Mind versus body: Perceived stress and biological stress are independently related to cognitive decline.

Chronic stress may increase risk of age-related cognitive decline. 'Stress', however, is a multidimensional construct and few studies have investigated the inter-relationship of subjective stress and biological stress with cognitive decline. In this study, we examine the relationship between perceived stress and two measures of biological stress - allostatic load, indexing stress at the physiological level and leukocyte telomere length, indexing stress at the cellular level - with cognitive decline over a 12-year period in adults aged 50 and older. 3,458 participants (aged ≥ 50) from The Irish Longitudinal study on Ageing with measurements of allostatic load, telomere length and perceived stress at baseline and repeated measures of cognitive function were included. Hierarchical linear regression models with adjustment for multiple potential confounders were applied, and repeated stratified by sex in sensitivity analyses. Higher perceived stress at baseline was associated with lower cognitive function (ß = -0.10, 95 % CI -0.12, -0.07, p <.001), with similar strength of associations across waves. There were significant interactions between measures of biological stress and wave; higher allostatic load was associated (X2(18) = 64.4; p <.001), and telomere length was borderline (X2(18) = 9.4; p =.09) associated with cognitive decline from 4-year follow-up onward. Sex stratified analyses revealed that the association between telomere length and cognitive decline was present in women only. Mutual adjustment did not attenuate associations in either case. The interactions between allostatic load and telomere length with perceived stress were not significant. Our findings suggest that subjective measures of stress and biological metrics may be independently related to cognitive function over time in older adults, hinting at the potential for different underlying mechanisms.

Comparisons of disease cluster patterns, prevalence and health factors in the USA, Canada, England and Ireland.

BACKGROUND: Identification of those who are most at risk of developing specific patterns of disease across different populations is required for directing public health policy. Here, we contrast prevalence and patterns of cross-national disease incidence, co-occurrence and related risk factors across population samples from the U.S., Canada, England and Ireland. METHODS: Participants (n = 62,111) were drawn from the US Health and Retirement Study (n = 10,858); the Canadian Longitudinal Study on Ageing (n = 36,647); the English Longitudinal Study of Ageing (n = 7938) and The Irish Longitudinal Study on Ageing (n = 6668). Self-reported lifetime prevalence of 10 medical conditions, predominant clusters of multimorbidity and their specific risk factors were compared across countries using latent class analysis. RESULTS: The U.S. had significantly higher prevalence of multimorbid disease patterns and nearly all diseases when compared to the three other countries, even after adjusting for age, sex, BMI, income, employment status, education, alcohol consumption and smoking history. For the U.S. the most at-risk group were younger on average compared to Canada, England and Ireland. Socioeconomic gradients for specific disease combinations were more pronounced for the U.S., Canada and England than they were for Ireland. The rates of obesity trends over the last 50 years align with the prevalence of eight of the 10 diseases examined. While patterns of disease clusters and the risk factors related to each of the disease clusters were similar, the probabilities of the diseases within each cluster differed across countries. CONCLUSIONS: This information can be used to better understand the complex nature of multimorbidity and identify appropriate prevention and management strategies for treating multimorbidity across countries.

Impaired orthostatic heart rate recovery is associated with smaller thalamic volume: Results from The Irish Longitudinal Study on Aging (TILDA).

