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Background While childhood social risk factors appear to be associated with adult obesity, it is unclear whether exposure to multiple childhood social risk factors is associated with accelerated weight gain during adulthood. Methods We used the Medical Research Council National Survey of Health and Development, a British population-based birth cohort study of participants born in 1946, height and weight were measured by nurses at ages 36, 43, 53 and 60–64 and self-reported at 20 and 26 years. The 9 childhood socioeconomic risk factors and 8 binary childhood psychosocial risk factors were measured, with 13 prospectively measured at age 4 years (or at 7 or 11 years if missing) and 3 were recalled when participants were age 43. Multilevel modelling was used to examine the association between the number of childhood social risk factors and changes in body mass index (BMI) with age. Results Increasing exposure to a higher number of childhood socioeconomic risk factors was associated with higher mean BMI across adulthood for both sexes and with a faster increase in BMI from 20 to 64 years, among women but not men. Associations remained after adjustment for adult social class. There was no evidence of an association between exposure to childhood psychosocial risk factors and mean BMI in either sex at any age. Conclusions Strategies for the prevention and management of weight gain across adulthood may need to tailor interventions in consideration of past exposure to multiple socioeconomic disadvantages experienced during childhood.

Background Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. Methods Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. Results The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. Conclusion This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from dual‐energy X‐ray absorptiometry scans in 1327 individuals (688 female) at 60 to 64 years in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two‐line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position, and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient, 0.023; 95% CI, 0.000‐0.047; P = .05) and direct angle measurement. Modest associations between walking age and less variation in anterior‐posterior vertebral size caudally (SSM6) were also observed (0.021; 95% CI, −0.002 to 0.044; P = .07). Sex interactions showed that later walking was associated with larger relative vertebral anterior‐posterior dimensions in men (SSM3; −0.043; 95% CI, −0.075 to 0.01; P = .01) but not women (0.018; 95% CI, −0.0007 to 0.043; P = .17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on the features of spine morphology with clinical significance.

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Background DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect/s of ageing it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline. Methods AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed and forced expiratory volume in one second[FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed. Results AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n=1388-1685). For example, a one year increase in AgeAccelPheno/AgeAccelGrim was associated with a 0.01ml[95%CI:0.01,0.02]/0.03ml[95%CI:0.01,0.05] lower mean FEV1. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p, This work was supported by the Economic and Social Research Council/Biotechnology and Biological Sciences Research Council [ES/N000404/1] and the UK Medical Research Council (MC_UU_12015/2).The UK Medical Research Council also provides core funding for the MRC National Survey of Health and Development and support for AW, RC, DK and RH [MC_UU_12019/1, MC_UU_12019/2, MC_UU_12019/4]. JM is supported by CLOSER through the Economic and Social Research Council [547821 GA3 ESRC]. The TwinsUK study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007–2013); National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London

Background In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life. Methods Participants were from the Medical Research Council National Survey of Health and Development (n = 1376). Four DNAm age acceleration (AgeAccel) biomarkers were measured when participants were aged 53 years: AgeAccelHannum; AgeAccelHorvath; AgeAccelLevine; and AgeAccelGrim. Exposure variables included: relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores); and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0–2 years, weight gain only), early childhood (2–4 years), middle childhood (4–7 years) and late childhood to adolescence (7–15 years); age at menarche; and pubertal stage for men at 14–15 years. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study (NCDS). Results A 1SD increase in relative weight gain in late childhood to adolescence was associated with 0.50 years (95% CI 0.20, 0.79) higher AgeAccelGrim. Although the CI includes the null, the estimate was similar in NCDS [0.57 years (95% CI − 0.01, 1.16)] There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥ 12 years had 1.20 years (95% CI 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche Conclusions Our findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, we found rapid weight gain during pubertal development, previously related to higher cardiovascular disease risk, to be associated with older AgeAccelGrim. Given this is an exploratory study, this finding requires replication.

BMI is correlated with circulating metabolites, but few studies discuss other adiposity measures, and little is known about metabolomic correlates of BMI from early life. We investigated associations between different adiposity measures, BMI from childhood through adulthood, and metabolites quantified from serum using (1)H NMR spectroscopy in 900 British men and women aged 60–64. We assessed BMI, waist-to-hip ratio (WHR), android-to-gynoid fat ratio (AGR), and BMI from childhood through adulthood. Linear regression with Bonferroni adjustment was performed to assess adiposity and metabolites. Of 233 metabolites, 168; 126; and 133 were associated with BMI, WHR, and AGR at age 60–64, respectively. Associations were strongest for HDL, particularly HDL particle size—e.g., there was 0.08 SD decrease in HDL diameter (95% CI: 0.07–0.10) with each unit increase in BMI. BMI-adjusted AGR or WHR were associated with 31 metabolites where there was no metabolome-wide association with BMI. We identified inverse associations between BMI at age 7 and glucose or glycoprotein at age 60–64 and relatively large LDL cholesteryl ester with postadolescent BMI gains. In summary, we identified metabolomic correlates of central adiposity and earlier-life BMI. These findings support opportunities to leverage metabolomics in early prevention of cardiovascular risk attributable to body fatness.

ObjectiveTo examine the associations of infertility, recurrent miscarriage, and stillbirth with the risk of first non-fatal and fatal stroke, further stratified by stroke subtypes.DesignIndividual participant pooled analysis of eight prospective cohort studies.SettingCohort studies across seven countries (Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012.Participants618 851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage, or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93 119 women were excluded. Of the participants, 275 863 had data on non-fatal and fatal stroke, 54 716 only had data on non-fatal stroke, and 288 272 only had data on fatal stroke.Main outcome and measuresNon-fatal strokes were identified through self-reported questionnaires, linked hospital data, or national patient registers. Fatal strokes were identified through death registry data.ResultsThe median follow-up for non-fatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) experienced a fatal stroke. Hazard ratios for non-fatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with higher risk of non-fatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively). Women with stillbirth were at 31% higher risk of non-fatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth were at 26% higher risk of fatal stroke (1.26, 1.15 to 1.39). The increased risk of stroke (non-fatal or fatal) associated with infertility or recurrent stillbirths was mainly driven by a single stroke subtype (non-fatal ischaemic stroke and fatal haemorrhagic stroke), while the increased risk of stroke (non-fatal or fatal) associated with recurrent miscarriages was driven by both subtypes.ConclusionA history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes. These findings could contribute to improved monitoring and stroke prevention for women with such a history.

ObjectivesTo investigate whether cross-sectional and longitudinal associations of body mass index (BMI) and waist circumference (WC) with back pain change with age and extend into later life.DesignBritish birth cohort study.SettingEngland, Scotland and Wales.ParticipantsUp to 3426 men and women from the MRC National Survey of Health and Development.Primary outcome measuresBack pain (sciatica, lumbago or recurring/severe backache all or most of the time) was self-reported during nurse interviews at ages 36, 43, 53 and 60–64 years and in a postal questionnaire using a body manikin at age 68.ResultsFindings from mixed-effects logistic regression models indicated that higher BMI was consistently associated with increased odds of back pain across adulthood. Sex-adjusted ORs of back pain per 1 SD increase in BMI were: 1.13 (95% CI: 1.01 to 1.26), 1.11 (95% CI: 1.00 to 1.23), 1.17 (95% CI: 1.05 to 1.30), 1.31 (95% CI: 1.15 to 1.48) and 1.08 (95% CI: 0.95 to 1.24) at ages 36, 43, 53, 60–64 and 68–69, respectively. Similar patterns of associations were observed for WC. These associations were maintained when potential confounders, including education, occupational class, height, cigarette smoking status, physical activity and symptoms of anxiety and depression were accounted for. BMI showed stronger associations than WC in models including both measures.ConclusionsThese findings demonstrate that higher BMI is a persistent risk factor for back pain across adulthood. This highlights the potential lifelong consequences on back pain of the rising prevalence of obesity within the population.

Highlights • Prolonged heavy drinkers had higher levels of NT-proBNP, an important cardiac biomarker for heart failure, than moderate drinkers. • This suggests a pathway through which prolonged heavy alcohol consumption may increase risk of this cardiovascular disease. • Heavy drinkers could be screened for NT-proBNP levels to identify those at high risk earlier in the clinical stages of heart failure and targeted for risk reduction strategies., Heavy alcohol consumption is associated with an increased risk of heart failure. We sought to investigate whether levels of NT-proBNP differ by alcohol consumption profiles, both current drinking as well as cumulative exposure to drinking over several decades in a general population sample. Methods Data on 2054 participants (49% male) were taken from the UK Medical Research Council National Survey for Health and Development, a longitudinal cohort study based on a nationally representative sample of births in 1946. Categories of long-term alcohol consumption were created based on consumption over 25 years of observations and compared with levels of NT-proBNP measured at mean age 63. Results We found that those who drank heavily (both currently and long-term) had higher levels of NT-proBNP than moderate drinkers, after adjusting for major confounders (age, sex, socio-economic position and smoking). As NT-proBNP has attracted attention as a biomarker for heart failure, this suggests a critical pathway through which heavy drinking may increase risk of this cardiovascular disease. When we looked at heavy drinkers who varied their intake over the decades, it was only the recently heavy group that had higher levels of NT-proBNP. Further work is needed to demonstrate whether effects are reversible upon cessation of heavy drinking, but this finding highlights the need to have repeated data to unpack dynamics over time. Conclusion Our findings suggest heavy drinkers could be screened for NT-proBNP levels in order to identify those at high risk earlier in the clinical stages of heart failure and targeted for risk reduction strategies.

