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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: Using gene-based tests (interaction sequence kernel association test [iSKAT]/iSKAT optimal unified test), 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.Results: 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 solute carrier family 24 member 4 [SLC24A4] in AA) were not significant after multiple testing correction (false discovery rate [FDR] < .05). In trans-ethnic meta-analysis, 2 genes interacted with childhood socioeconomic context (FDR < .05): mother's education by membrane-spanning 4-domains A4A (MS4A4A) on memory performance, and father's education by SLC24A4 on memory decline. Both interactions remained significant (p < .05) after adjusting for respondent's own educational attainment, apolipoprotein-ε4 allele (APOE ε4) status, lifestyle factors, body mass index, and comorbidities. For both interactions in EA and AA, the genetic effect was stronger in participants with low parental education.Conclusions: Examination of common and rare variants in genes discovered through genome-wide association studies 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. [ABSTRACT FROM AUTHOR]

Though T-cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T-cell subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the United States. 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 participants, a nationally representative study of adults older than 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 US adults older than 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. [ABSTRACT FROM AUTHOR]

Objectives This study aims to examine the relationship between childhood socioeconomic position (SEP) and cognitive function in later life within nationally representative samples of older adults in the United States and England, investigate whether these effects are mediated by later-life SEP, and determine whether social mobility from childhood to adulthood affects cognitive function and decline. Method Using data from the Health and Retirement Study (HRS) and the English Longitudinal Survey of Ageing (ELSA), we examined the relationships between measures of SEP, cognitive performance and decline using individual growth curve models. Results High childhood SEP was associated with higher cognitive performance at baseline in both cohorts and did not affect the rate of decline. This benefit dissipated after adjusting for education and adult wealth in the United States. Respondents with low childhood SEP, above median education, and high adult SEP had better cognitive performance at baseline than respondents with a similar childhood background and less upward mobility in both countries. Discussion These findings emphasize the impact of childhood SEP on cognitive trajectories among older adults. Upward mobility may partially compensate for disadvantage early in life but does not protect against cognitive decline. [ABSTRACT FROM AUTHOR]

Background Biobanks typically rely on volunteer-based sampling. This results in large samples (power) at the cost of representativeness (bias). The problem of volunteer bias is debated. Here, we (i) show that volunteering biases associations in UK Biobank (UKB) and (ii) estimate inverse probability (IP) weights that correct for volunteer bias in UKB. Methods Drawing on UK Census data, we constructed a subsample representative of UKB's target population, which consists of all individuals invited to participate. Based on demographic variables shared between the UK Census and UKB, we estimated IP weights (IPWs) for each UKB participant. We compared 21 weighted and unweighted bivariate associations between these demographic variables to assess volunteer bias. Results Volunteer bias in all associations, as naively estimated in UKB, was substantial—in some cases so severe that unweighted estimates had the opposite sign of the association in the target population. For example, older individuals in UKB reported being in better health, in contrast to evidence from the UK Census. Using IPWs in weighted regressions reduced 87% of volunteer bias on average. Volunteer-based sampling reduced the effective sample size of UKB substantially, to 32% of its original size. Conclusions Estimates from large-scale biobanks may be misleading due to volunteer bias. We recommend IP weighting to correct for such bias. To aid in the construction of the next generation of biobanks, we provide suggestions on how to best ensure representativeness in a volunteer-based design. For UKB, IPWs have been made available. [ABSTRACT FROM AUTHOR]

Telomere length (TL) is a widely used marker of biological aging and is associated with an increased risk of morbidity and mortality. Recently, there has been evidence for an association between TL and socioeconomic status (SES), particularly for measures of education and childhood SES. Individual differences in TL are also influenced by genetic factors, with heritability estimates from twin and sibling studies ranging from 34 to 82 percent. Yet the additive heritability of TL as a result ofmeasuredgenetic variations and the extent to which heritability is modified by SES is still unknown. Data from the Health and Retirement Study, a nationally representative cohort of older adults (mean age 69 years), were used to provide the first estimates of molecular-based heritability of TL using genome-wide complex trait analysis (GCTA). We found that additive genetic variance contributed 28 percent (p = .012) of total phenotypic variance of TL in the European American sample (n = 3,290). Estimation using the GCTA and KING Robust relationship inference methods did not differ significantly in this sample. None of the variance from the gene-by-SES interactions examined contributed significantly to the total TL variance. Estimation of heritability and genetic interaction with SES in the African American sample (n = 442) was too unstable to provide reliable estimates. [ABSTRACT FROM AUTHOR]

