Health Outcomes In Later Life Research Articles

Neighborhood-Level Disparities in Hypertension Prevalence and Treatment Among Middle-Aged Adults

Hypertension in middle-aged adults (35-50 years) is associated with poorer health outcomes in late life. Understanding how hypertension varies by race and ethnicity across levels of neighborhood disadvantage may allow for better characterization of persistent disparities. To evaluate spatial patterns of hypertension diagnosis and treatment by neighborhood socioeconomic position and racial and ethnic composition. In this cross-sectional study of middle-aged adults in Cuyahoga County, Ohio, who encountered primary care in 2019, geocoded electronic health record data were linked to the area deprivation index (ADI), a neighborhood disadvantage measure, at the US Census Block Group level (ie, neighborhood). Neighborhoods were stratified by ADI quintiles, with the highest quintile indicating the most disadvantage. Data were analyzed between August 7, 2023, and June 1, 2024. Essential hypertension. The primary outcome was a clinician diagnosis of essential hypertension. Spatial analysis was used to characterize neighborhood-level patterns of hypertension prevalence and treatment. Interaction analysis was used to compare hypertension prevalence by racial and ethnic group within similar ADI quintiles. A total of 56 387 adults (median [IQR] age, 43.1 [39.1-46.9] years; 59.8% female) across 1157 neighborhoods, which comprised 3.4% Asian, 31.1% Black, 5.5% Hispanic, and 60.0% White patients, were analyzed. A gradient of hypertension prevalence across ADI quintiles was observed, with the highest vs lowest ADI quintile neighborhoods having a higher hypertension rate (50.7% vs 25.5%) and a lower treatment rate (61.3% vs 64.5%). Of the 315 neighborhoods with predominantly Black (>75%) patient populations, 200 (63%) had a hypertension rate greater than 35% combined with a treatment rate of less than 70%; only 31 of 263 neighborhoods (11.8%) comprising 5% or less Black patient populations met this same criterion. Compared with a spatial model without covariates, inclusion of ADI and percentage of Black patients accounted for 91% of variation in hypertension diagnosis prevalence among men and 98% among women. Men had a higher prevalence of hypertension than women across race and ADI quintiles, but the association of ADI and hypertension risk was stronger in women. Sex prevalence differences were smallest between Black men and women, particularly in the highest ADI quintile (1689 [60.0%] and 2592 [56.0%], respectively). These findings show an association between neighborhood deprivation and hypertension prevalence, with disparities observed particularly among Black patients, emphasizing a need for structural interventions to improve community health.

Prevalence and early-life predictors of adverse childhood experiences: Longitudinal insights from a low-income country

BackgroundA sizeable literature shows that adverse childhood experiences (ACEs) are associated with poor health outcomes in later life. However, most studies on the prevalence and predictors of ACEs have been carried out in high-income countries using cross-sectional approaches. ObjectiveThe present study explores the prevalence and predictors of ACEs in Malawi, a low-income country, using prospective longitudinal data collected on adolescents. ParticipantsWe use data on 1375 adolescents and their biological mothers from the Malawi Longitudinal Study of Families and Health (MLSFH). ACEs were reported by adolescents over two survey waves, in 2017–18 and 2021. Predictors were reported by mothers in 2008 and 2010. MethodsMultivariate ordinary least square and logistic regression analyses of ACEs exposure reported by adolescents on indicators of family arrangements and resources. ResultsAdolescents report having been exposed to nearly seven ACEs on average. Among indicators of family arrangements and resources, the only significant predictors of cumulative ACEs exposure are polygyny (linked to parental absence) and mother's SF-12 mental health score (linked to physical abuse and witnessing domestic violence). ConclusionsACEs are much more prevalent in the low-income country under study than in middle- and high-income countries surveyed in prior research. Despite adversity being widespread, most indicators of family arrangements and resources highlighted in prior studies are not associated with adolescents' cumulative ACEs exposure in this context. Mothers' mental health in childhood nevertheless emerges as a significant predictor of adolescents' self-reported ACEs. These findings inform efforts aimed at preventing ACEs in high-adversity contexts.

