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1.  Patterns of Leisure-Time Physical Activity Participation in a British Birth Cohort at Early Old Age 
PLoS ONE  2014;9(6):e98901.
Using data from a nationally representative British birth cohort we characterized the type and diversity of leisure-time physical activity that 2,188 participants (age 60–64 years) engaged in throughout the year by gender and obesity. Participants most commonly reported walking (71%), swimming (33%), floor exercises (24%) and cycling (15%). Sixty-two percent of participants reported ≥2 activities in the past year and 40% reported diversity on a regular basis. Regular engagement in different types of activity (cardio-respiratory, balance/flexibility and strength) was reported by 67%, 19% and 11% of participants, respectively. We found gender differences, as well as differences by obesity status, in the activities reported, the levels of activity diversity and activity type. Non-obese participants had greater activity diversity, and more often reported activities beneficial for cardio-respiratory health and balance/flexibility than obese participants. These findings may be used to inform the development of trials of physical activity interventions targeting older adults, and those older adults with high body mass index.
doi:10.1371/journal.pone.0098901
PMCID: PMC4049596  PMID: 24911018
2.  Neuroticism and Extraversion in Youth Predict Mental Wellbeing and Life Satisfaction 40 Years Later 
Neuroticism and Extraversion are linked with current wellbeing, but it is unclear whether these traits in youth predict wellbeing decades later. We applied structural equation modelling to data from 4583 people from the MRC National Survey of Health and Development. We examined the effects of Neuroticism and Extraversion at ages 16 and 26 years on mental wellbeing and life satisfaction at age 60-64 and explored the mediating roles of psychological and physical health. Extraversion had direct, positive effects on both measures of wellbeing. The impact of Neuroticism on both wellbeing and life satisfaction was largely indirect through susceptibility to psychological distress and physical health problems. Personality dispositions in youth have enduring influence on wellbeing assessed about forty years later.
doi:10.1016/j.jrp.2013.06.005
PMCID: PMC3927052  PMID: 24563560
Neuroticism; Extraversion; Wellbeing; Life satisfaction; Cohort
3.  Levels of physical activity among a nationally representative sample of people in early old age: results of objective and self-reported assessments 
Background
Detailed assessment of physical activity (PA) in older adults is required to comprehensively describe habitual PA-levels in this growing population segment. Current evidence of population PA-levels is predominantly based on self-report.
Methods
We examined PA and sedentary behaviour in a nationally representative sample of British people aged 60–64, using individually-calibrated combined heart-rate and movement sensing and a validated questionnaire (EPAQ2), and the socio-demographic and behavioural factors that may explain between-individual variation in PA.
Results
Between 2006–2010, 2224 participants completed EPAQ2 capturing the past year’s activity in four domains (leisure, work, transportation and domestic life) and 1787 participants provided 2–5 days of combined-sensing data. According to objective estimates, median(IQR) physical activity energy expenditure (PAEE) was 33.5 (25.3-42.2) and 35.5 (26.6- 47.3) kJ/kg/day for women and men, respectively. Median (IQR) time spent in moderate-to-vigorous PA (MVPA; >3MET), light-intensity PA (1.5-3 MET) and sedentary (<1.5 MET) was 26.0 (12.3-48.1) min/day, 5.4 (4.2-6.7) h/day and 18.0 (16.6-19.4) h/day, respectively, in women; and 41.0 (18.8-73.0) min/day, 5.2 (4.0-6.5) h/day and 17.9 (16.3-19.4) h/day in men. PAEE and time spent in MVPA were lower and sedentary time was greater in obese individuals, those with poor health, and those with lower educational attainment (women only). Questionnaire-derived PAEE and MVPA tended to have similar patterns of variation across socio-demographic strata. In the whole sample, domestic PA had the greatest relative contribution to total questionnaire-derived PAEE (58%), whereas occupational PA was the main driver among employed participants (54%). Only 2.2% of participants achieved an average of >30 min MVPA per day combined with >60 min strength-training per week.
