Life-course Health Research Articles

Evaluation and comparison of nine growth and development-based measures of pubertal timing

BackgroundPubertal timing is heritable, varies between individuals, and has implications for life-course health. There are many different indicators of pubertal timing, and how they relate to each other is unclear. Our aim was to quantitatively compare nine indicators of pubertal timing.MethodsWe used data from questionnaires and height, weight, and bone measurements from ages 7–17 y in a population-based cohort of 4267 females and 4251 males to compare nine growth and development-based indicators of pubertal timing. We summarise age of each indicator, their phenotypic and genetic correlations, and how they relate to established genetic risk score (GRS) for puberty timing, and phenotypic childhood body composition measures.ResultsWe show that pubic hair in males (mean: 12.6 y) and breasts in females (11.5 y) are early indicators of puberty, and voice breaking (14.2 y) and menarche (12.7 y) are late indicators however, there is substantial variation between individuals in pubertal age. All indicators show evidence of positive phenotypic intercorrelations (e.g., r = 0.49: male genitalia and pubic hair ages), and positive genetic intercorrelations. An age at menarche GRS positively associates with all other pubertal age indicators (e.g., difference in female age at peak height velocity per SD higher GRS: 0.24 y, 95%CI: 0.21 to 0.26), as does an age at voice breaking GRS (e.g., difference in age at male axillary hair: 0.11 y, 0.07 to 0.15). Higher childhood fat mass and lean mass associated with earlier puberty timing.ConclusionsOur findings provide insights into the measurements of the timing of pubertal growth and development and illustrate value of various pubertal timing indicators in life-course research.

When in the lifecourse? Socioeconomic position across the lifecourse and biological health score

PurposeEducational attainment is associated with multiphysiological wear and tear. However, associations with measures of socioeconomic position (SEP) across different life-stages are not established. MethodsUsing regression models and data from 8105 participants from the UK Household Longitudinal Study (Understanding Society), we examined associations of lifecourse SEP with an overall biological health score (BHS). BHS is broader than usual measures of biological ‘wear and tear’ and is based on six physiological subsystems (endocrine, metabolic, cardiovascular, inflammatory/immune, liver, and kidney), with higher scores indicating worse health. Lifecourse SEP was based on respondents’ parental, first, and most recent occupations. ResultsAssociations with SEP at all life-stages demonstrated higher BHS with increasing disadvantage (e.g. slope index of inequality (SII) (95 % CI) for most recent SEP: 0.04 (0.02, 0.06)). There was little difference in the magnitude of associations for SEP measured at each life-stage. Cumulative disadvantage across the lifecourse showed a stepped association with increasing BHS (SII (95 % CI): 0.05 (0.04, 0.07)). Associations were largely driven by metabolic, cardiovascular, and inflammatory systems. ConclusionOur results suggest that disadvantaged SEP across the lifecourse contributes cumulatively to poorer biological health, highlighting that every life-stage should be a target for public health policies and intervention.

Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis

More than 57 million people have dementia worldwide. Evidence indicates a change in dementia prevalence and incidence in high-income countries, which is likely to be due to improved life-course population health. Identifying key modifiable risk factors for dementia is essential for informing risk reduction and prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) for dementia associated with modifiable risk factors. In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO, via Ovid, from database inception up to June 29, 2023, for population-derived or community-based studies and reviews reporting a PAF value for one or more modifiable risk factor for later-life dementia (prevalent or incident dementia in people aged ≥60 years), with no restrictions on dementia subtype, the sex or baseline age of participants, or the period of study. Articles were independently screened for inclusion by four authors, with disagreements resolved through consensus. Data including unweighted and weighted PAF values (weighted to account for communality or overlap in risk) were independently extracted into a predefined template by two authors and checked by two other authors. When five or more unique studies investigated a given risk factor or combination of the same factors, random-effects meta-analyses were used to calculate a pooled PAF percentage estimate for the factor or combination of factors. The review protocol was registered on PROSPERO, CRD42022323429. 4024 articles were identified, and 74 were included in our narrative synthesis. Overall, PAFs were reported for 61 modifiable risk factors, with sufficient data available for meta-analysis of 12 factors (n=48 studies). In meta-analyses, the highest pooled unweighted PAF values were estimated for low education (17·2% [95% CI 14·4-20·0], p<0·0001), hypertension (15·8% [14·7-17·1], p<0·0001), hearing loss (15·6% [10·3-20·9], p<0·0001), physical inactivity (15·2% [12·8-17·7], p<0·0001), and obesity (9·4% [7·3-11·7], p<0·0001). According to weighted PAF values, low education (9·3% [6·9-11·7], p<0·0001), physical inactivity (7·3% [3·9-11·2], p=0·0021), hearing loss (7·2% [5·2-9·7], p<0·0001), hypertension (7·1% [5·4-8·8], p<0·0001), and obesity (5·3% [3·2-7·4], p=0·0001) had the highest pooled estimates. When low education, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and diabetes were combined (Barnes and Yaffe seven-factor model; n=9 studies), the pooled unweighted and weighted PAF values were 55·0% (46·5-63·5; p<0·0001) and 32·0% (26·6-37·5; p<0·0001), respectively. The pooled PAF values for most individual risk factors were higher in low-income and middle-income countries (LMICs) versus high-income countries. Governments need to invest in a life-course approach to dementia prevention, including policies that enable quality education, health-promoting environments, and improved health. This investment is particularly important in LMICs, where the potential for prevention is high, but resources, infrastructure, budgets, and research focused on ageing and dementia are limited. UK Research and Innovation (Medical Research Council).

“We Can Transform This, We Can Change This”: Adolescent Sociopolitical Development as a Catalyst for Healthy Life-Span Development

In the late 1970s, adolescents in East Harlem, New York, participated in a program called the Youth Action Program where they worked collectively to address systemic issues causing inequities in their communities (e.g., inequities in housing and education). In the current study, we integrate the sociopolitical development framework with life-course health development to explore how participation in the program shaped adolescents’ skills and capacities for social transformation in ways that were health-promotive and informative for life trajectories. Data included retrospective interviews and member-checking focus group data of 10 former Youth Action Program members (current Mage = 63; 45% female; 55% male) from predominantly Black and Latinx backgrounds. We used reflexive thematic analysis and adopted a case study approach to highlight how participants’ adolescent experiences of sociopolitical development and resistance against oppressive circumstances propelled healthy life-course development. Specifically, participants were able to establish healthy lives through four health-promotive sociopolitical developmental processes: questioning the system not the self; carving out alternative spaces and pathways; building agency in a dehumanizing society; and finding purpose through committing to social change. Our study suggests that contemporary youth organizing programs can incorporate sustaining practices including the careful vetting and training of adult staff, pursuing tangible opportunities to create change, and embedding youth voice and leadership into programmatic structures to encourage healthy development via sociopolitical development.

Cohort profile: Life-course experiences and pregnancy (LEAP)-A retrospective pregnancy cohort for life-course reproductive health research.

Life course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging. The Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health. Participants in an ongoing prospective cohort study of weight-related health who identified as women. Retrospective cohort study. In 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80th percentile), moderate (20th-80th percentile), and low (<20th percentile) GWG z-score for gestational age and pre-pregnancy weight status. Nine hundred seventy-seven women (78%) completed the LEAP survey and 656 reported a live birth. Of these, 379 (58%) agreed to release medical records, and 250 records were abstracted (66% of the 379). Of the 977 survey respondents 769 (79%) reported attempting a pregnancy, and 656 (67%) reported at least one live birth. The validation subsample was similar to the overall cohort. Women with a high GWG had a higher adolescent BMI percentile and prevalence of unhealthy weight control behaviors than those with moderate or low GWG. LEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.