Longitudinal Analysis of Latvian Child Growth: Anthropometric Parameters Dynamics from Birth to Adolescence.

This study provides a comprehensive analysis of the physical development patterns from birth to adolescence, utilizing a longitudinal dataset of 70 children monitored from birth until 17 years of age. The research focuses on the variability of growth trajectories, emphasizing the role of genetic and environmental factors in influencing these patterns. Key findings indicate that most children undergo one or two periods of accelerated growth, with significant variability in the timing and magnitude of these growth spurts. The study also highlights the adaptive nature of growth changes over generations, influenced by ecological, nutritional, and socio-economic conditions. The longitudinal approach reveals critical insights into the timing of peak growth velocities, demonstrating that girls reach their growth peak approximately one year earlier than boys. The analysis of intergenerational growth patterns suggests a significant increase in average height over the century, attributed to genetic diversity and changes in lifestyle and nutrition. This study's findings emphasize the importance of updating physical development standards regularly to reflect the changing genetic and environmental landscape. The variability in growth patterns and their correlation with health outcomes in later life highlights the need for targeted public health strategies that address the underlying socio-economic and environmental determinants of health. This research contributes to the understanding of physical development trajectories and provides a foundation for future studies aimed at optimizing health outcomes from early childhood through adolescence. The primary objective of this article is to meticulously analyze the dynamics of height growth and accurately identify the periods of accelerated bodily development within the context of longitudinal research.

The long-run impacts of adolescent drinking: Evidence from Zero Tolerance Laws

This paper provides the first long-run assessment of adolescent alcohol control policies on later-life health and labor market outcomes. Our analysis exploits cross-state variation in the rollout of “Zero Tolerance” (ZT) Laws, which set strict alcohol limits for drivers under age 21 and led to sharp reductions in youth binge drinking. We adopt a difference-in-differences approach that combines information on state and year of birth to identify individuals exposed to the laws during adolescence and tracks the evolving impacts into middle age. We find that ZT Laws led to significant improvements in later-life health. Individuals exposed to the laws during adolescence were substantially less likely to suffer from cognitive and physical limitations in their 40s. The health effects are mirrored by improved labor market outcomes. These patterns cannot be attributed to changes in educational attainment or marriage. Instead, we find that affected cohorts were significantly less likely to drink heavily by middle age, suggesting an important role for adolescent initiation and habit-formation in affecting long-term substance use.

Unequal before death: The effect of paternal education on children’s old-age mortality in the United States

A growing body of research documents the relevance of parental education as a marker of family socio-economic status for children’s later-life health outcomes. A strand of this literature evaluates how the early-life environment shapes mortality outcomes during infancy and childhood. However, the evidence on mortality during the life course and old age is limited. This paper contributes to the literature by analysing the association between paternal education and children’s old-age mortality. We use data from Social Security Administration death records over the years 1988–2005 linked to the United States 1940 Census. Applying a family(cousin)- fixed-effects model to account for shared environment, childhood exposures, and common endowments that may confound the long-term links, we find that having a father with a college or high-school education, compared with elementary/no education, is associated with a 4.6- or 2.6-month-higher age at death, respectively, for the child, conditional on them surviving to age 47.

Multidimensional Deprivations and Associated Factors Among Older Adults in Urban Geographies of Nigeria: Implications for Poor Health Outcomes in Later Life.

Objectives: Many urban-dwelling older Nigerians are multidimensionally deprived and are unable to meet their daily financial, nutritional, and healthcare needs. This has implications for their health outcomes, yet it has been under-researched. This study assessed the multidimensional deprivation index (MDI) of urban-dwelling older Nigerians and the associated factors. Methods: The study analysed a weighted sample of 5,225 older persons aged ≥60 years from Nigeria's Demographic and Health Survey, 2018. MDI was estimated, and associations were examined using a multilevel multinomial logistic regression model. Results: Nationally, 75% of the older persons were multidimensionally deprived, with 27% severely deprived. Women (36%) were more severely deprived than men (20%). Those in the Northern regions (38%-40%) were the most deprived. Higher MD risk was associated with female gender and older ages ≥70-79years. Conversely, lower risk was associated with households headed by family and residence in educated communities. Community variation accounts for 10.4% and 35.9% of the MD and severe MD risks, respectively. Conclusion: This study suggests socioeconomic interventions that address gender disparities and target highly deprived regions, with consideration for individual and community characteristics.