Conclusions
The use of both self-report and objective monitoring to assess PA in early old age provides important information on the domains of PA, PAEE and time spent at different intensity levels. Our findings suggest PA levels are generally low and observed patterns of variation indicate specific subgroups who might benefit from targeted interventions to increase PA.
doi:10.1186/1479-5868-11-58
PMCID: PMC4038114  PMID: 24885497
Physical activity; Sedentary behaviour; Physical activity questionnaire; Combined sensing; Birth cohort; Old age
4.  A life-course approach to healthy ageing: maintaining physical capability 
Research on healthy ageing lacks an agreed conceptual framework and has not adequately taken into account the growing evidence that social and biological factors from early life onwards affect later health. We conceptualise healthy ageing within a life-course framework, separating healthy biological ageing (in terms of optimal physical and cognitive functioning, delaying the onset of chronic diseases, and extending length of life for as long as possible) from changes in psychological and social wellbeing. We summarise the findings of a review of healthy ageing indicators, focusing on objective measures of physical capability, such as tests of grip strength, walking speed, chair rises and standing balance, which aim to capture physical functioning at the individual level, assessing the capacity to undertake the physical tasks of daily living. There is robust evidence that higher scores on these measures are associated with lower rates of mortality, and more limited evidence of lower risk of morbidity, and of age-related patterns of change. Drawing on a research collaboration of UK cohort studies, we summarise what is known about the influences on physical capability in terms of lifetime socioeconomic position, body size and lifestyle, and underlying physiology and genetics; the evidence to date supports a broad set of factors already identified as risk factors for chronic diseases. We identify a need for larger longitudinal studies to investigate age-related change and ethnic diversity in these objective measures, the dynamic relationships between them, and how they relate to other component measures of healthy ageing. Robust evidence across cohort studies, using standardised measures within a clear conceptual framework, will benefit policy and practice to promote healthy ageing.
doi:10.1017/S0029665113003923
PMCID: PMC3981474  PMID: 24456831
Life course; Epidemiology; Healthy ageing; Physical capability; Cohort studies
5.  Physical Activity Across Adulthood in Relation to Fat and Lean Body Mass in Early Old Age: Findings From the Medical Research Council National Survey of Health and Development, 1946–2010 
American Journal of Epidemiology  2014;179(10):1197-1207.
Fat and lean body mass have important implications for health and physical functioning in older age, and physical activity is purported to be an important modifiable determinant. However, our evidence-based understanding of its role is limited. We examined the associations of physical activity, assessed both by self-report (using data on leisure time physical activity (LTPA) collected on 4 occasions over a 28-year period) and objectively (using 5-day heart rate and movement monitoring), with fat and lean mass at ages 60–64 years in 1,162 British participants from the Medical Research Council National Survey of Health and Development in 1946–2010. Higher objectively assessed physical activity energy expenditure (PAEE) at ages 60–64 years was associated with lower fat mass and android (abdominal):gynoid (hip) fat ratio (mean differences in fat mass per 1–standard deviation increase in PAEE were −0.79 kg/m1.2 in men (95% confidence interval: −1.08, −0.50) and −1.79 kg/m1.2 (95% confidence interval: −2.15, −1.42) in women). After adjustment for fat mass, higher PAEE was associated with higher appendicular lean mass. Both light and moderate-to-vigorous intensities of activity were associated with fat mass, and the latter was associated with lean mass. More frequent LTPA across adulthood was associated with lower fat mass (in women only) and higher appendicular lean mass (in both sexes, after adjustment for fat mass). These results support the promotion of LTPA across adulthood, as well as both light and moderate-to-vigorous intensities of activity among older adults.
doi:10.1093/aje/kwu033
PMCID: PMC4010186  PMID: 24722997
body fat distribution; motor activity; obesity; sarcopenia; sedentary lifestyle; skeletal muscle
6.  Childhood and Maternal Effects on Physical Health Related Quality of Life Five Decades Later: The British 1946 Birth Cohort 
PLoS ONE  2014;9(3):e88524.
