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.
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.
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.
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.
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.
Few studies have examined the impact of childhood obesity on later kidney disease, and consequently, our understanding is very limited.
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.
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.
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.
A low prevalence of CKD resulted in low statistical power. No documentation of chronicity for outcomes. All-white study population restricts generalizability.
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.
Childhood obesity; chronic kidney disease; estimated glomerular filtration rate
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.
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).
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.
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.
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.
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.
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).
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.
Knee osteoarthritis; Body mass index; Physical activity; Occupational activity
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.
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.
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.
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.
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.
Epigenomics; DNA methylation; life course; longitudinal studies
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.
geography; Great Britain; health status disparities; longitudinal studies; multilevel analysis; physical endurance; residence characteristics; socioeconomic factors
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.
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.
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.
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).
Childhood weight gain and childhood overweight conferred an increased susceptibility to later hypothyroidism and thyroid autoimmunity, particularly in women.
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.
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.
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.
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.
On average, older people remember less and walk more slowly than do younger persons. Some researchers argue that this is due in part to a common biologic process underlying age-related declines in both physical and cognitive functioning. Only recently have longitudinal data become available for analyzing this claim. We conducted a systematic review of English-language research published between 2000 and 2011 to evaluate the relations between rates of change in physical and cognitive functioning in older cohorts. Physical functioning was assessed using objective measures: walking speed, grip strength, chair rise time, flamingo stand time, and summary measures of physical functioning. Cognition was measured using mental state examinations, fluid cognition, and diagnosis of impairment. Results depended on measurement type: Change in grip strength was more strongly correlated with mental state, while change in walking speed was more strongly correlated with change in fluid cognition. Examining physical and cognitive functioning can help clinicians and researchers to better identify individuals and groups that are aging differently and at different rates. In future research, investigators should consider the importance of identifying different patterns and rates of decline, examine relations between more diverse types of measures, and analyze the order in which age-related declines occur.
aging; cognition; correlated change; longitudinal analysis; meta-analysis; physical functioning; systematic review
Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability.
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90 + years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p = 0.05, n = 11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures.
Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
► We examined associations between bone-related genotypes and physical capability. ► We conducted a meta-analysis on 12,836 middle-age adults. ► We found CASR may be associated with grip strength. ► No substantial support for specific bone mineral density variants and physical capability.
BMD, bone mineral density; OA, osteoarthritis; BMI, body mass index; SNP, single nucleotide polymorphism; CaPS, Caerphilly Prospective Study; ELSA, English Longitudinal Study of Ageing; HAS, Hertfordshire Ageing Study; HCS, Hertfordshire Cohort Study; LBC1921, The Lothian Birth Cohort 1921; NSHD, National Survey of Health and Development; HWE, Hardy–Weinberg equilibrium; WHR, waist–hip ratio; GWAS, genome-wide association studies; Aging; Grip strength; Calcium; Bone mineral density; Osteoarthritis
The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.
HPA axis; Physical capability; Healthy ageing
Older women and those of lower socioeconomic position (SEP) consistently constitute a larger portion of the disabled population than older men or those of higher SEP, yet no studies have examined when in the life course these differences emerge.
Prevalence of self-reported limitations in the upper body (gripping or reaching) and lower body (walking or stair climbing) at 43 and 53 years were utilized from 1,530 men and 1,518 women from the British 1946 birth cohort. Generalized linear models with a binomial distribution were used to examine the effects of gender, childhood and adult SEP, and the differences in the SEP effects by gender on the prevalence of limitations at age 43 years and changes in prevalence from 43 to 53 years.
For both genders, the prevalence of upper and lower body limitations were reported at 3%–5% at age 43 years. However, by age 53 years, women’s upper body limitations had increased to 28% and lower body limitations to 21%, whereas men’s limitations had only increased to 12% and 11%, respectively. Men and women whose father’s occupation was manual or whose adult head of household occupation was manual had higher prevalence of both limitations compared with those with non-manual backgrounds. These differences widened with age, especially in women. The effect of adult SEP on the prevalence of limitations was stronger than that of childhood SEP and was partly mediated by educational attainment.
Our findings provide the first evidence that prevention of disability in old age should begin early in midlife, especially for women from manual occupation households.