The Health and Retirement Study (HRS) is a nationally representative longitudinal survey of more than 37 000 individuals over age 50 in 23 000 households in the USA. The survey, which has been fielded every 2 years since 1992, was established to provide a national resource for data on the changing health and economic circumstances associated with ageing at both individual and population levels. Its multidisciplinary approach is focused on four broad topics—income and wealth; health, cognition and use of healthcare services; work and retirement; and family connections. HRS data are also linked at the individual level to administrative records from Social Security and Medicare, Veteran’s Administration, the National Death Index and employer-provided pension plan information. Since 2006, data collection has expanded to include biomarkers and genetics as well as much greater depth in psychology and social context. This blend of economic, health and psychosocial information provides unprecedented potential to study increasingly complex questions about ageing and retirement. The HRS has been a leading force for rapid release of data while simultaneously protecting the confidentiality of respondents. Three categories of data—public, sensitive and restricted—can be accessed through procedures described on the HRS website (hrsonline.isr.umich.edu). [ABSTRACT FROM PUBLISHER]

The article reports on the study conducted to determine if there were racial and ethnic disparities in glycemic control among middle-aged and older Americans with diabetes mellitus. The study was carried on one thousand two hundred thirty-three Americans who completed the survey on hemoglobin A1c (HbA1c). The result of a survey was associated in the clinical factors, access to and quality of diabetes health care, as well as self-management behaviors and attitudes of the respondents. The result shows there were no racial or ethnic differences in HbA1c levels in respondents not taking antihyperglycemic medications. There were worse glycemic control among Latino and African Americans than white Americans because of racial disparities on medication support.

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Polygenic scores are a strategy to aggregate the small, additive effects of single nucleotide polymorphisms across the genome. With phenotypes like Alzheimer's disease, which have a strong and well-established genomic locus (APOE), the cumulative effect of genetic variants outside of this area has not been well established in a population-representative sample. Methods: Here we examine the association between polygenic scores for Alzheimer's disease both with and without the APOE region (chr19: 45,384,477 to 45,432,606, build 37/hg 19) at different P value thresholds and dementia. We also investigate the addition of APOE-ε4 carrier status and its effect on the polygenic score—dementia association in the Health and Retirement Study using generalized linear models accounting for repeated measures by individual and use a binomial distribution, logit link, and unstructured correlation structure. Results: In a large sample of European ancestry participants of the Health and Retirement Study (n = 9872) with an average of 5.2 (standard deviation 1.8) visit spaced two years apart, we found that including the APOE region through weighted variants in a polygenic score was insufficient to capture the large amount of risk attributed to this region. We also found that a polygenic score with a P value threshold of 0.01 had the strongest association with the odds of dementia in this sample (odds ratio = 1.10 95%CI 1.0 to 1.2). Conclusion: We recommend removing the APOE region from polygenic score calculation and treating the APOE locus as an independent covariate when modeling dementia. We also recommend using a moderately conservative P value threshold (e.g. 0.01) when creating polygenic scores for Alzheimer's disease on dementia. These recommendations may help elucidate relationships between polygenic scores and regions of strong significance for phenotypes similar to Alzheimer's disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Older adults with dementia including Alzheimer's disease may have difficulty communicating their treatment preferences and thus may receive intensive end-of-life (EOL) care that confers limited benefits. Objective: This study compared the use of life-sustaining interventions during the last 90 days of life among Medicare beneficiaries with and without dementia. Methods: This cohort study utilized population-based national survey data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. Our sample included Medicare fee-for-service beneficiaries aged 65 years or older deceased between 2000 and 2016. The main outcome was receipt of any life-sustaining interventions during the last 90 days of life, including mechanical ventilation, tracheostomy, tube feeding, and cardiopulmonary resuscitation. We used logistic regression, stratified by nursing home use, to examine dementia status (no dementia, non-advanced dementia, advanced dementia) and patient characteristics associated with receiving those interventions. Results: Community dwellers with dementia were more likely than those without dementia to receive life-sustaining treatments in their last 90 days of life (advanced dementia: OR = 1.83 [1.42–2.35]; non-advanced dementia: OR = 1.16 [1.01–1.32]). Advance care planning was associated with lower odds of receiving life-sustaining treatments in the community (OR = 0.84 [0.74–0.96]) and in nursing homes (OR = 0.68 [0.53–0.86]). More beneficiaries with advanced dementia received interventions discordant with their EOL treatment preferences. Conclusions: Community dwellers with advanced dementia were more likely to receive life-sustaining treatments at the end of life and such treatments may be discordant with their EOL wishes. Enhancing advance care planning and patient-physician communication may improve EOL care quality for persons with dementia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Sample collection and preanalytical protocols may significantly impact the results of large-scale epidemiological studies incorporating blood-based biomarkers of neuropathology. Objective: To evaluate the stability and assay variability of several blood-based biomarkers of neuropathology for common preanalytical conditions. Methods: We collected serum and plasma samples from 41 participants and evaluated the effect of processing delay of up to 72 h when stored at 4∘C, three freeze-thaw cycles, and a combination of 48-h processing delay when stored at 4∘C and three freeze-thaw cycles on biomarker stability. Using the Simoa assay (Quanterix Inc.), we measured amyloid-β 40 (Aβ40), amyloid-β 42 (Aβ42), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (p-tau-181). Results: We found that Aβ40 and Aβ42 levels significantly decreased after a 24-h processing delay in both plasma and serum samples, and a single freeze-thaw cycle (p < 0.0001). Nevertheless, serum Aβ42/40 ratio remained stable with a processing delay up to 48 h while plasma Aβ42/40 ratio showed only small but significant increase with a delay up to 72 h. Both plasma and serum GFAP and NfL levels were only modestly affected by processing delay and freeze-thaw cycles. Plasma p-tau-181 levels notably increased with a 24-, 48-, and 72-h processing delay, but remained stable in serum. Intra-individual variation over two weeks was minimal for all biomarkers and their levels were substantially lower in serum when compared with plasma. Conclusion: These results suggest that standardizing preanalytical variables will allow robust measurements of biomarkers of neuropathology in population studies. [ABSTRACT FROM AUTHOR]

