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Chronic psychological stress is associated with accelerated biological aging, immune dysfunction, and premature morbidity and mortality. Changes in the relative proportions of T cell subpopulations are thought to be a characteristic of immunological aging; however, understanding of whether these changes are associated with chronic psychological stress is incomplete. This study investigated associations between chronic caregiving stress and distributions of T cell phenotypes in a sample of high stress mothers of children with Autism Spectrum Disorder (caregivers; n = 91) and low stress mothers of neurotypical children (controls; n = 88). Immune markers assessed were naïve (CD45RA + CD62L+), central memory (CD45RA-CD62L+), and effector memory (CD45RA-CD62L-) CD4+ and CD8+ T cells. We also examined the ratio of effector to naïve (E:N) CD4+ and CD8+ T cells. In models adjusted for age, body mass index, race/ethnicity, and antidepressant use, caregivers displayed higher percentages of effector memory CD8+ and CD4+ T cells as well as lower percentages of naïve CD8+ T cells and central memory CD8+ and CD4+ T cells compared to controls. Caregivers also displayed significantly higher E:N ratios for both CD4+ and CD8+ T cells. These findings were also independent of cytomegalovirus infection status. Furthermore, higher parental stress, across both groups, was related to several immune parameters. These findings provide preliminary evidence that chronic parental caregiving stress is associated with changes in relative proportions of T cell subpopulations that are consistent with accelerated immunological aging.

Few studies have collected intergenerational data to assess the association between educational mobility across multiple generations and offspring depression. Using data from the Sacramento Area Latino Study on Aging (1998-2008), we assessed the influence of intergenerational education on depressive symptoms over 10 years among 1,786 Latino individuals (mean age = 70.6 years). Educational mobility was classified as stable-low (low parental/low offspring education), upwardly mobile (low parental/high offspring education), stable-high (high parental/high offspring education), or downwardly mobile (high parental/low offspring education). Depressive symptoms were measured with the Center for Epidemiological Studies-Depression Scale (CES-D); higher scores indicated more depressive symptoms. To quantify the association between educational mobility and CES-D scores over follow-up, we used generalized estimating equations to account for repeated CES-D measurements and adjusted for identified confounders. Within individuals, depressive symptoms remained relatively stable over follow-up. Compared with stable-low education, stable-high education and upward mobility were associated with significantly lower CES-D scores (β = -2.75 and -2.18, respectively). Downwardly mobile participants had slightly lower CES-D scores than stable-low participants (β = -0.77). Our results suggest that sustained, low educational attainment across generations may have adverse mental health consequences, and improved educational opportunities in underresourced communities may counteract the adverse influence of low parental education on Latino depression.

Even after migration, immigrants and their descendants may continue to have ties to family and friends who remain in places of origin. Recent research suggests that these cross-border social ties have implications for health, although this scholarship has been limited to self-reported outcomes. Using data from the Sacramento Area Latino Study on Aging (SALSA), we estimate associations between cross-border social ties and inflammatory biomarkers among Latino adults (n = 1786). We find that immigrants who maintained any cross-border connection to family and friends in Latin America had significantly lower levels of baseline interleukin-6 (IL-6) and C-reactive protein (CRP) compared to their US-born counterparts with no cross-border ties. These results held for values of CRP at five-year follow-up for men only. In contrast, US-born women with cross-border ties to family and friends in Latin America had both significantly higher levels of CRP and significantly lower levels of tumor necrosis factor-alpha (TNF-α) at five-year follow-up relative to their US-born counterparts with no cross-border ties. We find descriptively that men who have cross-border ties are also less likely to be socially isolated within local contexts. Considering place-of-origin social connections may contribute critical nuance to studies of immigrant health, including disparities in inflammatory markers that may serve as indicators of underlying chronic disease.