Gender; Social class; Functional limitations; Longitudinal studies; Middle aged
The common C allele of rs314276 in LIN28B has been robustly associated with earlier age at menarche in girls and associated with earlier timing of other pubertal traits in both sexes.
Our objective was to explore the associations between rs314276, as a marker of earlier pubertal timing, and body mass index (BMI), weight, and height across the life course.
The rs314276 in LIN28B was genotyped in 1242 men and 1209 women born in 1946 and participating in the Medical Research Council National Survey of Health and Development. Birth weight was recorded, and height and weight were measured or self-reported repeatedly at 11 time points between ages 2 and 53 yr. Polynomial mixed models were used to test whether additive genetic associations with SD scores (SDS) for BMI and height changed with age between 0 and 53 yr.
Longitudinal analyses revealed age-dependent associations between rs314276 genotype and BMI (P < 0.001 for genotype-by-age2 interaction) and body weight (P < 0.001 for genotype-by-age2 interaction) in women, but not in men. In women only, the C allele at rs314276 was associated with higher BMI SDS from ages 15–43 yr. In contrast, C allele associations with shorter height SDS were apparent in both men and women and did not vary with age.
A common genetic variant in LIN28B that confers earlier puberty was associated with a prolonged increase in BMI during adolescence and early to mid-adulthood in women only. Such genetic associations may provide insights into the direct effects of pubertal timing on obesity risk.
To investigate the effect of menopausal transition and age on symptoms of urinary incontinence in midlife.
SUBJECTS AND METHODS
The study included a nationally representative cohort of 1211 women followed up since their birth in 1946 and annually from 48–54 years; their menopausal transition status and symptoms of stress, urge, and severe urinary incontinence (UI) at 7 consecutive years from ages 48–54 were assessed.
From Generalized Estimating Equations, women who became perimenopausal (‘pre-peri’) or those experiencing perimenopause for >1 year (‘peri-peri’) were more likely to have symptoms of stress UI than were postmenopausal women; the odds ratio (95% confidence interval) was; pre-peri 1.39 (1.11–1.73); and peri-peri 1.39 (1.4–1.71). Menopausal transition status was not associated with urge or severe UI. These relationships were not explained by age, childhood enuresis, reproductive factors, previous health status, body mass index and educational qualifications.
This study is unique in being able to disentangle the effects of age, menopausal transitions, and other life-long risk factors on UI. Menopausal transition was only related to stress UI, while increasing age was related to both stress and urge UI. This study suggests that there are both shared and distinct aetiological pathways leading to each type of UI.
menopause; stress incontinence; urge incontinence; severe incontinence
In this study, the authors investigate gender-specific effects of childhood socio-economic position (SEP) on adiposity and blood pressure at three time points in adulthood.
Mixed models were used to assess the association of childhood SEP with body mass index (BMI), waist circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) at ages 36, 43 and 53 years in a British birth cohort.
The adverse effect of lower childhood SEP on adiposity increased between ages 36 and 53 years in women (BMI: trend test: p=0.03) and remained stable in men, but the opposite was seen for SBP, where inequalities increased in men (p=0.01). Childhood SEP inequalities in DBP were stable with age in both men and women. Educational attainment mediated some but not all of the effects of childhood SEP on adiposity and SBP, and their rate of change; adult social class was a less important mediator.
Childhood SEP is important for adult adiposity and blood pressure across midlife, especially for BMI in women and for blood pressure in men. Thus, pathways to adult health differ for men and women, and public health policies aimed at reducing social inequalities need to start early in life and take account of gender.
Adult body mass index (BMI) has been consistently related to mortality, but little is known about the impact of earlier life BMI on adult mortality. The aim is to investigate the impact of childhood, adolescent and early adult BMI on premature adult all-cause mortality.
The British 1946 cohort study was used to assess the association of BMI in childhood, adolescence and adulthood with mortality 26–60 years (332 deaths). 4462 (83%) respondents were available for analysis at age 26 years. Splines were used in Cox regression to model the associations between BMI and mortality.