Objectives Measuring cognition in an aging populabtion is a public health priority. A move towards survey measurement via the web (as opposed to phone or in-person) is cost-effective but challenging as it may induce bias in cognitive measures. We examine this possibility using an experiment embedded in the 2018 wave of data collection for the U.S. Health and Retirement Study (HRS). Methods We utilize techniques from multiple group item response theory to assess the effect of survey mode on performance on the HRS cognitive measure. We also study the problem of attrition by attempting to predict dropout and via approaches meant to minimize bias in subsequent inferences due to attrition. Results We find evidence of an increase in scores for HRS respondents who are randomly assigned to the web-based mode of data collection in 2018. Web-based respondents score higher in 2018 than experimentally matched phone-based respondents, and they show much larger gains relative to 2016 performance and subsequently larger declines in 2020. The differential in favor of web-based responding is observed across all items, but is most pronounced for the Serial 7 task and numeracy items. Due to the relative ease of the web-based mode, we suggest a cutscore of 12 being used to indicate CIND (cognitively impaired but not demented) status when using the web-based version rather than 11. Discussion The difference in mode may be nonignorable for many uses of the HRS cognitive measure. In particular, it may require reconsideration of some cutscore-based approaches to identify impairment. [ABSTRACT FROM AUTHOR]

Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.e., p < 4.7 × 10−7), including two common SNPs in ABO that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare in European Caucasians (MAF < 0.1%) and the associations were driven by African American samples. There was no evidence for replication of these associations in either TOPMed Stroke samples (n = 5613 cases) or UK Biobank (n = 5874 stroke cases), although power to replicate was very low given the low allele frequencies of the associated variants and a shortage of samples from diverse ancestries. Our study highlights the need for acquiring large, well-powered diverse cohorts to study rare variants, and the technical challenges using array-based genotyping technologies for rare variant genotyping. [ABSTRACT FROM AUTHOR]