Importance Associations between affective symptoms and mortality have been evaluated, but studies have not examined timing or cumulative exposure to affective symptoms over the life course. Objectives To examine how lifetime accumulation and timing of affective symptoms are associated with mortality and identify potential explanatory factors. Design, Setting, and Participants Data were obtained from the MRC National Survey of Health and Development (1946 British birth cohort), a socially stratified, population-based sample originally consisting of 5362 singleton births in England, Wales, and Scotland during March 1946. The cohort has been followed up 24 times, most recently in 2014-2015. Eligible participants included those flagged for mortality with affective symptom data available at a minimum of 3 time points (n = 3001). Data analysis was conducted from July 2016 to January 2019. Exposures Affective symptoms were assessed at ages 13 to 15 years (teacher-rated questionnaire), 36 years (Present State Examination clinical semistructured interview), 43 years (Psychiatric Symptom Frequency questionnaire), and 53 years (General Health Questionnaire–28). Case-level affective symptoms were determined by those scoring in the top 16th percentile (ie, suggestive of a clinical diagnosis). Main Outcomes and Measures Mortality data were obtained from the UK National Health Service Central Register from age 53 to 68 years. Results Of 3001 study members (1509 [50.3%] female, 1492 [49.7%] male), 235 individuals (7.8%) died over a 15-year follow-up. After adjustment for sex, those who experienced case-level affective symptoms 1, 2, and 3 to 4 times had 76%, 87%, and 134% higher rates of premature mortality, respectively, compared with those who never experienced case-level symptoms. Case-level symptoms in adolescence only (ages 13-15 years) were associated with a 94% increased rate of mortality, which was unexplained after full adjustment for covariates (hazard ratio, 1.73; 95% CI, 1.10-2.72). Associations between participants with case-level symptoms multiple (2-4) times and mortality were predominately explained by adult health indicators and behaviors. For example, associations for those with case-level symptoms 3 to 4 times were most strongly attenuated by number of health conditions (32.1%), anxiolytic use (28.4%), lung function (24.6%), physical activity (23.9%), smoking (24.6%), antidepressant use (20.1%), diet (16.4%), pulse rate (12.7%), and adult social class (11.2%). Conclusions and Relevance Lifetime accumulation of affective symptoms may be associated with an increased rate of mortality, with explanatory pathways dependent on the duration and timing of symptoms. Future research into causal pathways and potential points of intervention should consider affective symptom history.

Background Poor performance in physical tests such as grip strength and walking speed is a risk factor for disability in old age, although whether such measures improve the discrimination of clinical prediction models when traditional clinical risk factors are already known is not clear. The prevalence of disability in mid-life is relatively low and hence screening in this age group may present an opportunity for early identification of those at increased future risk who may benefit most from preventative interventions. Methods Data were drawn from two waves of the Medical Research Council National Survey of Health and Development. We examined whether several chronic conditions, poor health behaviours and lower scores on three measures of physical performance (grip strength, chair rise speed and standing balance time) at age 53 were associated with self-reported mobility and/or personal care disability at age 69. We used the area under the curve statistic (AUC) to assess model discrimination. Results At age 69, 44% (826/1855) of participants reported mobility and/or personal care disability. Our final clinical prediction model included sex, knee osteoarthritis, taking 2+ medications, smoking, increased BMI and poor performance in all three physical tests, with an AUC of 0.740 compared with 0.708 for a model which did not include the performance measures. Conclusion Measures of physical performance in midlife improve discrimination in clinical prediction models for disability over 16 years. Importantly, these and similar measures are also potential targets of future diet, exercise and pharmacological intervention in mid-life.

Summary Background Evidence of the possible health benefits of social connectedness is increasing. We aimed to examine poor social connectedness as a possible barrier to participation in preventive health services among older people (aged 53–69 years). Methods We analysed data from a prospective cohort study of 5362 socially stratified births from the Medical Research Council National Survey of Health and Development enrolled in England, Scotland, and Wales in March 1946. At ages 68–69 years, participants reported participation in blood pressure and cholesterol measurement, eyesight and dental check-ups, influenza immunisation, and bowel and breast cancer screening. Our primary outcome measure summed participation across all these tests and services at ages 68–69 years. We tested associations between structural and functional social connectedness from ages 53 years to 69 years and total count of participation in these preventive services in Poisson models controlling for sex, education, occupational class, employment, chronic illnesses, and general practitioner consultations for health problems. Findings 940 (44%) of 2132 participants attended all preventive services within the recommended timeframes. At ages 68–69 years, being unmarried or not cohabiting (incident rate ratio [IRR] 1·33, 95% CI 1·20–1·47) and small personal social networks (IRR 1·51, 1·32–1·71) were independently associated with non-participation in more services, with associations consistent across most services. High social relationship quality at ages 68–69 years (IRR 0·91, 95% CI 0·87–0·95) and increasing social relationship quality from ages 53 years to 69 years (IRR 0·93, 0·89–0·97) were associated with low risk of non-participation. Interpretation Individuals with poor social connectedness appear to be at greater risk of not engaging in the full range of preventive services than individuals with good social connectedness. Improvement of access to social contacts and networks in older ages is already recommended for the maintenance of good mental health. This study suggests that social connectedness could also improve participation in a wide range of preventive health services, and hence could improve use of the health-care system and population health. Funding UK Medical Research Council.

Background Exposure to higher magnitude vertical impacts is thought to benefit bone health. The correlates of this high-impact physical activity (PA) in later life are unknown.Methods Participants were from the Cohort for Skeletal Health in Bristol and Avon, Hertfordshire Cohort Study and MRC National Survey of Health and Development. Associations of demographic, behavioural, physiological and psychological factors with vertical acceleration peaks ≥1.5 g (i.e. high-impact PA) from 7-day hip-worn accelerometer recordings were examined using linear regression.Results A total of 1187 participants (mean age = 72.7 years, 66.6% females) were included. Age, sex, education, active transport, self-reported higher impact PA, walking speed and self-rated health were independently associated with high-impact PA whereas BMI and sleep quality showed borderline independent associations. For example, differences in log-high-impact counts were 0.50 (P < 0.001) for men versus women and −0.56 (P < 0.001) for worst versus best self-rated health. Our final model explained 23% of between-participant variance in high impacts. Other correlates were not associated with high-impact activity after adjustment.Conclusions Besides age and sex, several factors were associated with higher impact PA in later life. Our findings help identify characteristics of older people that might benefit from interventions designed to promote osteogenic PA.

BackgroundThere are substantial socioeconomic inequalities in functional limitations in old age. Resilience may offer new insights into these inequalities by identifying constellations of factors that protect some individuals from developing functional limitations despite socioeconomic adversity.MethodsData from 1973 participants in the Medical Research Council National Survey of Health and Development (Great Britain), followed from birth until age 60–64, were used. Functional limitations were defined as reporting difficulty with at least 1 of 16 activities at age 60–64. Lifetime socioeconomic adversity was based on socioeconomic trajectories, categorised into three adversity levels. Analysis of covariance and regression models were used to compare psychosocial factors and health-related behaviours between a ‘Resilient’ group (high adversity but no functional limitations) and five groups with other combinations of adversity and limitations.ResultsPrevalence of functional limitations in high, intermediate and low adversity groups was 44%, 30% and 23% in men, and 61%, 55% and 49% in women, respectively. Compared with the other high adversity group, the resilient group had a lower prevalence of childhood illness (12% vs 19%) and obesity throughout ages 43–64 (70% vs 55%). Partially adjusted models also showed higher adolescent self-management, lower neuroticism, higher prevalence of volunteer work and physical activity (age 60–64) and lower prevalence of smoking (age 43) in the resilient. Marital status and contact frequency were not associated with resilience.ConclusionResults suggest protection against childhood illness, health-behavioural factors and self-regulation as targets for interventions across life that may particularly benefit those with long-term exposure to socioeconomic adversity.