Limited research has been done on the relationships between childhood factors and adult physical health related quality of life, with the underlying pathways not fully elucidated. Data from 2292 participants of the British 1946 birth cohort were used to examine the relationship of childhood characteristics and family environment with principal component summary (PCS) scores and the physical functioning (PF) subscale of the SF-36 at age 60–64 years. Impaired physical functioning was defined as the lowest quartile scores in the PF subscale. Childhood factors (father in manual social class versus non-manual (β =  −2.34; 95%CI: −3.39, −1.28) and poor maternal health versus good/excellent maternal health (β =  −6.18; −8.78, −3.57)) were associated with lower PCS scores at 60–64 years. Adult health behaviours (increasing BMI, lifelong smoking, and lower physical activity) at 53 years were identified as strong risk factors for lower PCS scores. After adjusting for these factors and education level (N = 1463), only poor maternal health remained unattenuated (β =  −5.07; −7.62, −2.51). Similarly poor maternal health doubled the risk of reporting impaired PF (Odds ratio =  2.45; 95%CI: 1.39, 4.30); serious illness in childhood (OR = 1.44; 1.01, 2.06) and lower educational level attained were also risk factors for impaired PF (N = 1526). While findings suggest the influence of father's social class on physical health related quality of life are mediated by modifiable adult social factors and health behaviours; health professionals should also be mindful of the inter-generational risk posed by poor maternal health on the physical health related quality of life of her offspring almost five decades later.
doi:10.1371/journal.pone.0088524
PMCID: PMC3966737  PMID: 24670776
7.  Comparison of the EPIC Physical Activity Questionnaire with Combined Heart Rate and Movement Sensing in a Nationally Representative Sample of Older British Adults 
PLoS ONE  2014;9(2):e87085.
Objectives
To compare physical activity (PA) subcomponents from EPIC Physical Activity Questionnaire (EPAQ2) and combined heart rate and movement sensing in older adults.
Methods
Participants aged 60–64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life) during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE), sedentary behaviour, light (LPA) and moderate-to-vigorous PA (MVPA) were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women).
Results
EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement) in men and women were 32.3 (−61.5 to 122.6) and 29.0 (−39.2 to 94.6) kJ/kg/day for PAEE; −4.6 (−10.6 to 1.3) and −6.0 (−10.9 to −1.0) h/day for sedentary time; −171.8 (−454.5 to 110.8) and −60.4 (−367.5 to 246.6) min/day for LPA; 91.1 (−159.5 to 341.8) and 55.4 (−117.2 to 228.0) min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho  = 0.12 to 0.36); the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women) and PAEE (rho = 0.26 men; rho = 0.25 women).
Conclusion
EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population.
doi:10.1371/journal.pone.0087085
PMCID: PMC3916297  PMID: 24516543
8.  Adolescent Self-Organization Predicts Midlife Memory in a Prospective Birth Cohort Study 
Psychology and Aging  2013;28(4):958-968.
Childhood and adolescent mental health have a lasting impact on adult life chances, with strong implications for subsequent health, including cognitive aging. Using the British 1946 birth cohort, the authors tested associations between adolescent conduct problems, emotional problems and aspects of self-organization, and verbal memory at 43 years and rate of decline in verbal memory from 43 to 60–64 years. After controlling for childhood intelligence, adolescent self-organization was positively associated with verbal memory at 43 years, mainly through educational attainment, although not with rate of memory decline. Associations between adolescent conduct and emotional problems and future memory were of negligible magnitude. It has been suggested that interventions to improve self-organization may save a wide range of societal costs; this study also suggests that this might also benefit cognitive function in later life.
doi:10.1037/a0033787
PMCID: PMC3906799  PMID: 24364401
self-organization; memory; life course
9.  Cognitive and Kidney Function: Results from a British Birth Cohort Reaching Retirement Age 
PLoS ONE  2014;9(1):e86743.
Background
Previous studies have found associations between cognitive function and chronic kidney disease. We aimed to explore possible explanations for this association in the Medical Research Council National Survey of Health and Development, a prospective birth cohort representative of the general British population.
Methods
Cognitive function at age 60–64 years was quantified using five measures (verbal memory, letter search speed and accuracy, simple and choice reaction times) and glomerular filtration rate (eGFR) at the same age was estimated using cystatin C. The cross-sectional association between cognitive function and eGFR was adjusted for background confounding factors (socioeconomic position, educational attainment), prior cognition, and potential explanations for any remaining association (smoking, diabetes, hypertension, inflammation, obesity).
Results
Data on all the analysis variables were available for 1306–1320 study members (depending on cognitive measure). Verbal memory and simple and choice reaction times were strongly associated with eGFR. For example, the lowest quartile of verbal memory corresponded to a 4.1 (95% confidence interval 2.0, 6.2) ml/min/1.73 m2 lower eGFR relative to the highest quartile. Some of this association was explained by confounding due to socioeconomic factors, but very little of it by prior cognition. Smoking, diabetes, hypertension, inflammation and obesity explained some but not all of the remaining association.
