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1.  Light Intensity Physical Activity and Sedentary Behavior in Relation to Body Mass Index and Grip Strength in Older Adults: Cross-Sectional Findings from the Lifestyle Interventions and Independence for Elders (LIFE) Study 
PLoS ONE  2015;10(2):e0116058.
Background
Identifying modifiable determinants of fat mass and muscle strength in older adults is important given their impact on physical functioning and health. Light intensity physical activity and sedentary behavior are potential determinants, but their relations to these outcomes are poorly understood. We evaluated associations of light intensity physical activity and sedentary time—assessed both objectively and by self-report—with body mass index (BMI) and grip strength in a large sample of older adults.
Methods
We used cross-sectional baseline data from 1130 participants of the Lifestyle Interventions and Independence for Elders (LIFE) study, a community-dwelling sample of relatively sedentary older adults (70-89 years) at heightened risk of mobility disability. Time spent sedentary and in light intensity activity were assessed using an accelerometer worn for 3–7 days (Actigraph GT3X) and by self-report. Associations between these exposures and measured BMI and grip strength were evaluated using linear regression.
Results
Greater time spent in light intensity activity and lower sedentary times were both associated with lower BMI. This was evident using objective measures of lower-light intensity, and both objective and self-reported measures of higher-light intensity activity. Time spent watching television was positively associated with BMI, while reading and computer use were not. Greater time spent in higher but not lower intensities of light activity (assessed objectively) was associated with greater grip strength in men but not women, while neither objectively assessed nor self-reported sedentary time was associated with grip strength.
Conclusions
In this cross-sectional study, greater time spent in light intensity activity and lower sedentary times were associated with lower BMI. These results are consistent with the hypothesis that replacing sedentary activities with light intensity activities could lead to lower BMI levels and obesity prevalence among the population of older adults. However, longitudinal and experimental studies are needed to strengthen causal inferences.
doi:10.1371/journal.pone.0116058
PMCID: PMC4315494  PMID: 25647685
2.  Childhood socioeconomic position and adult leisure-time physical activity: a systematic review protocol 
Systematic Reviews  2014;3(1):141.
Background
Participation in leisure-time physical activity benefits health and is thought to be more prevalent in higher socioeconomic groups. Evidence indicates that childhood socioeconomic circumstances may have long-term influences on adult health and behaviour; however, it is unclear if this extends to an influence on adult physical activity. The aim of this review is to examine whether a lower childhood socioeconomic position is associated with lower levels of leisure-time physical activity during adulthood.
Methods/design
Keywords will be used to systematically search five online databases and additional studies will be located through a search of reference lists. At least two researchers working independently will screen search results assess the quality of included studies and extract all relevant data. Studies will be included if they are English language publications that test the association between at least one indicator of childhood socioeconomic position and a leisure-time physical activity outcome measured during adulthood. Any disagreements and discrepancies arising during the conduct of the study will be resolved through discussion.
Discussion
This study will address the gap in evidence by systematically reviewing the published literature to establish whether childhood socioeconomic position is related to adult participation in leisure-time physical activity. The findings may be used to inform future research and policy.
Systematic review registration
PROSPERO CRD42014007063.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-141) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-141
PMCID: PMC4265411  PMID: 25480487
Socioeconomic inequalities; Occupation; Education; Socioeconomic position; Physical activity; Exercise; Life course
3.  Grip Strength across the Life Course: Normative Data from Twelve British Studies 
PLoS ONE  2014;9(12):e113637.
Introduction
Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol.
Methods
We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing).
Results
Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males’ peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position.
Conclusion
This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.
doi:10.1371/journal.pone.0113637
PMCID: PMC4256164  PMID: 25474696
4.  Job demand and control in mid-life and physical and mental functioning in early old age: do childhood factors explain these associations in a British birth cohort? 
BMJ Open  2014;4(10):e005578.