ObjectivesTo test whether developmental factors are associated with grip strength trajectories between 53 and 69 years, and operate independently or on the same pathway/s as adult factors.DesignBritish birth cohort study.SettingEngland, Scotland and Wales.Participants3058 men and women.Main outcome measuresGrip strength (kg) at ages 53, 60–64 and 69 were analysed using multilevel models to estimate associations with developmental factors (birth weight, growth parameters, motor and cognitive development) and father’s social class, and investigate adult factors that could explain observed associations, testing for age and sex interactions.ResultsIn men, heavier birth weight, beginning to walk ‘on time’, later puberty and greater weight 0–26 years and in women, heavier birth weight and earlier age at first standing were independently associated with stronger grip but not with its decline. The slower decline in grip strength (by 0.07 kg/year, 95% CI 0.02 to 0.11 per 1 SD, p=0.003) in men of higher cognitive ability was attenuated by adjusting for adult verbal memory.ConclusionsPatterns of growth and motor development have persisting associations with grip strength between midlife and old age. The strengthening associations with cognition suggest that, at older ages, grip strength increasingly reflects neural ageing processes. Interventions across life that promote muscle development or maintain muscle strength should increase the chance of an independent old age.

Objectives The life course determinants of midlife and later life cognitive function have been studied using longitudinal population-based cohort data, but far less is known about whether the pattern of these pathways is similar or distinct for clinically relevant cognitive state. We investigated this for Addenbrooke’s Cognitive Examination third edition (ACE-III), used in clinical settings to screen for cognitive impairment and dementia. Design Longitudinal birth cohort study. Setting Residential addresses in England, Wales and Scotland. Participants 1762 community-dwelling men and women of European heritage, enrolled since birth in the Medical Research Council (MRC) National Survey of Health and Development (the British 1946 birth cohort). Primary outcome ACE-III. Results Path modelling estimated direct and indirect associations between apolipoprotein E (APOE) status, father’s social class, childhood cognition, education, midlife occupational complexity, midlife verbal ability (National Adult Reading Test; NART), and the total ACE-III score. Controlling for sex, there was a direct negative association between APOE ε4 and the ACE-III score (β=−0.04 [–0.08 to –0.002], p=0.04), but not between APOE ε4 and childhood cognition (β=0.03 [–0.006 to 0.069], p=0.10) or the NART (β=0.0005 [–0.03 to 0.03], p=0.97). The strongest influences on the ACE-III were from childhood cognition (β=0.20 [0.14 to 0.26], p

Background Previous studies linking social activity and disability have been limited by focussing on self-reported physical performance in older adults (>65). We examined whether social participation in mid-life is associated with objective and subjective measures of physical performance in older age. Methods Participants of the Medical Research Council National Survey of Health and Development reported their involvement in social activities at ages 43 and 60–64 years; frequency of such involvement was classified into thirds. Physical performance was measured at age 60–64 using: grip strength; standing balance; chair rises; timed get-up-and-go; self-reported physical function from the Short Form-36. Multivariable regression was used to examine longitudinal associations between social participation and each physical performance measure. We also investigated whether change in social participation between 43 and 60–64 was associated with each outcome. Results In fully adjusted models, higher frequency of social participation at 43 was associated with faster chair rise (1.42 repetitions/min, 95% CI 0.45–2.39) and timed get-up-and-go speed (2.47 cm/s, 95% CI 0.27–4.67) and lower likelihood of self-report limitations (OR of low physical function 0.67, 95% CI 0.50–0.91) at 60–64 compared with low frequency. Better performance in objectively measured outcomes was observed only if higher social participation persisted over time whereas lower odds of self-reported limitations were found in all groups when compared to those with persistently low participation (ORs 0.43–0.56, all P≤0.02). Conclusion Our findings suggest that associations between higher levels of social participation in mid-life and better physical performance exist only if this social participation persists through to older age.

Physical capability, a key component of healthy aging, is associated with cardiovascular and other risk factors across life. We investigated whether midlife biomarkers of heart and kidney damage capturing the cumulative impact of long-term adverse exposures were associated with the level and decline in physical capability over 9 years of follow-up, taking account of systemic inflammatory biomarkers and conventional cardiovascular risk factors.We used data on 1736 men and women from the oldest British birth cohort study with walking speed, chair rise speed, balance time, and grip strength assessed at ages 60 to 64 and 69 years. We tested associations between logged and standardized measures of cystatin C, NT-proBNP (N-terminal pro-B-type natriuretic peptide), interleukin (IL)-6, and E-selectin at age 60 to 64 years with performance at age 69 years, adjusting for sex, height, and body mass index; then for performance at age 60 to 64 years. These biomarkers were mutually adjusted, and additionally adjusted for cardiovascular risk factors (pulse pressure, total/high density lipoprotein cholesterol, glycosylated hemoglobin), diabetes mellitus, cardiovascular and kidney disease, smoking status, and lifetime socioeconomic position.Cystatin C, NT-proBNP, and IL-6 (but not E-selectin) were inversely associated with all outcomes, adjusted for sex, height, and body mass index. For example, a 1-SD increase in logged NT-proBNP was associated with weaker grip (-0.63 kg, 95% CI, -0.99 to -0.28); the equivalent association for cystatin C was -0.60 kg (95% CI, -0.94 to -0.25) and for IL-6 was -0.76 kg (95% CI, -1.11 to -0.41). Most associations remained, albeit attenuated, after adjustment for previous performance and mutual adjustment of the biomarkers. NT-proBNP and IL-6 (but not cystatin C) were more strongly associated with the outcomes than many of the conventional risk factors after mutual adjustment.Higher levels of NT-proBNP may identify those in midlife at risk of accelerated physical decline. Before considering the use of NT-proBNP for risk stratification, further research should untangle whether these associations exist because the biomarker is an integrated measure of cumulative exposures to relevant stressors across life, or whether it is marking additional risk pathways. Randomized trials to reduce the rate of decline in physical capability or delay incident disability could benefit from including middle-aged adults and adding NT-proBNP and IL-6 as intermediate outcomes.

Several studies have documented that older workers who live in areas with higher unemployment rates are more likely to leave work for health and non-health reasons. Due to tracking of area disadvantage over the life course, and because negative individual health and socioeconomic factors are more likely to develop in individuals from disadvantaged areas, we do not know at what specific ages, and through which specific pathways, area unemployment may be influencing retirement age. Using data from the MRC National Survey of Health and Development, we use structural equation modelling to investigate pathways linking local authority unemployment at three ages (4y, 26y and 53y) to age of retirement (right-censored). We explored five hypothesized pathways: (1) residential tracking, (2) health, (3) employment status, (4) occupational class, and (5) education. Initially, pathways between life course area unemployment, each pathway and retirement age were assessed individually. Mediation pathways were tested in the full model. Our results showed that area unemployment tracked across the life course. Higher area unemployment at ages 4 and 53 were independently associated with earlier retirement age [1% increase = mean −0.64 (95% CI: −1.12, −0.16) and −0.25 (95% CI: −0.43, −0.06) years]. Both were explained by adjustment for individual employment status at ages 26 and 53 years. Higher area unemployment at age 26 was associated with poorer health and lower likelihood of employment at aged 53; and these 2 individual pathways were identified as the key mediators between area unemployment and retirement age. In conclusion, these results suggest that interventions designed to create local employment opportunities for young adults should lead to extended working through improved employment and health at mid-life.

Chronic mucus hypersecretion (CMH) is common among smokers and is associated with chronic obstructive pulmonary disease development and progression.To understand how the relationships between smoking, CMH, and chronic obstructive pulmonary disease develop during adult life, and facilitate earlier disease detection and intervention.We analyzed data on CMH, smoking, and lung function prospectively collected by the Medical Research Council National Survey of Health and Development, a nationally representative British cohort followed since birth in 1946. We analyzed the longitudinal relationships between smoking and CMH, how symptoms during life related to airflow limitation at 60-64 years, and how CMH duration between ages 43 and 60-64 years related to concurrent FEV1 decline.From 5,362 individuals enrolled at birth, 4,427 contributed data between ages 20 and 64 years (52% male; 63% ever-smoker). Among smokers CMH prevalence escalated between ages 36 and 43 from 7.6 ± 2.0% to 13.0 ± 2.6%. At these ages, symptoms were associated with a higher risk of subsequent airflow limitation (odds ratio [95% confidence interval], 3.70 [1.62-8.45] and 4.11 [1.85-9.13], respectively). Across adult life, CMH followed a dynamic remitting-relapsing course. Symptom prevalence following smoking cessation returned to levels seen among never-smokers. The longer CMH was present across three occasions (ages 43, 53, and 60-64 yr), the greater the concurrent FEV1 decline, corresponding to an additional decrement of 3.6 ± 2.5 ml/yr per occasion that CMH was present (P = 0.005).CMH among middle-aged smokers represents an early developmental phase of chronic obstructive pulmonary disease. Smoking-related CMH usually resolves following smoking cessation but the longer its duration the greater the FEV1 lost, suggesting the course of CMH across adult life may reflect the underlying course of airway disease activity.