Conclusions
These analyses support the notion of a shared pathophysiology of impaired cognitive and kidney function at older age, which precedes clinical disease. The implications of these findings for clinical care and research are important and under-recognised, though further confirmatory studies are required.
doi:10.1371/journal.pone.0086743
PMCID: PMC3901795  PMID: 24482683
10.  Weight Loss and Premature Death: The 1946 British Birth Cohort Study 
PLoS ONE  2014;9(1):e86282.
Objective
The relationship between weight loss and mortality has important clinical and public health significance but has proved to be complex. Evidence is mixed and particularly limited on the association between weight loss in mid-life and premature death (i.e. before 65 years of age), a small albeit important segment of total mortality. We aimed to study the association between midlife weight change and mortality accounting for health and lifestyle characteristics, and also considering potential bias due to preexisting chronic diseases and smoking status.
Design
Longitudinal, population-based, ‘the 1946 British’ birth cohort study.
Subjects and Measures
In 2750 men and women, mortality from age 53 through 65 years was analyzed according to categories of measured 10 year weight change between 43 and 53 years. Cox's hazard ratios (HR) were progressively adjusted for socio-demographic, lifestyle and health characteristics.
Results
Nearly 20% of participants lost weight and over 50% gained 5 kg or more in midlife. There were 164 deaths. Compared to those who gained between 2 and 5 kg, those who lost 5 kg or more had an increased risk of premature death independently of midlife physical activity, socio-economic circumstances and educational attainment. This association was unaltered when highest weight loss (lost more than 15 Kg) (p = 0.04) and early deaths were excluded (p<0.001), but was no longer significant after adjustment for cardiovascular risk factors and health status (HR = 1.8; 95% CI: 0.9 to 3.5).
Conclusion
The inverse association between weight loss in midlife and higher risk of premature death may be explained by vascular risk factors and ill health. In consideration of the burden of premature death, closer monitoring of weight loss in mid-life is warranted.
doi:10.1371/journal.pone.0086282
PMCID: PMC3897675  PMID: 24466002
11.  Social isolation and diurnal cortisol patterns in an ageing cohort☆ 
Psychoneuroendocrinology  2013;38(11):2737-2745.
Summary
Background
Social isolation may operate as a psychosocial stressor which disrupts functioning of the hypothalamic–pituitary–adrenocortical axis.
Methods
Using data from the MRC National Survey of Health and Development, we tested whether living alone, not being married and social network size were associated with diurnal cortisol patterns at 60–64 years. We hypothesised that recent onset compared with long-term isolation would be more strongly associated with cortisol awakening response, cortisol decline over the day and evening cortisol. Models were adjusted for sex, smoking, body mass index, alcohol intake, psychological distress and financial difficulties.
Results
Those widowed within the last three years had a 36% (95%CI 6%, 73%) higher night time cortisol than those who were currently married. Those newly living alone also had a higher night time cortisol and flatter diurnal slope than those living with others.
Conclusion
Independently of multiple behavioural and psychosocial correlates, recent onset of social isolation is related to diurnal cortisol patterns that increase the risk of morbidity and mortality.
doi:10.1016/j.psyneuen.2013.07.002
PMCID: PMC3820041  PMID: 23920224
NSHD; Psychosocial; HPA axis; Bereavement; Social isolation
12.  Physical activity levels across adult life and grip strength in early old age: updating findings from a British birth cohort 
Age and Ageing  2013;42(6):794-798.
Introduction: observational studies do not always find positive associations between physical activity and muscle strength despite intervention studies consistently showing that exercise improves strength in older adults. In previous analyses of the MRC National Survey of Health and Development (NSHD), the 1946 British birth cohort, there was no evidence of an association between leisure time physical activity (LTPA) across adulthood and grip strength at age 53. This study tested the hypothesis that cumulative benefits of LTPA across mid-life on grip strength will have emerged by age 60–64.
Methods: data from the MRC NSHD were used to investigate the associations between LTPA at ages 36, 43, 53 and 60–64 and grip strength at 60–64. Linear regression models were constructed to examine the effect of activity at each age separately and as a cumulative score, including adjustment for potential confounders and testing of life course hypotheses.
Results: there were complete longitudinal data available for 1,645 participants. There was evidence of a cumulative effect of LTPA across mid-life on grip strength at 60–64. Compared with the third of participants who reported the least LTPA participation across the four time points, those in the top third had on average 2.11 kg (95% CI: 0.88, 3.35) stronger grip after adjustments.