Obesity risk in young adults from the Jerusalem Perinatal Study (JPS): the contribution of polygenic risk and early life exposure

Background/ObjectivesThe effects of early life exposures on offspring life-course health are well established. This study assessed whether adding early socio-demographic and perinatal variables to a model based on polygenic risk score (PRS) improves prediction of obesity risk.MethodsWe used the Jerusalem Perinatal study (JPS) with data at birth and body mass index (BMI) and waist circumference (WC) measured at age 32. The PRS was constructed using over 2.1M common SNPs identified in genome-wide association study (GWAS) for BMI. Linear and logistic models were applied in a stepwise approach. We first examined the associations between genetic variables and obesity-related phenotypes (e.g., BMI and WC). Secondly, socio-demographic variables were added and finally perinatal exposures, such as maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) were added to the model. Improvement in prediction of each step was assessed using measures of model discrimination (area under the curve, AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI).ResultsOne standard deviation (SD) change in PRS was associated with a significant increase in BMI (β = 1.40) and WC (β = 2.45). These associations were slightly attenuated (13.7–14.2%) with the addition of early life exposures to the model. Also, higher mppBMI was associated with increased offspring BMI (β = 0.39) and WC (β = 0.79) (p < 0.001). For obesity (BMI ≥ 30) prediction, the addition of early socio-demographic and perinatal exposures to the PRS model significantly increased AUC from 0.69 to 0.73. At an obesity risk threshold of 15%, the addition of early socio-demographic and perinatal exposures to the PRS model provided a significant improvement in reclassification of obesity (NRI, 0.147; 95% CI 0.068–0.225).ConclusionsInclusion of early life exposures, such as mppBMI and maternal smoking, to a model based on PRS improves obesity risk prediction in an Israeli population-sample.

Influence of maternal folate depletion on Art3 DNA methylation in the murine adult brain; potential consequences for brain and neurocognitive health.

The developmental origins of health and disease hypothesis suggest early-life environment impacts health outcomes throughout the life course. In particular, epigenetic marks, including DNA methylation, are thought to be key mechanisms through which environmental exposures programme later-life health. Adequate maternal folate status before and during pregnancy is essential in the protection against neural tube defects, but data are emerging that suggest early-life folate exposures may also influence neurocognitive outcomes in childhood and, potentially, thereafter. Since folate is key to the supply of methyl donors for DNA methylation, we hypothesize that DNA methylation may be a mediating mechanism through which maternal folate influences neurocognitive outcomes. Using bisulphite sequencing, we measured DNA methylation of five genes (Art3, Rsp16, Tspo, Wnt16, and Pcdhb6) in the brain tissue of adult offspring of dams who were depleted of folate (n = 5, 0.4 mg folic acid/kg diet) during pregnancy (~19-21 days) and lactation (mean 22 days) compared with controls (n = 6, 2 mg folic acid/kg diet). Genes were selected as methylation of their promoters had previously been found to be altered by maternal folate intake in mice and humans across the life course, and because they have potential associations with neurocognitive outcomes. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice at 28 weeks of age (mean decrease 6.2%, P = .03). For the other genes, no statistically significant differences were found between folate depleted and control groups. Given its association with neurocognitive outcomes, we suggest Art3 warrants further study in the context of lifecourse brain health. We have uncovered a potential biomarker that, once validated in accessible biospecimens and human context, may be useful to track the impact of early-life folate exposure on later-life neurocognitive health, and potentially be used to develop and monitor the effects of interventions.

Life-Course Health Risk Assessment of PM2.5 Elements in China: Exposure Disparities by Species, Source, Age, Gender, and Location.