THE ASSOCIATION OF FRAILTY AND MORTALITY IN OLDER ADULTS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF COHORT STUDY

Abstract Frailty is associated with poor health outcomes in later life, improving lifespan and death through different mechanisms. This study aimed to systematically review the epidemiological evidence from cohort studies investigating the association between frailty and all-cause mortality, and to determine if frailty affects mortality in older adults. We searched for studies published and indexed in 4 electronic databases (EMBASE, PubMed, Cochrane Library, and Web of Science) and manual search and identified 28 cohort studies before Dec 31, 2022. We include studies if their design was longitudinal; the exposure of interest was measured frailty; the endpoint of interest was mortality; they provided a risk estimate (i.e., hazard ratio [HR]) and the corresponding 95% CI for the association between frailty and mortality. They used different indexes as their frailty as exposed definitions. Two investigators independently screened the full-text articles for inclusion. We used a random-effects model to obtain pooled HRs. Thirty-one studies were included for qualitative review, of which twenty-eight were eligible for meta-analysis, and included 67,114 individuals from 16 countries. Compared with healthy adults, frail adults had a significantly higher mortality risk. The pooled HR for mortality per increment of 0.1 frailty of community-dwelling adults was 2.33 (95% CI 2.05-2.65; I2 76.9%). The present study demonstrated that frailty was not only significantly related to an increased mortality risk but was also a strong predictor of mortality in community-dwelling adults.

EARLY-LIFE ORIGINS OF LATER-LIFE HEALTH AMONG OLDER BRAZILIANS: DIFFERENCES IN ASSOCIATIONS BY HEALTH CONDITION

Abstract Background A rich body of literature has linked poor childhood health to adverse adult health outcomes in later life. This association, however, has largely been studied in high-income countries. Less attention has been given to other country contexts where childhood exposures and adulthood socioeconomic conditions are vastly different. Brazil represents an important context due to the significant growth in older adult population, significant rise in life expectancy, and rapid industrialization that occurred since the 20th century. Method. Data come from the ELSI-Brazil Study, a nationally representative sample of older Brazilians. Logistic regression was used to predict the association between childhood conditions (socioeconomic adversity and poor health) and adult health conditions (heart conditions, heart failure, diabetes, and stroke). Results Poor child health was positively associated with stroke, heart disease, and heart failure, but was not associated with diabetes or high blood pressure. Poor child socioeconomic status was associated with diabetes and stroke but not associated with heart conditions, heart failure, or high blood pressure. Discussion The importance of childhood conditions for later life remained important in Brazil, but questions remain as to why certain conditions were found to be significant while others were not. Differences may stem from larger contextual changes such as the impact of globalization on food choices during adulthood for these cohorts. This study highlights the significance of contextual and conditional factors in comprehending the multifaceted dynamics underlying the association between early life conditions and later life health.

