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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.

STUDY QUESTION How does the risk of cardiovascular disease (CVD) vary with type and age of menopause? SUMMARY ANSWER Earlier surgical menopause (e.g. WHAT IS KNOWN ALREADY Earlier age at menopause has been linked to an increased risk of CVD mortality and all-cause mortality, but the extent that this risk of CVD varies by type of menopause and the role of postmenopausal HRT use in reducing this risk is unclear. STUDY DESIGN, SIZE, DURATION Pooled individual-level data of 203 767 postmenopausal women from 10 observational studies that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Postmenopausal women who had reported menopause (type and age of menopause) and information on non-fatal CVD events were included. Type of menopause (natural menopause and surgical menopause) and age at menopause (categorised as MAIN RESULTS AND THE ROLE OF CHANCE Compared with natural menopause, surgical menopause was associated with over 20% higher risk of CVD (HR 1.22, 95% CI 1.16–1.28). After the stratified analysis by age at menopause, a graded relationship for incident CVD was observed with lower age at menopause in both types of natural and surgical menopause. There was also a significant interaction between type of menopause and age at menopause (P LIMITATIONS, REASONS FOR CAUTION Self-reported data on type and age of menopause, no information on indication for the surgery (e.g. endometriosis and fibroids) and the exclusion of fatal CVD events may bias our results. WIDER IMPLICATIONS OF THE FINDINGS In clinical practice, women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures and early diagnosis of CVD. Our findings also suggested that timing of menopause should be considered as an important factor in risk assessment of CVD for women. The findings on CVD lend some support to the position that elective bilateral oophorectomy (surgical menopause) at hysterectomy for benign diseases should be discouraged based on an increased risk of CVD. STUDY FUNDING/COMPETING INTEREST(S) InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). GDM is supported by Australian National Health and Medical Research Council Principal Research Fellowship (APP1121844). There are no competing interests.

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.

ObjectiveTo examine the association between age at period cessation and trajectories of anthropometry, blood pressure, lipids and glycated haemoglobin (HbA1c) from midlife to age 69 years.MethodsWe used data from the UK Medical Research Council National Survey of Health and Development to examine the association between age at period cessation and trajectories of systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC) from 36 to 69 years and trajectories of triglyceride, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and HbA1c from 53 to 69 years.ResultsWe found no evidence that age at period cessation was associated with trajectories of log triglyceride, LDL-C and HDL-C from 53 to 69 years and trajectories of SBP or DBP from 36 to 69 years, regardless of whether period cessation occurred naturally or due to hysterectomy. While we found some evidence of associations of age at period cessation with log BMI, log WC and log HbA1c, patterns were not consistent and differences were small at age 69 years, with confidence intervals that spanned the null value.ConclusionHow and when women experience period cessation is unlikely to adversely affect conventional cardiovascular risk factors across mid and later life. Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impact over the long term is small.

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.

The one-legged balance test is widely used as a fall risk screening tool in both clinical and research settings. Despite rising fall prevalence in midlife, there is little evidence examining balance and fall risk in those aged65 years. This study investigated the longitudinal associations between one-legged balance and the number of falls between ages 53 and 68 years.The study included 2,046 individuals from the Medical Research Council National Survey of HealthDevelopment, a British birth cohort study. One-legged balance times (eyes open, maximum: 30 seconds) were assessed at ages 53 years (1999) and 60-64 years (2006-2010). Fall history within the last year (none, 1, ≥2) was self-reported at ages 60-64 years and 68 years (2014). Multinomial logistic regressions assessed the associations between balance and change in balance with subsequent falls. Models adjusted for anthropometric, socioeconomic, behavioral, health status, and cognitive indicators. Analysis occurred between 2019 and 2022.Balance performance was not associated with single falls. Better balance performance at age 53 years was associated with decreased risk of recurrent falls at ages 60-64 years and 68 years, with similar associations between balance at age 60-64 years and recurrent falls at age 68 years. Those with consistently lower balance times (15 seconds) were at greater risk (RRR=3.33, 95% CI=1.91, 5.80) of recurrent falls at age 68 years in adjusted models than those who could balance for 30 seconds at ages 53 years and 60-64 years.Lower balance and consistently low or declining performance were associated with a greater subsequent risk of recurrent falls. Earlier identification and intervention of those with poor balance ability can help to minimize the risk of recurrent falls in aging adults.