Key stages in people's lives have particular relevance for their health; the life-course approach stresses the importance of these stages. Here, we applied a life-course approach to analyze the health risks associated with PM2.5-bound elements, which were measured at three sites with varying environmental conditions in eastern China. Road traffic was found to be the primary source of PM2.5-bound elements at all three locations, but coal combustion was identified as the most important factor to induce both cancer risk (CR) and noncancer risk (NCR) across all age groups due to the higher toxicity of elements such as As and Pb associated with coal. Nearly half of NCR and over 90% of CR occurred in childhood (1-6 years) and adulthood (>18 years), respectively, and females have slightly higher NCR and lower CR than males. Rural population is found to be subject to the highest health risks. Synthesizing previous relevant studies and nationwide PM2.5 concentration measurements, we reveal ubiquitous and large urban-rural environmental exposure disparities over China.

Quantification of the effect of in utero events on lifetime resilience in dairy cows

Currently, the dairy industry is facing many challenges that could affect its sustainability, including climate change and public perception of the industry. As a result, interest is increasing in the concept of identifying resilient animals, those with a long productive lifespan, as well as good reproductive performance and milk yield. There is much evidence that events in utero, that is, the developmental origins of health and disease hypothesis, alter the life-course health of offspring and we hypothesized that these could alter resilience in calves, where resilience is identified using lifetime data. The aim of this study was to quantify lifetime resilience scores (LRS) using an existing scoring system, based on longevity with secondary corrections for age at first calving and calving interval, and to quantify the effects of in utero events on the LRS using 2 datasets. The first was a large dataset of cattle on 83 farms in Great Britain born from 2006 to 2015 and the second was a smaller, more granular dataset of cattle born between 2003 and 2015 in the Langhill research herd at Scotland's Rural College. Events during dam's pregnancy included health events (lameness, mastitis, use of an antibiotic or anti-inflammatory medication), the effect of heat stress as measured by temperature-humidity index, and perturbations in milk yield and quality (somatic cell count, percentage fat, percentage protein and fat:protein ratio). Daughters born to dams that experienced higher temperature-humidity indexes while they were in utero during the first and third trimesters of pregnancy had lower LRS. Daughter LRS were also lower where milk yields or median fat percentages in the first trimester were low, and when milk yields were high in the third trimester. Dam LRS was positively associated with LRS of their offspring; however, as parity of the dam increased, LRS of their calves decreased. Similarly, in the Langhill herd, dams of a higher parity produced calves with lower LRS. Additionally, dams that recorded a high maximum locomotion score in the third trimester of pregnancy were negatively associated with lower calf LRS in the Langhill herd. Our results suggest that events that occur during pregnancy have lifelong consequences for the calf's lifetime performance. However, experience of higher temperature-humidity indexes, higher dam LRS, and mothers in higher parities explained a relatively small proportion of variation in offspring LRS, which suggests that other factors play a substantial role in determining calf LRS. Although "big data" can contain a considerable amount of noise, similar findings between the 2 datasets indicate it is likely these findings are real.

Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice.

An interdisciplinary fetal-neonatal neurology (FNN) program over the first 1,000 days teaches perspectives of the neural exposome that are applicable across the life span. This curriculum strengthens neonatal neurocritical care, pediatric, and adult neurology training objectives. Teaching at maternal-pediatric hospital centers optimally merges reproductive, pregnancy, and pediatric approaches to healthcare. Phenotype-genotype expressions of health or disease pathways represent a dynamic neural exposome over developmental time. The science of uncertainty applied to FNN training re-enforces the importance of shared clinical decisions that minimize bias and reduce cognitive errors. Trainees select mentoring committee participants that will maximize their learning experiences. Standardized questions and oral presentations monitor educational progress. Master or doctoral defense preparation and competitive research funding can be goals for specific individuals. FNN principles applied to practice offer an understanding of gene-environment interactions that recognizes the effects of reproductive health on the maternal-placental-fetal triad, neonate, child, and adult. Pre-conception and prenatal adversities potentially diminish life-course brain health. Endogenous and exogenous toxic stressor interplay (TSI) alters the neural exposome through maladaptive developmental neuroplasticity. Developmental disorders and epilepsy are primarily expressed during the first 1,000 days. Communicable and noncommunicable illnesses continue to interact with the neural exposome to express diverse neurologic disorders across the lifespan, particularly during the critical/sensitive time periods of adolescence and reproductive senescence. Anomalous or destructive fetal neuropathologic lesions change clinical expressions across this developmental-aging continuum. An integrated understanding of reproductive, pregnancy, placental, neonatal, childhood, and adult exposome effects offers a life-course perspective of the neural exposome. Exosome research promises improved disease monitoring and drug delivery starting during pregnancy. Developmental origins of health and disease principles applied to FNN practice anticipate neurologic diagnoses with interventions that can benefit successive generations. Addressing health care disparities in the Global South and high-income country medical deserts require constructive dialogue among stakeholders to achieve medical equity. Population health policies require a brain capital strategy that reduces the global burden of neurologic diseases by applying FNN principles and practice. This integrative neurologic care approach will prolong survival with an improved quality of life for persons across the lifespan confronted with neurological disorders.