The epigenome likely interacts with traditional and genetic risk factors to influence blood pressure. We evaluated whether 13 previously reported DNA methylation sites (CpGs) are associated with systolic (SBP) or diastolic (DBP) blood pressure, both individually and aggregated into methylation risk scores (MRS), in 3070 participants (including 437 African ancestry (AA) and 2021 European ancestry (EA), mean age = 70.5 years) from the Health and Retirement Study. Nine CpGs were at least nominally associated with SBP and/or DBP after adjusting for traditional hypertension risk factors (p < 0.05). MRSSBP was positively associated with SBP in the full sample (β = 1.7 mmHg per 1 standard deviation in MRSSBP; p = 2.7 × 10−5) and in EA (β = 1.6; p = 0.001), and MRSDBP with DBP in the full sample (β = 1.1; p = 1.8 × 10−6), EA (β = 1.1; p = 7.2 × 10−5), and AA (β = 1.4; p = 0.03). The MRS and BP-genetic risk scores were independently associated with blood pressure in EA. The effects of both MRSs were weaker with increased age (pinteraction < 0.01), and the effect of MRSDBP was higher among individuals with at least some college education (pinteraction = 0.02). In AA, increasing MRSSBP was associated with higher SBP in females only (pinteraction = 0.01). Our work shows that MRS is a potential biomarker of blood pressure that may be modified by traditional hypertension risk factors. [ABSTRACT FROM AUTHOR]

Background: Cellular changes in adaptive immune system accompany the process of aging and contribute to an aging-related immune phenotype (ARIP) characterized by decrease in naïve T-cells (TN) and increase in memory T-cells (TM). A population-representative marker of ARIP and its associations with biological aging and age-related chronic conditions have not been studied previously. Methods: We developed two ARIP indicators based on well understood age-related changes in T cell distribution: TN/(TCM (Central Memory) + TEM (Effector Memory) + TEFF (Effector)) (referred as TN/TM) in CD4 + and CD8 + T-cells. We compared them with existing ARIP measures including CD4/CD8 ratio and CD8 + TN cells by evaluating associations with chronological age and the Klemera Doubal measure of biological age (measured in years) using linear regression, multimorbidity using multinomial logistic regression and two-year mortality using logistic regression. Results: CD8 + TN and CD8 + TN/TM had the strongest inverse association with chronological age (beta estimates: -3.41 and -3.61 respectively; p-value < 0.0001) after adjustment for sex, race/ethnicity and CMV status. CD4 + TN/TM and CD4 + TN had the strongest inverse association with biological age (β = -0.23; p = 0.003 and β = -0.24; p = 0.004 respectively) after adjustment for age, sex, race/ethnicity and CMV serostatus. CD4/CD8 ratio was not associated with chronological age or biological age. CD4 + TN/TM and CD4 + TN was inversely associated with multimorbidity. For CD4 + TN/TM, people with 2 chronic conditions had an odds ratio of for 0.74 (95%CI: 0.63–0.86 p = 0.0003) compared to those without any chronic conditions while those with 3 chronic conditions had an odds ratio of 0.75 (95% CI: 0.63–0.90; p = 0.003) after adjustment for age, sex, race/ethnicity, CMV serostatus, smoking, and BMI. The results for the CD4 + TN subset were very similar to the associations seen with the CD4 + TN/TM. CD4 + TN/TM and CD4 + TN were both associated with two-year mortality (OR = 0.80 (95% CI: 0.67–0.95; p = 0.01) and 0.81 (0.70–0.94; p = 0.01), respectively). Conclusion: CD4 + TN/TM and CD4 + TN had a stronger association with biological age, age-related morbidity and mortality compared to other ARIP measures. Future longitudinal studies are needed to evaluate the utility of the CD4 + subsets in predicting the risk of aging-related outcomes. [ABSTRACT FROM AUTHOR]