The thalamus is a central hub of the autonomic network and thalamic volume has been associated with high-risk phenotypes for sudden cardiac death. Heart rate response to physiological stressors (e.g., standing) and the associated recovery patterns provide reliable indicators of both autonomic function and cardiovascular risk. Here we examine if thalamic volume may be a risk marker for impaired heart rate recovery in response to orthostatic challenge. The Irish Longitudinal Study on Aging involves a nationally representative sample of older individuals aged ≥50 years. Multimodal brain magnetic resonance imaging and orthostatic heart rate recovery were available for a cross-sectional sample of 430 participants. Multivariable regression and linear mixed-effects models were adjusted for head size, age, sex, education, body mass index, blood pressure, history of cardiovascular diseases and events, cardiovascular medication, diabetes mellitus, smoking, alcohol intake, timed up-and-go (a measure of physical frailty), physical exercise and depression. Smaller thalamic volume was associated with slower heart rate recovery (-1.4 bpm per 1 cm3 thalamic volume, 95% CI -2.01 to -0.82; p < .001). In multivariable analysis, participants with smaller thalamic volumes had a mean heart rate recovery -2.7 bpm slower than participants with larger thalamic volumes (95% CI -3.89 to -1.61; p < .001). Covariates associated with smaller thalamic volume included age, history of diabetes, and heavy alcohol consumption. Thalamic volume may be an indicator of the structural integrity of the central autonomic network. It may be a clinical biomarker for stratification of individuals at risk of autonomic dysfunction, cardiovascular events, and sudden cardiac death.

Patterning of educational attainment across inflammatory markers: Findings from a multi-cohort study.

BACKGROUND: Evidence suggests that the inflammatory reaction, an adaptive response triggered by a variety of harmful stimuli and conditions involved in the risk and development of many chronic diseases, is a potential pathway through which the socioeconomic environment is biologically embedded. Difficulty in interpreting the role of the inflammatory system in the embodiment dynamic arises because of heterogeneity across studies that use a limited but varied number of inflammatory markers. There is no consensus in the literature as to which inflammatory markers beyond the C-reactive protein and to a lesser extent interleukin 6 are related to the social environment. Accordingly, we aimed to investigate the association between educational attainment, and several markers of inflammation - C-reactive protein, fibrinogen, interleukin 6, interleukin 1ß and tumor necrosis factor α- in 6 European cohort studies. METHODS: Up to 17,470 participants from six European cohort studies with data on educational attainment, health behaviors and lifestyle factors, and at least two different inflammatory markers. Four sub-datasets were drawn with varying numbers of participants to allow pairwise comparison of the social patterning of C-reactive protein and any other inflammatory markers. To evaluate within each sub-dataset the importance of the context and cohort specificities, linear regression-based analyses were performed separately for each cohort and combined in a random effect meta-analysis to determine the relationship between educational attainment and inflammation. RESULTS: We found that the magnitude of the relationship between educational attainment and five inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin 6 and 1ß and tumor necrosis factor α) was variable. By far the most socially patterned biomarker was C-reactive protein, followed by fibrinogen and to lesser extent interleukin 6, where a low educational attainment was associated with higher inflammation even after adjusting for health behaviours and body mass index. No association was found with interleukin 1ß and tumor necrosis factor α. CONCLUSIONS: Our study suggests different educational patterning of inflammatory biomarkers. Further large-scale research is needed to explore social differences in the inflammatory cascade in greater detail and the extent to which these differences contribute to social inequalities in health.

Socioeconomic disadvantage and health in early childhood: a population-based birth cohort study from Portugal.

BACKGROUND: Measuring early socioeconomic inequalities in health provides evidence to understand the patterns of disease. Thus, our aim was to determine which children's health outcomes are patterned by socioeconomics and to what extent the magnitude/direction of the differences vary by socioeconomic measure and outcome. METHODS: Data on early childhood (4 years) health was obtained from Generation XXI birth cohort (n = 8647). A total of 27 health outcomes and 13 socioeconomic indicators at the individual level and neighbourhood level were used to calculate the relative index of inequality (RII). RESULTS: Socioeconomic inequalities were evident across 21 of the 27 health outcomes. Education, occupation and income more often captured inequalities, compared with neighbourhood deprivation or employment status. Using highest maternal education as reference category, we observed that seizures (RII = 8.64), obesity (2.94), abdominal obesity (2.66), urinary tract infection (2.26), language/speech problems (2.24), hypertension (2.08) and insulin resistance (1.33) were heavily socially patterned, much more common in disadvantaged children. Contrastingly, eczema (0.26) and rhinitis (0.26) were more common among more advantaged children. CONCLUSIONS: Socioeconomic inequalities were evident for almost every health outcome assessed, although with varying magnitude/direction according to the socioeconomic indicator and outcome. Our results reinforce that the social gradient in health manifests early in childhood.

