The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

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.

High prevalence of frequent attendance in the over 65s.

INTRODUCTION: Characteristics of older frequent users of Emergency Departments (EDs) are poorly understood. Our aim was to examine the characteristics of the ED frequent attenders (FAs) by age (under 65 and over 65 years). METHODS: We examined the prevalence of FA attending the ED of an Urban Teaching Hospital in a cross-sectional study between 2009 and 2011. FA was defined as an individual who presented to the ED four or more times over a 12-month period. Randomly selected groups of FA and non-FA from two age groups (under 65 and over 65 years) were then examined to compare the characteristics between older FAs and non-FAs and older FAs and younger FAs. Logistic regression was used to calculate the odds ratio and 95% confidence intervals for 12-month mortality in FA compared with non-FA aged at least 65 years. RESULTS: Overall, 137 150 ED attendances were recorded between 2009 and 2011. A total of 21.6% were aged at least 65 years, 4.4% of whom were FAs, accounting for 18.4% of attendances by patients older than 65 years. There was a bimodal age distribution of FA (mean±SD; under 65 years 40±12.7; and over 65 years 76.9±7.4). Older FAs were five times more likely to present outside normal working hours and 5.5 times more likely to require admission. Cardiovascular emergencies were the most common complaint, in contrast with the younger FA group, where injury and psychosocial conditions dominated. The odds ratio for death at 12 months was 2.07 (95% confidence interval 0.93-4.63; P=0.07), adjusting for age and sex. CONCLUSION: One-in-five ED patients older than 65 years of age are FAs. Older FAs largely present with complex medical conditions. Enhanced access to expert gerontology assessment should be considered as part of effective intervention strategies for older ED users.

Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation.

Low socioeconomic status (SES) is associated with earlier onset of age-related chronic conditions and reduced life-expectancy, but the underlying biomolecular mechanisms remain unclear. Evidence of DNA-methylation differences by SES suggests a possible association of SES with epigenetic age acceleration (AA). We investigated the association of SES with AA in more than 5,000 individuals belonging to three independent prospective cohorts from Italy, Australia, and Ireland. Low SES was associated with greater AA (ß = 0.99 years; 95% CI 0.39,1.59; p = 0.002; comparing extreme categories). The results were consistent across different SES indicators. The associations were only partially modulated by the unhealthy lifestyle habits of individuals with lower SES. Individuals who experienced life-course SES improvement had intermediate AA compared to extreme SES categories, suggesting reversibility of the effect and supporting the relative importance of the early childhood social environment. Socioeconomic adversity is associated with accelerated epigenetic aging, implicating biomolecular mechanisms that may link SES to age-related diseases and longevity.

Quantitative falls risk estimation through multi-sensor assessment of standing balance.

Falls are the most common cause of injury and hospitalization and one of the principal causes of death and disability in older adults worldwide. Measures of postural stability have been associated with the incidence of falls in older adults. The aim of this study was to develop a model that accurately classifies fallers and non-fallers using novel multi-sensor quantitative balance metrics that can be easily deployed into a home or clinic setting. We compared the classification accuracy of our model with an established method for falls risk assessment, the Berg balance scale. Data were acquired using two sensor modalities--a pressure sensitive platform sensor and a body-worn inertial sensor, mounted on the lower back--from 120 community dwelling older adults (65 with a history of falls, 55 without, mean age 73.7 ± 5.8 years, 63 female) while performing a number of standing balance tasks in a geriatric research clinic. Results obtained using a support vector machine yielded a mean classification accuracy of 71.52% (95% CI: 68.82-74.28) in classifying falls history, obtained using one model classifying all data points. Considering male and female participant data separately yielded classification accuracies of 72.80% (95% CI: 68.85-77.17) and 73.33% (95% CI: 69.88-76.81) respectively, leading to a mean classification accuracy of 73.07% in identifying participants with a history of falls. Results compare favourably to those obtained using the Berg balance scale (mean classification accuracy: 59.42% (95% CI: 56.96-61.88)). Results from the present study could lead to a robust method for assessing falls risk in both supervised and unsupervised environments.

Assessment of cognitive decline through quantitative analysis of the timed up and go test.