Background: It has been hypothesised that intrauterine exposures are important for subsequent prostate cancer risk. Prior epidemiological studies have used birthweight as a proxy of cumulative intrauterine exposures to test this hypothesis, but results have been inconsistent partly because of limited statistical power. Methods: We investigated birthweight in relation to prostate cancer in the Medical Research Council (MRC) National Survey of Health and Development (NSHD) using Cox proportional hazards models. We then conducted a meta-analysis of birthweight in relation to total and aggressive/lethal prostate cancer risks, combining results from the NSHD analysis with 13 additional studies on this relationship identified from a systematic search in four major scientific literature databases through January 2015. Results: Random-effects models found that per kg increase in birthweight was positively associated with total (OR=1.02, 95% confidence interval (95% CI)=1.00, 1.05; I2=13%) and aggressive/lethal prostate cancer (OR=1.08, 95% CI=0.99, 1.19; I2=40%). Sensitivity analyses restricted to studies with birthweight extracted from medical records demonstrated stronger positive associations with total (OR=1.11, 95% CI=1.03, 1.19; I2=0%) and aggressive/lethal (OR=1.37, 95% CI=1.09, 1.74; I2=0%) prostate cancer. These studies heavily overlapped with those based in Nordic countries. Conclusions: This study provides evidence that heavier birthweight may be associated with modest increased risks of total and aggressive/lethal prostate cancer, which supports the hypothesis that intrauterine exposures may be related to subsequent prostate cancer risks.

OBJECTIVES: The finding that migrants to high-income countries have lower rates of morbidity and mortality than non-migrants, controlling for socioeconomic position, is often attributed to the “healthy migrant” hypothesis, which suggests that only the healthiest individuals choose to migrate. This prospective study investigates the healthy migrant hypothesis in a cohort of British emigrants using pre-migration health indicators. We also investigate how early-life health characteristics relate to age at emigration and whether or not the emigrant returned home. METHODS: Data are from the Medical Research Council National Survey of Health and Development, a nationally representative cohort study of people born in England, Scotland or Wales in March 1946. Childhood socio-economic position, health and cognitive ability were compared between 4,378 non-emigrants and 984 emigrants. Of the emigrants, 427 emigrated before age 20 and 557 after that age; 602 emigrants remained abroad and 382 returned home. RESULTS: Emigrants had better childhood health (especially greater height), higher childhood socio-economic position and better childhood cognitive ability at age 8 than non-emigrants. Return emigrants were very similar to emigrants who remained abroad. CONCLUSIONS: We found support for the healthy migrant hypothesis in a cohort of British emigrants. Our findings improve an understanding of how health is distributed within and across nations.

Highlights • We used general practitioners (GP) to validate self-reported diabetes in the UK. • 94.9% of 157 GPs confirmed their patient diabetes diagnosis. • Mean difference between self-reported and confirmed age at diagnosis was 0.6 years., The aim of this study was to validate self-reported diabetes and age at diagnosis among a sample of the British population, using general practitioners (GPs) as the reference standard. Using data from the Medical Research Council National Survey of Health and Development (NSHD), self-reported diabetes was determined either in response to a direct question at five follow-ups between 1977 and 2010, or from other self-reported medical information. A validation questionnaire was sent to the GP for all participants who reported a diagnosis of diabetes and gave permission to contact their GP (172). The validity of self-reported diabetes was assessed by calculating the percentage of self-reported diabetes cases that were confirmed by their GP, i.e. the positive predictive value (PPV). The difference between self-reported and GP-confirmed age at diagnosis was analysed with a Bland–Altman plot. Completed questionnaires were obtained from 157 GPs (91.2%). Of these, 149 confirmed their patient self-reported diabetes diagnosis (PPV = 94.9%). Results were similar when self-reported diabetes was assessed by responses to direct questions only (PPV = 95.4%). The average difference between self-reported and GP-reported age at diagnosis was 0.6 years (95% CI 0.2–1.1). We conclude that among the British population questionnaires are a valid method to assess GP-diagnosed diabetes, as measured by responses to a direct question or by patient-reported medical information.

Background We examined associations of objectively measured physical activity ( PA ) and sedentary time with cardiovascular disease biomarkers at age 60 to 64 years. This included investigation of sex differences and the extent to which associations may be mediated by adiposity. Methods and Results Participants were 795 men and 827 women aged 60 to 64 years from the Medical Research Council National Survey of Health and Development. Combined heart rate and movement sensors worn for 5 consecutive days were used to derive overall PA energy expenditure, kJ /kg per day) and time spent sedentary (PA (>3 metabolic equivalent of tasks). Linear regression models were used to relate each PA parameter to inflammatory (C‐reactive protein, interleukin‐6), endothelial (tissue‐plasminogen activator, E‐selectin) and adipokine (leptin, adiponectin) markers extracted from fasting blood samples. Greater time in light PA and moderate‐to‐vigorous intensity PA and less sedentary time were associated with more favorable biomarker levels. For C‐reactive protein, interleukin‐6, and leptin, these differences were greater among women than men. For example, % differences (95% confidence intervals) in leptin for men and women per SD increases in sedentary time: 7.9 (2.7, 13.0) and 20.6 (15.3, 25.8); light intensity PA : −3.8 (−8.9, 12.7) and −17.7 (−23.1, −12.4), moderate‐to‐vigorous intensity PA : −12.9 (−17.9, −8.0) and −18.3 (−23.4, −13.1). Fat mass mediated a greater proportion of these associations in women than men. Conclusions Greater light PA and moderate‐to‐vigorous intensity PA and less sedentary time in early old age were associated with more favorable cardiovascular biomarker profiles. Fat mass partially mediated these associations but more strongly in women than men, which explained sex differences.

This study examined associations between motor performance in early life and leisure-time physical activity (LTPA) participation across adulthood, and whether these changed with age.Data were from 2526 participants from the Medical Research Council National Survey of Health and Development. Motor indicators were mother-reported ages at first standing and walking, teacher-rated games ability at age 13, and finger- and foot-tapping speed at age 15. LTPA was reported at ages 36, 43, 53, 60-64, and 68 years and classed at each age as none, moderate (1-4/mo), or regular (≥5/mo). Associations were examined using mixed-effects Poisson regression models with robust error variance.Better ability at games and faster tapping speed were associated with more frequent participation in LTPA across adulthood, for example, fully adjusted relative risk of regular LTPA across adulthood (vs none) for above-average ability (vs below average or average) = 1.46 (95% CI 1.32, 1.61); and per 10-unit higher number of finger-taps/15 seconds = 1.04 (95% CI 1.02, 1.07). These associations did not vary by age (P ≥ .33 for interactions with age at LTPA). Ages at reaching motor milestones were not associated with LTPA (eg, fully adjusted relative risk of regular LTPA across adulthood for walking ≤10 and ≥18 months (vs 11-17 months) were 1.01 (95% CI 0.86, 1.20) and 0.89 (95% CI 0.75, 1.06) respectively.Better ability at games and faster tapping speed in adolescence were associated with greater participation in LTPA throughout adult life; from age 36 up to age 68. Childhood motor skill interventions may therefore have the potential to promote lifelong LTPA.

Highlights • Recurrent lifetime affective problems predict diminished late-life cognitive state. • Those with affective problems only once do not show risk of lower cognitive state. • Recurrence, rather than timing, of problems is more predictive. • These associations remain even when controlling for prior childhood cognition. • The risk of lower cognitive state is already manifest in early old age (age 69)., Background Affective problems increase the risk of dementia and cognitive impairment, yet the life course dimension of this association is not clearly understood. We aimed to investigate how affective problems across the life course relate to later-life cognitive state. Methods Data from 1269 participants from the Medical Research Council National Survey of Health and Development (NSHD, the British 1946 birth cohort) were used. Prospectively-assessed measures of affective symptoms spanning ages 13–69 and categorised into case-level thresholds. Outcomes consisted of a comprehensive measure of cognitive state (Addenbrooke's Cognitive Examination (ACE-III)), verbal memory, and letter search speed and accuracy at age 69. Results Complementary life course models demonstrated that having 2 or more case-level problems across the life course was most strongly associated with poorer cognitive outcomes, before and after adjusting for sex, childhood cognition, childhood and midlife occupational position and education. Limitations A disproportionate loss to follow-up of those who had lower childhood cognitive scores may have led to underestimation of the strength of associations. Discussion Using a population-based prospective study we provide evidence that recurrent lifetime affective problems predicts poorer later-life cognitive state, and this risk can be already manifest in early old age (age 69). Our findings raise the possibility that effective management to minimise affective problems reoccurring across the life course may reduce the associated risk of cognitive impairment and decline.