Personality and preventive healthcare utilisation: Evidence from the Irish Longitudinal Study on Ageing.

There is extensive empirical evidence that personality is associated with many outcomes and behaviours, such as educational outcomes, labour market participation, savings behaviour, health behaviours, physical health status and mortality. Use of preventive healthcare services (e.g., vaccinations, screening, etc.) is a potential pathway explaining the link between personality and health, and is an important component of healthy ageing. We examine the association between personality traits (the 'Big Five') and a variety of preventive healthcare utilisation measures in the older population. Using data from the Irish Longitudinal Study on Ageing (TILDA), we estimate Poisson models of preventive healthcare utilisation (influenza vaccination, blood cholesterol test, breast lump check, mammogram, prostate examination, prostate-specific antigen (PSA) test). We find that openness to experience is a significant predictor of breast lump check and mammogram in women aged 65+ after adjustment for other confounders and multiple hypothesis testing. While uptake of many preventive healthcare services remains below national recommendations for the older population, with the exception of breast lump checks and mammograms for women aged 65+, we find little evidence to link this heterogeneity in uptake to personality.

Maternal educational inequalities in measured body mass index trajectories in three European countries.

BACKGROUND: Social inequalities in the prevalence of childhood overweight and obesity are well-established, but less is known about when the social gradient first emerges and how it evolves across childhood and adolescence. OBJECTIVE: This study examines maternal education differentials in children's body mass trajectories in infancy, childhood and adolescence using data from four contemporary European child cohorts. METHODS: Prospective data on children's body mass index (BMI) were obtained from four cohort studies-Generation XXI (G21-Portugal), Growing Up in Ireland (GUI) infant and child cohorts, and the Millennium Cohort Study (MCS-UK)-involving a total sample of 41,399 children and 120,140 observations. Children's BMI trajectories were modelled by maternal education level using mixed-effect models. RESULTS: Maternal educational inequalities in children's BMI were evident as early as three years of age. Children from lower maternal educational backgrounds were characterised by accelerated BMI growth, and the extent of the disparity was such that boys from primary-educated backgrounds measured 0.42 kg/m2 (95% CI 0.24, 0.60) heavier at 7 years of age in G21, 0.90 kg/m2 (95% CI 0.60, 1.19) heavier at 13 years of age in GUI and 0.75 kg/m2 (95% CI 0.52, 0.97) heavier in MCS at 14 years of age. The corresponding figures for girls were 0.71 kg/m2 (95% CI 0.50, 0.91), 1.31 kg/m2 (95% CI 1.00, 1.62) and 0.76 kg/m2 (95% CI 0.53, 1.00) in G21, GUI and MCS, respectively. CONCLUSIONS: Maternal education is a strong predictor of BMI across European nations. Socio-economic differentials emerge early and widen across childhood, highlighting the need for early intervention.

The Great Recession and the Health of Young Children: A Fixed-Effects Analysis in Ireland.

Economic recessions have been linked to adult health, but few studies have examined how recessions influence the health of young children. This study examined the impact of life transitions linked to the recent financial crisis on the health of young children in Ireland. Data came from the Growing Up in Ireland Infant Cohort Study (n = 11,134), which assessed children before (2008), during (2011), and after (2013) the Great Recession that followed the financial crisis of 2008 and incorporated questions on the impacts of the financial crisis on families. Using fixed-effects models to control for confounding, we found that a reduction in welfare benefits during the recession was associated with a significant increase in the risks of asthma (ß = 0.014, 95% confidence interval (95% CI): 0.004, 0.023) and atopy (ß = 0.014, 95% CI: 0.001, 0.027). While parental job loss was not associated with child health, a reduction in working hours was associated with increased reports of child health problems (ß = 0.024, 95% CI: 0.004, 0.043), as were difficulties affording basic necessities (ß = 0.019, 95% CI: 0.001, 0.038). Results suggest that failing to protect vulnerable families and children during economic recessions may have long-lasting implications for child health.