Conclusions: increased levels of LTPA across mid-life were associated with stronger grip at age 60–64, in both men and women. As these associations have emerged since age 53, it suggests that LTPA across adulthood may prevent decline in grip strength in early old age.
doi:10.1093/ageing/aft124
PMCID: PMC3809720  PMID: 23981980
physical activity; longitudinal study; grip strength; life course models; older people
13.  A life course approach to physical capability: findings from the HALCyon research programme 
BMC Proceedings  2013;7(Suppl 4):S4.
doi:10.1186/1753-6561-7-S4-S4
PMCID: PMC3892187  PMID: 24899922
14.  Population Genomics of Cardiometabolic Traits: Design of the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium 
PLoS ONE  2013;8(8):e71345.
Substantial advances have been made in identifying common genetic variants influencing cardiometabolic traits and disease outcomes through genome wide association studies. Nevertheless, gaps in knowledge remain and new questions have arisen regarding the population relevance, mechanisms, and applications for healthcare. Using a new high-resolution custom single nucleotide polymorphism (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked to cardiometabolic disease, the University College-London School-Edinburgh-Bristol (UCLEB) consortium of highly-phenotyped population-based prospective studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate individual absolute and population attributable risks based on individual SNPs and their combination; (3) investigate mechanisms leading to altered risk factor profiles and CVD events; and (4) use Mendelian randomisation to undertake studies of the causal role in CVD of a range of cardiovascular biomarkers to inform public health policy and help develop new preventative therapies.
doi:10.1371/journal.pone.0071345
PMCID: PMC3748096  PMID: 23977022
15.  Timing of Voice Breaking in Males Associated with Growth and Weight Gain Across the Life Course 
Background:
In contrast to the many studies in females, there are few data in males on the relationships between childhood growth and weight gain and the timing of pubertal maturation and its relevance to adult body mass index (BMI) and body composition.
Methods:
A total of 2008 males in the 1946 British Birth Cohort Study had assessment of pubertal status including voice-breaking status (no change, starting, or complete) at age 14 yr. These responses were related to growth measurements at birth (weight only) and at 2, 4, 6, 7, 11, 14, 20, 26, 36, 43, 53, and 60–64 yr. Body composition was assessed by dual-energy x-ray absorptiometry at 60–64 yr.
Results:
Males with more advanced voice-breaking status at age 14 yr had similar birth weights compared with other males; they showed faster weight gain from 0–2 yr and had higher mean weight and BMI at age 2 yr. Subsequently, they continued to accelerate in weight and BMI, and also in height, and maximum differences in body size were seen at age 14 yr. Adult height did not differ between groups, but males with advanced voice breaking had higher adult BMI and greater whole-body lean mass and greater android fat mass at 60–64 yr.
Conclusion:
Similar to females with earlier menarche, the trajectory to earlier sexual maturation in males is manifested by faster early postnatal growth and weight gain and leads to higher adult BMI. Timing of pubertal maturation has potential relevance to adult disease risks in males. We also describe conditional height difference in sd score as a proxy marker of pubertal timing in males.
doi:10.1210/jc.2011-3445
PMCID: PMC3579950  PMID: 22654120
16.  Early-Life Overweight Trajectory and CKD in the 1946 British Birth Cohort Study 
Background
Few studies have examined the impact of childhood obesity on later kidney disease, and consequently, our understanding is very limited.
Study Design
Longitudinal population-based cohort.
Setting & Participants
The Medical Research Council National Survey of Health and Development, a socially stratified sample of 5,362 singletons born in 1 week in March 1946 in England, Scotland, and Wales, of which 4,340 were analyzed.
Predictor
Early-life overweight latent classes (never, prepubertal only, pubertal onset, or always), derived from repeated measurements of body mass index between ages 2 and 20 years.
Outcomes & Measurements
The primary outcome was chronic kidney disease (CKD), defined as creatinine- or cystatin C–based estimated glomerular filtration rate (eGFRcr and eGFRcys, respectively) <60 mL/min/1.73 m2 or urine albumin-creatinine ratio (UACR) ≥3.5 mg/mmol measured at age 60-64 years. Associations were explored through regression analysis, with adjustment for socioeconomic position, smoking, physical activity level, diabetes, hypertension, and overweight at ages 36 and 53 years.