Many statistical methods have been developed that treat within-subject correlation that accompanies the clustering of subjects in longitudinal data settings as a nuisance parameter, with the focus of analytic interest being on mean outcome or profiles over time. However, there is evidence that in certain settings, underlying variability in subject measures may also be important in predicting future health outcomes of interest. Here, we develop a method for combining information from mean profiles and residual variance to assess associations with categorical outcomes in a joint modeling framework. We consider an application to relating word recall measures obtained over time to dementia onset from the Health and Retirement Survey. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: This project evaluated if by focusing on process changes and tool use rather than key indicator rates, the use of evidence-based therapies in patients with acute myocardial infarction (AMI) would increase.Background: The use of tools designed to improve quality of care in the American College of Cardiology AMI Guidelines Applied in Practice Pilot Project resulted in improved adherence to evidence-based therapies for patients, but overall, tool use was modest.Methods: The current project, implemented in five hospitals, was modeled after the previous project, but with greater emphasis on tool use. This allowed early identification of barriers to tool use and strategies to overcome barriers. Main outcome measures were AMI quality indicators in pre-measurement (January 1, 2001 to June 30, 2001) and post-measurement (December 15, 2001 to March 31, 2002) samples.Results: One or more tools were used in 93% of patients (standard orders = 82%, and discharge document = 47%). Tool use was associated with significantly higher adherence to most discharge quality indicator rates with increases in aspirin, angiotensin-converting enzyme inhibitors, and smoking cessation and dietary counseling. Patients undergoing coronary artery bypass grafting (CABG) had low rates of discharge indicators. Patients undergoing percutaneous coronary revascularization were more likely to receive evidence-based therapies.Conclusions: These data validate the results of the pilot project that quality of AMI care can be improved through the use of guideline-based tools. Identifying and overcoming barriers to tool use led to substantially higher rates of tool use. The low rates of adherence to quality indicators in patients undergoing CABG suggest that these patients should be particularly targeted for quality improvement efforts. [Copyright &y& Elsevier]

Background Many DNA methylation-based indicators have been developed as summary measures of epigenetic aging. We examine the associations between 13 epigenetic clocks, including 4 second generation clocks, as well as the links of the clocks to social, demographic, and behavioral factors known to be related to health outcomes: sex, race/ethnicity, socioeconomic status, obesity, and lifetime smoking pack-years. Methods The Health and Retirement Study is the data source which is a nationally representative sample of Americans over age 50. Assessment of DNA methylation was based on the EPIC chip and epigenetic clocks were developed based on existing literature. Results The clocks vary in the strength of their relationships with age, with each other and with independent variables. Second generation clocks trained on health-related characteristics tend to relate more strongly to the sociodemographic and health behaviors known to be associated with health outcomes in this age group. Conclusions Users of this publicly available data set should be aware that epigenetic clocks vary in their relationships to age and to variables known to be related to the process of health change with age. [ABSTRACT FROM AUTHOR]

Background: Many DNA methylation-based indicators have been developed as summary measures of epigenetic aging. We examine the associations between 13 epigenetic clocks, including 4 second generation clocks, as well as the links of the clocks to social, demographic, and behavioral factors known to be related to health outcomes: sex, race/ethnicity, socioeconomic status, obesity, and lifetime smoking pack-years.Methods: The Health and Retirement Study is the data source which is a nationally representative sample of Americans over age 50. Assessment of DNA methylation was based on the EPIC chip and epigenetic clocks were developed based on existing literature.Results: The clocks vary in the strength of their relationships with age, with each other and with independent variables. Second generation clocks trained on health-related characteristics tend to relate more strongly to the sociodemographic and health behaviors known to be associated with health outcomes in this age group.Conclusions: Users of this publicly available data set should be aware that epigenetic clocks vary in their relationships to age and to variables known to be related to the process of health change with age. [ABSTRACT FROM AUTHOR]

In vivo antithrombotic efficacy of GPIIb/IIIa receptor antagonists (m7E3, MK-383 and DMP-728) was studied with respect to their ex vivo platelet inhibition in heparinized platelet-rich plasma (hPRP) and citrated platelet-rich plasma (cPRP) using a canine model of carotid artery thrombosis. For each drug group (n = 6), the right carotid artery was used as control vessel and resulting occlusive thrombus was kept in situ to examine the direct thrombolytic efficacy of the antagonists. Thirty minutes after occlusion of control vessel, a low or high dose of each antagonist was administered and the left carotid artery was used as test vessel. All control vessels occluded within 86–96 min in response to electrolytic injury. The incidence of occlusion with lower doses of m7E3, DMP-728, and MK-383 was 100, 33 and 100%, respectively; corresponding times to occlusion were 174, 220 and 118 min. Lower doses inhibited ADP- or AA-induced platelet aggregation in cPRP (>80%). Incidence of occlusion with high doses of m7E3, DMP-728 and MK-383 was 33, 0 and 0%, respectively; corresponding times to occlusion were 209, >240 and >240 min. Higher doses inhibited aggregation in cPRP (>80%), but only partially in hPRP (45–66%). Dose-dependent prolongation of bleeding time occurred with all antagonists. None of the antagonists lyzed preformed thrombi in control vessels. The results indicate that ex vivo platelet aggregation conducted in hPRP, as opposed to conventional cPRP, provides a better assessment of the in vivo efficacy of GPIIb/IIIa receptor antagonists. [ABSTRACT FROM AUTHOR]