Kidney Disease in Women is Associated with Disadvantaged Childhood Socioeconomic Position.

BACKGROUND: Socioeconomic position (SEP) is an important determinant of health and it is dynamic across the entire lifespan. We sought to investigate the relationship between life-course SEP and chronic kidney disease (CKD) using 3 conceptual models: critical period, pathway and accumulation. METHODS: Cross-sectional analysis of 4,996 participants from The Irish Longitudinal Study on Ageing, a nationally representative cohort of community-dwelling adults aged ≥50 years. We defined childhood and adulthood SEP according to father's and respondent's occupation respectively. SEP was categorised as high (reference), intermediate, low and never worked. CKD was defined as a glomerular filtration rate < 60 mL/min/1.73 m2 estimated from the combination of creatinine and cystatin C. We used logistic regression to estimate the age-adjusted association between SEP and CKD separately in men and women. RESULTS: Low childhood SEP was strongly associated with CKD in women, after adjusting for adulthood SEP (OR 1.90 [95% CI 1.24-2.92]), supporting the critical period hypothesis. This association was not explained by traditional CKD risk factors. Women who experienced low childhood SEP and whose circumstances improved in adulthood also had increased odds of CKD, further supporting a critical period effect in childhood. There was comparatively less evidence in support of the pathway or accumulation models. We did not observe a statistically significant association between SEP and CKD in men. CONCLUSIONS: Our findings suggest that women exposed to disadvantaged SEP in childhood represent an at-risk group in whom there may be opportunities for identification of CKD and facilitation of health-promoting behaviours from an early age.

Speed of Heart Rate Recovery in Response to Orthostatic Challenge.

RATIONALE: Speed of heart rate recovery (HRR) may serve as an important biomarker of aging and mortality. OBJECTIVE: To examine whether the speed of HRR after an orthostatic maneuver (ie, active stand from supine position) predicts mortality. METHODS AND RESULTS: A longitudinal cohort study involving a nationally representative sample of community-dwelling older individuals aged ≥50 years. A total of 4475 participants completed an active stand at baseline as part of a detailed clinic-based cardiovascular assessment. Beat-to-beat heart rate and blood pressure responses to standing were measured during a 2-minute window using a finometer and binned in 10-s intervals. We modeled HRR to the stand by age group, cardiovascular disease burden, and mortality status using a random effects model. Mortality status during a mean follow-up duration of 4.3 years served as the primary end point (n=138). Speed of HRR in the immediate 20 s after standing was a strong predictor of mortality. A 1-bpm slower HRR between 10 and 20 s after standing increased the hazard of mortality by 6% controlling for established risk factors. A clear dose-response relationship was evident. Sixty-nine participants in the slowest HRR quartile died during the observation period compared with 14 participants in the fastest HRR quartile. Participants in the slowest recovery quartile were 2.3× more likely to die compared with those in the fastest recovery quartile. CONCLUSIONS: Speed of orthostatic HRR predicts mortality and may aid clinical decision making. Attenuated orthostatic HRR may reflect dysregulation of the parasympathetic branch of the autonomic nervous system.

Fiscal crises and personal troubles: the great recession in Ireland and family processes.

BACKGROUND: Social disadvantage is often associated with worse child psychological adjustment which itself is implicated in educational failure and poor adult social position. The family stress model holds that the association between social disadvantage and psychological adjustment stems from the impact of economic pressure on parental mental health mediated through the parent/child relationship. METHODS: We take advantage of a natural experiment offered by the 'great recession' in Ireland between 2008 and 2012. Structural equation models using causal modelling and Longitudinal data from the Growing Up in Ireland cohort study are used to test whether the experience of recession in families impacts on children's psychological adjustment and whether this occurs directly or is mediated by the processes identified in the family stress model. RESULTS: More than 70% of families experienced a reduction in income between 2008 and 2011 and 26% reported cutting back on basics such as clothing and food. Family experience of recession was significantly associated with negative change in all of the components of the family stress model, particularly parental mental health. However, less than half of the effect of recession was mediated by the processes of the family stress model. Tests showed that a model with a direct effect of recession on child psychological adjustment provided a better fit to the data. CONCLUSIONS: Recession and economic pressure had a significant effect on child psychological adjustment, but only a minority of this effect was indirect via the mental health of parents and parent/child relationship. The family stress model only offers a partial account of the mechanisms through which economic hardship impacts on families and children.