Supplemental Digital Content is Available in the Text. In a British birth cohort study, 4 distinct long-term back pain profiles were identified, each of which was associated with different early life risk factors., This study aimed to (1) characterise long-term profiles of back pain across adulthood and (2) examine whether childhood risk factors were associated with these profiles, using data from 3271 participants in the Medical Research Council National Survey of Health and Development. A longitudinal latent class analysis was conducted on binary outcomes of back pain at ages 31, 36, 43, 53, 60 to 64, and 68 years. Multinomial logistic regression models were used to examine associations between selected childhood risk factors and class membership; adjusted for sex, adult body size, health status and behaviours, socioeconomic position, and family history of back pain. Four profiles of back pain were identified: no or occasional pain (57.7%), early-adulthood only (16.1%), mid-adulthood onset (16.9%), and persistent (9.4%). The “no or occasional” profile was treated as the referent category in subsequent analyses. After adjustment, taller height at age 7 years was associated with a higher likelihood of early-adulthood only (relative risk ratio per 1 SD increase in height = 1.31 [95% confidence interval: 1.05-1.65]) and persistent pain (relative risk ratio = 1.33 [95% confidence interval: 1.01-1.74]) in women (P for sex interaction = 0.01). Factors associated with an increased risk of persistent pain in both sexes were abdominal pain, poorest care in childhood, and poorer maternal health. Abdominal pain and poorest housing quality were also associated with an increased likelihood of mid-adulthood onset pain. These findings suggest that there are different long-term profiles of back pain, each of which is associated with different early life risk factors. This highlights the potential importance of early life interventions for the prevention and management of back pain.

To investigate longitudinal associations between polypharmacy and cognitive and physical capability and to determine whether these associations differ with cumulative exposure to polypharmacy.Prospective birth cohort study.England, Scotland, and Wales.An eligible sample of men and women from the Medical Research Council National Survey of Health and Development with medication data at age 69 (N=2,122, 79%).Cognitive capability was assessed using a word learning test, visual search speed task, and the Addenbrooke's Cognitive Examination, Third Edition (ACE-III). Physical capability was measured using chair rise speed, standing balance time, walking speed, and grip strength.Polypharmacy (5-8 prescribed medications) was present in 18.2% of participants at age 69 and excessive polypharmacy (≥9 prescribed medications) in 4.7%. Both were associated with poorer cognitive and physical capability in models adjusted for sex, education, and disease burden. Stronger associations were found for excessive polypharmacy (e.g., difference in mean ACE-III scores comparing polypharmacy=-2.0, 95% CI=-2.8 to -1.1 and excessive polypharmacy=-2.9, 95% CI=-4.4 to -1.4 with no polypharmacy). Participants with polypharmacy at age 60 to 64 and at age 69 showed stronger Negative associations with cognitive and physical capability were stronger still in participants with polypharmacy at both age 60 to 64 and at age 69 (e.g. difference in mean chair rise speed, comparing polypharmacy with no polypharmacy at both ages=-3.9, 95% CI=-5.2 to -2.6 and at age 60-64 only=-2.5, 95% CI=-4.1 to -0.9).Polypharmacy at age 60 to 64 and age 69 was associated with poorer physical and cognitive capability, even after adjusting for disease burden. Stronger negative associations were seen in participants with longstanding polypharmacy, suggesting a cumulative, dose-dependent relationship (where dose is the number of prescribed medications). Future research aiming to improve cognitive and physical capability should consider interventions to reduce the duration and level of polypharmacy at younger ages, in addition to optimizing disease control with appropriate medications.

We aimed to examine whether back pain across adulthood was associated with spine shape at age 60–64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60–64 years. Cumulative exposure to back pain was then derived by counting the number of ages at which back pain was reported. Statistical shape modelling was used to characterise thoracolumbar spine shape using lateral dual-energy x-ray absorptiometry images which were ascertained at age 60–64 years. Linear regression models were used to test associations of spine shape modes (SM) with: (1) cumulative exposure to back pain; (2) back pain reports during different periods of adulthood. After adjusting for sex, higher cumulative exposure to back pain across adulthood was associated with wedge-shaped L4-5 disc (lower SM4 scores) and smaller disc spaces (higher SM8 scores) in both sexes. In addition, reporting of back pain at ages 53 and/or 60–64 years was associated with smaller L4-5 disc space (lower SM6 scores) in men but not women. These findings suggest that back pain across adulthood may be associated with specific variations in spine shapes in early old age.

Objective To investigate the prevalence of urgency urinary incontinence (UUI) at age 68 years and the contribution of vascular risk factors to male and female UUI pathogenesis in addition to the associations with raised body mass index (BMI). Subjects and methods In all, 1 762 participants from the Medical Research Council (MRC) National Survey for Health and Development birth cohort who answered the International Consultation on Incontinence Questionnaire short form (ICIQ‐SF), at age 68 years, were included. Logistic regression was used to estimate associations between UUI and earlier life vascular risk factors including: lipid status, diabetes, hypertension, BMI, previous stroke or transient ischaemic attack (TIA) diagnosis; adjusting for smoking status, physical activity, co‐presentation of stress UI symptoms, educational attainment; and in women only, type of menopause, age at period cessation, and use of hormone replacement therapy (HRT). Results UUI was reported by 12% of men and 19% of women at age 68 years. Female sex, previous stroke or TIA diagnosis, increased BMI and hypertension (in men only) at age 60–64 years were independent risk factors for UUI. Female sex, increased BMI, and a previous diagnosis of stroke/TIA increased the relative risk of more severe UUI symptoms. Type and timing of menopause and HRT use did not alter the estimated associations between UUI and vascular risk factors in women. Conclusion Multifactorial mechanisms lead to UUI and vascular risk factors may contribute to the pathogenesis of bladder overactivity in addition to higher BMI. Severe UUI appears to be a distinct presentation with more specific contributory mechanisms than milder UUI.

© 2017, © The Author(s) 2017. Objective: This study presents three approaches, that is, cumulative risk, factor analysis, and latent class analysis, to summarize exposure to multiple childhood social risk factors and to compare their utility when examining associations with physical capability and common affective symptoms in adults aged 60 to 64 years. Methods: Data came from the U.K. Medical Research Council (MRC) National Survey of Health and Development, with prospective childhood social risk factor data collected in 1950 to 1957 and retrospectively in 1989. Physical capability and common affective symptom data were collected in 2006 to 2011. Results: The cumulative risk approach and factor analysis provided evidence that children who were exposed to multiple social risk factors had lower levels of physical capability and more symptoms of common affective symptoms in later life. Discussion: The cumulative social risk approach and the use of factor analysis to identify contexts of social risk, may offer viable methods for linking multiple childhood social risk exposure to aging outcomes.

BackgroundDelirium affects 25% of older inpatients and is associated with long-term cognitive impairment and future dementia. However, no population studies have systematically ascertained cognitive function before, cognitive deficits during, and cognitive impairment after delirium. Therefore, there is a need to address the following question: does delirium, and its features (including severity, duration, and presumed aetiologies), predict long-term cognitive impairment, independent of cognitive impairment at baseline?MethodsThe Delirium and Population Health Informatics Cohort (DELPHIC) study is an observational population-based cohort study based in the London Borough of Camden. It is recruiting 2000 individuals aged ≥70 years and prospectively following them for two years, including daily ascertainment of all inpatient episodes for delirium. Daily inpatient assessments include the Memorial Delirium Assessment Scale, the Observational Scale for Level of Arousal, and the Hierarchical Assessment of Balance and Mobility. Data on delirium aetiology is also collected. The primary outcome is the change in the modified Telephone Interview for Cognitive Status at two years.DiscussionDELPHIC is the first population sample to assess older persons before, during and after hospitalisation. The cumulative incidence of delirium in the general population aged ≥70 will be described. DELPHIC offers the opportunity to quantify the impact of delirium on cognitive and functional outcomes. Overall, DELPHIC will provide a real-time public health observatory whereby information from primary, secondary, intermediate and social care can be integrated to understand how acute illness is linked to health and social care outcomes.