Results
2.3% of study participants had eGFRcr <60 mL/min/1.73 m2, 1.7% had eGFRcys <60 mL/min/1.73 m2, and 2.9% had UACR ≥3.5 mg/mmol. Relative to being in the never-overweight latent class, being in the pubertal-onset– or always-overweight latent classes was associated with eGFRcys-defined CKD (OR, 2.04; 95% CI, 1.09-3.82). Associations with CKD defined by eGFRcr (OR, 1.27; 95% CI, 0.71-2.29) and UACR (OR, 1.33; 95% CI, 0.70-2.54) were less marked, but in the same direction. Adjustment for lifestyle and health factors had little impact on effect estimates.
Limitations
A low prevalence of CKD resulted in low statistical power. No documentation of chronicity for outcomes. All-white study population restricts generalizability.
Conclusions
Being overweight in early life was found to be associated with eGFRcys-defined CKD in later life. The associations with CKD defined by eGFRcr and UACR were less marked, but in the same direction. Reducing or preventing overweight in the early years of life may significantly reduce the burden of CKD in the population.
doi:10.1053/j.ajkd.2013.03.032
PMCID: PMC3719096  PMID: 23714172
Childhood obesity; chronic kidney disease; estimated glomerular filtration rate
17.  Telomere Length and Physical Performance at Older Ages: An Individual Participant Meta-Analysis 
PLoS ONE  2013;8(7):e69526.
Background
Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with physical performance.
Methods
Using data from four UK adult cohorts (ages 53–80 years at baseline), we undertook cross-sectional and longitudinal analyses. We analysed each study separately and then used meta-analytic methods to pool the results. Physical performance was measured using walking and chair rise speed, standing balance time and grip strength. Telomere length was measured by quantitative real-time polymerase chain reaction (PCR) in whole blood at baseline and follow-up (time 1, time 2).
Results
Total sample sizes in meta-analyses ranged from 1,217 to 3,707. There was little evidence that telomere length was associated with walking speed, balance or grip strength, though weak associations were seen with chair rise speed and grip strength at baseline (p = 0.02 and 0.01 respectively). Faster chair rise speed at follow-up, was associated with a smaller decline in telomere length between time 1 and time 2 (standardised coefficient per SD increase 0.061, 95% CI 0.006, 0.115, p = 0.03) but this was consistent with chance (p = 0.08) after further adjustment.
Conclusions
Whereas shortening of leukocyte telomeres might be an important measure of cellular ageing, there is little evidence that it is a strong biomarker for physical performance.
doi:10.1371/journal.pone.0069526
PMCID: PMC3724915  PMID: 23922731
18.  Body mass index, occupational activity, and leisure-time physical activity: an exploration of risk factors and modifiers for knee osteoarthritis in the 1946 British birth cohort 
Background
Knee osteoarthritis (kOA) risk is increased by obesity and physical activities (PA) which mechanically stress the joint. We examined the associations of midlife kOA with body mass index (BMI) and activity exposure across adult life and their interaction.
Methods
Data are from a UK birth cohort of 2597 participants with a clinical assessment for kOA at age 53. At ages 36, 43 and 53 BMI (kg/m2), self-reported leisure-time PA, and occupational activity (kneeling/squatting; lifting; climbing; sitting; assigned using a job-exposure matrix) were ascertained. Associations were explored using the multiplicative logistic model.
Results
BMI was strongly and positively associated with kOA in men and women. Men and women in manual occupations also had greater odds of kOA; there was a weak suggestion that kOA risk was higher among men exposed to lifting or kneeling at work. For men, the only evidence of a multiplicative interaction between BMI and activities was for lifting (p = 0.01) at age 43; BMI conferred higher kOA risk among those most-likely to lift at work (OR per increase in BMI z-score: 3.55, 95% CI: 1.72-7.33). For women, the only evidence of an interaction was between BMI and leisure-time PA (p = 0.005) at age 43; BMI conferred higher kOA risk among those at higher PA levels (OR per increase in BMI z-score: 1.59, 95% CI: 1.26-2.00 in inactive; 1.70, 95% CI: 1.14-2.55 (less-active); and 4.44; 95% CI: 2.26-8.36 (most-active).