Objectives
Adverse work-related exposures have been linked with decreased physical and mental functioning in later life, however, whether childhood factors explain the associations between work exposures and functioning is unknown. Our aim was to investigate if job demand and control in mid-life were related to self-reported physical and mental functioning in early old age and whether childhood factors explained these associations.
Design
Prospective cohort study.
Setting
England, Scotland and Wales.
Participants and outcome measures
Data come from the UK Medical Research Council National Survey of Health and Development, a cohort with follow-up since birth in 1946. 1485 occupationally active study members had data available on job demand and control in mid-life and on physical and mental functioning assessed using the Short Form-36 questionnaire at 60–64 years.
Results
Those with higher job control in mid-life had better physical functioning than those who reported lower job control (β 0.51, 95% CI 0.02 to 1.01, p=0.04 adjusted for adult confounders). Those with higher job demand in mid-life had poorer mental functioning (β −0.82, 95% CI −1.14 to −0.51, p<0.001). Associations between job control and mental functioning were similar but less pronounced. Adjustment for childhood factors (father's and mother's educational attainment, parents’ interest in school at age 7 and cognitive ability at age 8) partially explained the association between job control and physical functioning, but did not explain the association between job demand and mental functioning.
Conclusions
Job demand and control in mid-life are differentially associated with mental and physical functioning in early old age and some of these associations may be partially explained by childhood factors.
doi:10.1136/bmjopen-2014-005578
PMCID: PMC4202008  PMID: 25319998
EPIDEMIOLOGY; OCCUPATIONAL & INDUSTRIAL MEDICINE; PUBLIC HEALTH; SPORTS MEDICINE
5.  Physical capability and subsequent positive mental wellbeing in older people: findings from five HALCyon cohorts 
Age (Dordrecht, Netherlands)  2013;36(1):10.1007/s11357-013-9553-8.
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) five to ten years later. Data were drawn from five British cohorts participating in the HALCyon 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 (3 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.
doi:10.1007/s11357-013-9553-8
PMCID: PMC3818137  PMID: 23818103
physical capability; positive mental wellbeing; grip strength; walking speed; chair rise time
6.  Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme 
Age  2014;36(4):9673.
The APOE ε2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ε2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301 (SORT1) from eight cohorts of adults aged between 44 and 90 + years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ε4 effect on semantic fluency z score = −0.02; 95 % CI = −0.05 to 0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within studies that negative effects of APOE ε4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-014-9673-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s11357-014-9673-9
PMCID: PMC4150901  PMID: 25073452
Ageing; Apolipoprotein E; Cognition; Single nucleotide polymorphism
7.  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
8.  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
9.  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
10.  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
11.  Body Mass Index From Age 15 Years Onwards and Muscle Mass, Strength, and Quality in Early Old Age: Findings From the MRC National Survey of Health and Development 
Background.
As more people live more of their lives obese, it is unclear what impact this will have on muscle mass, strength, and quality. We aimed to examine the associations of body mass index (BMI) from age 15 years onwards with low muscle mass, strength, and quality in early old age.
Methods.
A total of 1,511 men and women from a British birth cohort study with BMI measured at 15, 20, 26, 36, 43, 53, and 60–64 years and dual-energy x-ray absorptiometry scans at 60–64 years were included. Four binary outcomes identified those in the bottom sex-specific 20% of (a) appendicular lean mass (ALM) index (kilogram per square meter), (b) ALM residuals (derived from sex-specific models in which ALM (kilogram) = β0 + β1 height [meter] + β2 fat mass [kilogram]), (c) grip strength (kilogram), (d) muscle quality (grip strength [kilogram]/arm lean mass [kilogram]). Associations of BMI with each outcome were tested.
Results.
Higher BMI from age 15 years was associated with lower odds of low ALM but higher odds of low muscle quality (per 1 SD increase in BMI at 36 years, odds ratio of low ALM residuals = 0.50 [95% CI: 0.43, 0.59], and muscle quality = 1.50 [1.29, 1.75]). Greater gains in BMI were associated with lower odds of low ALM index but higher odds of low muscle quality. BMI was not associated with grip strength.
