Abstract Growing evidence has linked inflammatory processes to cognitive decline and dementia. This work examines whether an epigenetic marker of C-reactive protein (CRP), a common clinical ...inflammatory biomarker, may mediate the relationship between educational attainment and cognition. We first evaluated whether 53 previously reported CRP-associated DNA methylation sites (CpGs) are associated with CRP, both individually and aggregated into a methylation risk score (MRSCRP), in 3 298 participants from the Health and Retirement Study (HRS, mean age = 69.7 years). Forty-nine CpGs (92%) were associated with the natural logarithm of CRP in HRS after adjusting for age, sex, smoking, BMI, genetic ancestry, and white blood cell counts (p < .05), and each standard deviation increase in MRSCRP was associated with a 0.38 unit increase in lnCRP (p = 4.02E-99). In cross-sectional analysis, for each standard deviation increase in MRSCRP, total memory score and total cognitive score decreased, on average, by 0.28 words and 0.43 items, respectively (p < .001). Further, MRSCRP mediated 6.9% of the relationship between high school education and total memory score in a model adjusting for age, sex, and genetic ancestry (p < .05); this was attenuated to 2.4% with additional adjustment for marital status, APOE ε4 status, health behaviors, and comorbidities (p < .05). Thus, CRP-associated methylation may partially mediate the relationship between education and cognition at older ages. Further research is warranted to determine whether DNA methylation at these sites may improve current prediction models for cognitive impairment in older adults.
Later life cognitive function is influenced by genetics as well as early- and later-life socioeconomic context. However, few studies have examined the interaction between genetics and early childhood ...factors. Using gene-based tests (iSKAT/iSKAT-O), we examined whether common and/or rare exonic variants in 39 gene regions previously associated with cognitive performance, dementia, and related traits had an interaction with childhood socioeconomic context (parental education and financial strain) on memory performance or decline in European ancestry (EA, N=10,468) and African ancestry (AA, N=2,252) participants from the Health and Retirement Study. Of the 39 genes, 22 in EA and 19 in AA had nominally significant interactions with at least one childhood socioeconomic measure on memory performance and/or decline; however, all but one (father's education by SLC24A4 in AA) were not significant after multiple testing correction (FDR <0.05). In trans-ethnic meta-analysis, two genes interacted with childhood socioeconomic context (FDR <0.05): mother's education by MS4A4A on memory performance, and father's education by SLC24A4 on memory decline. Both interactions remained significant (p<0.05) after adjusting for respondent's own educational attainment, APOE ε4 status, lifestyle factors, BMI, and comorbidities. For both interactions in EA and AA, the genetic effect was stronger in participants with low parental education. Examination of common and rare variants in genes discovered through GWAS shows that childhood context may interact with key gene regions to jointly impact later life memory function and decline. Genetic effects may be more salient for those with lower childhood socioeconomic status.
Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels ...may help guide early prevention and treatment efforts for dyslipidemia.
We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids.
After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7 mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment.
Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages.
OBJECTIVES
To examine racial and ethnic differences in knowledge about oneʼs dementia status.
DESIGN
Prospective cohort study.
SETTING
The 2000 to 2014 Health and Retirement Study.
PARTICIPANTS
Our ...sample included 8,686 person‐wave observations representing 4,065 unique survey participants, aged 70 years or older, with dementia, as identified by a well‐validated statistical prediction model based on individual demographic and clinical characteristics.
MEASUREMENTS
Primary outcome measure was knowledge of oneʼs dementia status, as reported in the survey. Patient characteristics included race/ethnicity, age, sex, survey year, cognition, function, comorbidity, and whether living in a nursing home.
RESULTS
Among subjects identified as having dementia by the prediction model, 43.5% to 50.2%, depending on the survey year, reported that they were informed of the dementia status by their physician. This proportion was lower among Hispanics (25.9%‐42.2%) and non‐Hispanic blacks (31.4%‐50.5%) than among non‐Hispanic whites (47.7%‐52.9%). Our fully adjusted regression model indicated lower dementia awareness among non‐Hispanic blacks (odds ratio OR = 0.74; 95% confidence interval CI = 0.58‐0.94) and Hispanics (OR = 0.60; 95% CI = 0.43‐0.85), compared to non‐Hispanic whites. Having more instrumental activity of daily living limitations (OR = 1.65; 95% CI = 1.56‐1.75) and living in a nursing home (OR = 2.78; 95% CI = 2.32‐3.32) were associated with increased odds of subjects reporting being told about dementia by a physician.
CONCLUSION
Less than half of individuals with dementia reported being told by a physician about the condition. A higher proportion of non‐Hispanic blacks and Hispanics with dementia may be unaware of their condition, despite higher dementia prevalence in these groups, compared to non‐Hispanic whites. Dementia outreach programs should target diverse communities with disproportionately high disease prevalence and low awareness. J Am Geriatr Soc 68:1763‐1770, 2020.
Background
Research on racial and ethnic disparities in costs of care during the course of dementia is sparse. We analyzed Medicare expenditures for beneficiaries with dementia to identify when ...during the course of care costs are the highest and whether they differ by race and ethnicity.
Methods
We analyzed data from the 2000–2016 Health and Retirement Study (HRS) linked with corresponding Medicare claims to estimate total Medicare expenditures for four phases: (1) the year before a dementia diagnosis, (2) the first year following a dementia diagnosis, (3) ongoing care for dementia after the first year, and (4) the last year of life. We estimated each patient's phase‐specific and disease course Medicare expenditures by using a race‐specific survival model and monthly expenditures adjusted for patient characteristics. We investigated healthcare utilization by service type across races/ethnicities and phases of care.