NEW MEASURES AND POPULATION PREVALENCE OF VISION IMPAIRMENT IN NHATS

Abstract The National Health and Aging Trends Study (NHATS) is a nationally representative panel study of older U.S. adults that in 2021 (Round 11) added to its annual protocol a suite of objective visual function measures consisting of distance visual acuity, near visual acuity, and contrast sensitivity tests. These measures were developed to approximate clinical gold-standard tests, while allowing for administration on a tablet in participants’ homes. The tests were found to have good agreement with clinical gold-standards based on their limits of agreement, correlations, and lack of systematic bias between tests. In the initial 2021 fielding of the NHATS visual function measures, 27.8% (25.5%-30.1%) of U.S. adults over age 70 had one or more visual impairment (VI) (distance VI: 10.3% [8.9%-11.7%]; near VI: 22.3% [20.3%-24.3%]; contrast sensitivity impairment: 10.0% [8.5%-11.4%]), and the prevalence was highest among those who were older, had less education, lower income, and were of Hispanic ethnicity and non-White race. Additionally, the adjusted prevalence ratio for dementia was significantly higher among those with each type of VI compared to those with normal vision (moderate/severe distance VI=1.72 [1.26-2.35]; any near VI=1.40 [1.16-1.69]-; contrast sensitivity impairment =1.31 [1.04-1.66]). Since few other national studies of older adults include objective visual function measures, NHATS now serves as a vital resource for the study of vision epidemiology and the impact of VI and blindness on later-life health outcomes and trajectories.

Associations between plasma metal/metalloid mixtures and the risk of central obesity: A prospective cohort study of Chinese adults

Central obesity has increased rapidly over the past decade and posed a substantial disease burden worldwide. Exposure to metals/metalloids has been acknowledged to be involved in the development of central obesity through regulation of cortisol, insulin resistance, and glucocorticoid receptor reduction. Despite the importance, it is lack of prospective study which comprehensively evaluate the relations between multiple metals exposure and central obesity. We explored the prospective associations of plasma metal concentrations with central obesity in a prospective study of the Dongfeng-Tongji cohort. The present study included 2127 participants with a 6.87-year mean follow-up duration. We measured 23 plasma metal/metalloid concentrations at baseline. The associations between metals and incident central obesity were examined utilizing the Cox proportional hazard regression in single and multiple metals models. Additionally, we applied elastic net (ENET), Bayesian kernel machine regression (BKMR), plasma metal score (PMS), and quantile-based g-computation (Qgcomp) models to explore the joint associations of metal mixtures with central obesity. After adjusting potential confounders, we found significant associations of plasma manganese (Mn) and thallium (Tl) concentrations with a higher risk of central obesity, whereas plasma rubidium (Rb) concentration was associated with a lower risk of central obesity both in single and multiple metals models (all FDR <0.05). The ENET and Qqcomp models verified similar metals (Mn, Rb, and Tl) as important predictors for central obesity. The results of both BKMR model and PMS suggested cumulative exposure to metal mixtures was associated with a higher risk of central obesity. Our findings suggested that co-exposure to metals was associated with a higher risk of central obesity. This study expands our knowledge that the management of metals/metalloids exposure may be beneficial for the prevention of new-onset central obesity, which may subsequently alleviate the disease burden of late-life health outcomes.

Associations of adverse childhood experiences with common psychiatric disorder in later life: results from the China mental health survey

BackgroundAssociations between adverse childhood experiences (ACEs) and common psychiatric disorders among older Chinese individuals have not been well reported. The objectives of this study are to examine the prevalence of ACEs and the associations of ACEs with common psychiatric disorders among older adults in China.MethodsThe study used data from the China Mental Health Survey (CMHS), a nationally representative epidemiological survey, which used computer-assisted personal interviewing (CAPI), logistic regression models were used to examine community-based adult psychiatric disorders and associated risk factors. Finally, 2,317 individuals aged 60 years or over were included in the CMHS. The national prevalence of ACEs in older adults were estimated and logistic regression were used to analyse the association between ACEs and past-year psychiatric disorders.ResultsPrevalence of ACEs among older adults in China was 18.1%. The three most common types of ACEs were neglect (11.6%), domestic violence (9.2%), and parental loss (9.1%). This study proved the association between ACEs and common past-year psychiatric disorders in older adults. ACEs increased the risk of past-year psychiatric disorders in older adults. After adjustment for age, sex, marital status, employment status, education, rural or urban residence, region, and physical diseases, the association between ACEs and past-year psychiatric disorders were still significant.ConclusionsACEs are linked to an increased risk for past-year psychiatric disorders in older adults. ACEs may have long-term effects on older adults’ mental well-being. Preventing ACEs may help reduce possible adverse health outcomes in later life.

