TY - JOUR T1 - Dried blood spot based biomarkers in the Health and Retirement Study: 2006 to 2016. JF - American Journal of Human Biology Y1 - 2024 A1 - Jung K Kim A1 - Faul, Jessica A1 - Weir, David R A1 - Crimmins, Eileen M KW - Biomarkers KW - C-reactive protein KW - Cystatin C KW - Dried Blood Spot Testing KW - Retirement AB -

INTRODUCTION: The Health and Retirement Study (HRS) has collected biomarker data over multiple waves. Such data can help improve our understanding of health changes in individuals and the causal pathways related to health. There are, however, technical challenges to using the HRS dried blood spots (DBS) biomarker data due to changes over time in assay protocols, platforms, and laboratories. We provide technical and summary information on biological indicators collected as part of the HRS from 2006 to 2016 that should be helpful to users of the data.

METHODS: We describe the opportunities and challenges provided by the HRS DBS data as well as insights provided by the data. The HRS collected DBS from its nationally representative sample of respondents 51 years of age or older from 2006 to 2016. DBS-based biomarkers were collected from half the sample in 2006, 2010, and 2014, and from the other half of the sample in 2008, 2012, and 2016. These DBS specimens were used to assay total and HDL cholesterol, glycosylated hemoglobin, C-reactive protein, and cystatin C from 2006 to 2016, and Interleukin 6 was added in 2014/2016. Samples included approximately 6000 individuals at each wave, and completion rates ranged from 81% to 90%. HRS transformed DBS values into venous blood equivalents to make them more comparable to those of the whole blood-based assays collected in most other studies and to facilitate longitudinal analysis.

RESULTS: Distribution of changes over time by age shows that total cholesterol levels decreased for each age, while HbA1c levels increased. Cystatin C shows a clear age gradient, but a number of other markers do not. Non-Hispanic Black persons and Hispanic respondents have a higher incidence of risk levels of each biomarker except for CRP among non-Hispanic Black older persons.

CONCLUSION: These public-use DBS data provide analysis opportunities that can be used to improve our understanding of health change with age in both populations and among individuals.

VL - 36 IS - 2 ER - TY - RPRT T1 - Documentation of lnterleukin-6 (IL-6) Assays from Dried Blood Spots 2014 and 2016 Y1 - 2023 A1 - Crimmins, Eileen A1 - Jessica Faul A1 - Jung K Kim A1 - David R Weir KW - User guide AB - This document describes the collection of lnterleukin-6 (IL-6) in 2014 and 2016 Assays from Dried Blood Spots. PB - Institute for Social Research, University of Michigan CY - Ann Arbor, MI ER - TY - JOUR T1 - Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality. JF - PNAS Y1 - 2023 A1 - Jessica Faul A1 - Jung K Kim A1 - Levine, Morgan E A1 - Bharat Thyagarajan A1 - David R Weir A1 - Eileen M. Crimmins KW - Acceleration KW - Aging KW - Biomarkers KW - Cross-Sectional Studies KW - DNA Methylation KW - Epigenesis KW - genetic AB -

Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using "second and third generation clocks," PhenoAge, GrimAge, and DunedinPACE, is consistently a significant predictor of health outcomes including cross-sectional cognitive dysfunction, functional limitations and chronic conditions assessed 2 y after DNAm measurement, and 4-y mortality. PC-based epigenetic age acceleration measures do not significantly change the relationship of DNAm-based age acceleration measures to health outcomes or mortality compared to earlier versions of these measures. While the usefulness of DNAm-based age acceleration as a predictor of later life health outcomes is quite clear, other factors such as demographics, SES, mental health, and health behaviors remain equally, if not more robust, predictors of later life outcomes.