Background: In increasingly ageing populations, there is an emergent need to develop a robust prediction model for estimating an individual absolute risk for all-cause mortality, so that relevant assessments and interventions can be targeted appropriately. The objective of the study was to derive, evaluate and validate (internally and externally) a risk prediction model allowing rapid estimations of an absolute risk of all-cause mortality in the following 10 years.Methods: For the model development, data came from English Longitudinal Study of Ageing study, which comprised 9154 population-representative individuals aged 50-75 years, 1240 (13.5%) of whom died during the 10-year follow-up. Internal validation was carried out using Harrell's optimism-correction procedure; external validation was carried out using Health and Retirement Study (HRS), which is a nationally representative longitudinal survey of adults aged ≥50 years residing in the United States. Cox proportional hazards model with regularisation by the least absolute shrinkage and selection operator, where optimisation parameters were chosen based on repeated cross-validation, was employed for variable selection and model fitting. Measures of calibration, discrimination, sensitivity and specificity were determined in the development and validation cohorts.Results: The model selected 13 prognostic factors of all-cause mortality encompassing information on demographic characteristics, health comorbidity, lifestyle and cognitive functioning. The internally validated model had good discriminatory ability (c-index=0.74), specificity (72.5%) and sensitivity (73.0%). Following external validation, the model's prediction accuracy remained within a clinically acceptable range (c-index=0.69, calibration slope β=0.80, specificity=71.5% and sensitivity=70.6%). The main limitation of our model is twofold: 1) it may not be applicable to nursing home and other institutional populations, and 2) it was developed and validated in the cohorts with predominately white ethnicity.Conclusions: A new prediction model that quantifies absolute risk of all-cause mortality in the following 10-years in the general population has been developed and externally validated. It has good prediction accuracy and is based on variables that are available in a variety of care and research settings. This model can facilitate identification of high risk for all-cause mortality older adults for further assessment or interventions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Traditional manual gating strategies are often time-intensive, place a high burden on the analyzer, and are susceptible to bias between analyzers. Several automated gating methods have shown to exceed performance of manual gating for a limited number of cell subsets. However, many of the automated algorithms still require significant manual interventions or have yet to demonstrate their utility in large datasets. Therefore, we developed an approach that utilizes a previously published automated algorithm (OpenCyto framework) with a manually created hierarchically cell gating template implemented, along with a custom developed visualization software (FlowAnnotator) to rapidly and efficiently analyze immunophenotyping data in large population studies. This approach allows pre-defining populations that can be analyzed solely by automated analysis and incorporating manual refinement for smaller downstream populations. We validated this method with traditional manual gating strategies for 24 subsets of T cells, B cells, NK cells, monocytes and dendritic cells in 931 participants from the Health and Retirement Study (HRS). Our results show a high degree of correlation (r ≥ 0.80) for 18 (78%) of the 24 cell subsets. For the remaining subsets, the correlation was low (<0.80) primarily because of the low numbers of events recorded in these subsets. The mean difference in the absolute counts between the hybrid method and manual gating strategy of these cell subsets showed results that were very similar to the traditional manual gating method. We describe a practical method for standardization of immunophenotyping methods in large scale population studies that provides a rapid, accurate and reproducible alternative to labor intensive manual gating strategies. [ABSTRACT FROM AUTHOR]

Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to assess how well physiological measures, including biomarkers and genetic indicators, predict receipt of Social Security Administration (SSA) disability benefits among U.S. adults aged 51 to 65 years. Method: We used data from the 2006 to 2012 waves of the Health and Retirement Study (HRS), linked to SSA administrative data. Using logistic regression, we predicted benefit receipt (either Social Security Disability Insurance or Supplemental Security Income) using 19 distinct physiological markers, adjusting for age, sex, race, and select medication use. We then calculated the propensity (i.e., predicted probability) that each HRS respondent received benefits and assessed how well propensity score–based classifications could identify beneficiaries and nonbeneficiaries. Results: Thirteen percent of respondents received benefits. Using the propensity score cut point that maximized the sum of sensitivity and specificity, the model correctly predicted 75.9% of beneficiaries and 73.5% of nonbeneficiaries. Discussion: Physiological measures have moderate power to predict SSA disability benefit receipt. [ABSTRACT FROM AUTHOR]

Abstract Variability induced by delayed cell processing and cell cryopreservation presents unique challenges for immunophenotyping in large population studies. We conducted a pilot study to evaluate the effect of delayed cell processing and cryopreservation on cell percentages obtained by immunophenotyping. We collected blood from 20 volunteers and compared the effect of (a) delayed cell processing up to 72 h (b) cryopreservation and (c) the combined effect of delayed cell processing and cryopreservation on immunophenotyping of 31 cell subsets that included several subsets of T, B, Natural Killer (NK) cells, monocytes and dendritic cells using both whole blood collected in EDTA tubes and peripheral blood mononuclear cells collected in CPT tubes. We found the delayed cell processing up to 72 h or cryopreservation alone did not significantly affect the percentages T cells, dendritic cells or monocytes but significantly increased the percentage of B cells and NK cells (p for trend ≤0.01) but. However combination of delayed cell processing up to 72 h and cryopreservation significantly increased the percentage of T cells as compared to cells processed immediately (p for trend <0.0001) while a delayed cell processing followed by cryopreservation decreased the percentage of NK cells (p for trend <0.0001). Total B-cells increased significantly with a 24–48 h delay in cell processing and cryopreservation but not at 72 h. The percentages of monocytes and dendritic cells remained unaffected by the combination of delayed cell processing and cryopreservation. These findings suggest that immunophenotyping of several immune cell subsets can be successfully implemented in large population studies as long as blood is processed within 48 h of biospecimen collection though some cell subsets may be more susceptible to a combination of delayed cell processing and cryopreservation. [ABSTRACT FROM AUTHOR]

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms.Methods: Using data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts.Results: No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 × 10(-8) ) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10(-7) ). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10(-7) ) and rs4542757 (intronic to DCC, P = 7.31 × 10(-7) ). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 × 10(-10) ; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample.Conclusions: Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities. [ABSTRACT FROM AUTHOR]

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been. [ABSTRACT FROM AUTHOR]

Background: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.Methods: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.Results: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).Conclusions: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain-behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective—population neuroscience—that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas. [ABSTRACT FROM AUTHOR]

The objective of this study was to use nationally-representative data on Americans greater than 50 years of age to determine the association between grip strength and inflammation as independent predictors of incident disability, chronic multimorbidity and dementia. Middle age and older adults (n = 12,618) from the 2006–2008 waves of the Health and Retirement Study with 8-years of follow-up were included. Longitudinal modeling was performed to examine the association between baseline grip strength (normalized to body mass: NGS) and high sensitivity C-reactive protein (hs-CRP) (≥3.0 mg/L) with incident physical disabilities (i.e., ≥2 limitations to activities of daily living), chronic multimorbidity (≥2 of chronic conditions), and dementia. The odds of incident disability were 1.25 (95% CI: 1.20–1.30) and 1.31 (95% CI: 1.26–1.36) for men and women respectively, for each 0.05-unit lower NGS. The odds of incident chronic multimorbidity were 1.14 (95% CI: 1.08–1.20) and 1.14 (95% CI: 1.07–1.21) for men and women respectively for each 0.05-unit lower NGS. The odds of incident dementia were 1.10 for men (95% CI: 1.02–1.20) for each 0.05-unit lower NGS, but there was no significant association for women. Elevated hs-CRP was only associated with chronic multimorbidity among men (OR = 1.29; 95% CI: 1.00–1.73) and women (OR = 1.60; 95% CI: 1.26–2.02). Our findings indicate a robust inverse association between NGS and disability and chronic, multimorbidity in older men and women, and dementia in men. Elevated hs-CRP was only associated with chronic multimorbidity in men and women. Healthcare providers should implement measures of grip strength in routine health assessments and discuss the potential dangers of weakness as well as interventions to improve strength with their patients. [ABSTRACT FROM AUTHOR]

The article investigates the relative benefits of the Guidelines Applied in Practice (GAP) program of the American College of Cardiology in men and women with acute myocardial infarction (AMI) in Michigan. In the post-GAP sample, the use of evidence-based care was higher. It includes the use of β-blockers and aspirin in men and women at hospital discharge and lipid-lowering agent use in men. Mortality rates at one year in patients with AMI may be decreased by the GAP discharge tool.