Temperature around conception and metabolic health in adulthood: Evidence from the UK Biobank

Abstract Background Mice studies and correlational evidence among humans suggest that paternal cold exposure around conception is associated with improved metabolic outcomes among the offspring, which is caused by an increase in their amount of active brown fat. Especially the 2 weeks prior to conception are relevant as epigenetic programming during spermatogenesis takes place. Causal evidence on humans is thus far lacking. We overcome this challenge by exploiting quasi-random temperature variation around conception and studying metabolic health in a large sample. Methods We combine daily temperature data with individual-level data from UK Biobank (N = 430,000, birth years 1934 - 1971) and link quasi-random temperature variations around conception to later-life metabolic health outcomes. We do not use actual temperatures, since conceiving during cold months or living in cold areas may be associated with socioeconomic and other characteristics that may affect offspring later-life metabolic health. Instead, we utilize deviations from the temperature that is to be expected for a certain place at a certain time point in a natural experiment framework. Date of conception is estimated from date of birth and our main exposure is temperature variation in the 2 weeks before conception. Since pregnancy length varies, temperatures during several time windows around conception are considered. Results Individuals who were conceived when it was one degree Celsius colder than usually have a lower BMI (-0.018; 95% CI -0.033, -0.003), waist circumference (-0.038; 95% CI -0.071, -0.004), as well as lower levels of triglycerides (-0.004; 95% CI -0.007, -0.001) and cholesterol (-0.013; 95% CI -0.017, -0.010). Conclusions Comparatively subtle environmental shocks such as temperature variations around conception are causally associated with long-term metabolic health. This study points to the importance of future research on similar potential health externalities of rising global temperatures. Key messages • Colder temperatures around conception lead to improved metabolic health outcomes in adulthood, including lower BMI, waist circumference, and levels of triglycerides and cholesterol. • Subtle environmental factors during the periconceptional period can have long-term health impacts, highlighting the need for further research on potential health externalities of climate change.

Negative wealth shocks in later life and subsequent cognitive function in older adults in China, England, Mexico, and the USA, 2012–18: a population-based, cross-nationally harmonised, longitudinal study

Household wealth is positively related to cognitive health outcomes in later life. However, the association between negative wealth shocks and cognitive function in later life, and whether this association might differ across countries at different levels of economic development, is unclear. We aimed to investigate whether negative wealth shocks in later life are associated with cognitive function in older adults in China, England, Mexico, and the USA, and whether this association is modified by country income level. For this population-based, cross-nationally harmonised, longitudinal study, data were analysed from core interviews of the population-based US Health and Retirement Study (2012 and 2016) and its partner studies in China (the China Health and Retirement Longitudinal Study; 2015 and 2018), England (the English Longitudinal Study of Ageing; 2012 and 2016), and Mexico (Mexican Health and Aging Study; 2012 and 2015-16), and their respective Harmonized Cognitive Assessment Protocols (HCAPs). Negative wealth shocks over the follow-up periods of the respective cohorts were defined in two ways: an extreme loss of 75% or greater from the baseline amount of wealth, and a decline in within-population wealth quintile rank. The primary outcome was the harmonised general cognitive function (GCF) factor score, which was constructed with factor analysis on the HCAP neuropsychological assessments of memory, orientation, attention, executive function, and verbal fluency performance (mean 0; SD 1). We used sampling-weighted, multivariable-adjusted linear models to examine associations. Data from 9465 participants were included in this analysis: 3796 from China, 1184 from England, 1193 from Mexico, and 3292 from the USA. The mean baseline age of participants was 68·5 (SD 5·4) years in China (49·8% women), 72·0 (7·0) years in England (54·6% women), 70·6 (6·8) years in Mexico (55·1% women), and 72·7 (7·5) years in the USA (60·4% women). A wealth loss of 75% or greater was negatively associated with subsequent cognitive function in the USA (β -0·16 SD units; 95% CI -0·29 to -0·04) and China (-0·14; -0·21 to -0·07), but not in England (-0·01; -0·24 to 0·22) or Mexico (-0·11; -0·24 to 0·03). Similarly, within-population wealth quintile rank declines were negatively associated with subsequent cognitive function in the USA (β -0·07 per quintile rank decline; 95% CI -0·11 to -0·03) and China (β -0·07; -0·09 to -0·04), but not in England (-0·05; -0·11 to 0·01) or Mexico (-0·03; -0·07 to 0·01). The impact of wealth shocks in later life on subsequent lower level of cognitive function of older adults in China, England, Mexico, and the USA differed across macro-level socioeconomic structures. These findings suggest that government policies and social safety nets in countries with different levels of economic development might have a role in protecting older adults from adverse health effects of wealth losses in later life. US National Institute on Aging, US National Institutes of Health.

