantly associated with a higher risk of self-reported prevalent stroke or TIA (OR 1.03, 95% CI: 1.02-1.05, p = 0.0002). Lp(a)&gt;77 nmol/L (5 th quintile) was significantly associated with higher risk of self-reported prevalent stroke or TIA (OR 1.8, 95% CI: 1.2-2.8, p = 0.009) compared to Lp(a) &lt;6 nmol/L (1 st quintile) as reference. A ten unit increase in Lp(a) was significantly associated with higher odds of cerebral injury (OR 1.03, 95% CI: 1.02-1.05, p&lt;0.0001). Lp(a)&gt;77 nmol/L was significantly associated with cerebral injury (OR 1.8, 95% CI 1.3- 2.6, p=0.002) as compared to Lp(a) &lt;6 nmol/L. A ten unit increase in Lp(a) was also significantly associated with increasing WMH volume (β 0.02, p=0.0002). Conclusions: Lp(a) is significantly associated with self-reported prevalent stroke or TIA, brain MRI evidence of cerebral injury, and WMH, in a large diverse population of Hispanics/Latinos, suggesting that Lp(a) may be a modifiable risk factor for cerebrovascular disease.

Life's Essential 8 and Incident Hypertension Among US Hispanic/Latino Adults: Results From the Hispanic Community Health Study/Study of Latinos.

Life's Essential 8 (LE8) is a new metric to define cardiovascular health. We aimed to describe LE8 among Hispanics/Latinos and its association with incident hypertension. The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a study of Hispanic/Latino adults aged 18 to 74 years from 4 US communities. At visit 1 (2008-2011), information on behavioral and clinical factors (diet, smoking status, physical activity, sleep duration, body mass index, blood pressure, cholesterol, fasting glucose, and medication use) were measured and used to estimate an LE8 score (range, 0-100) for 14 772 participants. Hypertension was defined as systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, or self-reported use of antihypertensive medications. Among the 5667 participants free from hypertension at visit 1, we used Poisson regression models to determine the multivariable adjusted association between LE8 and incident hypertension in 2014 to 2017. All analyses accounted for the complex survey design of the study. Mean population age was 41 years, and 21.6% (SE, 0.7) had high cardiovascular health (LE8 ≥80). Mean LE8 score (68.2; SE, 0.3) varied by Hispanic/Latino background (P<0.05), ranging from 72.6 (SE, 0.3) among Mexican Americans to 62.2 (SE, 0.4) among Puerto Ricans. Each 10-unit decrement in LE8 score was associated with a 22% increased risk of hypertension over ≈6 years (incident density ratio, 1.22 [95% CI, 1.16-1.29]). Only 1 in 5 Hispanic/Latino adults had high cardiovascular health, and LE8 varied substantially across Hispanic/Latino background groups. Improvements in other components of cardiovascular health may result in a lower risk of developing hypertension.

Cardiac Abnormalities in Hispanic/Latina Women With Prior De Novo Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy (HDP) are associated with long-term maternal risks for cardiovascular disease for reasons that remain incompletely understood. The HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a multi-center community-based cohort of Hispanic/Latino adults recruited 2008 to 2011, was used to evaluate the associations of history of de novo HDP (gestational hypertension, preeclampsia, eclampsia) with echocardiographic measures of cardiac structure and function in Hispanic/Latina women with ≥1 prior pregnancy and the proportion of association mediated by current hypertension (>140/90 mm Hg or antihypertensive therapy). The study cohort included 5168 Hispanic/Latina women with an average age (SD) of 58.7 (9.7) years at time of echocardiogram. Prior de novo HDP was reported by 724 (14%) of the women studied and was associated with lower left ventricle (LV) ejection fraction -0.66 (95% confidence interval [CI], -1.21 to -0.11), higher LV relative wall thickness 0.09 (95% CI, 0-0.18), and 1.39 (95% CI, 1.02-1.89) higher risk of abnormal LV geometry after adjusting for blood pressure and other confounders. The proportion of the association mediated by current hypertension between HDP and LV ejection fraction was 0.09 (95% CI, 0.03-0.45), LV relative wall thickness was 0.28 (95% CI, 0.16-0.51), abnormal LV geometry was 0.14 (95% CI, 0.12-0.48), concentric left ventricular hypertrophy was 0.31 (95% CI, 0.19-0.86), and abnormal LV diastolic dysfunction was 0.58 (95% CI, 0.26-0.79). In a large cohort of Hispanic/Latina women those with history of de novo HDP had detectable and measurable subclinical alterations in cardiac structure and both systolic and diastolic dysfunction that were only partially mediated by current hypertension.