Context: Quality of care of patients with acute myocardial infarction (AMI) has received intense attention. However, it is unknown if a structured initiative for improving care of patients with AMI can be effectively implemented at a wide variety of hospitals. Objective: To measure the effects of a quality improvement project on adherence to evidence-based therapies for patients with AMI. Design and Setting: The Guidelines Applied in Practice (GAP) quality improvement project, which consisted of baseline measurement, implementation of improvement strategies, and remeasurement, in 10 acute-care hospitals in southeast Michigan. Patients: A random sample of Medicare and non-Medicare patients at baseline (July 1998–June 1999; n = 735) and following intervention (September 1–December 15, 2000; n = 914) admitted at the 10 study centers for treatment of confirmed AMI. A random sample of Medicare patients at baseline (January–December 1998; n = 513) and at remeasurement (March–August 2001; n = 388) admitted to 11 hospitals that volunteered, but were not selected, served as a control group. Intervention: The GAP project consisted of a kickoff presentation; creation of customized, guideline-oriented tools designed to facilitate adherence to key quality indicators; identification and assignment of local physician and nurse opinion leaders; grand rounds site visits; and premeasurement and postmeasurement of quality indicators. Main Outcome Measures: Differences in adherence to quality indicators (use of aspirin, β-blockers, and angiotensin-converting enzyme [ACE] inhibitors at discharge; time to reperfusion; smoking cessation and diet counseling; and cholesterol assessment and treatment) in ideal patients, compared between baseline and postintervention samples and among Medicare patients in GAP hospitals and the control group. Results: Increases in adherence to key treatments were seen in the administration of aspirin (81% vs 87%; P =... [ABSTRACT FROM AUTHOR]

Both social and genetic factors contribute to cognitive impairment and decline, yet genetic factors identified through genome-wide association studies (GWAS) explain only a small portion of trait variability. This "missing heritability" may be due to rare, potentially functional, genetic variants not assessed by GWAS, as well as gene-by-social factor interactions not explicitly modeled. Gene-by-social factor interactions may also operate differently across race/ethnic groups. We selected 39 genes that had significant, replicated associations with cognition, dementia, and related traits in published GWAS. Using gene-based analysis (SKAT/iSKAT), we tested whether common and/or rare variants were associated with episodic memory performance and decline either alone or through interaction with education in >10,000 European ancestry (EA) and >2200 African ancestry (AA) respondents from the Health and Retirement Study (HRS). Nine genes in EA and five genes in AA were associated with memory performance or decline (p < 0.05), and these effects did not attenuate after adjusting for education. Interaction between education and CLPTM1 on memory performance was significant in AA (p = 0.003; FDR-adjusted p = 0.038) and nominally significant in EA (p = 0.026). In both ethnicities, low memory performance was associated with CLPTM1 genotype (rs10416261) only for those with less than high school education, and effects persisted after adjusting for APOE ε4. For over 70% of gene-by-education interactions across the genome that were at least nominally significant in either ethnic group (p < 0.05), genetic effects were only observed for those with less than high school education. These results suggest that genetic effects on memory identified in this study are not mediated by education, but there may be important gene-by-education interactions across the genome, including in the broader APOE genomic region, which operate independently of APOE ε4. This work illustrates the importance of developing theoretical frameworks and methodological approaches for integrating social and genomic data to study cognition across ethnic groups. • Investigates genetic effects on longitudinal trajectories of memory performance. • Evaluates whether education modifies genetic effects on memory trajectories. • Genetic effects on memory were not mediated by educational attainment. • Education may offset genetic influences on memory performance and decline. [ABSTRACT FROM AUTHOR]