Resilience, Accelerated Aging and Persistently Poor Health: Diverse Trajectories of Health in Malawi.

Individuals age at vastly different rates resulting in significant within-population heterogeneity in health and aging outcomes. This diversity in health and aging trajectories has rarely been investigated among low-income aging populations that have experienced substantial hardships throughout their lifecourses. Utilizing 2006-2018 data from the Malawi Longitudinal Study of Families and Health (MLSFH) and estimating group-based trajectory models (GBTM), our analyses identified three distinct lifecourse health trajectories: (1) comparatively good initial mental and physical health that persisted throughout the lifecourse ("resilient aging"); (2) relatively good initial mental and physical health that started to deteriorate during mid-adulthood ("accelerated aging"); and (3) poor initial mental and physical health that further declined over the lifecourse ("aging with persistently poor health"). For both physical and mental health, men were more likely to enjoy resilient aging than women. Predictors other than gender of trajectory membership sometimes confirmed, and sometimes contradicted, hypotheses derived from high-income country studies. Our analyses highlight the long arm of early life conditions and gender in determining aging trajectories and show that a non-trivial sub-population is characterized by aging with persistently poor health. The study uncovers widening gaps in health outcomes between those who age with resilience and those who experience accelerated aging.

Population-level interventions for the primary prevention of dementia: a complex evidence review

BackgroundDementia is a leading, global public health challenge. Recent evidence supporting a decrease in age-specific incidence of dementia in high-income countries (HICs) suggests that risk reduction is possible through improved life-course public health. Despite this, efforts to date have been heavily focused on individual-level approaches, which are unlikely to significantly reduce dementia prevalence or inequalities in dementia. In order to inform policy, we identified the population-level interventions for dementia risk reduction with the strongest evidence base. MethodsWe did this complex, multistage, evidence review to summarise the empirical, interventional evidence for population-level interventions to reduce or control each of the 12 modifiable life-course risk factors for dementia identified by the Lancet commission. We conducted a series of structured searches of peer-reviewed and grey literature databases (eg, Medline, Trip database, Cochrane library, Campbell Collaboration, the WHO, and Google Scholar), in January, March, and June, 2023. Search terms related to risk factors, prevention, and population-level interventions, without language restrictions. We extracted evidence of effectiveness and key contextual information to aid consideration and implementation of interventions by policymakers. We performed a narrative synthesis and evidence grading, and we derived a population-level dementia risk reduction intervention framework, structured by intervention type. This study is registered with PROSPERO, ID:CRD42023396193. FindingsWe identified clear and consistent evidence for the effectiveness of 26 population-level interventions to reduce the prevalence of nine of the risk factors, of which 23 have been empirically evaluated in HICs, and 16 in low-income and middle-income countries. We identified interventions that acted through fiscal levers (n=5; eg, removing primary school fees), marketing or advertising levers (n=5; eg, plain packaging of tobacco products), availability levers (n=8; eg, cleaner fuel replacement programmes for cooking stoves), and legislative levers (n=8; eg, mandated provision of hearing protective equipment at noisy workplaces). We were not able to recommend any interventions for diabetes (other than indirectly through action on obesity and physical inactivity), depression, or social isolation. InterpretationThis complex evidence review provides policymakers and public health professionals with an evidence-based framework to help develop and implement population-level approaches for dementia risk reduction that could significantly reduce the population's risk of dementia and reduce health inequalities. FundingNone.