Foreign-born Hispanics have better cardiometabolic health upon arrival in the US than their US-born counterparts, yet this advantage diminishes as duration of residence in the US increases. Underlying mechanisms explaining this paradox have been understudied. Using data from the Sacramento Area Latino Study on Aging (SALSA), this study examined immigration history (immigrant generation and duration of US residence) in relation to biomarkers of inflammation (interleukin-6 (IL-6), soluble forms of type 1 and 2 receptors of tumor necrosis factor-alpha (sTNF-R1 and sTNF-R2), C-reactive protein (CRP), leptin, adiponectin) in a sample of 1,290 predominantly Mexican-origin immigrants. Second and ≥3rd generation immigrants had higher IL-6 and leptin levels than 1st generation immigrants living in the US for less than 15 years (2nd generation percent difference = 45.9; 95% CI: 24.7, 70.7 and 3rd generation percent difference = 41.8; 95% CI: 17.7, 70.4). CRP and sTNF-R1 levels were higher among ≥3rd generation immigrants than 1st generation immigrants with less than 15 years of US residency. Worse inflammatory profiles were observed among Mexican-origin immigrants with longer US immigration histories, independent of health, and behavioral factors. Additional research is warranted to understand the factors that shape trajectories of biological risk across generations of Hispanics.

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS.

ObjectivesExternal validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA.DesignMatched case-control study.SettingThirteen active surveillance sites for invasive pneumococcal disease in the USA.ParticipantsCases were identified from active surveillance and controls were age and zip code matched.Outcome measuresSocioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment.ResultsWe enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p

INTRODUCTION: The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline. METHODS: We analyzed Framingham Heart Study Offspring Cohort data (n = 2296; 46% male; baseline age M = 62, SD = 9, range = 25–101 y). We measured cognitive decline across two decades of neuropsychological‐testing follow‐up. We measured pace of aging using the DunedinPACE epigenetic clock. Analysis tested if participants with faster DunedinPACE values experienced more rapid cognitive decline compared with those with slower DunedinPACE values. RESULTS: Participants with faster DunedinPACE had poorer cognitive functioning at baseline and experienced more rapid cognitive decline over follow‐up. Results were robust to confounders and consistent across population strata. Findings were similar for the PhenoAge and GrimAge epigenetic clocks. DISCUSSION: Faster pace of aging is a risk factor for preclinical cognitive decline. Metrics of biological aging may inform risk stratification in clinical trials and prognosis in patient care. Highlights: Faster DunedinPACE is associated with preclinical cognitive aging. Higher baseline cognition was protective of DunedinPACE‐associated cognitive decline. The DunedinPACE association with cognitive decline explained a fourth of dementia risk. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) have increased in prevalence. Objective: This article describes the Add Health Parent Study (AHPS) Phase 2, a study of social, behavioral, and biological factors influencing healthy aging and risk for AD/ADRD, in a national sample of adults aged 58–90. Methods: Sample members are parents of the National Longitudinal Study of Adolescent to Adult Health (Add Health) cohort, initially interviewed in Add Health in midlife (1994-95). AHPS Phase 1 (2015–17) collected longitudinal data on a random subsample of parents and their spouse/partners, who were mostly Non-Hispanic (NH) White. AHPS Phase 2 will collect the same longitudinal socio-behavioral, and health survey data on all remaining NH Black and Hispanic parents (Black and Hispanic Supplement, BHS). Additionally, Phase 2 will collect cognitive and DNA data from AHPS Phase 1 and BHS sample parents and their current spouse/partners. Results: Funded by the National Institute on Aging, recruitment will occur between June 2025 and May 2026, producing an expected total AHPS sample of 5506 parents and their spouse/partners. Conclusions: The AHPS will be the first longitudinal cohort study powered to address multigenerational racial/ethnic disparities in AD/ADRD risk and protective factors across race/ethnic groups and socioeconomic strata. [ABSTRACT FROM AUTHOR]

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age.

BackgroundComorbidity (COM) is an important issue in aging. Cardiovascular disease (CVD) and osteoarthritis separately and together may modify the trajectories of functional decline. This analysis examines whether specific and unrelated COMs influence functional change differently and vary by gender.MethodsA cohort study of 1,789 (aged 60 years and older) Mexican Americans was followed annually for up to 10 years. We created four groups of COM (CVD alone, lower body osteoarthritis alone [OA], neither, or both). We employed mixed effects Poisson models with Instrumental Activities of Daily Living (IADL) as the outcome. We tested whether the association between COM and decline in functional status differed by gender.ResultsIADL impairments in those with CVD, OA, or both were significantly higher at baseline and increased more rapidly over time compared to those with neither condition. Compared to women with no COM, the number of IADL impairments in women with CVD alone were 1.36 times greater, with OA were 1.35 times greater, and both conditions were 1.26 times greater. Compared to men with no COM, IADL impairments in men with CVD alone were 1.15 times greater, OA alone were 1.12 times greater, and both were 1.26 times greater.ConclusionsOver time, the influence of COM on functional decline differs by specific combinations of COM and by gender. Aggregate COM scales obscure the biological and temporal heterogeneity in the effects of COM. Time-dependent-specific COMs better assess the development of impairment. Women experience a higher burden of functional impairment due to COM than men.