Sleep Phenotypes predict self‐reported measures of cognition and mild cognitive impairment in diverse Hispanics/Latinos

AbstractBackgroundThe Hispanic Community Health Study/Study of Latinos (HCHS/SOL) showed that self‐reported cognitive decline (SCD) is associated with objectively assessed cognition. In HCHS/SOL, sleep phenotypes using empirically derived latent class/cluster analyses are associated with brain vascular outcomes. Since these measures may predict cognitive decline and dementia, we examined the associations between sleep phenotypes, SCD and mild cognitive impairment (MCI) among a diverse sample of Hispanics/Latinos living in the United States.MethodHCHS/SOL is prospective cohort study designed using a multisite (Bronx, NY, Chicago, IL, Miami, FL, San Diego, CA) multistage probability sample. SCD was measured as part of SOL‐INCA, an HCHS/SOL ancillary study. SOL‐INCA obtained repeated cognitive tests, seven‐years apart and the Everyday Cognition Short Form (ECog‐12). The ECog‐12 is a self‐rated questionnaire of current multiple cognitively relevant functional abilities compared to 10‐years ago administered to 5,563 SOL‐INCA participants aged ≥ 50 years. We used latent class analysis using 15 common sleep related symptoms, home sleep apnea test and four comorbidities to derive three sleep phenotypes: (1) Minimally Symptomatic group (49.6%), (2) Disturbed Sleep group (17.1%), and (3) Daytime Sleepiness group (33.3%). We used survey regression to evaluate associations between visit‐1 sleep phenotypes and the ECog‐12 (linear) cognitive domains (memory, language, executive function, and global) and MCI (logistic) using the minimally symptomatic sleep group as the reference. Models were adjusted for age, education, sex, background, field center, insurance, body mass index, cigarette use, alcohol use, cardiovascular disease, language preference, and respiratory event index.ResultAverage age was 64.34±8.25 years and 55% were female. In fully adjusted models, participants with disturbed sleep had worse global cognition β = 0.18 [0.14;0.22], memory β = 0.21 [0.16;0.26], language β = 0.23 [0.17;0.29], and executive function β = 0.16 [0.12;0.21]. Compared to the reference, we observed stronger associations in participants with daytime sleepiness; global cognition β = 0.22 [0.16;0.27], memory β = 0.26 [0.19;0.32], language β = 0.26 [0.19;0.34], and executive function β = 0.20 [0.15;0.26]. Adults with disturbed sleep, OR = 1.44 [1.08;1.93], and daytime sleepiness OR = 1.67 [1.16;2.40] had higher odds of MCI.ConclusionEmpirically derived sleep phenotypes capturing disturbed sleep and sleepiness had associations with self‐reported cognitive function and MCI in this sample of U.S. Hispanic/Latino adults.

Childhood and life‐course socioeconomic position and cognitive function in adult population of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