Life-Course Brain Health as a Determinant of Late-Life Mental Health: American Association for Geriatric Psychiatry Expert Panel Recommendations

This position statement of the Expert Panel on Brain Health of the American Association for Geriatric Psychiatry (AAGP) emphasizes the critical role of life course brain health in shaping mental well-being during the later stages of life. Evidence posits that maintaining optimal brain health earlier in life is crucial for preventing and managing brain aging-related disorders such as dementia/cognitive decline, depression, stroke, and anxiety. We advocate for a holistic approach that integrates medical, psychological, and social frameworks with culturally tailored interventions across the lifespan to promote brain health and overall mental well-being in aging adults across all communities. Furthermore, our statement underscores the significance of prevention, early detection, and intervention in identifying cognitive decline, mood changes, and related mental illness. Action should also be taken to understand and address the needs of communities that traditionally have unequal access to preventive health information and services. By implementing culturally relevant and tailored evidence-based practices and advancing research in geriatric psychiatry, behavioral neurology, and geroscience, we can enhance the quality of life for older adults facing the unique challenges of aging. This position statement emphasizes the intrinsic link between brain health and mental health in aging, urging healthcare professionals, policymakers, and a broader society to prioritize comprehensive strategies that safeguard and promote brain health from birth through later years across all communities. The AAGP Expert Panel has the goal of launching further activities in the coming months and years.

How and where does "care" fit within seminal life-course approaches? A narrative review and critical analysis.

To map the concepts of the caring life-course theory that are used in life-course approaches from different disciplines; establish whether there is a common recognition of, or language used, to describe care in those life-course approaches; and identify the role and contribution of care to the life-course literature. This discursive paper uses a narrative review process to explore points of convergence and divergence between life-course approaches and the caring life-course theory. Categories for analysis were developed deductively and inductively, focusing on the constructs of fundamental care, capacity and capability, care network, care transition, care trajectory and care biography. We identified four disciplinary perspectives: (1) life-course sociology; (2) life-course epidemiology; (3) lifespan developmental psychology; and (4) life-course health development. While six core constructs of the caring life-course theory were described, either explicitly or implicitly, in existing life-course approaches, no single approach fully describes the role and contribution of care across the lifespan. Life-course approaches have largely neglected the contribution and role of care in informing the life-course discourse. This review highlights the significance of care beyond traditional healthcare settings and recognizes it as a fundamental human need for well-being and development, which can contribute to existing life-course literature. There is a need to understand care as a complex system and embrace a whole-system, life-course approach to enable nurses and other healthcare professionals to provide high-quality, patient-centred care. Incorporating care within a life-course approach provides opportunities to integrate and deliver care centred around the person, their life transitions, trajectories and care networks, including informal carers and healthcare professionals. Patients or members of the public were not involved in this study as it is a discursive paper based on the relevant literature.

Adverse childhood and adulthood experiences and risk of new-onset cardiovascular disease with consideration of social support: a prospective cohort study