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.

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

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.

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.

Importance: Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD. Objective: To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause. Design, Setting, and Participants: Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019. Exposures: Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older. Main Outcomes and Measures: First nonfatal CVD event, including coronary heart disease and stroke events. Results: A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (

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.

Objective: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. Design: A pooled analysis of six cohort studies. Setting: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). Population: 18 555 women from the UK, USA and Australia. Methods: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. Main outcome measures: Hot flushes and night sweats. Results: Frequency data showed that early menarche ≤11 years was associated with an increased risk of ‘often’ hot flushes (RRR 1.48, 95% CI 1.24–1.76) and night sweats (RRR 1.59, 95% CI 1.49–1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94–1.42) and 1.27 (95% CI 1.01–1.58) for ‘severe’ hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and ‘often’ VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of ‘severe’ VMS. Conclusions: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. Tweetable abstract: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

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:Frequent and severe vasomotor symptoms during menopause are linked with adverse health outcomes. Understanding modifiable lifestyle factors for the risk of vasomotor menopausal symptoms is important to guide preventive strategies. OBJECTIVE:We investigated the associations between body mass index and smoking, their joint effects with the risk of vasomotor symptoms, and whether the associations differed by menopausal stage. STUDY DESIGN:The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events pooled data on 21,460 midlife women from 8 studies (median age, 50 years; interquartile range, 49-51 years) for the cross-sectional analysis. Four studies provided data for the prospective analysis (n=11,986). Multinomial logistic regression models with 4 categories of frequency/severity for the outcome of vasomotor symptoms were used to estimate relative risk ratios and 95% confidence intervals that were adjusted for within-study correlation and covariates. RESULTS:At baseline, nearly 60% of the women experienced vasomotor symptoms. One-half of them were overweight (30%) or obese (21%), and 17% were current smokers. Cross-sectional analyses showed that a higher body mass index and smoking more cigarettes with longer duration and earlier initiation were all associated with more frequent or severe vasomotor symptoms. Never smokers who were obese had a 1.5-fold (relative risk ratio, 1.52; 95% confidence interval, 1.35-1.73) higher risk of often/severe vasomotor symptoms, compared with never smokers who were of normal-weight. Smoking strengthened the association because the risk of often/severe vasomotor symptoms was much greater among smokers who were obese (relative risk ratio, 3.02; 95% confidence interval, 2.41-3.78). However, smokers who quit at

Background: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. Methods: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40–44 years (early menopause), 45–49 years (relatively early), 50–51 years (reference category), 52–54 years (relatively late), and 55 years or older (late menopause). Findings: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50–51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age

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.