Sub-clinical orthostatic hypotension is associated with greater subjective memory impairment in older adults.

INTRODUCTION: Orthostatic blood pressure (BP) is a measure of cardiovascular autonomic function. Orthostatic BP dysregulation may lie on the causal pathway to dementia. Subjective memory impairment (SMI) is commonly reported by older people some of whom may progress to dementia. We hypothesised that sub-clinical orthostatic hypotension would be associated with SMI and explored these associations according to sex. METHODS: Cross-sectional analysis of data from 4340 participants aged 50 and over collected during the first wave (2009-2011) of the cohort study, The Irish Longitudinal Study on Ageing. Subjective memory was rated according to a 5-point scale ranging from 'poor' to 'excellent'. BP was measured during orthostatic stress using continuous non-invasive beat-to-beat recording over 2 min. RESULTS: 2% reported 'poor' subjective memory, 12.3% 'fair' , 38% 'good', 33% 'very good' and 14.6% 'excellent'. After controlling for several potential confounding factors including cardiovascular risk, objective cognition, and depressive symptoms mean systolic orthostatic BP was lowest in those with poor subjective memory: 92.2 mmHg (CI95% = 87.1, 97.3) versus excellent 99.3 mmHg (CI95% = 97.4, 101.2); p = 0.011. Further adjustment for supine systolic BP suggested that men with poor subjective memory reached the lowest average systolic orthostatic BP and had the greatest impairment in systolic orthostatic BP stabilisation to baseline levels at 10 s post-stand (-6.64 mmHg; CI95% = -11.49, -1.79; p = 0.007). CONCLUSIONS: Sub-clinical orthostatic hypotension is associated with SMI, and there are sex-specific relationships evident in this population-based cohort. Subtle cardiovascular autonomic dysfunction may represent a modifiable risk marker at an early stage of cognitive decline in older adults. Copyright © 2016 John Wiley & Sons, Ltd.

The effect of pregnancy intention on maternal prenatal behaviours and parent and child health: results of an irish cohort study.

BACKGROUND: Unintended pregnancy is associated with increased risk for adverse neonatal and early childhood outcomes spanning an array of indicators, but it remains unclear whether these risks hold independent of other biological, social and environmental risk factors. METHODS: This study uses data from the first wave of the 'Growing Up in Ireland Study', a large nationally representative cohort study of more than 11 000 infants, to examine the risk factors associated with unintended pregnancy. Adopting a staged approach to the analysis, the study investigates whether pregnancy intention influences maternal health behaviours during pregnancy independent of background characteristics, and whether pregnancy intention carries any additional risk for adverse infant and maternal health outcomes when we adjust for background characteristics and prenatal behaviours. RESULTS: The study confirmed that sociodemographic factors are strongly associated with unintended pregnancy and that unintended pregnancy is associated with a range of health compromising behaviours that are known to be harmful to the developing fetus. While there was little evidence to suggest that pregnancy intention was associated with adverse neonatal outcomes or developmental delay independent of other covariates, there was strong evidence that intention status had a bearing on the mother's psychosocial health. Unintended pregnancy was associated with increased risk of depression (risk ratio 1.36 [95% confidence interval 1.19, 1.54]), and higher parenting stress (risk ratio 1.27 [95% confidence interval 1.16, 1.38]). CONCLUSIONS: Ascertaining the mother's pregnancy intention during the first antenatal visit may represent a means for monitoring those at greatest risk for adverse mother and child outcomes.