Cognitive decline and dementia have emerged as major challenges in modern healthcare with enormous associated societal and economic costs. Shifting demographics, owing to increasing numbers of people aged over 65 have greatly increased the potential scale of this problem in years to come. We report a novel quantitative method for assessment of cognitive decline (defined as a decline in mini mental state examination (MMSE) score of three or more) using quantitative parameters derived from body-worn inertial sensors. We sought to determine if baseline quantitative parameters and changes from baseline at follow-up, in those parameters could be used to automatically classify participants as cognitively declined or intact. Quantitative movement parameters were obtained at a baseline clinical assessment and in a follow-up assessment approximately 2 years later, using shank mounted triaxial gyroscopes. Data were obtained from 189 community dwelling older adults (aged over 60, 59 male, 130 female, mean age: 70.43 ± 6.57) while performing the timed up and go test. Nine participants who were deemed to be cognitively impaired at baseline (MMSE < 24) were excluded from analysis. Results suggest that quantitative parameters measured at baseline are 75.94% accurate in predicting cognitive decline in participants who were cognitively intact at baseline. A combination of baseline quantitative movement parameters and the change at follow-up (compared to baseline) in these parameters were 88.78% accurate in classifying final cognitive status in participants deemed cognitively intact at baseline. The reported method may be suitable for use as a portable cognitive screening tool, prompting further specialist clinical investigation and may also form part of a tool for longitudinal monitoring of cognitive function.

Quantitative falls risk assessment using the timed up and go test.

Falls are a major problem in older adults worldwide with an estimated 30% of elderly adults over 65 years of age falling each year. The direct and indirect societal costs associated with falls are enormous. A system that could provide an accurate automated assessment of falls risk prior to falling would allow timely intervention and ease the burden on overstretched healthcare systems worldwide. An objective method for assessing falls risk using body-worn kinematic sensors is reported. The gait and balance of 349 community-dwelling elderly adults was assessed using body-worn sensors while each patient performed the "timed up and go" (TUG) test. Patients were also evaluated using the Berg balance scale (BBS). Of the 44 reported parameters derived from body-worn kinematic sensors, 29 provided significant discrimination between patients with a history of falls and those without. Cross-validated estimates of retrospective falls prediction performance using logistic regression models yielded a mean sensitivity of 77.3% and a mean specificity of 75.9%. This compares favorably to the cross-validated performance of logistic regression models based on the time taken to complete the TUG test (manually timed TUG) and the Berg balance score. These models yielded mean sensitivities of 58.0% and 57.8%, respectively, and mean specificities of 64.8% and 64.2%, respectively. Results suggest that this method offers an improvement over two standard falls risk assessments (TUG and BBS) and may have potential for use in supervised assessment of falls risk as part of a longitudinal monitoring protocol.

Impact of a dedicated syncope and falls facility for older adults on emergency beds.

BACKGROUND: syncope and falls are common symptoms in older adults. Dedicated facilities for these symptoms are emerging in the UK. To date, justification for resource allocation for these day case facilities is lacking. A dedicated syncope and falls day case facility for older adults was set up in Newcastle in 1991 (at the Royal Victoria Infirmary). The facility provided rapid access for assessment of appropriate patients from the community, the accident and emergency department, or emergency admissions. Activity and performance in 1999 were compared with peer inner-city teaching hospitals and with previous performance in 1990 at the Royal Victoria Infirmary to determine whether the facility had influenced emergency activity. OBJECTIVE: to describe the impact of the facility on emergency bed activity and performance for the diagnostic categories of syncope, falls, collapses, gait abnormalities and dizziness. DESIGN: descriptive study. SETTING: syncope and falls day case facility. METHODS: performance and activity for Healthcare Resource Groups and ICD codes relevant to falls and syncope were compared for adults over 65 years attending the Royal Victoria Infirmary and thirteen peer hospitals. Activity and performance before the facility was set up (1990) at the Royal Victoria Infirmary were also compared with 1999 data. RESULTS: syncope and collapse is the 6th commonest reason for acute hospital attendance of over 65-year olds in the UK. In 1999, the Royal Victoria Infirmary was at variance by-6616 bed days compared with other the other Trusts for these diagnoses. This equates to 18 beds occupied in that year. The degree of emergency activity for the relevant diagnoses (Healthcare Resource Groups data) was much less than at peer trusts-35% versus 97%. The average length of stay for admitted patients was also shorter for Royal Victoria Infirmary than peers-2.4 versus 8.6 days. Acute length of stay at the Royal Victoria Infirmary was reduced from 10.9 days in 1990 to 2.7 days in 1999 (ICD 10 data). In 1991 all activity was emergency. CONCLUSION: the striking variance in bed days in 1999 is due to lower emergency activity and shorter length of stay at the Royal Victoria Infirmary. This is attributed to the dedicated rapid access day-case facility. This has relevant resource implications for planning of future facilities and implementation of National Service Framework standards for falls and intermediate care.