Results
Adjusted mean total Medicare expenditures for non‐Hispanic (NH) Black ($165,730) and Hispanic beneficiaries with dementia ($160,442) exceeded corresponding expenditures for NH Whites ($136,326). In the year preceding and immediately following initial dementia diagnosis, mean Medicare expenditures for NH Blacks ($26,337 and $20,429) exceeded expenditures for Hispanics and NH Whites ($21,399–23,176 and 17,182–18,244). The last year of life was responsible for the greatest cost contribution: $51,294 (NH Blacks), $47,469 (Hispanics), and $39,499 (NH Whites). These differences were driven by greater use of high‐cost services (e.g., emergency department, inpatient and intensive care), especially during the last year of life.
Conclusions
NH Black and Hispanic beneficiaries with dementia had higher disease course Medicare expenditures than NH Whites. Expenditures were highest for NH Black beneficiaries in every phase of care. Further research should address mechanisms of such disparities and identify methods to improve communication, shared decision‐making, and access to appropriate services for all populations.
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.
Despite evidence suggesting race and ethnicity are important factors in responses to environmental exposures, drug therapies, and disease risk, few studies focus on the health needs of racially- and ...ethnically-diverse aging adults.The objective of this study was to determine the burden of 10 health conditions across race and ethnicity for a nationally-representative sample of aging Americans.Data from the 1998 to 2014 waves of the Health and Retirement Study, an ongoing longitudinal-panel study, were analyzed.Those aged over 50 years who identified as Black, Hispanic, or White were included. There were 5510 Blacks, 3423 Hispanics, and 21,168 Whites in the study.At each wave, participants reported if they had cancer, chronic obstructive pulmonary disease, congestive heart failure, diabetes, back pain, hypertension, a fractured hip, myocardial infarction, rheumatism or arthritis, and a stroke. Disability-adjusted life years (DALYs) were calculated for each health condition by race and ethnicity. Ranked DALYs determined how race and ethnicity was differentially impacted by the burden of each health condition. Sample weights were utilized to make DALY estimates nationally-representative.Weighted DALY estimates (in thousands) ranged from 1405 to 55,631 for Blacks, 931 to 28,442 for Hispanics, and 15,313 to 295,623 for Whites. Although the health conditions affected each race and ethnicity differently, hypertension had the largest number of DALYs, and hip fractures had the fewest across race and ethnicity. In total, there were an estimated 198,621, 101,462, and 1,187,725 DALYs for older Black, Hispanic, and White aging adults.Our findings indicate that race and ethnicity may be influential on health and disease for aging adults in the United States. Monitoring DALYs may help guide the flow of health-related expenditures, improve the impact of health interventions, advance inclusive health care for diverse aging adult populations, and prepare healthcare providers for serving the health needs of aging adults.
High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several ...small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10−8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.
Chronic, low-level systemic inflammation associated with aging, or inflammaging, is a risk factor for several chronic diseases and mortality. Using data from the Health and Retirement Study, we ...generated a continuous latent variable for systemic inflammation from seven measured indicators of inflammation and examined associations with another biomarker of biological aging, DNA methylation age acceleration measured by epigenetic clocks, and 4-year mortality (
N
= 3,113). We found that greater systemic inflammation was positively associated with DNA methylation age acceleration for 10 of the 13 epigenetic clocks, after adjustment for sociodemographics and chronic disease risk factors. The latent variable for systemic inflammation was associated with 4-year mortality independent of DNA methylation age acceleration and was a better predictor of 4-year mortality than any of the epigenetic clocks examined, as well as mortality risk factors, including obesity and multimorbidity. Inflammaging and DNA methylation age acceleration may represent different biological processes contributing to mortality risk. Leveraging multiple measured inflammation markers to capture inflammaging is important for biology of aging research.
Background
We examined racial and ethnic differences in medication use for a representative US population of patients with Alzheimer's disease and related dementias (ADRD).
Methods
We examined ...cholinesterase inhibitors and memantine initiation, non‐adherence, and discontinuation by race and ethnicity, using data from the 2000–2016 Health and Retirement Study linked with Medicare and Medicaid claims.
Results
Among newly diagnosed ADRD patients (n = 1299), 26% filled an ADRD prescription ≤90 days and 36% ≤365 days after diagnosis. Among individuals initiating ADRD‐targeted treatment (n = 1343), 44% were non‐adherent and 24% discontinued the medication during the year after treatment initiation. Non‐Hispanic Blacks were more likely than Whites to not adhere to ADRD medication therapy (odds ratio: 1.50 95% confidence interval: 1.07–2.09).
Discussion
Initiation of ADRD‐targeted medications did not vary by ethnoracial group, but non‐Hispanic Blacks had lower adherence than Whites. ADRD medication non‐adherence and discontinuation were substantial and may relate to cost and access to care.
HIGHLIGHTS
Initiation of anti‐dementia medications among newly diagnosed Alzheimer's disease and related dementias (ADRD) patients was low in all ethnoracial groups.
ADRD medication non‐adherence and discontinuation were substantial and may relate to cost and access to care.
Compared to Whites, Blacks and Hispanics had lower use, poorer treatment adherence, and more frequent discontinuation of ADRD medication, but when controlling for disease severity and socioeconomic factors, racial disparities diminish.
Our findings demonstrate the importance of adjusting for socioeconomic characteristics and disease severity when studying medication use and adherence in ADRD patients.
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