Life-course generational placements and health and wellbeing in later life

Abstract Previous research has demonstrated that family transitions, specifically births and deaths of preceding and following generations within families, are associated with individuals' later-life wellbeing and health. However, lifecourse, family systems and role theories suggest that this relationship might be complex because, as individuals age, they can experience multiple such events and their effects might be interconnected. Therefore, this study asks whether and how transitions into and out of multiple intergenerational family roles are associated with later-life wellbeing and health. We account for the occurrence, timing and ordering of the parents' death and the birth of the first child and grandchild. To this end, we use the concept of ‘generational placement trajectories’. They capture the vertical position of individuals in their intergenerational family over age and reflect the changing family roles and kinship reservoir of individuals across their lifecourse. Applying sequence, cluster and regression analyses to data from the German Ageing Survey (N = 3,617), we investigate associations between generational placement trajectories from birth to age 60 and four dimensions of later-life wellbeing and health, namely life satisfaction, depressiveness, functional limitations and physical health problems. Results support, first, the notion of salutary effects of a larger kinship reservoir and multiple social roles in the family and, second, indicate that ‘off-time’ transitions are associated negatively with various later-life wellbeing and health outcomes. Importantly, the effect of temporal deviations from the ‘normative’ family lifecourse might be affected by individual socio-economic differences. We enhance previous research by demonstrating that the occurrence, timing and ordering of transitions into and out of multiple kin relations and family roles across the lifecourse relate to individuals' later-life wellbeing and health.

Implementing a Digital Depression Prevention Program in Australian Secondary Schools: Cross-Sectional Qualitative Study

Background Depression is common during adolescence and is associated with adverse educational, employment, and health outcomes in later life. Digital programs are increasingly being implemented in schools to improve and protect adolescent mental health. Although digital depression prevention programs can be effective, there is limited knowledge about how contextual factors influence real-world delivery at scale in schools. Objective The purpose of this study was to examine the contextual factors that influence the implementation of the Future Proofing Program (FPP) from the perspectives of school staff. The FPP is a 2-arm hybrid type 1 effectiveness-implementation trial evaluating whether depression can be prevented at scale in schools, using an evidence-based smartphone app delivered universally to year 8 students (13-14 years of age). Methods Qualitative interviews were conducted with 23 staff from 20 schools in New South Wales, Australia, who assisted with the implementation of the FPP. The interviews were guided by our theory-driven logic model. Reflexive thematic analysis, using both deductive and inductive coding, was used to analyze responses. Results Staff perceived the FPP as a novel (“innovative approach”) and appropriate way to address an unmet need within schools (“right place at the right time”). Active leadership and counselor involvement were critical for planning and engaging; teamwork, communication, and staff capacity were critical for execution (“ways of working within schools”). Low student engagement and staffing availability were identified as barriers for future adoption and implementation by schools (“reflecting on past experiences”). Conclusions Four superordinate themes pertaining to the program, implementation processes, and implementation barriers were identified from qualitative responses by school staff. On the basis of our findings, we proposed a select set of recommendations for future implementation of digital prevention programs delivered at scale in schools. These recommendations were designed to facilitate an organizational change and help staff to implement digital mental health programs within their schools. International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2020-042133

Socio-ecological predictors of dietary inflammatory scores and associations with childhood and adolescent adiposity: A protocol for a rapid scoping review of observational studies.