Paediatric chronic illness and educational failure: the role of emotional and behavioural problems.

BACKGROUND: Chronic illness in childhood is associated with worse educational outcomes. The association is usually explained via lowered cognitive development, decreased readiness to learn and school absence. However, this paper examines whether worse psychological adjustment may also play a role. METHODS: We use data from the Growing Up in Ireland study, a cohort study, which collected data on 8,568 nine-year-old children through the Irish national school system using a two-stage sampling method. Maximum likelihood path analytic models are used to assess the direct effect of child chronic illness on reading and maths test scores and the mediating role of emotional and behavioural problems. RESULTS: In unadjusted analyses, children with a mental and behavioural condition scored 14.5 % points less on reading tests and 16.9 % points less on maths tests than their healthy peers. Children with non-mental and behavioural conditions scored 3 % points less on both tests, a significant difference. Mental and behavioural (OR, 9.58) and other chronic conditions (OR, 1.61) were significantly more likely to have 'high' levels of difficulties on the SDQ. Path analysis models showed that the association between chronic illness and educational test scores was completely mediated by emotional and behavioural problems controlling for school absence and bullying by peers. CONCLUSIONS: Child and adolescent chronic illness can have significant effects on educational development and a long-lasting impact on future life-chances. The psychological adjustment of the child is important in mediating the effect of chronic illness on educational outcomes. Interventions should target this developmental pathway.

The effect of breastfeeding on neuro-development in infancy.

The present study examines whether breastfeeding is associated with neuro-developmental advantages at 9 months of age on a standardised measure of infant development in a large cohort study of Irish children. It is hypothesised that if breast-milk confers an independent benefit, infants who were never breastfed will have reached fewer developmental milestones than those who were partially or exclusively breastfed, after controlling for putative confounding variables. Families with infants aged 9-months were recruited as part of a nationally representative sample for the birth cohort of the Growing Up in Ireland study (n = 11,134). Information was collected from mothers on breastfeeding practices, socio-demographic characteristics and developmental progress during a household interview. Parent-report items on development covered communication, gross motor, fine motor, problem solving and personal-social skills. Analysis of pass/fail status in each developmental domain using binary logistic regression showed a positive effect of any breastfeeding on gross motor, fine motor, problem solving and personal-social skills (but not communication) and these remained after adjustment for a range of confounding variables. There was, however, little evidence of a dose-response effect or advantage of exclusive over partial breastfeeding. A clear advantage of breastfeeding on infant development was demonstrated. However, the lack of a dose-response association on pass rates suggests that the breastfeeding effect may be confounded by other unobserved factors or that there is a critical threshold during which time the effect of breast milk may be particularly salient for bolstering brain development.

Intergenerational Social Mobility and Allostatic Load in Midlife and Older Ages: A Diagonal Reference Modeling Approach.

OBJECTIVES: This study aims to understand the association of life-course intergenerational social mobility with allostatic load (AL) burden in midlife and older ages in Ireland. METHODS: The study involved biological data for 3,987 older adults participating in The Irish Longitudinal Study on Ageing (TILDA). Intergenerational social mobility was characterized using the cross-classification of origin socioeconomic position (SEP; i.e., father's occupation) and destination SEP (i.e., own occupation). AL was operationalized using 12 biomarkers tapping cardiovascular, metabolic, renal, and immune system dysregulation. Diagonal reference modeling (DRM) and ordinary least square regression techniques were applied to explore the effect of social mobility on AL burden. RESULTS: A total of 55.5% experienced intergenerational mobility: 37.5% were upwardly mobile, 18.0% were downwardly mobile. A social gradient in AL was observed among the socially non-mobile. Destination SEP (b = 0.74, 95% CI = 0.57, 0.92) predominated in influence over origin, although both life stages exerted significant influence on later-life AL. Social mobility in either direction was not associated with AL burden. Mobility coefficients were substantially small across a large variety of model specifications. DISCUSSION: Findings provide evidence for an accumulation model of social inequalities in which disparities in health are diluted rather than increased by social mobility (i.e., gradient constraint), with the socially mobile having an AL score that is intermediate between their origin class and destination class. This implies that the effects of origin SEP on health are not immutable, but are instead responsive to changing socioeconomic circumstances across the life course.

