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1.  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
2.  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
3.  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
4.  A Multi-Cohort Study of Polymorphisms in the GH/IGF Axis and Physical Capability: The HALCyon Programme 
PLoS ONE  2012;7(1):e29883.
Background
Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four 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 evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.
Conclusion
Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.
doi:10.1371/journal.pone.0029883
PMCID: PMC3254646  PMID: 22253814
5.  Education-related differences in physical performance after age 60: a cross-sectional study assessing variation by age, gender and occupation 
BMC Public Health  2013;13:641.
Background
Having a low level of education has been associated with worse physical performance. However, it is unclear whether this association varies by age, gender or the occupational categories of manual and non-manual work. This study examined whether there are education-related differences across four dimensions of physical performance by age, gender or occupational class and to what extent chronic diseases and lifestyle-related factors may explain such differences.
Methods
Participants were a random sample of 3212 people, 60 years and older, both living in their own homes and in institutions, from the Swedish National Study on Aging and Care, in Kungsholmen, Stockholm. Trained nurses assessed physical performance in grip strength, walking speed, balance and chair stands, and gathered data on education, occupation and lifestyle-related factors, such as physical exercise, body mass index, smoking and alcohol consumption. Diagnoses of chronic diseases were made by the examining physician.
Results
Censored normal regression analyses showed that persons with university education had better grip strength, balance, chair stand time and walking speed than people with elementary school education. The differences in balance and walking speed remained statistically significant (p < 0.05) after adjustment for chronic diseases and lifestyle. However, age-stratified analyses revealed that the differences were no longer statistically significant in advanced age (80+ years). Gender-stratified analyses revealed that women with university education had significantly better grip strength, balance and walking speed compared to women with elementary school education and men with university education had significantly better chair stands and walking speed compared to men with elementary school education in multivariate adjusted models. Further analyses stratified by gender and occupational class suggested that the education-related difference in grip strength was only evident among female manual workers, while the difference in balance and walking speed was only evident among female and male non-manual workers, respectively.
Conclusions
Higher education was associated with better lower extremity performance in people aged 60 to 80, but not in advanced age (80+ years). Our results indicate that higher education is associated with better grip strength among female manual workers and with better balance and walking speed among female and male non-manual workers, respectively.
doi:10.1186/1471-2458-13-641
PMCID: PMC3733740  PMID: 23842209
Educational status; Aging; Chronic diseases; Muscle strength; Walking; Postural balance
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.  The physical capability of community-based men and women from a British cohort: the European Prospective Investigation into Cancer (EPIC)-Norfolk study 
BMC Geriatrics  2013;13:93.
Background
The European Working Group for Sarcopenia in Older People (EWGSOP) published a case-finding algorithm for sarcopenia, recommending muscle mass measurement in older adults with low grip strength (women <20 kg; men <30 kg) or slow walking speed (≤0.8 m/s). However, the implications of adopting this algorithm into clinical practice are unclear. Therefore, we aimed to explore the physical capability of men and women from a British population-based cohort study.
Methods
In the European Prospective Investigation into Cancer-Norfolk study, 8,623 community-based adults (48-92 years old) underwent assessment of grip strength, walking speed, timed chair stands and standing balance. The proportion of older men and women (≥65 years) fulfilling EWGSOP criteria for muscle mass measurement was estimated. Additionally, cross-sectional associations of physical capability with age and sex were explored using linear and logistic regression.
Results
Approximately 1 in 4 older participants (28.8%) fulfilled criteria for muscle mass measurement with a greater proportion of women than men falling below threshold criteria (33.6% versus 23.6%). Even after adjustment for anthropometry, women were 12.4 kg (95% Confidence Interval [CI] 12.0, 12.7) weaker, took 12.0% (95% CI 10.0, 14.0) longer to perform five chair stands and were 1.82 (95% CI 1.48, 2.23) times more likely to be unable to hold a tandem stand for 10 seconds than men, although usual walking speed was similar. Physical capability was inversely associated with age and per year, walking speed decreased by 0.01 m/s (95% CI 0.01, 0.01) and grip strength decreased by 0.49 kg (men; 95% CI 0.46, 0.51) and 0.25 kg (women; 95% CI 0.23, 0.27). Despite this, there was still variation within age-groups and not all older people had low physical capability.