VL - 120 IS - 9 ER - TY - JOUR T1 - Racial/Ethnic Differences in Biological Aging and Their Life Course Socioeconomic Determinants: The 2016 Health and Retirement Study. JF - Journal of Aging and Health Y1 - 2023 A1 - Farina, Mateo P A1 - Jung K Kim A1 - Eileen M. Crimmins KW - accelerated biological aging KW - racial/ethnic disparities AB -

This study examined differences in accelerated biological aging among non-Hispanic Blacks, Hispanics, and non-Hispanic Whites in the United States and assessed whether including life course socioeconomic conditions attenuated observed racial/ethnic differences. Data came from the Venous Blood Collection Subsample of the Health and Retirement Study. We used a comprehensive summary measure of biological age (BA-22). We determined whether key lifetime socioeconomic conditions contributed to racial/ethnic differences in biological aging. Findings indicated that non-Hispanic Blacks and Hispanics have accelerated aging, and non-Hispanic Whites have decelerated aging. Racial/ethnic differences were strongly tied to educational attainment. We also observed a significant difference by birthplace for Hispanics. US-born Hispanics had accelerated biological aging, whereas foreign-born Hispanics did not. In age-stratified analyses, these racial/ethnic differences were found for adults aged 56-74, but not for adults aged 75+. These findings provide insight into biological differences underlying racial/ethnic disparities in health.

ER - TY - JOUR T1 - Age-related differences in T cell subsets in a nationally representative sample of people over age 55: Findings from the Health and Retirement Study. JF - The Journals of Gerontology, Series A Y1 - 2022 A1 - Bharat Thyagarajan A1 - Jessica Faul A1 - Vivek, Sithara A1 - Jung K Kim A1 - Nikolich-Žugich, Janko A1 - David R Weir A1 - Eileen M. Crimmins KW - Aging KW - CMV Seropositivity AB -

Though T cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T cells subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the US. We evaluated the counts of T cell subsets including total, CD4+ and CD8+ T cells, and their naïve (Tn), effector memory (Tem) and effector subsets, in the context of age, sex and exposure to cytomegalovirus (CMV) infection among 8,848 Health and Retirement Study (HRS) participants, a nationally representative study of adults over 55 years. Total T cells (CD3+) and CD4+ cells declined markedly with age; CD8+ T cells declined somewhat less. While CD4+ T cell declines with age occurred for both CMV seropositive and CMV seronegative groups, total T cells and CD8+ cells were both substantially higher among the CMV seropositive group. Numbers of Tn CD4+ and CD8+ cells were strongly and inversely related to age, were better conserved among women, and were independent of CMV seropositivity. By contrast, accumulation of the CD8+ and CD4+ Tem and effector subsets was CMV-associated. This is the first study to provide counts of T cell subsets by age and sex in a national sample of older US adults over the age of 55 years. Understanding T cell changes with age and sex is an important first step in determining strategies to reduce its impact on age-related diseases and susceptibility to infection.

VL - 77 IS - 5 ER - TY - JOUR T1 - Links between inflammation and immune functioning with cognitive status among older Americans in the Health and Retirement Study. JF - Brain, Behavior, & Immunity - Health Y1 - 2022 A1 - Farina, Mateo P A1 - Jung K Kim A1 - Hayward, Mark D A1 - Eileen M. Crimmins KW - Biomarkers KW - Dementia KW - immune functioning KW - Inflammation AB -

Elevated inflammation and poor immune functioning are tied to worse cognitive health. Both processes are fundamental to aging and are strongly implicated in the development of age-related health outcomes, including cognitive status. However, results from prior studies evaluating links between indicators of inflammation and immune function and cognitive impairment have been inconsistent due to biomarker selection, sample selection, and cognitive outcome. Using the Health and Retirement Study (HRS), a nationally representative study of older adults in the United States, we assessed how indicators of inflammation (neutrophil-lymphocyte ratio (NLR), albumin, CRP, IL6, IL10, IL-1Ra, sTNFR1, and TGFβ1) and immune functioning (CMV, CD4 T/T and CD8 T/T) are associated with cognitive status. First, to examine the association between each biomarker and cognitive status, we tested whether markers of inflammation and immune functioning varied across cognitive status categories. We found that dementia and cognitive impairment without dementia (CIND) were associated with elevated inflammation and poorer immune functioning across biomarkers except for CD4 T/T. Next, we estimated multinomial logistic regression models to assess which biomarkers would continue to be associated with dementia and CIND, net of each other. In these models, albumin, cytokines, CMV, CD4 T/T and CD8 T/T are associated with cognitive status. Because poor immune functioning and increased inflammation are associated with cognitive impairment, improving immune functioning and reducing inflammation may provide a mechanism for reducing ADRD risk in the population.