AbstractBackgroundThe Hispanic/Latino population experiences extensive socioeconomic adversity across the lifespan and is at greater risk of cognitive decline. Yet little is known about the role of life‐course socioeconomic position (SEP) and cognitive function in this population. We assessed the association between childhood SEP and cognitive function in Hispanic/Latino adults, whether this association is mediated by midlife SEP, and whether socioeconomic mobility is associated with cognitive function.MethodWe used baseline data (2008‐2011) from 9556 adults aged 45‐74 years of the Hispanic Community Health Study/Study of Latino (HCHS/SOL), a multi‐center cohort study conducted in four major U.S cities. We determined childhood SEP using parental educational attainment. Midlife SEP was determined through an index combining participants’ education and household income. We classified participants into socioeconomic mobility categories from childhood to adulthood (e.g., persisting low, upward mobility). Cognitive function was ascertained using neurocognitive tests, including the Six‐Item Screener; Brief‐Spanish English Verbal Learning Test Sum and Recall, Controlled Oral Word Association (or Word Frequency), and the Digit Symbol Substitution Test. Using confirmatory factor analysis and these tests we created a global cognition score. We also standardized z‐score of these neurocognitive measures. Survey linear regression models were performed adjusting for age, sex, Hispanic background, U.S born, smoking, depression, and cardiovascular factors. We also conducted mediation analysis to decompose the direct effect of childhood SEP on cognition and the indirect effect through midlife SEP.ResultChildhood SEP showed a graded association with cognitive function in adulthood with a dose‐response relationship across levels of parental education (β and [95% Confidence Interval (CI)]): Elementary/middle school vs. No schooling 0.34 [0.25‐0.43]; High school (HS) vs. No schooling: 0.53 [0.42‐0.64]; and &gt;HS vs. No schooling: 0.68 [0.57‐0.79]). High midlife SEP was also associated with greater cognitive function relative to low midlife SEP. 37% (95% CI 32%‐44%) of the association between childhood SEP and cognition was mediated through midlife SEP. Holding a high SEP over the life‐course was associated with greater cognitive performance (β: 0.90, 95% CI: 0.79‐1.00) as compared with a persisting low SEP.ConclusionThis study provides evidence that childhood and life‐course SEP influence cognitive performance in adulthood

Associations between Anxious‐Depression and Cognitive Change, Function, and Impairment: Results from the Hispanic Community Healthy Study/Study of Latinos‐Investigations of Neurocognitive Aging

AbstractBackgroundAnxiety and depression often co‐occur and both are risk factors for Alzheimer’s disease and related dementias (ADRD). This study sought to examine associations between anxiety and depressive symptoms with cognitive change, function and impairment among middle‐aged and older Hispanics/Latinos.MethodData included 6,162 middle‐aged and older Hispanic/Latinos adults (Age M = 63.4 years, SD = ±8.2 years; 55% female) enrolled in the Study of Latinos‐Investigation of Neurocognitive Aging study (SOL‐INCA), an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Participants completed the Spielberger State‐Trait Anxiety Inventory 10‐item (STAI‐10) and Center for Epidemiology Scale for Depression 10‐item (CESD‐10) at HCHS/SOL Visit 1 (2008‐2011). Outcomes of interest include cognitive function at Visit 2, change in cognition from Visit 1 to 2 (approximately 7‐years later in SOL‐INCA), and mild cognitive impairment status (MCI; NIA‐AA diagnostic criteria) at Visit 2. Latent class analysis (LCA) was used to derive phenotypes of anxious‐depression using both STAI‐10 and CESD‐10 items. The phenotypes were used as exposures in survey generalized linear regression models for cognitive function, change, and MCI. Covariables included age, sex, education, income, heritage, center, and antianxiety/antidepressant medication use.ResultLCA results demonstrated 3 classes of anxious‐depression (Low; 62%, Moderate; 30%, and High; 8%). We found consistent negative associations between the Moderate and High group with cognitive function, from baseline. Participants in the High group had more pronounced associations (p&lt;.001) than the Moderate group (p&lt;.01) vs. the Low group, after covariate adjustments. We found consistent negative associations with MCI whereby both Moderate (OR = 1.62, CI = [1.12; 2.33], p&lt;.05) and High (OR = 1.64, CI = [1.25; 2.16], p&lt;.001) groups were associated with higher odds ratios for MCI. However, there were no associations with cognitive change.ConclusionThis study demonstrated the utility of the anxious‐depression construct when investigating the relationships between co‐occurring anxiety and depressive symptoms with cognitive aging among Hispanics/Latinos. Anxious‐depression was negatively associated with cognitive function and MCI status, demonstrating unique effects of co‐occurring anxiety and depressive symptoms among older Hispanic/Latinos. However, further replications are required to evaluate the longitudinal effects of anxious‐depression on cognitive outcomes.