BackgroundThe relationship between adverse childhood experiences (ACEs) and adverse adulthood experiences (AAEs) and their association with incident cardiovascular disease (CVD) have not been extensively studied. Considering social support, we evaluated the complex relations of ACEs and AAEs with incident CVD.MethodsThis prospective cohort study used data from the 2014 life course survey and the 2015 and 2018 surveys of the China Health and Retirement Longitudinal Study, a national survey of Chinese adults aged ≥ 45 years from 28 provinces across China. The study population included 5836 individuals (mean [SD] age, 59.59 [8.22] years, 49.7% were males). Information on ACEs, AAEs, young adulthood social support, health behavior factors, health status factors, and demographics was measured. Cox regression models, the difference method to estimate the mediation proportion, and the additive and multiplicative interactions were performed. Subgroup and sensitivity analyses were also conducted.ResultsDuring follow-up, 789 incident cases of CVD occurred. The fully adjusted model, including demographics, health behaviors, health status factors (e.g., depressive symptoms), and social support as control variables, demonstrated that the overall number of ACEs (Hazard ratio [HR]: 1.11, 95% CI: 1.08 to 1.14) and AAEs (HR: 1.19, 95% CI: 1.16 to 1.22) were associated with an increased risk of incident CVD. A dose–response relationship existed between the number of ACEs or AAEs and incident CVD risk. The overall AAEs were found to mediate 17.7% (95% CI: 8.2 to 34.2%) of the association between ACEs and incident CVD. Moreover, a significant additive interaction between ACEs and AAEs was detected (RERI [95% CI]: 0.32 [0.09 to 0.56]). Compared with adults without exposure to both ACE and AAE, those with exposure to both at least one ACE and one AAE indicator had the highest risk of incident CVD (HR: 1.96, 95% CI: 1.72 to 2.23).ConclusionsExposure to ACEs or AAEs was independently associated with an increased risk of incident CVD among Chinese middle-aged and older adults in a dose–response manner, and the overall AAEs partially mediated the association between ACEs and incident CVD. Preventive measures aimed at addressing either ACEs or AAEs alone may not significantly reduce the risk of CVD later in life. The necessity of a comprehensive life-course health strategy targeting the prevention of adversity merits increased attention.

Protective effect of restorative possibilities on cognitive function and mental health in children and adolescents: A scoping review including the role of physical activity

BackgroundThe exposome approach can be a powerful tool for understanding the intertwining of social, physical, and internal influences that shape mental health and cognitive development throughout childhood. To distil conceptual models for subsequent analyses, the EU-funded project Early Environmental quality and Life-course mental health effects (Equal-Life) has conducted literature reviews on potential mediators linking the exposome to these outcomes. We report on a scoping review and a conceptual model of the role of restorative possibilities and physical activity.MethodsPeer-reviewed studies published since the year 2000 in English, on the association between the exposome and mental health/cognition in children/adolescents, and quantitatively investigating restoration/restorative quality as a mediating variable were considered. Database searches were last updated in December 2022. We used an unstructured expert-driven approach to fill in gaps in the reviewed literature.ResultsFive records of three distinct studies were identified, indicating a scarcity of empirical evidence in this newly developing research area. Not only were these studies few in numbers, but also cross-sectional, lending only tentative support to the idea that perceived restorative quality of adolescent's living environment might mediate the association between greenspace and mental health. Physical activity emerged as a mediator leading to better psychological outcomes in restorative environments. We provide a critical discussion of potential caveats when investigating the restoration mechanism in children and propose a hierarchical model including restoration, physical activity, and relational dynamics between children and their environment, including social context, as well as restorative environments other than nature.ConclusionsIt is justified to further explore the role of restoration and physical activity as mediators in the association between early-life exposome and mental health/cognitive development. It is important to consider the child perspective and specific methodological caveats. Given the evolving conceptual definitions/operationalizations, Equal-Life will attempt to fill in a critical gap in the literature.