We tested the association between APOE-ε4 and processing speed and memory between ages 43 and 69 in a population-based birth cohort. Analyses of processing speed (using a timed letter search task) and episodic memory (a 15-item word learning test) were conducted at ages 43, 53, 60-64 and 69 years using linear and multivariable regression, adjusting for gender and childhood cognition. Linear mixed models, with random intercepts and slopes, were conducted to test the association between APOE and the rate of decline in these cognitive scores from age 43 to 69. Model fit was assessed with the Bayesian Information Criterion. A cross-sectional association between APOE-ε4 and memory scores was detected at age 69 for both heterozygotes and homozygotes (β=−0.68 & β=−1.38 respectively, p=.03) with stronger associations in homozygotes; no associations were observed before this age. Homozygous carriers of APOE-ε4 had a faster rate of decline in memory between ages 43 and 69, when compared to noncarriers, after adjusting for gender and childhood cognition (β=−0.05, p=.04). There were no cross-sectional or longitudinal associations between APOE-ε4 and processing speed. We conclude that APOE-ε4 is associated with a subtly faster rate of memory decline from midlife to early old age; this may be due to effects of APOE-ε4 becoming manifest around the latter stage of life. Continuing follow-up will determine what proportion of this increase will become clinically significant.

Maintenance of healthy cognitive ageing is vital for independence and wellbeing in the older general population. We investigated the association between blood metabolites and cognitive function and decline. Participants from the MRC National Survey of Health and Development (NSHD, the British 1946 birth cohort) were studied; 233 nuclear magnetic resonance circulating metabolite measures were quantified in 909 men and women at ages 60–64. Short-term and delayed verbal memory and processing speed were concurrently assessed and these tests were repeated at age 69. Linear regression analyses tested associations between metabolites and cognitive function at ages 60–64, and changes in these measures by age 69, adjusting for childhood cognition, education, socio-economic status and lifestyle factors. In cross-sectional analyses, metabolite levels, particularly fatty acid composition and different lipid sub-classes, were associated with short-term verbal memory (4 measures in females and 11 measures in the whole sample), delayed verbal memory (2 measures in females) and processing speed (8 measures in males and 2 measures in the whole sample) (p

Background:Aging is associated with declines in physical capability; however, some individuals demonstrate high well-being despite this decline, i.e. they are “resilient.” We examined socioeconomic position (SEP) and resilience and the influence of potentially modifiable behavioral resources, i.e. social support and leisure time physical activity (LTPA), on these relationships.Methods:Data came from the Medical Research Council National Survey of Health and Development, a nationally-representative birth cohort study. Resilience–vulnerability at age 60–64 years (n = 1,756) was operationalized as the difference between observed and expected levels of well-being, captured by the Warwick–Edinburgh Mental Well-being Scale (WEMWBS), given the level of performance-based physical capability. SEP was assessed by father's and own social class, parental education, and intergenerational social mobility. PA and structural/functional social support were reported at ages 53 years and 60–64 years. Path analysis was used to examine mediation of SEP and resilience–vulnerability through LTPA and social support.Results:Participants in the highest social class had scores on the resilience to vulnerability continuum that were an average of 2.3 units (β = 0.46, 95% CI 0.17, 0.75) higher than those in the lowest social class. Greater LTPA (β = 0.58, 95% CI 0.31, 0.85) and social support (β = 3.27, 95% CI 2.90, 3.63) were associated with greater resilience; LTPA partly mediated participant social class and resilience (23.4% of variance).Conclusions:Adult socioeconomic advantage was associated with greater resilience. Initiatives to increase LTPA may contribute to reducing socioeconomic inequalities in this form of resilience in later life.

Summary: Background: Socioeconomic inequalities in childhood body-mass index (BMI) have been documented in high-income countries; however, uncertainty exists with regard to how they have changed over time, how inequalities in the composite parts (ie, weight and height) of BMI have changed, and whether inequalities differ in magnitude across the outcome distribution. Therefore, we aimed to investigate how socioeconomic inequalities in childhood and adolescent weight, height, and BMI have changed over time in Britain. Methods: We used data from four British longitudinal, observational, birth cohort studies: the 1946 Medical Research Council National Survey of Health and Development (1946 NSHD), 1958 National Child Development Study (1958 NCDS), 1970 British Cohort Study (1970 BCS), and 2001 Millennium Cohort Study (2001 MCS). BMI (kg/m2) was derived in each study from measured weight and height. Childhood socioeconomic position was indicated by the father's occupational social class, measured at the ages of 10–11 years. We examined associations between childhood socioeconomic position and anthropometric outcomes at age 7 years, 11 years, and 15 years to assess socioeconomic inequalities in each cohort using gender-adjusted linear regression models. We also used multilevel models to examine whether these inequalities widened or narrowed from childhood to adolescence, and quantile regression was used to examine whether the magnitude of inequalities differed across the outcome distribution. Findings: In England, Scotland, and Wales, 5362 singleton births were enrolled in 1946, 17 202 in 1958, 17 290 in 1970, and 16 404 in 2001. Low socioeconomic position was associated with lower weight at childhood and adolescent in the earlier-born cohorts (1946–70), but with higher weight in the 2001 MCS cohort. Weight disparities became larger from childhood to adolescence in the 2001 MCS but not the earlier-born cohorts (pinteraction=0·001). Low socioeconomic position was also associated with shorter height in all cohorts, yet the absolute magnitude of this difference narrowed across generations. These disparities widened with age in the 2001 MCS (pinteraction=0·002) but not in the earlier-born cohorts. There was little inequality in childhood BMI in the 1946–70 cohorts, whereas inequalities were present in the 2001 cohort and widened from childhood to adolescence in the 1958–2001 cohorts (pinteraction

As populations are ageing, more emphasis is placed on healthy ageing. Over the past decades, food consumption patterns and food availability have also changed drastically, and therefore this study aimed to describe these changes in an ageing population.Subjects/Methods:Food consumption of participants from the Medical Research Council National Survey on Health and Development, a British birth cohort study, was assessed using a 5-day estimated food records at 60-64 years (2006-11), 53 years (1999), 43 years (1989) and 36 years (1982). Only those who recorded ≥3 days at all four time points were included in the analyses, n=989 (n=438 men and n=551 women); trends were tested using the Friedman test.Results:Consumption of white bread, whole milk, fats and oils, meat and meat products, alcoholic drinks, coffee, sugar, preserves and confectionery decreased (P

Background: Very few studies have assessed whether socioeconomic and psychosocial adversity during childhood are associated with objective measures of ageing later in life. We assessed associations of socioeconomic position (SEP) and total psychosocial adversity during childhood, with objectively measured cognitive and physical capability in women during mid-life.Methods: Adverse childhood experiences were retrospectively reported at mean ages 28-30 years in women from the Avon Longitudinal Study of Parents And Children (N=2,221). We investigated associations of childhood SEP and total psychosocial adversity, with composite measures of cognitive and physical capability at mean age 51 years. Results: There was evidence that, compared to participants who’s fathers had ‘professional’ occupations, participants who’s father’s had ‘managerial/technical’, ‘skilled non-manual’, ‘skilled manual’ and ‘partly or unskilled manual’ occupations had, on average, lower physical and cognitive capability. There was a clear trend for increasing magnitudes of association with lowering childhood SEP. There was also evidence that greater total psychosocial adversity in childhood was associated with lower physical capability. Total psychosocial adversity in childhood was not associated with cognitive capability.Conclusions: Lower SEP in childhood is detrimental to cognitive and physical capability in mid-life, at least in part, independently of subsequent SEP in adulthood. Greater psychosocial adversity in childhood is associated with poorer physical capability, independently of social disadvantage in childhood. Our findings highlight the need for interventions to both identify and support children experiencing socioeconomic or psychosocial of adversity as early as possible.

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

This study examined associations between leisure-time physical activity (LTPA) across adulthood (from age 36) and cardiovascular disease (CVD) biomarkers at age 60-64.LTPA was reported by study participants from the MRC National Survey of Health and Development at ages 36, 43, 53 and 60-64 (n = 1754) and categorised as inactive, moderately active (1-4/month) or most active (5+/month) at each age. Linear regression was used to examine associations between a cumulative adulthood LTPA score (range = 0-8), and change in LTPA between ages 36 and 60-64 (i.e. always inactive, became inactive, became active, always active) and inflammatory [C-reactive protein (CRP), interleukin-6 (IL-6)], endothelial [tissue-Plasminogen Activator (t-PA), E-selectin] and adipokine [leptin, adiponectin] measures extracted from overnight fasting blood samples at age 60-64.The more active a participant was over adulthood, the better their biomarker profile, e.g. fully-adjusted difference in t-PA (both sexes) and adiponectin (women) per unit increase in the LTPA score (95% confidence interval) = -2.2% (-3.6; -0.8) and 2.0% (0.2; 3.8). Those that became active at age 60-64 showed slightly healthier biomarker profiles than those that became inactive [e.g. fully-adjusted difference in IL-6 = -9.9% (-23.9; 4.1) vs. -3.8% (-12.4; 4.8)], although the best profiles were seen for those always active [IL-6: -15.0% (-24.2; -5.7)], when compared with the always inactive group.Greater accumulation of LTPA across adulthood was associated with a more favourable CVD biomarker profile in early old age. Earlier uptake and long-term maintenance of LTPA may provide the greatest benefits for CVD prevention.