Sleep breathing patterns and neurocognitive function in a diverse Hispanic/Latino cohort

AbstractBackgroundSleep disorders are common in patients with Alzheimer’s Disease (AD). Obstructive sleep apnea (OSA), characterized by intermittent cessation of breathing and hypoxemia, has been associated with increased risk of AD and worse cognitive function. However, the interacting effects of neurocognitive function with sleep breathing patterns, independent of the apnea‐hypopnea index, (a measure of OSA severity) have not been carefully studied. We use a novel approach to analyzing home sleep apnea data to examine breathing patterns and their relationships with neurocognitive function.MethodThe Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective multicenter study of diverse Latinos. Around 16,000 diverse Hispanic/Latinos were recruited from four major metropolitan cities. Participants used an ARES unirecorder device for a single night of unsupervised at home recording. We used python package “bycycle” to cannula data (sampled at 10Hz). Bycycle uses a time domain approach to parameterizing rhythmic time‐series data. We extracted breathing rate (breaths per minute), breathing variability (interquartile range of breathing rate) and time spent in inhalation phase (percent time). Participants ages ≥45 (unweighted n = 5,957) were tested in their preferred language using a brief battery including: B‐SEVLT (3‐trials sum) and Delayed Recall (memory), World Fluency (verbal fluency), and Digit Symbol Substitution (executive function). Covariates used in our models are described in Table 1. All presented estimates were weighted for appropriate generalization to the HCHS/SOL target population.ResultIn unadjusted models, all breathing measures were negatively associated with cognitive function, but only breathing rate remained significant after full covariate adjustment (Figure 1). We found significant interactions between breathing rate and sex, as well as age for verbal fluency models. Being female and older age were associated with steeper slopes of cognitive under‐performance for both breathing rate and breathing variability (Figure 2).ConclusionThese results suggest that breathing patterns outside apneas‐hypopneas may be as critical in understanding sleep related changes and cognitive function in an aging population. Given cessation of breathing during an apnea‐hypopnea event, breathing variability may add more precision to account for varying oxygen demands. Further studies should examine whether breathing instability is also associated with cognitive decline, impairment, and dementia.

Association of Epigenetic Aging with Cognitive Aging in Diverse Hispanics/Latinos

AbstractBackgroundAge‐related DNA methylation (DNAm) changes occur in specific regions of the genome and have been shown to be correlated with an individual’s chronological age. Multiple “epigenetic clocks” have been developed to estimate an individual’s DNAm age, which reflect different aspects of the multidimensional aging process. Age acceleration, the deviation of the DNAm‐estimated age from the chronological age, has been proposed as a novel biomarker of aging. We investigated the association between multiple measures of age acceleration and cognitive aging phenotypes in diverse Hispanic and Latino adults.MethodsWe estimated epigenetic age acceleration from 5 epigenetic clocks in 2188 Hispanic and Latino adults (mean age 56.7 years; 64.6% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) who had available blood DNA methylation data at the baseline visit and neurocognitive data. These included first generation clocks, Horvath and Hannum clocks; second generation PhenoAge and GrimAge; and third generation DunedinPACE (Pace of Aging). We used mixed models to test the association of each of these measures with a global measure of cognitive function (PC1) at the baseline visit and with mild cognitive impairment at a follow‐up visit approximately 7 years later.ResultsThere were significant cross‐sectional associations between lower global cognitive function and greater age acceleration based on Hannum, Horvath, PhenoAge, and DunedinPACE algorithms. In addition, a greater age acceleration based on DunedinPACE was strongly associated with a higher risk of MCI 7 years later (Table).ConclusionBiological aging is associated with lower cognitive function and risk of MCI in diverse Hispanic and Latino adults. DunedinPACE, a third generation epigenetic clock, may be a more sensitive predictor of cognitive aging outcomes than previous generation clocks.