Metabolic syndrome accelerates epigenetic ageing in older adults: Findings from The Irish Longitudinal Study on Ageing (TILDA).

Metabolic syndrome (MetS) is a risk factor for the development of diabetes, cardiovascular disease, and all-cause mortality. It has an estimated prevalence of 40 % among older adults. Epigenetic clocks, which measure biological age based on DNA methylation (DNAm) patterns, are a candidate biomarker for ageing. GrimAge is one such clock which is based on levels of DNAm at 100 Cytosine-phosphate-Guanine (CpG) sites. This study hypothesised that those with MetS have 'accelerated ageing' (biological age greater than their chronological age) as indexed by GrimAge. This study examined MetS's association with GrimAge age acceleration (AA) using data from a subsample of 469 participants of the Irish Longitudinal Study on Ageing (TILDA). MetS was defined by National Cholesterol Education Program Third Adult Treatment Panel (ATP III) and International Diabetes Foundation (IDF) criteria, operationalised using the conventional binary cut-off, and as a count variable ranging from 0 to 5, based on the presence of individual components. This study also explored inflammation (as measured by C reactive protein) and metabolic dysfunction (as measured by adiponectin) as possible mediating factors between MetS and GrimAge AA. We found that MetS as defined by IDF criteria was associated with GrimAge AA of 0.63 years. When MetS was treated as a count, each unit increase in MetS score was associated with over 0.3 years GrimAge AA for both ATP III and IDF criteria. Inflammation mediated approximately one third of the association between MetS and GrimAge AA, suggesting that chronic subclinical inflammation observed in MetS has a relationship with DNAm changes consistent with a faster pace of ageing. Metabolic dysfunction mediated the association between MetS and GrimAge AA to a lesser extent (16 %). These data suggest that chronic subclinical inflammation observed in MetS has a relationship with DNAm changes consistent with a greater pace of ageing.

Examining the Impact of Socioeconomic Position Across the Life Course on Cognitive Function and Brain Structure in Healthy Aging.

This study explores the relationship of life-course intergenerational social mobility with cognitive function and brain structure in older adults using Diagonal Reference Models. Data from the Irish Longitudinal Study on Ageing, a population-based cohort of adults aged 50 years and older (N = 4 620 participants; mean age: 66.1; standard deviation: 9.1; 55% female) was used for analysis. Brain magnetic resonance imaging data were available for 464 participants. Social mobility was characterized as the difference between childhood socioeconomic position (SEP; ie, father's occupation) and adulthood SEP (ie, own occupation). The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), cortical thickness, and total gray matter volume (GMV) served as global cognitive and brain measures. Exploratory analyses included the volumes of the ventromedial prefrontal cortex (vmPFC), anterior cingulate (AC), hippocampus, and amygdala. A social gradient in cognitive function was observed among the intergenerationally stable; brain structure was not as clearly socially patterned. Adulthood SEP was significantly associated with MoCA (weight = 0.76; p < .001), MMSE (weight = 0.91; p < .001), GMV (weight = 0.77; p = .002), and AC volume (weight = 0.76; p < .001), whereas childhood SEP was associated with vmPFC volume (weight = 1.00; p = .003). There was no independent association of social mobility with any of the outcomes. Together our results suggest that both childhood and adulthood SEP are important in shaping later-life brain health, but that adulthood SEP predominates in terms of its influence. This is potentially an important insight as it suggests that brain health may be modifiable if socioeconomic circumstances change.

Life-course socioeconomic factors are associated with markers of epigenetic aging in a population-based study.