Conclusions.
Given increases in the global prevalence of obesity, cross-cohort comparisons of sarcopenia need to consider our findings that greater gains in BMI are associated with higher muscle mass but not with grip strength and therefore with lower muscle quality.
doi:10.1093/gerona/glu039
PMCID: PMC4158414  PMID: 24682351
Sarcopenia; Obesity; Life course epidemiology; Muscle mass; Strength and quality.
12.  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
13.  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
14.  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
15.  How to get started with a systematic review in epidemiology: an introductory guide for early career researchers 
Archives of Public Health  2013;71(1):21.
Background
Systematic review is a powerful research tool which aims to identify and synthesize all evidence relevant to a research question. The approach taken is much like that used in a scientific experiment, with high priority given to the transparency and reproducibility of the methods used and to handling all evidence in a consistent manner.
Early career researchers may find themselves in a position where they decide to undertake a systematic review, for example it may form part or all of a PhD thesis. Those with no prior experience of systematic review may need considerable support and direction getting started with such a project. Here we set out in simple terms how to get started with a systematic review.
Discussion
Advice is given on matters such as developing a review protocol, searching using databases and other methods, data extraction, risk of bias assessment and data synthesis including meta-analysis. Signposts to further information and useful resources are also given.
Conclusion
A well-conducted systematic review benefits the scientific field by providing a summary of existing evidence and highlighting unanswered questions. For the individual, undertaking a systematic review is also a great opportunity to improve skills in critical appraisal and in synthesising evidence.
doi:10.1186/0778-7367-71-21
PMCID: PMC3844862  PMID: 23919540
Systematic review; Systematic review methods; Meta-analysis; Early career researchers; Evidence synthesis; Observational studies
16.  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
17.  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
18.  The Bidirectional Association between Depressive Symptoms and Gait Speed: Evidence from the English Longitudinal Study of Ageing (ELSA) 
PLoS ONE  2013;8(7):e68632.
Background
Depressive symptoms and physical performance are inversely associated, but it is unclear whether their association is bidirectional. We examined whether the association between depressive symptoms and physical performance measured using gait speed is bidirectional.
Methods
We used a national sample of 4,581 community-dwelling people aged 60 years and older from the English Longitudinal Study of Ageing (from 2002–03 to 2008-09). We fitted Generalized Estimating Equation (GEE) regression models to analyse repeated measurements of gait speed (m/sec) and elevated depressive symptoms (defined as a score of ≥4 on the eight-item Center for Epidemiological Studies-Depression scale).
Results
Slower gait speed was associated with elevated depressive symptoms both concurrently and two years later. After adjustment for previous depressive symptoms and sociodemographic, clinical, lifestyle, psychosocial, and cognitive factors the concurrent association was partially explained (Odds Ratio [OR] 0.42, 95% confidence interval [CI], 0.30 to 0.59, per 1m/sec increase in gait speed) and the two-year lagged association fully (OR 0.75, 95% CI, 0.56 to 1.00). Elevated depressive symptoms were associated with slower gait speed. Full adjustment for covariates (including previous gait speed) partially explained both the concurrent (β regression coefficient [β] -0.038, 95% CI, -0.050 to -0.026, for participants with elevated depressive symptoms compared with those with no or one symptom) and the two-year lagged associations (β -0.017, 95% CI, -0.030 to -0.005). Subthreshold depressive symptoms (defined as a score of two or three on the eight-item Center for Epidemiological Studies-Depression scale) were also associated with slower gait speed. Full adjustment for covariates partially explained both the concurrent (β -0.029, 95% CI, -0.039 to -0.019, for participants with subthreshold symptoms compared with those with no or one symptom) and the two-year lagged associations (β -0.011, 95% CI, -0.021 to -0.001).