Admixture mapping of cognitive function in diverse Hispanic and Latino adults

AbstractBackgroundGenome‐wide association studies (GWAS) conducted primarily in populations of European ancestry have revealed the polygenic nature of cognitive abilities [1, 2] but genetic discoveries in other populations, including Hispanics/Latinos, are lagging. Genetically, US Hispanics/Latinos have uniquely admixed genomes, encompassing African, Amerindian, and European ancestries.[3] Admixture patterns in genomic regions (local ancestry) can be leveraged in gene mapping when frequencies of trait‐associated genetic variants located within these regions differ between ancestries.MethodWe conducted genome‐wide admixture mapping analyses followed by fine mapping to identify genetic variants associated with cognitive function in 7,140 Hispanic and Latino adults (mean age 55 years; 60.5% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Five measures of cognitive function were investigated: Six‐Item Screener (SIS), Brief Spanish English Verbal Learning Test (SEVLT), Word Fluency Test (WFT), Digit Symbol Substitution Test (DSST), and a measure of general cognitive function (PC1). We tested the identified variants for replication in independent samples with similar neurocognitive measures.ResultWe identified 9 significant local ancestry‐associated regions for the 5 cognitive tests. Counts of African ancestry on at 13q12.11, 4q14, 10p12.2 and 9p22.1 were associated with DSST, PC1, SIS, and WFT, respectively. Counts of Amerindian ancestry at 1q25.2 were associated with DSST; and at 12q14.2 and 12q15 with SIS. Counts of European ancestry at 8p22 were associated with SEVLT; and at 13q12.13 with, both, DSST and PC1. Fine mapping via SNP association testing in each region identified genetic variants that partially or totally explained the admixture signal. While statistical evidence of independent replication of the prioritized variants was generally weak, with only two replicated associations at chr8p22 and chr13q12.13, there was strong biological support for the observed associations to cognitive function. For example, the prioritized variant at 8q22 is an eQTL for CNOT7, which regulates synaptic plasticity and is essential for hippocampal‐dependent learning and memory [4].ConclusionOur admixture mapping analyses identified multiple novel loci associated with measures of cognitive function. This demonstrates the effectiveness of admixture mapping in complementing GWAS [5] and provides an opportunity to identify genetic loci that may be particularly relevant in underrepresented populations.

The relationship between obstructive sleep apnea and haemoglobin A1c and the moderating role of glycaemic status in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

This study investigated the relationship between obstructive sleep apnea and haemoglobin A1c (HbA1c) among Hispanics/Latinos in the United States and assessed whether this relationship was moderated by glycaemic status. This was a cross-sectional analysis of the Hispanic Community Health Study/Study of Latinos cohort. The sample consisted of 13,394 participants with valid measures of obstructive sleep apnea, HbA1c, and study covariates. Obstructive sleep apnea was assessed with the apnea-hypopnea index and categorised as obstructive sleep apnea if the apnea-hypopnea index was ≥5 events/h. HbA1c measures were obtained through fasting blood samples. Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG) and use of antihyperglycaemic medications were used to define glycaemic status (i.e., normoglycaemia [FPG < 5.6 mmol/L (< 100 mg/dL) and 2h-PG < 7.8 mmol/L (140 mg/dL)], prediabetes [FPG 5.6-6.9 mmol/L (100-125 mg/dL), and/or 2h-PG 7.8-11.0 mmol/L (140-199 mg/dL)], diabetes without treatment [FPG > 7.0 mmol/L (≥ 126 mg/dL) and/or 2h-PG ≥ 11.1 mmol/L (≥ 200 mg/dL)], and diabetes with treatment. Multivariable linear regression was used to calculate adjusted least square means. Overall, 25.9% of the sample had obstructive sleep apnea and 49.2% had normal glycaemic levels, 36.1% had prediabetes, 6.5% diabetes without receiving treatment, and 8.3% diabetes and undergoing treatment for it. Participants with obstructive sleep apnea had significantly higher adjusted mean HbA1c (adjusted mean [standard error] 5.85 [0.03)]) than those without (5.70 [0.02)]; p < 0.001). Models stratified by diabetes status showed that the association between obstructive sleep apnea (versus not) and higher HbA1c was only for participants with normal glycaemic status (adjusted mean [standard error] 5.27 [0.01] versus 5.30 [0.01]; p = 0.013) and prediabetes (5.59 [0.01] versus 5.66 [0.01]; p < 0.001). In conclusion, obstructive sleep apnea was associated with higher HbA1c in a diverse sample of Hispanic/Latino adults in the United States. This association was present only for participants with normal glycaemic status or with prediabetes. Studies are needed to further understand the clinical implications of the association between obstructive sleep apnea and HbA1c according to glycaemic status.

Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion

The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA. Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids. We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation. Described in methods.

Abstract 18553: Different Leg Symptoms and the Presence of Peripheral Artery Disease in the Community: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Study

Introduction: Intermittent claudication is manifestation of lower extremity peripheral artery disease (PAD). However, most patients with PAD either have atypical leg symptoms or no symptoms. To what extent leg symptoms are associated with the presence of PAD in the community is unknown. Methods: We studied 8,402 HCHS/SOL participants aged 45 and older (mean age 56.2 years, 54% female) without a clinical diagnosis of PAD. We categorized leg symptoms with walking into: (a) typical calf pain (calf pain on exertion relieved within 10 min after stopping); (b) atypical calf pain (same as (a) except no quick relief after 10 min); (c) non-calf pain (exertional leg pain but not in calf); and (d) leg pain at rest (ever pain during standing or sitting) based on a questionnaire. PAD was defined as an ankle-brachial index (ABI) ≤0.9. We first quantified the associations of leg symptoms with the presence of PAD using multivariable logistic regression. Then, we assessed the validity of different leg symptoms to identify PAD. All analyses accounted for survey weighting. Results: The prevalence of PAD was 4.8% (95% CI 4.1-6.0%). The prevalence of leg symptoms are displayed in Figure 1A (e.g., 1.9% for typical calf pain). In multivariable logistic models, only typical calf pain was significantly associated with PAD, and its adjusted OR exceeded 5 (5.52 [95% CI 2.60-11.7], Figure 1A). In terms of validity, typical calf pain had 98.5% specificity, but the sensitivity was ~10% (Figure 1B) and the positive predictive value was 24.1%. The c-statistic of this leg symptom classification for detecting PAD was 0.58. Conclusions: In Hispanics/Latinos without clinical history of PAD, only typical calf pain on exertion was robustly associated with the presence of PAD. However, the limited positive predictive value and discrimination indicate the need to optimize the target population and/or further refine leg symptoms to utilize them to detect PAD in the community.

Abstract 12340: Association of Liver Enzymes With Incident Cardiovascular Disease Events and All-Cause Mortality in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Metabolic associated fatty liver disease (MAFLD) is a significant contributor to chronic liver disease on a global scale, encompassing a broad range of systemic impacts, including an increased risk of cardiovascular disease (CVD). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are commonly utilized indicators of liver injury in this context. Despite the high prevalence of MAFLD among Hispanic/Latino populations, there is a scarcity of research focusing on this specific demographic. Aim: To investigate the relationship between liver disease, incident CVD, and mortality in a representative Hispanic/Latino population, using non-invasive markers. Methods: A total of 14,149 participants recruited between 2008-2011 in HCHS/SOL aged 18-74 years with no pre-existing CVD at study baseline were included in this study. The outcome of interest was a composite of adjudicated incident CVD and all-cause mortality. Participants who had liver function tests (LFTs) AST &gt; 37 IU/mL or ALT &gt; 40 IU/mL for men, and AST or ALT &gt; 31 IU/mL for women were classified as having elevated LFTs. MAFLD was defined as a fatty liver index score &gt;60 and: type 2 diabetes, body mass index&gt;25 kg/m 2 or at least two metabolic risk abnormalities. Survey-weighted cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for our composite outcome by elevated LFTs. Interaction terms assessed the relationship between elevated LFTs and MAFLD. Results: The study population was 40 years old on average, 53.4% female and had 403 weighted CVD and all-cause mortality events. Elevated LFTs and MAFLD alone were not associated with incident CVD and all-cause mortality (HR: 1.24; CI: 0.89-1.71). MAFLD modified the relationship between elevated LFTs and CVD (P=0.04). Among those with MAFLD, elevated LFTs were not associated with CVD (HR: 1.01; CI:0.70-1.46), but among those without MAFLD, elevated LFTs were associated with CVD (HR: 2.05; CI:1.17-3.58). Conclusions: Among Hispanic/Latinos without MAFLD, elevated LFTs were associated with CVD and all-cause mortality. Additional research is needed to elucidate the relationship between liver disease and CVD in the Hispanic/Latino population.