Conclusions
At the very least, our study suggests that more active individuals (at work and in leisure) may see a greater reduction in risk of kOA from avoiding a high BMI than those less active.
doi:10.1186/1471-2474-14-219
PMCID: PMC3726290  PMID: 23883324
Knee osteoarthritis; Body mass index; Physical activity; Occupational activity
19.  Associations between a Polymorphism in the Pleiotropic GCKR and Age-Related Phenotypes: The HALCyon Programme 
PLoS ONE  2013;8(7):e70045.
Background
The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI), blood lipid levels, lung function, and cognitive and physical capability.
Results
We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score = −0.04, p-value = 0.0001, n = 16,251). Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability.
Conclusion
Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.
doi:10.1371/journal.pone.0070045
PMCID: PMC3720952  PMID: 23894584
20.  Physical capability and subsequent positive mental wellbeing in older people: findings from five HALCyon cohorts 
Age  2013;36(1):445-456.
Objective measures of physical capability are being used in a growing number of studies as biomarkers of healthy ageing. However, very little research has been done to assess the impact of physical capability on subsequent positive mental wellbeing, the maintenance of which is widely considered to be an essential component of healthy ageing. We aimed to test the associations of grip strength and walking, timed get up and go and chair rise speeds (assessed at ages 53 to 82 years) with positive mental wellbeing assessed using the Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS) 5 to 10 years later. Data were drawn from five British cohorts participating in the Healthy Ageing across the Life Course research collaboration. Data from each study were analysed separately and then combined using random-effects meta-analyses. Higher levels of physical capability were consistently associated with higher subsequent levels of wellbeing; for example, a 1SD increase in grip strength was associated with an age and sex-adjusted mean difference in WEMWBS score of 0.81 (0.25, 1.37), equivalent to 10 % of a standard deviation (three studies, N = 3,096). When adjusted for body size, health status, living alone, socioeconomic position and neuroticism the associations remained albeit attenuated. The finding of these consistent modest associations across five studies, spanning early and later old age, highlights the importance of maintaining physical capability in later life and provides additional justification for using objective measures of physical capability as markers of healthy ageing.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-013-9553-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s11357-013-9553-8
PMCID: PMC3818137  PMID: 23818103
Physical capability; Positive mental wellbeing; Grip strength; Walking speed; Chair rise time
21.  The role of longitudinal cohort studies in epigenetic epidemiology: challenges and opportunities 
Genome Biology  2012;13(6):246.
Longitudinal cohort studies are ideal for investigating how epigenetic patterns change over time and relate to changing exposure patterns and the development of disease. We highlight the challenges and opportunities in this approach.
doi:10.1186/gb-2012-13-6-246
PMCID: PMC3446311  PMID: 22747597
Epigenomics; DNA methylation; life course; longitudinal studies
22.  Area Deprivation Across the Life Course and Physical Capability in Midlife: Findings From the 1946 British Birth Cohort 
American Journal of Epidemiology  2013;178(3):441-450.
Physical capability in later life is influenced by factors occurring across the life course, yet exposures to area conditions have only been examined cross-sectionally. Data from the National Survey of Health and Development, a longitudinal study of a 1946 British birth cohort, were used to estimate associations of area deprivation (defined as percentage of employed people working in partly skilled or unskilled occupations) at ages 4, 26, and 53 years (residential addresses linked to census data in 1950, 1972, and 1999) with 3 measures of physical capability at age 53 years: grip strength, standing balance, and chair-rise time. Cross-classified multilevel models with individuals nested within areas at the 3 ages showed that models assessing a single time point underestimate total area contributions to physical capability. For balance and chair-rise performance, associations with area deprivation in midlife were robust to adjustment for individual socioeconomic position and prior area deprivation (mean change for a 1-standard-deviation increase: balance, −7.4% (95% confidence interval (CI): −12.8, −2.8); chair rise, 2.1% (95% CI: −0.1, 4.3)). In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic position (−5.1%, 95% CI: −8.7, −1.6). Interventions aimed at reducing midlife disparities in physical capability should target the socioeconomic environment of individuals—for standing balance, as early as childhood.
doi:10.1093/aje/kwt003
PMCID: PMC3727343  PMID: 23788665
geography; Great Britain; health status disparities; longitudinal studies; multilevel analysis; physical endurance; residence characteristics; socioeconomic factors
23.  Genetic Variants Influencing Biomarkers of Nutrition Are Not Associated with Cognitive Capability in Middle-Aged and Older Adults123 
The Journal of Nutrition  2013;143(5):606-612.
Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on Z-score for carriers vs. noncarriers: −0.05 (95% CI: −0.09, −0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D–raising allele of rs2282679 [pooled β per T allele: −0.03 (95% CI: −0.05, −0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
doi:10.3945/jn.112.171520
PMCID: PMC3738233  PMID: 23468552
24.  Childhood Weight Gain and Thyroid Autoimmunity at Age 60–64 Years: The 1946 British Birth Cohort Study 
Background:
Complex bidirectional relationships have been described between body weight, thyroid function, and risk of thyroid disorders, including thyroid autoimmunity. We used a life-course approach to examine the potential association of childhood or adult body weight with the risk of thyroid autoimmunity and other thyroid disorders at age 60–64 years in a large population-based birth cohort study.
Methods:
In the UK Medical Research Council 1946 British Birth Cohort study, at age 60–64 years, 1277 women and 1185 men (78% of the target sample) responded to a postal questionnaire, which included questions on thyroid disease and thyroid medication. Circulating antithyroid peroxidase antibodies, free T4, and TSH concentrations were measured in 1057 women and 997 men at a subsequent clinic visit. Birth weight was recorded, and height and weight were measured at ages 2, 4, 6, 7, 11, 15 years and also repeatedly in adulthood.
Results:
At age 60–64 years, 10.9% of women (139 of 1277) and 2.3% of men (27 of 1185) reported they were taking T4, and 11.5% of women (122 of 1057) and 3.3% of men (33 of 997) had positive anti-TPO antibodies (>100 IU/mL), consistent with thyroid autoimmunity. Among women, both T4 use and positive anti-TPO antibodies at age 60–64 years were positively associated with childhood body weight, childhood overweight, and adult body mass index. Childhood weight gain between 0 and 14 years of age was positively associated with later T4 use (odds ratio 1.21, 95% confidence interval 1.03–1.42) and positive anti-TPO antibodies (1.21, 1.00–1.47). Women who were overweight or obese at age 14 years (127 of 972) had a higher risk of later positive anti-TPO antibodies (2.05, 1.12–3.76). In men and women without any thyroid disorders, serum free T4 concentrations were inversely associated with concurrent body mass index (P = .002).
Conclusions:
Childhood weight gain and childhood overweight conferred an increased susceptibility to later hypothyroidism and thyroid autoimmunity, particularly in women.
doi:10.1210/jc.2012-3761
PMCID: PMC3651609  PMID: 23436917
25.  Body Mass Index, Muscle Strength and Physical Performance in Older Adults from Eight Cohort Studies: The HALCyon Programme 
PLoS ONE  2013;8(2):e56483.
Objective
To investigate the associations of body mass index (BMI) and grip strength with objective measures of physical performance (chair rise time, walking speed and balance) including an assessment of sex differences and non-linearity.
Methods
Cross-sectional data from eight UK cohort studies (total N = 16 444) participating in the Healthy Ageing across the Life Course (HALCyon) research programme, ranging in age from 50 to 90+ years at the time of physical capability assessment, were used. Regression models were fitted within each study and meta-analysis methods used to pool regression coefficients across studies and to assess the extent of heterogeneity between studies.
Results
Higher BMI was associated with poorer performance on chair rise (N = 10 773), walking speed (N = 9 761) and standing balance (N = 13 921) tests. Higher BMI was associated with stronger grip strength in men only. Stronger grip strength was associated with better performance on all tests with a tendency for the associations to be stronger in women than men; for example, walking speed was higher by 0.43 cm/s (0.14, 0.71) more per kg in women than men. Both BMI and grip strength remained independently related with performance after mutual adjustment, but there was no evidence of effect modification. Both BMI and grip strength exhibited non-linear relations with performance; those in the lowest fifth of grip strength and highest fifth of BMI having particularly poor performance. Findings were similar when waist circumference was examined in place of BMI.
Conclusion
Older men and women with weak muscle strength and high BMI have considerably poorer performance than others and associations were observed even in the youngest cohort (age 53). Although causality cannot be inferred from observational cross-sectional studies, our findings suggest the likely benefit of early assessment and interventions to reduce fat mass and improve muscle strength in the prevention of future functional limitations.
doi:10.1371/journal.pone.0056483
PMCID: PMC3577921  PMID: 23437142

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