In both genders, adult BMI from 20 years onwards showed a consistent U-shaped relationship with adult mortality (overall p value <0.05 for BMI at ages 20, 26 and 36 years). In women, a similar relationship was observed for adolescent BMI at 15 years (p=0.02); the HR comparing women with low BMI (2 SDs below mean) versus mean BMI was 2.96 (95% CI 1.26 to 6.97). The corresponding HR for women with BMI 2 SDs above the mean was 1.97 (0.95 to 4.10). BMI in childhood was generally not associated with adult mortality except female BMI at 4 years where a U-shaped relationship was observed (p=0.02); HR for BMI 2 SDs below mean versus mean was 2.13 (0.97 to 4.70) and the corresponding HR for 2 SDs above the mean was 1.67 (0.85 to 3.28). This association was not attenuated by subsequent BMI change or mediators.
High and low BMI from early adulthood were related to adult premature mortality suggesting that promoting a normal weight in early adulthood could prevent premature mortality.
The association between lifelong body mass index (BMI) and cognitive function has not been comprehensively studied.
In more than 2000 men and women born in 1946, we tested associations between BMI gain at 15, 20, 26, 36, 43, and 53 years with respect to the previous measure (gain at age 15 years with respect to BMI at age 11 years), and semantic fluency (animal naming) and cognitive reserve (the National Adult Reading Test) at age 53 years, and verbal memory (word list recall) and speed/concentration (letter cancellation) at ages 43 and 53 years. Measures of BMI gain were adjusted in stages for childhood intelligence, education, socioeconomic position (SEP), lifestyle, and vascular risk factors.
Independent of childhood intelligence, BMI gain between ages 26 and 36 years was associated with lower memory scores (β per SD increase in BMI in men = −0.11; 95% confidence interval [CI]: −0.19, −0.02), verbal fluency (β in women = −0.11; 95% CI: −0.20, −0.02), and lower National Adult Reading Test score (β in women = −0.08; 95% CI: −0.15, −0.01), but not with speed/concentration (β in men = 0.02; 95% CI: −0.11, 0.07). Associations were largely explained by educational attainment and SEP (P ≥ .10). However, BMI gain at 53 years in men was independently associated with better memory (β = 0.12; 95% CI: 0.03, 0.22), and both underweight (β = −1.54; 95% CI: −2.52, −0.57) and obese (β = −0.30; 95% CI: −2.52, −0.57) women at 53 years had significantly lower memory scores.
The adverse effect of higher BMI gain on midlife cognitive function and cognitive reserve is independent of childhood intelligence but not of education and SEP. The independent association between greater BMI gain in midlife and better cognitive function deserves further investigation.
Epidemiology; Cognitive function; Body size; Adiposity; Vascular risk factors
Background Educational attainment is highly correlated with social inequalities in adult cognitive health; however, the nature of this correlation is in dispute. Recently, researchers have argued that educational inequalities are an artefact of selection by individual differences in prior cognitive ability, which both drives educational attainment and tracks across the rest of the life course. Although few would deny that educational attainment is at least partly determined by prior cognitive ability, a complementary, yet controversial, view is that education has a direct causal and lasting benefit on cognitive development.
Methods We use observational data from three birth cohorts, with cognition measured in adolescence and adulthood. Ordinary least squares regression was used to model the relationship between adolescent cognition and adult fluid cognition and to test the sensitivity of our analyses to sample selection, projection and backdoor biases using propensity score matching.
Results We find that having a university education is correlated with higher fluid cognition in adulthood, after adjustment for adolescent cognition. We do not find that adolescent cognition, gender or parental social class consistently modify this effect; however, women benefited more in the 1946 sample from Great Britain.
Conclusions In all three birth cohorts, substantial educational benefit remained after adjustment for adolescent cognition and parental social class, offsetting an effect equivalent of 0.5 to 1.5 standard deviations lower adolescent cognition. We also find that the likelihood of earning a university degree depends in part on adolescent cognition, gender and parental social class. We conclude that inequalities in adult cognition derive in part from educational experiences after adolescence.
Educational benefits; cognitive selection; class reproduction; life course; cognitive health; adolescent cognition
The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, though not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For lifecourse physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (p-value=0.09, n=7672 in males; p-value=0.90, n=7839 in females), standing balance, timed get up and go or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population.