VL - 26 ER - TY - JOUR T1 - Socioeconomic status and immune aging in older US adults in the health and retirement study. JF - Biodemography and Social Biology Y1 - 2022 A1 - Klopack, Eric T A1 - Bharat Thyagarajan A1 - Jessica Faul A1 - Meier, Helen C S A1 - Ramasubramanian, Ramya A1 - Jung K Kim A1 - Crimmins, Eileen M KW - Child KW - Educational Status KW - ethnicity KW - Hispanic or Latino KW - Retirement KW - Social Class AB -

Socioeconomic and demographic factors including educational attainment, race and ethnicity, and childhood socioeconomic status (SES) are powerful predictors of inequalities in aging, morbidity, and mortality. Immune aging, including accumulation of late-differentiated, senescent-like lymphocytes and lower levels of naïve lymphocytes, may play a role in the development of the age-related health inequalities. This study used nationally representative data from more than 9,000 US adults from the Health and Retirement Study to investigate associations between educational attainment, race and ethnicity, and childhood SES and lymphocyte percentages. Respondents with lower educational attainment, Hispanic adults, and those who had a parent with less than a high school education had lymphocyte percentages consistent with more immune aging compared to those with greater educational attainment, non-Hispanic White adults, and respondents who had parents with a high school education, respectively. Associations between education, Hispanic ethnicity, and parents' education and late differentiated senescent-like T lymphocytes (TemRA) and B cells were largely driven by cytomegalovirus (CMV), suggesting it is a factor in observed SES inequalities in immunosenescence. Naïve T lymphocytes may be particularly affected by socioeconomic position and may therefore be of particular interest to research interested in inequalities in health and aging.

VL - 67 IS - 3-4 ER - TY - JOUR T1 - Trends in Dementia Prevalence, Incidence, and Mortality in the United States (2000-2016). JF - Journal of Aging and Health Y1 - 2022 A1 - Mateo P Farina A1 - Yuan S Zhang A1 - Jung K Kim A1 - Mark D Hayward A1 - Eileen M. Crimmins KW - dementia incidence KW - educational composition AB -

The prevalence of dementia has declined in the United States; how this parallels to changes in incidence and mortality, and how improvements in educational attainment may have influences these trends, is not known. Using the Health and Retirement Study (2000-2016), we estimated logistic regression models to examine trends in dementia prevalence and incidence, and mortality for those with and without dementia. The relative decline was about 2.4% per year for dementia prevalence and 1.9% for dementia incidence. Mortality declined similarly for those with and without dementia. Improved educational attainment accounted for decline in incidence, some of the decline in prevalence, and had a negligible role in mortality. The declines in dementia incidence provide evidence that dementia prevalence should continue to decline in the near future. These declines are most likely largely driven by continued improvements in older adult education.

VL - 34 IS - 1 ER - TY - JOUR T1 - The Importance of Improving Educational Attainment for Dementia Prevalence Trends from 2000-2014, among Older non-Hispanic Black and White Americans. JF - The Journals of Gerontology, Series B Y1 - 2021 A1 - Mark D Hayward A1 - Mateo P Farina A1 - Yuan S Zhang A1 - Jung K Kim A1 - Eileen M. Crimmins KW - Cognitive health KW - Educational attainment AB -

OBJECTIVES: While a number of studies have documented a notable decline in age-standardized prevalence in dementia in the U.S. population, relatively little is known about how dementia has declined for specific age and race groups, and the importance of changing educational attainment on the downward trend. We assess 1) how the trends in dementia prevalence may have differed across age and race groups and 2) the role of changing educational attainment in understanding these trends.