Cognitive capabilities change in later life, although their onset and rate of decline, and how they are shaped by lifetime socioeconomic position, childhood cognition and adult health status are all unclear.From the Medical Research Council National Survey of Health and Development, we analysed 3,192 participants undergoing one or more cognitive assessments at ages 43, 53, 60-64 and 69. Linear mixed models described cognitive trajectories, adjusting for factors across the life course.For both search speed and verbal memory, better performance at age 43 (the intercept) was associated with higher paternal and own education, childhood cognition, and adult occupational class. For search speed, the trajectory was best described as a quadratic function (decline of 45.6 letters/5-years + 4.6 letters). Verbal memory showed a linear decline of 0.20 words/5-years between ages 43 and 60 and a steeper linear decline of 0.95 words/5-years between ages 60 and 69. Decline in verbal memory in the latter period was steeper in those with higher educational achievements at age 26 (additional 0.28 words/5-years for highest attainment).Decline in verbal memory and search speed across midlife is evident, though with different non-linear trajectories. By implication, pathways to cognitive impairment and dementia in older age may have their origins in this period.

Supplemental digital content is available in the text., Objective The aim of the study was to test the hypothesis that higher childhood cognitive ability is associated with reduced risk of decline in physical capability in late midlife. Methods Participants were 1954 men and women from the Medical Research Council National Survey of Health and Development with complete data on cognitive ability at age of 15 years and measures of grip strength and chair rise speed at ages of 53 and 60 to 64 years. Using multinomial logistic regression, associations of childhood cognitive ability with categories of change in grip strength and chair rise speed (i.e., decline, stable high, stable low, reference) were investigated. Adjustments were made for potential confounders from early life and adult mediators including health behaviors, educational level, and cognitive ability at age of 53 years. Results Higher childhood cognitive scores were associated with reduced risks of decline in grip strength and chair rise speed, for example, the sex-adjusted relative-risk ratio of decline (versus reference) in grip strength per 1SD increase in childhood cognitive score was 0.82 (95% confidence interval = 0.73–0.92). Higher childhood cognitive scores were also associated with reduced risk of stable low and increased likelihood of stable high chair rise speed. Conclusions These findings suggest that childhood cognitive ability may be related to decline in physical capability in late midlife. A number of life course pathways are implicated, including those linking childhood and adult cognitive ability. Future research aiming to identify new opportunities to prevent or minimize age-related declines in physical capability may benefit from considering the potential role of neurodevelopmental as well as neurodegenerative pathways.

Background To describe the development of polypharmacy and its components in a British birth cohort in its seventh decade and to investigate socioeconomic and gender differences independent of disease burden. Methods Data from the MRC National Survey for Health and Development were analysed to determine the prevalence and composition of polypharmacy at age 69 and changes since ages 60 to 64. Multinomial regression was used to test associations between gender, education and occupational social class and total, cardiological and non-cardiological polypharmacy controlling for disease burden. Results At age 69, 22.8% of individuals were taking more than 5 medications. There was an increase in the use of 5 to 8 medications (+ 2.3%) and over 9 medications (+ 0.8%) between ages 60–64 and 69. The greatest increases were found for cardiovascular (+ 13.4%) and gastrointestinal medications (+ 7.3%). Men experienced greater cardiological polypharmacy, women greater non-cardiological polypharmacy. Higher levels of education were associated with lower polypharmacy independent of disease burden, with strongest effects seen for over five cardiological medications (RRR 0.3, 95% CI 0.2–0.5 p

BACKGROUND: Both adverse early life exposures and adult smoking can negatively influence adult lung function trajectory but few studies consider how the impact of early life exposures may be modified by subsequent smoking. METHODS: The Medical Research Council National Survey of Health and Development is a nationally representative cohort, initially of 5362 individuals, followed since enrolment at birth in March 1946. Using data collected prospectively across life and multilevel modelling we investigated how the relationships between early life exposures (infant lower respiratory infection, manual social class, home overcrowding and pollution exposure) and FEV1 and FVC trajectories between ages 43 and 60-64 were influenced by smoking behaviour. RESULTS: Among 2172 individuals, there were synergistic interactions of smoking with infant respiratory infection (P=0.04) and early life home overcrowding (P=0.009), for FEV1 at 43 years. Within smoker-stratified models, there were FEV1 deficits among ever-smokers associated with infant lower respiratory infection (-108.2ml; P=0.001) and home overcrowding (-89.2ml; P=0.002) which were not evident among never-smokers (-15.9ml; P=0.69 and -13.7ml; P=0.70 respectively). FVC modelling, including 1960 individuals, yielded similar results. FEV1 decline was greater in smokers (P