Conclusions
The inverse association between gait speed and depressive symptoms appears to be bidirectional.
doi:10.1371/journal.pone.0068632
PMCID: PMC3706406  PMID: 23874698
19.  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
20.  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
21.  Menopausal Characteristics and Physical Functioning in Older Adulthood in the NHANES III 
Menopause (New York, N.y.)  2012;19(3):283-289.
Objective
We hypothesized that natural menopause would be related to better physical functioning compared to surgical menopause and that later age at menopause would be related to better physical functioning.
Methods
Our sample comprised 1765 women aged ≥ 60 years who participated in the National Health and Nutrition Examination Survey III, a cross-sectional study representative of the United States population. Women recalled age at final menstrual period and age at removal of the uterus and ovaries and reported age, race and ethnicity, height, weight, educational attainment, smoking status, number of children, and use of estrogen therapy. Respondents completed a walk trial and chair rises and reported functional limitations.
Results
Women with a surgical menopause had chair rise times that were an average of 4.4% slower than those of women with natural menopause (95% CI 0.56, 8.27). Women with natural menopause at age ≥ 55 years had an average walking speed 0.05 meters/second (95% CI 0.01, 0.10) faster than women with natural menopause at age < 45 years. Later ages at natural and surgical menopause were also related to lower self-reported functional limitation. Women with surgical menopause at age ≥ 55 years had odds of functional limitation 0.52 times (95% CI 0.29, 0.95) those of women with surgical menopause at age < 40 years, with similar patterns for natural menopause.
Conclusions
Women with surgical menopause and earlier age at menopause had worse physical function in older adulthood. These groups of women may benefit from interventions to prevent functional decline.
doi:10.1097/gme.0b013e3182292b06
PMCID: PMC3258455  PMID: 21993081
menopause; physical functioning; women’s health
22.  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
23.  The Dynamic Relationship Between Physical Function and Cognition in Longitudinal Aging Cohorts 
Epidemiologic Reviews  2013;35(1):33-50.
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.
doi:10.1093/epirev/mxs004
PMCID: PMC3578448  PMID: 23349427
aging; cognition; correlated change; longitudinal analysis; meta-analysis; physical functioning; systematic review
24.  Type and Timing of Menopause and Later Life Mortality Among Women in the Iowa Established Populations for the Epidemiological Study of the Elderly Cohort 
Journal of Women's Health  2012;21(1):10-16.
Abstract
Background
The relationship between menopausal characteristics and later life mortality is unclear. We tested the hypotheses that women with surgical menopause would have increased all-cause and cardiovascular mortality compared with women with natural menopause, and that women with earlier ages at natural or surgical menopause would have greater all-cause and cardiovascular mortality than women with later ages at menopause.
Methods
Women who participated in the Iowa cohort of the Established Populations for the Epidemiologic Study of the Elderly (n=1684) reported menopausal characteristics and potential confounding variables at baseline and were followed up for up to 24 years. Participants were aged 65 years or older at baseline and lived in rural areas. We used survival analysis to examine the relationships between menopausal characteristics and all-cause and cardiovascular mortality.
Results
A total of 1477 women (87.7% of respondents) died during the study interval. Women with an age at natural menopause ≥55 years had increased all-cause and cardiovascular disease mortality compared with women who had natural menopause at younger ages. Type of menopause and age at surgical menopause were not related to mortality. These patterns persisted after adjustment for potential confounding variables.
Conclusions
Among an older group of women from a rural area of the United States, later age at natural menopause was related to increased all-cause and cardiovascular mortality. Monitoring the cardiovascular health of this group of older women may contribute to improved survival times.
doi:10.1089/jwh.2011.2745
PMCID: PMC3256559  PMID: 21970557
25.  Genetic markers of bone and joint health and physical capability in older adults: the HALCyon programme 
Bone  2013;52(1):278-285.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
Highlights
► 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.
doi:10.1016/j.bone.2012.10.004
PMCID: PMC3526776  PMID: 23072920
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

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