METHOD: This paper estimates a series of logistic regression models using data from the Health and Retirement Study (2000-2014) to assess the relative annual decline in dementia prevalence and the importance of improving educational attainment for non-Hispanic Whites and non-Hispanic Blacks.

RESULTS: Consistent with other studies, we found significant declines in dementia for non-Hispanic Blacks and non-Hispanic Whites across this period. Nonetheless, these declines were not uniform across age and race groups. Non-Hispanic Blacks aged 65-74 had the steepest decline in this period. We also found that improved educational attainment in the population was fundamentally important in understanding declining dementia prevalence in the United States.

DISCUSSION: This study shows the importance of improvement in educational attainment in the early part of the 20 th century to understand the downward trend in dementia prevalence in the United States from 2000 to 2014.

VL - 76 IS - 9 ER - TY - JOUR T1 - Quest for a summary measure of biological age: The Health and Retirement Study. JF - Geroscience Y1 - 2021 A1 - Eileen M. Crimmins A1 - Bharat Thyagarajan A1 - Jung K Kim A1 - David R Weir A1 - Jessica Faul KW - Biological age KW - Biomarkers KW - Phenotypic age KW - TAME markers AB -

Measures of biological age and its components have been shown to provide important information about individual health and prospective change in health as there is clear value in being able to assess whether someone is experiencing accelerated or decelerated aging. However, how to best assess biological age remains a question. We compare prediction of health outcomes using existing summary measures of biological age with a measure created by adding novel biomarkers related to aging to measures based on more conventional clinical chemistry and exam measures. We also compare the explanatory power of summary biological age measures compared to the individual biomarkers used to construct the measures. To accomplish this, we examine how well biological age, phenotypic age, and expanded biological age and five sets of individual biomarkers explain variability in four major health outcomes linked to aging in a large, nationally representative cohort of older Americans. We conclude that different summary measures of accelerated aging do better at explaining different health outcomes, and that chronological age has greater explanatory power for both cognitive dysfunction and mortality than the summary measures. In addition, we find that there is reduction in the variance explained in health outcomes when indicators are combined into summary measures, and that combining clinical indicators with more novel markers related to aging does best at explaining health outcomes. Finally, it is hard to define a set of assays that parsimoniously explains the greatest amount of variance across the range of health outcomes studied here. All of the individual markers considered were related to at least one of the health outcomes.