BackgroundMenopausal vasomotor symptoms (ie, hot flashes and night sweats) have been associated with unfavorable risk factors and surrogate markers of cardiovascular disease, but their association with clinical cardiovascular disease events is unclear.ObjectiveTo examine the associations between different components of vasomotor symptoms, timing of vasomotor symptoms, and risk of cardiovascular disease.Study designWe harmonized and pooled individual-level data from 23,365 women in 6 prospective studies that contributed to the International Collaboration for a Life Course Approach to Women's Reproductive Health and Chronic Disease Events consortium. Women who experienced cardiovascular disease events before baseline were excluded. The associations between frequency (never, rarely, sometimes, and often), severity (never, mild, moderate, and severe), and timing (before or after age of menopause; ie, early or late onset) of vasomotor symptoms and incident cardiovascular disease were analyzed. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.ResultsIn the adjusted model, no evidence of association was found between the frequency of hot flashes and incident cardiovascular disease, whereas women who reported night sweats "sometimes" (hazard ratio, 1.22; 95% confidence interval, 1.02-1.45) or "often" (hazard ratio, 1.29; 95% confidence interval, 1.05-1.58) had higher risk for cardiovascular disease. Increased severity of either hot flashes or night sweats was associated with higher risk of cardiovascular disease. The hazards ratios of cardiovascular disease in women with severe hot flashes, night sweats, and any vasomotor symptoms were 1.83 (95% confidence interval, 1.22-2.73), 1.59 (95% confidence interval, 1.07-2.37), and 2.11 (95% confidence interval, 1.62-2.76), respectively. Women who reported severity of both hot flashes and night sweats had a higher risk for cardiovascular disease (hazard ratio, 1.55; 95% confidence interval, 1.24-1.94) than those with hot flashes alone (hazard ratio, 1.33; 95% confidence interval, 0.94-1.88) and night sweats alone (hazard ratio, 1.32; 95% confidence interval, 0.84-2.07). Women with either early-onset (hazard ratio, 1.38; 95% confidence interval, 1.10-1.75) or late-onset (hazard ratio, 1.69; 95% confidence interval, 1.32-2.16) vasomotor symptoms had an increased risk for incident cardiovascular disease compared with women who did not experience vasomotor symptoms.ConclusionSeverity rather than frequency of vasomotor symptoms (hot flashes and night sweats) was associated with increased risk of cardiovascular disease. Vasomotor symptoms with onset before or after menopause were also associated with increased risk of cardiovascular disease.

Using data from 1,184 women in the MRC National Survey of Health and Development, we estimated associations between education and Ryff’s environmental mastery scale scores at age 52. Confirmatory factor analysis indicated two subscales, here termed mastery skills and mastery accomplishments. Low education was associated with higher mastery skills. This was partly explained by childhood socioeconomic position, as mastery was lower among those with fathers in the most and least advantaged occupational classes. Education was not associated with mastery accomplishments in unadjusted models. Lower ambitions for family/home were associated with higher mastery accomplishments and may have partly suppressed as an association between education and mastery accomplishments. This study highlights childhood as well as adult correlates of mastery and adds to mounting evidence that higher mastery is not universally found among those who are more educated.

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.

BackgroundMany women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.MethodsA pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.ResultsAt baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).ConclusionsDifficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.

Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome.

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.

Background: Although lifespan is increasing, there is no evidence to suggest that older people are experiencing better health in their later years than previous generations. Nutrition, at all stages of life, plays an important role in determining health and wellbeing. Methods: A roundtable meeting of UK experts on nutrition and ageing considered key aspects of the diet–ageing relationship and developed a consensus position on the main priorities for research and public health actions that are required to help people live healthier lives as they age. Results: The group consensus highlighted the requirement for a life course approach, recognising the multifactorial nature of the impact of ageing. Environmental and lifestyle influences at any life stage are modified by genetic factors and early development. The response to the environment at each stage of life can determine the impact of lifestyle later on. There are no key factors that act in isolation to determine patterns of ageing and it is a combination of environmental and social factors that drives healthy or unhealthy ageing. Too little is known about how contemporary dietary patterns and sedentary lifestyles will impact upon healthy ageing in future generations and this is a priority for future research. Conclusions: There is good evidence to support change to lifestyle (i.e. diet, nutrition and physical) activity in relation to maintaining or improving body composition, cognitive health and emotional intelligence, immune function and vascular health. Lifestyle change at any stage of life may extend healthy lifespan, although the impact of early changes appears to be greatest.