Diet-related inflammation is associated with adiposity. Obesity and inflammation in early life may have adverse health outcomes in later life; however, the socio-ecological predictors of a pro-inflammatory diet in childhood and adolescence are not well understood. This rapid scoping review aims to summarise the current state of research from observational studies investigating socio-ecological predictors (childhood, parental, familial, demographic and chronobiological risk factors) and their association with diet-associated inflammation and adiposity in children and adolescents. This scoping review will be conducted using the frameworks based on the Joanna Briggs Institute and Arksey and O'Malley and the Population, Concept and Context (PCC) mnemonic. Searches were conducted in OVID Medline, Cinahl and Embase, with adaptations as required. The piloted study selection process will utilise two reviewers for study selection, with reference lists checked for included studies. A third reviewer will moderate disagreements. Data will be extracted by one reviewer and calibrated by a second reviewer. The results will be reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and PRISMA-ScR flow diagram. The main findings will be synthesised into themes and concepts narratively. Tables and graphs will present frequencies, study details and categorical descriptions. This scoping review will provide an overview of the research conducted to date regarding predictors of diet-related inflammation in childhood and their associations with adiposity. Better understanding of the factors associated with a more inflammatory diet in childhood may be useful for clinicians and policy makers when designing and implementing health interventions.

General dimensions of human brain morphometry inferred from genome-wide association data.

Understanding the neurodegenerative mechanisms underlying cognitive decline in the general population may facilitate early detection of adverse health outcomes in late life. This study investigates genetic links between brain morphometry, ageing and cognitive ability. We develop Genomic Principal Components Analysis (Genomic PCA) to model general dimensions of brain-wide morphometry at the level of their underlying genetic architecture. Genomic PCA is applied to genome-wide association data for 83 brain-wide volumes (36,778 UK Biobank participants) and we extract genomic principal components (PCs) to capture global dimensions of genetic covariance across brain regions (unlike ancestral PCs that index genetic similarity between participants). Using linkage disequilibrium score regression, we estimate genetic overlap between those general brain dimensions and cognitive ageing. The first genetic PCs underlying the morphometric organisation of 83 brain-wide regions accounted for substantial genetic variance (R2 =40%) with the pattern of component loadings corresponding closely to those obtained from phenotypic analyses. Genetically more central regions to overall brain structure - specifically frontal and parietal volumes thought to be part of the central executive network - tended to be somewhat more susceptible towards age (r=-0.27). We demonstrate the moderate genetic overlap between the first PC underlying each of several structural brain networks and general cognitive ability (rg =0.17-0.21), which was not specific to a particular subset of the canonical networks examined. We provide a multivariate framework integrating covariance across multiple brain regions and the genome, revealing moderate shared genetic etiology between brain-wide morphometry and cognitive ageing.

Abstract P129: Age at Menarche Associated With Cardiovascular Disease Risk Factors and History Among African American Women: The Jackson Heart Study