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
The ACTN3 R577X (rs1815739) genotype has been associated with
athletic status and muscle phenotypes, although not consistently. Our objective
was to conduct a meta-analysis of the published literature on athletic status
and investigate its associations with physical capability in several new
population-based studies. Relevant data were extracted from studies in the
literature, comparing genotype frequencies between controls and sprint/power and
endurance athletes. For life course physical capability, data were used from two
studies of adolescents and seven studies in the Healthy Ageing across the Life
Course (HALCyon) collaborative research program, involving individuals aged
between 53 and 90+ years. We found evidence from the published literature
to support the hypothesis that in Europeans the RR genotype is more common among
sprint/power athletes compared with their controls. There is currently no
evidence that the X allele is advantageous to endurance athleticism. We found no
association between R577X and grip strength (P = 0.09,
n = 7,672 in males; P =
0.90, n = 7,839 in females), standing balance, timed get
up and go, or chair rises in our studies of physical capability. The
ACTN3 R577X genotype is associated with sprint/power
athletic status in Europeans, but does not appear to be associated with
objective measures of physical capability in the general population. Hum Mutat
32:1–11, 2011. © 2011 Wiley-Liss, Inc.
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
The medical needs of older people are growing because the proportion of the older population is increasing and disease boundaries are widening. This study describes the distribution and clustering of 15 common clinical disorders requiring medical treatment or supervision in a representative British cohort approaching retirement, and how health tracked across adulthood.
Methods and Findings
The data come from a cohort of 2661 men and women, 84% of the target sample, followed since birth in England, Scotland and Wales in 1946, and assessed at 60–64 years for: cardio and cerebro-vascular disease, hypertension, raised cholesterol, renal impairment, diabetes, obesity, hypothyroidism, hyperthyroidism, anaemia, respiratory disease, liver disease, psychiatric problems, cancers, atrial fibrillation on ECG and osteoporosis. We calculated the proportions disorder-free, with one or more disorders, and the level of undiagnosed disorders; and how these disorders cluster into latent classes and relate to health assessed at 36 years. Participants had, on average, two disorders (range 0–9); only 15% were disorder-free. The commonest disorders were hypertension (54.3%, 95% CI 51.8%–56.7%), obesity (31.1%, 28.8%–33.5%), raised cholesterol (25.6%, 23.1–28.26%), and diabetes or impaired fasting glucose (25.0%, 22.6–27.5%). A cluster of one in five individuals had a high probability of cardio-metabolic disorders and were twice as likely than others to have been in the poorest health at 36 years. The main limitations are that the native born sample is entirely white, and a combination of clinical assessments and self reports were used.
Most British people reaching retirement already have clinical disorders requiring medical supervision. Widening disease definitions and the move from a disease-based to a risk-based medical model will increase pressure on health services. The promotion of healthy ageing should start earlier in life and consider the individual's ability to adapt to and self manage changes in health.
Poorer cognitive ability in youth is a risk factor for later mental health problems but it is largely unknown whether cognitive ability, in youth or in later life, is predictive of mental wellbeing. The purpose of this study was to investigate whether cognitive ability at age 11 years, cognitive ability in later life, or lifetime cognitive change are associated with mental wellbeing in older people.
We used data on 8191 men and women aged 50 to 87 years from four cohorts in the HALCyon collaborative research programme into healthy ageing: the Aberdeen Birth Cohort 1936, the Lothian Birth Cohort 1921, the National Child Development Survey, and the MRC National Survey for Health and Development. We used linear regression to examine associations between cognitive ability at age 11, cognitive ability in later life, and lifetime change in cognitive ability and mean score on the Warwick Edinburgh Mental Wellbeing Scale and meta-analysis to obtain an overall estimate of the effect of each.
People whose cognitive ability at age 11 was a standard deviation above the mean scored 0.53 points higher on the mental wellbeing scale (95% confidence interval 0.36, 0.71). The equivalent value for cognitive ability in later life was 0.89 points (0.72, 1.07). A standard deviation improvement in cognitive ability in later life relative to childhood ability was associated with 0.66 points (0.39, 0.93) advantage in wellbeing score. These effect sizes equate to around 0.1 of a standard deviation in mental wellbeing score. Adjustment for potential confounding and mediating variables, primarily the personality trait neuroticism, substantially attenuated these associations.
Associations between cognitive ability in childhood or lifetime cognitive change and mental wellbeing in older people are slight and may be confounded by personality trait differences.