The biology of inequalities in health: The LIFEPATH project

Socioeconomic differences in health have been consistently observed worldwide. Physical health deteriorates more rapidly with age among men and women with lower socioeconomic status (SES) than among those with higher SES. The biological processes underlying these differences are best understood by adopting a life course approach. In this paper we introduce the pan- European LIFEPATH project which uses multiple cohorts - including biomarker data - to investigate ageing as a phenomenon with two broad stages across life: build-up and decline. The ‘build-up’ stage, from conception and early intra-uterine life to late adolescence or early twenties, is characterised by rapid successions of developmentally and socially sensitive periods. The second stage, starting in early adulthood, is a period of ‘decline’ from maximum attained health to loss of function, overt disease and death. LIFEPATH adopts a study design that integrates social science and public health approaches with biology (including molecular epidemiology), using well-characterised population cohorts and omics measurements (particularly epigenomics). LIFEPATH includes information and biological samples from 17 cohorts, including several with extensive phenotyping and repeat biological samples, and a very large cohort (1 million individuals) without biological samples (WHIP, from Italy). The countries that are covered by the cohorts are France, Italy, Portugal, Ireland, UK, Finland, Switzerland and Australia. These cohorts are only a small proportion of all cohorts available in Europe, but we have chosen them for the combination of good measures of socioeconomic status, risk factors for non-communicable diseases (NCDs) and biomarkers already measured (or availability of blood samples for further testing). The majority of cohorts include ‘hard’ outcomes (diabetes, cancer, Cardiovascular Disease (CVD), total mortality), and the extensively phenotyped cohorts also include several measurements of the functional components of healthy ageing, including frailty, impaired vision, cognitive function, renal and brain function, osteoporosis, sleep disturbances and mental health. All age groups are represented with two birth cohorts, one cohort of adolescents and several cohorts encompassing young adults (age 18 and above). Furthermore, there is a strong representation of elderly subjects in seven cohorts. The specific objectives of the project are: (a) to show that healthy ageing is an achievable goal for society; (b) to improve the understanding of the mechanisms through which healthy ageing pathways diverge by SES, by investigating life course biological pathways using omic technologies; (c) to examine the consequences of the current economic recession on health and the biology of ageing (and the consequent increase in social inequalities); (d) to provide updated, relevant and innovative evidence for healthy ageing policies (particularly ‘health in all policies’) using both observational studies and an experimental approach based on a reanalysis of data from a ‘conditional cash transfer’ randomised experiment in New York and new data collected as part of an earned income tax credit randomised experiment in Atlanta and New York. To achieve these objectives, data are used from three categories of studies: 1. national census-based followup data to obtain mortality by socioeconomic status; 2. cohorts with intense phenotyping and repeat biological samples; 3. large cohorts with biological samples. With these objectives and methodologies, LIFEPATH seeks to provide updated, relevant and innovative evidence to underpin future policies and strategies for the promotion of healthy ageing, targeted disease prevention and clinical interventions that address the issue of social disparities in ageing and the social determinants of health. The present paper describes the design and some initial results of LIFEPATH as an example of the integration of social and biological sciences to provide evidence for public health policies

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: A multi-cohort analysis

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: A multi-cohort analysis

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: A multi-cohort analysis

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity

A Longitudinal Study of Transitions Between Informal and Formal Care in Alzheimer Disease Using Multistate Models in the European ICTUS Cohort.

Item does not contain fulltextBACKGROUND: We aimed to describe longitudinal patterns of care in community-dwelling European patients with Alzheimer disease (AD), and determine patient-, caregiver-, and country-related predictors of transitions across different care levels. METHODS: Two-year follow-up data from ICTUS cohort (1375 patients with AD, 12 countries) were analyzed using multistate Markov models to describe transitions across states of care and identify their predictors. Results : Of the patients, 61.3% stayed in the same state during follow-up, and only 9.5% experienced >/=2 changes between states. Six-month transition probabilities were 11% for informal to formal care and 13% for formal to informal care (in the community). Older age, male gender, poorer cognitive and behavioral scores, and country of residence were associated with transitioning from informal to formal care, but only country of residence was associated with the reverse transition. DISCUSSION: Changes between different types of care were rare during follow-up, and country factors in particular influenced these transitions

Living alone with alzheimer's disease and the risk of adverse outcomes : results from the plan de soin et d'aide dans la maladie d'Alzheimer study

Objectives To examine whether living alone predicted hospitalizations, nursing home admission, weight loss, and death in individuals with mild to moderate Alzheimer's disease (AD) over 2 years of follow-up. Design Data are from the Plan de Soin et d'Aide dans la maladie d'Alzheimer study, a 24-month trial with a cluster randomization of memory clinics in two arms: a multidomain intervention and usual care. Setting Memory clinics in France (N = 50). Participants Community-dwelling individuals with AD with a Mini-Mental State Examination score between 12 and 26 and an identified caregiver. Measurements A neurogeriatric evaluation was conducted twice a year in the intervention group and annually in the control group. Hospitalizations, nursing home admission, weight loss, and death occurring during the past year were recorded. Information on sociodemographic characteristics, clinical conditions, therapy, and physical and cognitive status was recorded. Results At inclusion, 348 (30.8%) of the 1,131 participants lived alone. Living alone did not increase the risk of mortality or weight loss in individuals with mild to moderate AD, but significant associations with risk of hospitalization (hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 1.01-1.74) and institutionalization (HR = 2.53, 95% CI = 1.84-3.47) were reported. A protective effect of physical function on institutionalization and mortality was found. Conclusion These results might support clinicians in making decisions about institutionalization of individuals with AD living alone or improving home health care, such as increasing screening and managing functional impairment in this complex population