Menarche is the onset of menstruation and is a definitive indication of female puberty. The average age at menarche has steadily declined worldwide over the past century. While many cardiovascular conditions have their start during youth, age at menarche may also play a role in predicting the risk for cardiovascular disease (CVD). Of particular importance is the disproportionately high number of CVDs that affect African Americans, which contributes greatly to the disparities in life expectancy between African Americans and Whites. This study aims to address a gap in knowledge about African American women’s health by examining the association between age at menarche and CVD. We assessed the hypothesis that an earlier age at menarche is associated with increased odds of CVD risk factors and history for women in the Jackson Heart Study. This study was a secondary analysis of baseline data from 2,458 females in the Jackson Heart Study, a longitudinal cohort study of African Americans in the Jackson, MS metropolitan area. Early menarche was defined as menarche occurring at less than 12 years of age. Cardiovascular disease risk factors included hypertension, diabetes, obesity, and abdominal obesity (waist circumference &gt;88cm). Cardiovascular disease history included coronary heart disease, heart attack, and stroke. The association between early menarche and CVD risk factors and history was examined using multivariable logistic regression models, controlling for physical activity, nutrition, smoking, alcohol use, education, income, and oral contraceptive use. The prevalence of CVD risk factors and CVD history was higher for women with an early age at menarche (&lt;12 years) than for other women. After adjusting for covariates, early age at menarche was associated with greater odds of hypertension (OR, 1.47 [95% CI, 1.17-1.84]), obesity (OR, 1.77 [95% CI, 1.43, 2.19]), abdominal obesity (OR, 1.87 [95% CI, 1.44, 2.41)], history of coronary heart disease (OR, 1.98 [95% CI, 1.33, 2.94]), and history of heart attack (OR, 1.76 [95% CI, 1.09, 2.84]). Early age at menarche was not significantly associated with diabetes or stroke history. In conclusion, in this large sample of African American women in the Jackson Heart Study, we observed that menarche before 12 years of age was associated with increased odds of CVD risk factors and CVD history compared to those with menarche after 12 years of age. These findings highlight the importance of exposures during youth and childhood which may contribute to poor health outcomes in later life.

Atypical maternal interaction is associated with elevated levels of hair cortisol in children.

The quality of maternal caregiving is an important factor in the healthy development of a child. One consequence of prolonged insensitive and atypical maternal interaction behavior (e.g., withdrawing from interactions with the child and role-reversal, i.e., the takeover of the parental role or parts of it by the child) in mother-child-dyads can cause alteration of the child's stress response system. Higher salivary cortisol concentrations were reported in infants and toddlers directly after negative interactions with their parents. However, no study to date has examined the association between atypical maternal interaction behavior and hair cortisol concentrations (HCC) in infants. Here, we studied the association of maternal interaction behavior with HCC of the child. Mother-child dyads (N = 112) participated in the longitudinal study My Childhood-Your Childhood. The AMBIANCE scale and its subscales were used to assess atypical maternal interaction behavior during the Strange Situation Procedure. Chronic stress levels in the child were assessed by HCC of 3 cm hair strands at the age of 12 months. Maternal educational level (operationalized in highest education level) served as a control variable. Robust multiple linear regression analyses revealed that role/boundary confusion was associated with HCC, i.e., the higher atypical interaction behavior of the mother the higher the HCC in the children. By measuring hair cortisol in this study, it is possible to determine the average long-term activity of the child's stress response system.Thus, atypical maternal interaction behavior could be a risk factor for persistent stress in children, contributing to a higher risk for negative health outcomes in later life. The results of this study highlight the importance of early intervention programs that focus on the relationship between mother and child.

Epigenetics and the Exposome: DNA Methylation as a Proxy for Health Impacts of Prenatal Environmental Exposures.

The accumulation of every day exposures can impact health across the life course, but our understanding of such exposures is impeded by our ability to delineate the relationship between an individual's early life exposome and later life health effects. Measuring the exposome is challenging. Exposure assessed at a given time point captures a snapshot of the exposome but does not represent the full spectrum of exposures across the life course. In addition, the assessment of early life exposures and their effects is often further challenged by lack of relevant samples and the time gap between exposures and related health outcomes in later life. Epigenetics, specifically DNA methylation, has the potential to overcome these barriers as environmental epigenetic perturbances can be retained through time. In this review, we describe how DNA methylation can be framed in the world of the exposome. We offer three compelling examples of common environmental exposures, including cigarette smoke, the endocrine active compound bisphenol A (BPA), and the metal lead (Pb), to illustrate the application of DNA methylation as a proxy to measure the exposome. We discuss areas for future explorations and current limitations of this approach. Epigenetic profiling is a promising and rapidly developing tool and field of study, offering us a unique and powerful way to assess the early life exposome and its effects across different life stages.