Adverse socioeconomic circumstances negatively affect the functioning of biological systems, but the underlying mechanisms remain only partially understood. Here, we explore the associations between life-course socioeconomic factors and four markers of epigenetic aging in a population-based setting. We included 684 participants (52 % women, mean age 52.6 ± 15.5 years) from a population and family-based Swiss study. We used nine life-course socioeconomic indicators as the main exposure variables, and four blood-derived, second generation markers of epigenetic aging as the outcome variables (Levine's DNAmPhenoAge, DunedinPoAm38, GrimAge epigenetic age acceleration (EAA), and the mortality risk score (MS)). First, we investigated the associations between socioeconomic indicators and markers of epigenetic aging via mixed-effect linear regression models, adjusting for age, sex, participant's recruitment center, familial structure (random-effect covariate), seasonality of blood sampling, and technical covariates. Second, we implemented counterfactual mediation analysis to investigate life-course and intermediate mechanisms underlying the socioeconomic gradient in epigenetic aging. Effect-size estimates were assessed using regression coefficients and counterfactual mediation parameters, along with their respective 95 % confidence intervals. Individuals reporting a low father's occupation, adverse financial conditions in childhood, a low income, having financial difficulties, or experiencing unfavorable socioeconomic trajectories were epigenetically older and had a higher mortality risk score than their more advantaged counterparts. Specifically, this corresponded to an average increase of 1.1-1.5 years for Levine's epigenetic age (ß and 95 %CI range, ß (minimum and maximum): 1.1-1.5 95 %CI[0.0-0.2; 2.3-3.0]), 1.1-1.5 additional years for GrimAge (ß: 1.1-1.5 95 %CI[0.2-0.6; 1.9-3.0]), a 1-3 % higher DunedinPoAm38 age acceleration (ß: 0.01-0.03 95 %CI[0.00; 0.03-0.04]), and a 10-50 % higher MS score (ß: 0.1-0.4 95 %CI[0.0-0.2; 0.3-0.4]) for the aforementioned socioeconomic indicators. By exploring the life-course mechanisms underlying the socioeconomic gradient in epigenetic aging, we found that both childhood and adulthood socioeconomic factors contributed to epigenetic aging, and that detrimental lifestyle factors mediated the relation between socioeconomic circumstances in adulthood and EAA (31-89 % mediated proportion). This study provides emerging evidence for an association between disadvantaged life-course socioeconomic circumstances and detrimental epigenetic aging patterns, supporting the "sensitive-period" life-course model. Counterfactual mediation analyses further indicated that the effect of socioeconomic factors in adulthood operates through detrimental lifestyle factors, whereas associations involving early-life socioeconomic factors were less clear.

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.

BACKGROUND: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. METHODS: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary (SAM) axis, parasympathetic nervous system functioning, oxidative stress, immunological/inflammatory, cardiovascular, respiratory, lipidemia, anthropometric, glucose metabolism, kidney, and liver. We use individual-participant-data meta-analysis and exploit natural heterogeneity in the number and type of biomarkers that have been used across studies, but a common set of health outcomes (grip strength, walking speed, and self-rated health), to determine the optimal configuration of parameters to define the concept. RESULTS: There was at least one biomarker within 9/12 physiological systems that was reliably and consistently associated in the hypothesised direction with the three health outcomes in the meta-analysis of these cohorts: dehydroepiandrosterone sulfate (DHEAS), low frequency-heart rate variability (LF-HRV), C-reactive protein (CRP), resting heart rate (RHR), peak expiratory flow (PEF), high density lipoprotein cholesterol (HDL-C), waist-to-height ratio (WtHR), HbA1c, and cystatin C. An index based on five biomarkers (CRP, RHR, HDL-C, WtHR and HbA1c) available in every study was found to predict an independent outcome - mortality - as well or better than more elaborate sets of biomarkers. DISCUSSION: This study has identified a brief 5-item measure of AL that arguably represents a universal and efficient set of biomarkers for capturing physiological 'wear and tear' and a further biomarker (PEF) that could usefully be included in future data collection.