VL - 43 IS - 1 ER - TY - JOUR T1 - Dried blood spots: Effects of less than optimal collection, shipping time, heat, and humidity JF - American Journal of Human Biology Y1 - 2020 A1 - Eileen M. Crimmins A1 - Yuan S Zhang A1 - Jung K Kim A1 - Frochen, Stephen A1 - Kang, Hyewon A1 - Shim, Hyunju A1 - Jennifer A Ailshire A1 - Potter, Alan A1 - Cofferen, Jake A1 - Jessica Faul KW - Dried Blood Spot Testing AB - Abstract Objectives This study investigates how factors related to collection, storage, transport time, and environmental conditions affect the quality and accuracy of analyses of dried blood spot (DBS) samples. Methods Data come from the 2016 Health and Retirement Study (HRS) DBS laboratory reports and the HRS merged with the National Climatic Data Center (NCDC) Global Historical Climate Network Daily (NCDC GHCN-Daily) and the NCDC Local Climatological Data, by zip code. We ran regression models to examine the associations between assay values based on DBS for five analytes (total cholesterol, high-density lipoprotein (HDL) cholesterol, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and cystatin C) and the characteristics of DBS cards and drops, shipping time, and temperature, and humidity at the time of collection. Results We found cholesterol measures to be sensitive to many factors including small spots, shipping time, high temperature and humidity. Small spots in DBS cards are related to lower values across all analytes. Longer DBS transit time before freezing is associated with lower values of total and HDL cholesterol and cystatin C. Results were similar whether or not venous blood sample values were included in equations. Conclusions Small spots, long shipping time, and exposure to high temperature and humidity need to be avoided if possible. Quality of spots and cards and information on shipping time and conditions should be coded with the data to make adjustments in values when necessary. The different results across analytes indicate that results cannot be generalized to all DBS assays. VL - 32 IS - 5 ER - TY - JOUR T1 - Female vulnerability to the effects of smoking on health outcomes in older people JF - PloS one Y1 - 2020 A1 - Haghani, Amin A1 - Thalida E. Arpawong A1 - Jung K Kim A1 - Lewinger, Juan Pablo A1 - Caleb E Finch A1 - Eileen M. Crimmins KW - Cardiovascular disease KW - Smoking KW - Women's Health AB - Cigarette smoking is among the leading risk factors for mortality and morbidity. While men have a higher smoking prevalence, mechanistic experiments suggest that women are at higher risk for health problems due to smoking. Moreover, the comparison of smoking effects on multiple conditions and mortality for men and women has not yet been done in a population-based group with race/ethnic diversity. We used proportional hazards models and restricted mean survival time to assess differences in smoking effects by sex for multiple health outcomes using data from the U.S. Health and Retirement Study (HRS), a population-representative cohort of individuals aged 50+ (n = 22,708, 1992-2014). Men had experienced more smoking pack-years than women (22.0 vs 15.6 average pack-years). Age of death, onset of lung disorders, heart disease, stroke, and cancer showed dose-dependent effects of smoking for both sexes. Among heavy smokers (>28 pack-years) women had higher risk of earlier age of death (HR = 1.3, 95%CI:1.03-1.65) and stroke (HR = 1.37, 95%CI:1.02-1.83). Risk of cancer and heart disease did not differ by sex for smokers. Women had earlier age of onset for lung disorders (HR = 2.83, 95%CI:1.74-4.6), but men risk due to smoking were higher (Smoking-Sex interaction P<0.02) than women. Passive smoke exposure increased risk of earlier heart disease (HR = 1.33, 95%CI:1.07-1.65) and stroke (HR:1.54, 95%CI:1.07-2.22) for non-smokers, mainly in men. Smoking cessation after 15 years partially attenuated the deleterious smoking effects for all health outcomes. In sum, our results suggest that women are more vulnerable to ever smoking for earlier death and risk of stroke, but less vulnerable for lung disorders. From an epidemiological perspective, sex differences in smoking effects are important considerations that could underlie sex differences in health outcomes. These findings also encourage future mechanistic experiments to resolve potential mechanisms of sex-specific cigarette smoke toxicity. VL - 15 SN - 1932-6203 UR - https://pubmed.ncbi.nlm.nih.gov/32497122 IS - 6 U1 - 32497122[pmid] U4 - PONE-D-20-03538[PII] JO - PLoS One ER - TY - JOUR T1 - Racial and educational disparities in cognitive life expectancies. JF - The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences Y1 - 2020 A1 - Mateo P Farina A1 - Mark D Hayward A1 - Eileen M. Crimmins A1 - Jung K Kim KW - Cognition & Reasoning KW - Mortality KW - Racial/ethnic differences AB -

OBJECTIVES: We estimate life expectancy with and without dementia for Americans 65 years and older by education and race to examine how these stratification systems combine to shape disparities in later-life cognitive health.

METHOD: Based on the Health and Retirement Study (2000-2014), we use a multivariate, incidence-based life table approach to estimate life expectancy by cognitive health status for race-education groups. The models also simulate group differences in the prevalence of dementia implied by these rates.