PurposeLow educational attainment has been associated with depression among Latinos. However, few studies have collected intergenerational data to assess mental health effects of educational mobility across generations.MethodsUsing data from the Niños Lifestyle and Diabetes Study, we assessed the influence of intergenerational education on depressive symptoms among 603 Mexican-origin individuals. Intergenerational educational mobility was classified: stable-low (low parent and/or low offspring education), upwardly mobile (low parent and/or high offspring education), stable-high (high parent and/or high offspring education), or downwardly mobile (high parent and/or low offspring education). High depressive symptoms were defined as scoring ≥10 on the Center for Epidemiological Studies Depression Scale-10 (CESD-10). We examined prevalence ratios (PRs) for depressive symptoms with levels of educational mobility. We used general estimating equations with log-binomial models to account for within-family clustering, adjusting for age, gender, and offspring and parent nativity.ResultsCompared with stable-low participants, the lowest prevalence of CESD-10 score ≥10 occurred in upwardly mobile (PR = 0.55; 95% confidence interval [CI] = 0.39-0.78) and stable-high (PR = 0.62; 95% CI = 0.44-0.87) participants. Downwardly mobile participants were also less likely to have a CESD-10 score ≥10 compared with stable-low participants (PR = 0.65; 95% CI = 0.38-1.11), although the estimate was not statistically significant.ConclusionsSustained stress from low intergenerational education may adversely affect depression. Latinos with stable-low or downwardly mobile intergenerational educational attainment may need closer monitoring for depressive symptoms.

ObjectiveThe purpose of this study was to examine the association of intergenerational education and country of birth with waist circumference, metabolic syndrome, and type 2 diabetes among older adult Latinos in the United States.MethodsWe used cross-sectional data from the Sacramento Area Latino Study on Aging, a cohort of older adult Mexican-American Latinos (mean age = 70 years). At baseline, we measured waist circumference and assessed metabolic syndrome and diabetes according to established guidelines (N = 1,789). Participants were classified as US-born or foreign-born based on self-reported birth country. Participants reported their parents' education level (≥6 vs.

ObjectiveThe purpose of this study was to examine the association of intergenerational education and country of birth with waist circumference, metabolic syndrome, and type 2 diabetes among older adult Latinos in the United States.MethodsWe used cross-sectional data from the Sacramento Area Latino Study on Aging, a cohort of older adult Mexican-American Latinos (mean age = 70 years). At baseline, we measured waist circumference and assessed metabolic syndrome and diabetes according to established guidelines (N = 1,789). Participants were classified as US-born or foreign-born based on self-reported birth country. Participants reported their parents' education level (≥6 vs.

BackgroundThe purpose of this manuscript is to describe the PhenX RISING network and the site experiences in the implementation of PhenX measures into ongoing population-based genomic studies.MethodsEighty PhenX measures were implemented across the seven PhenX RISING groups, thirty-three of which were used at more than two sites, allowing for cross-site collaboration. Each site used between four and 37 individual measures and five of the sites are validating the PhenX measures through comparison with other study measures. Self-administered and computer-based administration modes are being evaluated at several sites which required changes to the original PhenX Toolkit protocols. A network-wide data use agreement was developed to facilitate data sharing and collaboration.ResultsPhenX Toolkit measures have been collected for more than 17,000 participants across the PhenX RISING network. The process of implementation provided information that was used to improve the PhenX Toolkit. The Toolkit was revised to allow researchers to select self- or interviewer administration when creating the data collection worksheets and ranges of specimens necessary to run biological assays has been added to the Toolkit.ConclusionsThe PhenX RISING network has demonstrated that the PhenX Toolkit measures can be implemented successfully in ongoing genomic studies. The next step will be to conduct gene/environment studies.