Background Increasing age is the biggest risk factor for dementia, of which Alzheimer’s disease is the commonest cause. The pathological changes underpinning Alzheimer’s disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment – including β-amyloid depostion, vascular disease, network breakdown and atrophy – to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms. Methods/design This paper outlines the clinical, cognitive and imaging protocol of “Insight 46”, a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71 years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer’s disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60–64 years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24 month) data collection covering clinical, neuropsychological, β-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73). Discussion Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69 years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer’s disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery., The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (102318; 104781, 120315, 123885, 129619, 286284, 134309, 126925, 121584, 124282, 129378, 117787, 250207, 258753, 41071, 77299, 124243, 1114194, 24300796); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la Recherche; Agency for Health Care Policy Research (HS06516); Age UK Research into Ageing Fund; Åke Wiberg Foundation; ALF/LUA Research Grant in Gothenburg; ALFEDIAM; ALK-Abello´ A/S (Hørsholm, Denmark); American Heart Association (13POST16500011, 10SDG269004); Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; AstraZeneca; Australian Associated Brewers; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); Avera Research Institute; Bayer Diagnostics; Becton Dickinson; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); Biocentrum Helsinki; Boston Obesity Nutrition Research Center (DK46200); British Heart Foundation (RG/10/12/28456, SP/04/002); Canada Foundation for Innovation; Canadian Institutes of Health Research (FRN-CCT-83028); Cancer Research UK; Cardionics; Center for Medical Systems Biology; Center of Excellence in Complex Disease Genetics and SALVECenter of Excellence in Genomics (EXCEGEN); Chief Scientist Office of the Scottish Government; City of Kuopio; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF–1333-00124, DFF–1331-007308); Danish Diabetes Academy; Danish Medical Research Council; Department of Psychology and Education of the VU University Amsterdam; Diabetes Hilfs- und Forschungsfonds Deutschland; Dutch Brain Foundation; Dutch Ministry of Justice; Emil Aaltonen Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (IUT20-60, IUT24-6); Estonian Ministry of Education and Research (3.2.0304.11-0312); European Commission (230374, 284167, 323195, 692145, FP7 EurHEALTHAgeing-277849, FP7 BBMRI-LPC 313010, nr 602633, HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, FP6 LSHM-CT-2004-005272, FP5 QLG2-CT-2002-01254, FP6 LSHG-CT-2006-01947, FP7 HEALTH-F4-2007-201413, FP7 279143, FP7 201668, FP7 305739, FP6 LSHG-CT-2006-018947, HEALTH-F4-2007-201413, QLG1-CT-2001-01252); European Regional Development Fund; European Science Foundation (EuroSTRESS project FP-006, ESF, EU/QLRT-2001-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 03IS2061A); Federal State of Mecklenburg - West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Food Standards Agency; Fondation de France; Fonds Santé; Genetic Association Information Network of the Foundation for the National Institutes of Health; German Diabetes Association; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); German Research Council (SFB-1052, SPP 1629 TO 718/2-1); GlaxoSmithKline; Göran Gustafssons Foundation; Göteborg Medical Society; Health and Safety Executive; Heart Foundation of Northern Sweden; Icelandic Heart Association; Icelandic Parliament; Imperial College Healthcare NHS Trust; INSERM, Réseaux en Santé Publique, Interactions entre les déterminants de la santé; Interreg IV Oberrhein Program (A28); Italian Ministry of Economy and Finance; Italian Ministry of Health (ICS110.1/RF97.71); John D and Catherine T MacArthur Foundation; Juho Vainio Foundation; King's College London; Kjell och Märta Beijers Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); Leiden University Medical Center; Lilly; LMUinnovativ; Lundbeck Foundation; Lundberg Foundation; Medical Research Council of Canada; MEKOS Laboratories (Denmark); Merck Santé; Mid-Atlantic Nutrition Obesity Research Center (P30 DK72488); Ministère de l’Économie, de l’Innovation et des Exportations; Ministry for Health, Welfare and Sports of the Netherlands; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science of the Netherlands; MRC Human Genetics Unit; MRC-GlaxoSmithKline Pilot Programme Grant (G0701863); Municipality of Rotterdam; Netherlands Bioinformatics Centre (2008.024); Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Genomics Initiative; Netherlands Organisation for Health Research and Development (904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192); Netherlands Organisation for Health Research and Development (2010/31471/ZONMW); Netherlands Organisation for Scientific Research (10-000-1002, GB-MW 940-38-011, 100-001-004, 60-60600-97-118, 261-98-710, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MaGW 452-04-314, GB-MaGW 452-06-004, 175.010.2003.005, 175.010.2005.011, 481-08-013, 480-05-003, 911-03-012); Neuroscience Campus Amsterdam; NHS Foundation Trust; Novartis Pharmaceuticals; Novo Nordisk; Office National Interprofessionel des Vins; Paavo Nurmi Foundation; Påhlssons Foundation; Päivikki and Sakari Sohlberg Foundation; Pierre Fabre; Republic of Croatia Ministry of Science, Education and Sport (108-1080315-0302); Research Centre for Prevention and Health, the Capital Region for Denmark; Research Institute for Diseases in the Elderly (014-93-015, RIDE2); Roche; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Executive Health Department (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du Diabète; State of Bavaria; Stroke Association; Swedish Diabetes Association; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20140543); Swedish Research Council (2015-03657); Swedish Medical Research Council (K2007-66X-20270-01-3, 2011-2354); Swedish Society for Medical Research; Swiss National Science Foundation (33CSCO-122661, 33CS30-139468, 33CS30-148401); Tampere Tuberculosis Foundation; The Marcus Borgström Foundation; The Royal Society; The Wellcome Trust (084723/Z/08/Z, 088869/B/09/Z); Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar Söderberg's Foundation; UK Department of Health; UK Diabetes Association; UK Medical Research Council (MC_U106179471, G0500539, G0600705, G0601966, G0700931, G1002319, K013351, MC_UU_12019/1); UK National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre; UK National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; UK National Institute for Health Research (RP-PG-0407-10371); Umeå University Career Development Award; United States – Israel Binational Science Foundation Grant (2011036); University Hospital Oulu (75617); University Medical Center Groningen; University of Tartu (SP1GVARENG); National Institutes of Health (AG13196, CA047988, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSC271201100004C, HHSN268200900041C, HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268201500001I, HL36310, HG002651, HL034594, HL054457, HL054481, HL071981, HL084729, HL119443, HL126024, N01-AG12100, N01-AG12109, N01-HC25195, N01-HC55015, N01-HC55016, N01-HC55018, N01-HC55019, N01-HC55020, N01-HC55021, N01-HC55022, N01-HD95159, N01-HD95160, N01-HD95161, N01-HD95162, N01-HD95163, N01-HD95164, N01-HD95165, N01-HD95166, N01-HD95167, N01-HD95168, N01-HD95169, N01-HG65403, N02-HL64278, R01-HD057194, R01-HL087641, R01-HL59367, R01HL-086694, R01-HL088451, R24-HD050924, U01-HG-004402, HHSN268200625226C, UL1-RR025005, UL1-RR025005, UL1-TR-001079, UL1-TR-00040, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, DA12854, MH081802, MH66206, R01-D004215701A, R01-DK075787, R01-DK089256, R01-DK8925601, R01-HL088451, R01-HL117078, R01-DK062370, R01-DK072193, DK091718, DK100383, DK078616, 1Z01-HG000024, HL087660, HL100245, R01DK089256, 2T32HL007055-36, U01-HL072515-06, U01-HL84756, NIA-U01AG009740, RC2-AG036495, RC4-AG039029, R03 AG046389, 263-MA-410953, 263-MD-9164, 263-MD-821336, U01-HG004802, R37CA54281, R01CA63, P01CA33619, U01-CA136792, U01-CA98758, RC2-MH089951, MH085520, R01-D0042157-01A, MH081802, 1RC2-MH089951, 1RC2-MH089995, 1RL1MH08326801, U01-HG007376, 5R01-HL08767902, 5R01MH63706:02, HG004790, N01-WH22110, U01-HG007033, UM1CA182913, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221); USDA National Institute of Food and Agriculture (2007-35205-17883); Västra Götaland Foundation; Velux Foundation; Veterans Affairs (1 IK2 BX001823); Vleugels Foundation; VU University’s Institute for Health and Care Research (EMGO+, HEALTH-F4-2007-201413) and Neuroscience Campus Amsterdam; Wellcome Trust (090532, 091551, 098051, 098381); Wissenschaftsoffensive TMO; and Yrjö Jahnsson Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Objectives Supportive social relationships have been found to be related to fewer sleep problems and better sleep quality. We examined associations between positive and negative support from the nominated close person across 15 years of follow-up with sleep quality in older age. Methods MRC National Survey of Health and Development study members reported sleep quality at age 68 (n = 2446). Cumulative exposure to and changes in positive and negative support were derived from data at age 53, 60–64 and 68 years. Pittsburgh Sleep Quality Index scores were regressed on social support measures adjusted for i) gender only then additionally ii) education, marital status, number in household, limiting illness, body mass index, caregiving, iii) and affective symptoms. Results Greater exposure to positive support and lower exposure to negative support over 15 years were independently associated with better sleep quality at age 68. Sleep quality was poorer for those who experienced declining positive support or increasing negative support. Those who nominated their spouse/partner as their closest person at age 53 but not at age 68 had poorer sleep quality than those who nominated their spouse on both occasions. These associations were not explained by the covariates, including affective symptoms. Conclusions Based on repeat data on support from the closest person, this study finds a link between declining social relationship quality and poor sleep quality. Whilst acknowledging that the association may be bi-directional, the study suggests that interventions to improve older people's social relationships may have benefits for sleep., Highlights • We prospectively examined close social relationships and older people's sleep quality. • Greater cumulative positive support over 15 years was associated with better sleep. • Independently of this, lower exposure to negative support was linked to better sleep. • Nominating spouse as the closest person at baseline but not follow-up was linked to poorer sleep. • Associations were not fully attenuated by education, marital status, illness or depression.

Background Studies assessing associations of childhood psychosocial adversity (e.g. sexual abuse, physical neglect, parental death), as opposed to socioeconomic adversity, with cardiovascular disease (CVD) risk factors in adulthood are scarce. We aimed to assess associations of various forms of psychosocial adversity and cumulative adversity in childhood, with multiple CVD risk factors in mid-life. Methods Participants were from the MRC National Survey of Health and Development. Childhood psychosocial risk factors were reported prospectively by parents from 1950-1957, and retrospectively by participants at mean age 43 years in 1989. CVD risk factors were assessed at mean age 60-64 years in 2006-2011. Associations of a summary score of total psychosocial adversity and CVD risk in adulthood were assessed. Results There was no consistent evidence that cumulative psychosocial adversity, nor any specific form of psychosocial adversity in childhood, was associated with CVD risk factors in late adulthood. There was some evidence that parental death in the first 15 years was associated with higher SBP (Beta: 0.23, 95% confidence interval: 0.06 to 0.40, P=0.01) and DBP (Beta: 0.15, 95% confidence interval: -0.01 to 0.32, P=0.07). Conclusions We found no evidence that exposure to greater psychosocial adversity, or specific forms of psychosocial adversity during childhood is associated with adult CVD risk factors. Further large population studies are needed to clarify whether parental death is associated with higher systolic and diastolic blood pressure. Electronic supplementary material The online version of this article (10.1186/s12939-017-0656-1) contains supplementary material, which is available to authorized users.

Obesity has been linked with shorter telomere length, both of which have been implicated in ageing, but the impact of early life adiposity on telomere length is unclear.We included 2,479 participants from the MRC National Survey of Health and Development with measurements of body mass index, waist and hip circumference, and leukocyte telomere length (LTL) at age 53, of whom 1,000 had second measurements at ages 60-64. Relative LTL was measured with rt-PCR. Linear regression was performed to investigate associations between adiposity and LTL. Body mass index from childhood through adulthood was used to assess adiposity across the life course.We found no cross-sectional associations between adiposity measures and LTL at ages 53 or 60-64. Longitudinally, each unit gain in waist circumference weakly corresponded with a 0.06% (95% CI: -1.31 to 0.10) LTL decrease annually, with association approaching statistical significance (p = 0.09). Being overweight at ages 6 and 15 corresponded to a nonsignificant shorter LTL at age 53 and they were associated with 2.06% (95% CI: 0.05-4.08%) and 4.26% (1.98-6.54%) less LTL attrition in midlife, respectively, compared to those who were not overweight.There is a weak indication that greater telomere loss was seen with greater concurrent body mass index gain. Adolescent overweight corresponded to shorter telomeres in midlife, albeit weakly, and with less subsequent attrition. Our findings point toward potential pathways which may link adiposity and ageing outcomes.