Aims: Female reproductive history has been inconsistently associated with risk of type 2 diabetes. We examined the prospective associations between aspects of a woman's reproductive history and incident diabetes. Methods: This study pooled 126,721 middle‐aged women's individual data from eight cohort studies contributing to the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE). Associations between age at menarche, age at first birth, parity and menopausal status with incident diabetes were examined using generalized linear mixed models with binomial distribution and robust variance. We stratified by body mass index (BMI) when there was evidence of a statistical interaction with BMI. Results: Over a median follow‐up of 9 years, 4,073 cases of diabetes were reported. Non‐linear associations with diabetes were observed for age at menarche, parity and age at first birth. Compared with menarche at age 13, menarche at ≤10 years was associated with 18% increased risk of diabetes (Relative Risk [RR] 1.18, 95% Confidence interval [95%CI]: 1.02–1.37) after adjusting for BMI. After stratifying by BMI, the increase risk was only observed in women with BMI >25 kg/m2. A U‐shape relation was observed between parity and risk of diabetes. Compared with pre‐/peri‐menopausal women, women with a hysterectomy/oophorectomy had an increased risk of diabetes (RR 1.17, 95% CI: 1.07–1.29). Conclusions: Several markers of a woman's reproductive history appear to be modestly associated with future risk of diabetes. Maintaining a normal weight in adult life may ameliorate any increase in risk conferred by early onset of menarche.

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.

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.

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.

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.

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

Objective We investigated whether cognitive performance between ages 43 and 69 years was associated with timing of menopause, controlling for hormone replacement therapy, childhood cognitive ability, and sociobehavioral factors. Methods We used data from 1,315 women participating in the Medical Research Council National Survey of Health and Development (a British birth cohort study) with known age at period cessation and up to 4 assessments of verbal memory (word-learning task) and processing speed (letter-cancellation task) at ages 43, 53, 60–64, and 69. We fitted multilevel models with linear and quadratic age terms, stratified by natural or surgical menopause, and adjusted for hormone replacement therapy, body mass index, smoking, occupational class, education, and childhood cognitive ability. Results Verbal memory increased with later age at natural menopause (0.17 words per year, 95% confidence interval [CI]: 0.07–0.27, p = 0.001); an association remained, albeit attenuated, after full adjustment (0.09, 95% CI: 0.02–0.17, p = 0.013). Verbal memory also increased with later age at surgical menopause (0.16, 95% CI: 0.06–0.27, p = 0.002), but this association was fully attenuated after adjustment. Search speed was not associated with age at menopause. Conclusion Our findings suggest lifelong hormonal processes, not just short-term fluctuations during the menopause transition, may be associated with verbal memory, consistent with evidence from a variety of neurobiological studies; mechanisms are likely to involve estrogen receptor β function. Further follow-up is required to assess fully the clinical significance of these associations.

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.

ObjectivesOur aim was to investigate the association of epigenetic age and physical capability in later life. Having a higher epigenetic than chronological age (known as age acceleration (AA)) has been found to be associated with an increased rate of mortality. Similarly, physical capability has been proposed as a marker of ageing due to its consistent associations with mortality.SettingThe MRC National Survey of Health and Development (NSHD) cohort study.ParticipantsWe used data from 790 women from the NSHD who had DNA methylation data available.DesignEpigenetic age was calculated using buccal cell (n=790) and matched blood tissue (n=152) from 790 female NSHD participants. We investigated the association of AA at age 53 with changes in physical capability in women from ages 53 to 60–64. Regression models of change in each measure of physical capability on AA were conducted. Secondary analysis focused on the relationship between AA and smoking, alcohol, body mass index (BMI) and socioeconomic position.Outcome measuresThree objective measures of physical capability were used: grip strength, standing balance time and chair rise speed.ResultsEpigenetic age was lower than chronological age (mean 53.4) for both blood (50.3) and buccal cells (42.8). AA from blood was associated with a greater decrease in grip strength from ages 53 to 60–64 (0.42 kg decrease per year of AA, 95% CI 0.03, 0.82 kg; p=0.03, n=152), but no associations were observed with standing balance time or chair rise speed. Current smoking and lower BMI were associated with lower epigenetic age from buccal cells.ConclusionsWe found evidence that AA in blood is associated with a greater decrease in grip strength in British females aged between 53 and 60–64, but no association with standing balance time or chair rise speed was found.

Current evidence on the association between body mass index (BMI) and age at menopause remains unclear. We investigated the relationship between BMI and age at menopause using data from 11 prospective studies. A total of 24,196 women who experienced menopause after recruitment was included. Baseline BMI was categorised according to the WHO criteria. Age at menopause, confirmed by natural cessation of menses for ≥ 12 months, was categorised as

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.

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.