Dimensions of early-life adversity and SLC6A4 methylation in emerging adults

Growing evidence suggests that epigenetic pathways, including DNA methylation (DNAm), play a role in the biological embedding of early-life adversity (ELA) and life-course health, but how remains unclear. We explore epigenetic pathways indicated by DNAm of the stress-regulating gene, SLC6A4, including how DNAm is shaped by distinct life-course dimensions of ELA, including developmental contexts characterized by threat and deprivation. We investigate whether and how life-course dimensions of ELA are associated with SLC6A4 methylation (SLC6A4m) using data from 370 cohort members from the Youth Emotion Project. Participants were recruited from two US high schools and followed prospectively, with DNA collection in early adulthood and ELA measures based on coded responses from the Childhood Trauma Interview. Adjusted linear regressions of mean SLC6A4m across 71 CpG sites on ELA reveal a strong and robust association, including a dose-response relationship between SLC6A4m and increased ELA severity. Each additional high-severity event was associated with a 0.052 percentage point increase in mean percent SLC6A4m (p<0.001). When modeled separately, both childhood and adolescent ELA predict SLC6A4m, and when modeled jointly, adolescent ELA alone predicts SLC6A4m. Additionally, the ELA- SLC6A4m relationship varies by ELA type. Across childhood and adolescence, deprivation is positively associated with greater SLC6A4m. Adolescent threat is also positively associated with SLC6A4m, but the association is not statistically significant. Results suggest prioritizing early-life interventions for promoting healthy stress regulation, including preventing adversity and its harmful effects, with close attention to adolescence and high-deprivation development settings.

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.

Environmental health perceptions of urban youth from low-income communities: A qualitative photovoice study and framework.

Children are amongst the most susceptible groups to environmental exposures, for both immediate and life-course health outcomes. Despite their increased susceptibility, children's knowledge, experiencesand voices are understudied. A deeper understanding of children's environmental health perceptions has the potential to better inform policy, develop targeted interventionsand improve public health outcomes. In this study, our community-academic partnership used the Photovoice research method to examine how urban children from low-income communities perceive environmental influences on their health. Twenty children, ages 10-12, took photographs and participated in focus group interviews regarding their perspectives on how the environment influences their health. Qualitative analyses revealed five major thematic categories: environmental exposures, environmental health sentiments, environmental health outcomes, interest in environmental healthand environmental health solutions. We used the findings to develop an environmental health perspective theoretical framework that can inform future work designed to promote the environmental health and well-being of children from low-income communities in urban communities. Photovoice enabledchildren from low-income communities to capture and communicate their environmental health perceptions. These findings have the potential to inform and identify potential targets and opportunities for environmental health interventions and promotion in their communities. Partnerships with community-based organizations were central to the present study. By design, these community-based partners were involved in the conduct and procedures of the study.

Life-course Factors and Later Life Health in Eastern and Western Europe

Human development and ageing are lifelong processes, where earlier life conditions and events are interlinked with later life outcomes. Patterns of inequality within and among cohorts emerge over time as products of the interplay between institutional arrangements and individual life, often dependent on childhood or earlier life circumstances. The life conditions and experiences of older adults in Eastern and Western Europe differ significantly, but whether their cumulative effects on later life outcomes vary across these two regions has not been compared. We explore the effects of socioeconomic position, the experience of a period of hunger, the dispossession of assets, and discrimination suffered by parents in respondents’ life courses on later life health inequalities in Europe. Self-reported health, everyday activity limitations, and cognitive functioning are the main outcomes that provide an adequate overview of different health domains. We mainly use data from the seventh wave of the Survey of Health, Ageing, and Retirement in Europe (SHARE 2017) and restrict our sample to respondents aged 65 and older from 26 European countries (N=41,566). We find that older people in Eastern Europe fare worse in self-rated health and everyday activity limitations than Western Europeans, while Eastern Europeans indicate somewhat better outcomes in cognitive functioning. A disadvantaged socioeconomic position in childhood and adulthood has the strongest association with all health outcomes, followed by the experience of hunger over the life course for the whole of Europe. However, we do not find diverging associations between life-course factors and health outcomes in Eastern and Western Europe. We argue that self-reported health, everyday activity limitations and cognitive functioning have to be analysed within their own frameworks and cannot yield conclusions that are uniform for all health outcomes. Moreover, major generalisations either about Eastern or Western Europe must be treated with caution as the regions have very different historical as well as demographic developments and thus cannot be treated as uniform. * This article belongs to a special issue on “Demographic Developments in Eastern and Western Europe Before and After the Transformation of Socialist Countries”.