RESULTS: The life table results document notable race-education differences in dementia and dementia-free life expectancy, as well as stark differences in implied dementia prevalence. At each education level, blacks can expect to live more years with dementia and they have significantly higher rates of dementia prevalence. This distribution of disparities in the older population is anchored by two groups -- blacks without a high school diploma and whites with some college or more.

DISCUSSION: Dementia experience and dementia burden differ dramatically along race-education lines. Race and education combine to exaggerate disparities and they both have enduring effects. Future research should explicitly consider how race and education combine to influence dementia in the older American population.

VL - 75 IS - 7 ER - TY - RPRT T1 - Documentation of Blood-Based Biomarkers in the 2014 Health and Retirement Study Y1 - 2017 A1 - Eileen M. Crimmins A1 - Jessica Faul A1 - Jung K Kim A1 - David R Weir PB - Survey Research Center, Institute for Social Research, University of Michigan CY - Ann Arbor, MI ER - TY - RPRT T1 - Documentation of Biomarkers in the 2010 and 2012 Health and Retirement Study Y1 - 2015 A1 - Eileen M. Crimmins A1 - Jessica Faul A1 - Jung K Kim A1 - David R Weir KW - Biomarkers KW - Meta-analyses KW - Survey Methodology PB - Survey Research Center, University of Michigan CY - Ann Arbor, Michigan ER - TY - JOUR T1 - Validation of blood-based assays using dried blood spots for use in large population studies. JF - Biodemography Soc Biol Y1 - 2014 A1 - Eileen M. Crimmins A1 - Jung K Kim A1 - Heather McCreath A1 - Jessica Faul A1 - David R Weir A1 - Teresa Seeman KW - Biomarkers KW - C-reactive protein KW - Cholesterol KW - Cholesterol, HDL KW - Cystatin C KW - Dried Blood Spot Testing KW - Glycated Hemoglobin A KW - Humans KW - Middle Aged KW - Reference Values KW - Reproducibility of Results AB -

Assessment of health in large population studies has increasingly incorporated measures of blood-based biomarkers based on the use of dried blood spots (DBS). The validity of DBS assessments made by labs used by large studies is addressed by comparing assay values from DBS collected using conditions similar to those used in the field with values from whole blood samples. The DBS approach generates values that are strongly related to whole blood levels of HbA1c, cystatin C, and C-reactive protein. Assessing lipid levels reliably with DBS appears to be a greater challenge. However, even when DBS values and values from venous blood are highly correlated, they are often on a different scale, and using conventional cutoffs may be misleading.

VL - 60 UR - http://www.tandfonline.com/doi/abs/10.1080/19485565.2014.901885 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24784986?dopt=Abstract JO - Biodemography and Social Biology ER - TY - RPRT T1 - Documentation of Biomarkers in the 2006 and 2008 Health and Retirement Study Y1 - 2013 A1 - Eileen M. Crimmins A1 - Jessica Faul A1 - Jung K Kim A1 - Heidi M Guyer A1 - Kenneth M. Langa A1 - Mary Beth Ofstedal A1 - Amanda Sonnega A1 - Robert B Wallace A1 - David R Weir KW - Health Conditions and Status KW - Healthcare KW - Methodology AB - Biomarkers refer to the general range of physiological, metabolic, biochemical, endocrine and genetic measures that can be obtained in living organisms. The term is most commonly used to refer to one-time biochemical or hematological measures made on blood or other available bodily fluids, but perhaps the term should be used for a broader range of measures. In 2006 and 2008, HRS included the following biomarkers measurements, administered in this order: Saliva collection for DNA extraction; Blood spot collection for cholesterol, hemoglobin A1C, CRP and cystatin C analysis (results for C-reactive protein and cystatin C are forthcoming). This report describes the following for each of the measures listed above: Rationale and key citations; Sample description; Measure description; Equipment; Protocol description; Special instructions. PB - Institute for Social Research, University of Michigan CY - Ann Arbor, Michigan U4 - Biomarker data/survey Methods/health measures ER -