Conclusions
Every effort to optimise functional health in later life should be made since poor function is not inevitable. However, if the EWGSOP sarcopenia case-finding algorithm is endorsed, large proportions of older people could qualify for muscle mass measurement which is not commonly available. Considering population ageing, further discussion is needed over the utility of muscle mass measurement in clinical practice.
doi:10.1186/1471-2318-13-93
PMCID: PMC3846689  PMID: 24020915
Ag(e)ing; Sarcopenia; Hand strength; Physical capability; Sex factors
8.  Absence of association of a SNP in the TERT-CLPTM1L locus with age-related phenotypes in a large multi-cohort study: the HALCyon program 
Aging cell  2011;10(3):520-532.
Summary
Background
Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other ageing traits such as physical capability have not been reported.
Methods
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from 9 UK cohorts were genotyped for the single nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses.
Results
No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score=0.02, 95% CI: -0.01- 0.04, p-value=0.12, n=18,737), physical performance tests (e.g. pooled beta for grip strength=-0.02, 95% CI:-0.045- 0.006, p-value=0.14, n=11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment.
Conclusion
The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multi-cohort study suggests that whilst this SNP may be associated with cancer, it is not an important contributor to other markers of ageing.
doi:10.1111/j.1474-9726.2011.00687.x
PMCID: PMC3094481  PMID: 21332924
Aging; ageing; middle-aged; telomere; cognition; physical
9.  Absence of association of a single-nucleotide polymorphism in the TERT-CLPTM1L locus with age-related phenotypes in a large multicohort study: the HALCyon programme 
Aging Cell  2011;10(3):520-532.
Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other aging traits such as physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from nine UK cohorts were genotyped for the single-nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses. No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score = 0.02, 95% CI: −0.01 to 0.04, P-value = 0.12, n = 18 737), physical performance tests (e.g. pooled beta for grip strength = −0.02, 95% CI: −0.045 to 0.006, P-value = 0.14, n = 11 711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment. The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multicohort study suggests that while this SNP may be associated with cancer, it is not an important contributor to other markers of aging.
doi:10.1111/j.1474-9726.2011.00687.x
PMCID: PMC3094481  PMID: 21332924
aging; cognition; middle-aged; physical; telomere
10.  Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis 
Psychoneuroendocrinology  2013;38(1):40-49.
Summary
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.
doi:10.1016/j.psyneuen.2012.04.016
PMCID: PMC3533133  PMID: 22658392
HPA axis; Physical capability; Healthy ageing
11.  The relationship between walking speed and changes in cardiovascular risk factors during a 12-day walking tour to Santiago de Compostela: a cohort study 
BMJ Open  2012;2(3):e000875.
Objectives
Physical exercise has beneficial effects on cardiovascular risk factors. Knowledge about the effect of exercise intensity, specifically walking speed, on cardiovascular risk factors is limited. We report the relationship between walking speed and changes in cardiovascular risk factors in participants of a 12-day walking tour to Santiago de Compostela.
Design
Prospective cohort study.
Setting
Single-centre study with healthy middle-aged volunteers.
Participants
Healthy middle-aged men (n=15) and women (n=14). Subjects using lipid-lowering medication were excluded.
Intervention
Participants walked 281±10 km of the classical route to Santiago de Compostela in 12 days in 2009.
Primary and secondary outcome measures
Walking speed was recorded and blood pressure, weight, waist circumference, lipids and glucose were measured every other day. Changes in risk factors were compared between gender-pooled groups with faster and slower walking speed. Second, the relationship between walking speed and changes in risk factors was quantified using a linear mixed effects model.
Results
In the faster walking speed (4.6±0.2 km/h) group, high-density lipoprotein cholesterol (HDL-c) increased more than in the slower walking speed (4.1±0.2 km/h) group (difference in change between groups: 0.20; 95% CI −0.02 to 0.42 mmol/l), while low-density lipoprotein cholesterol (LDL-c) and total cholesterol decreased more in the slower walking speed group (differences in changes between groups: LDL-c: −0.50; 95% CI −0.88 to −0.12 mmol/l and total cholesterol: −0.75; 95% CI −1.19 to −0.31 mmol/l). A 1 km/h higher walking speed was related to an increase in HDL-c (0.24; 95% CI 0.12 to 0.30 mmol/l), LDL-c (0.18; 95% CI −0.16 to 0.42 mmol/l) and total cholesterol (0.36; 95% CI 0.12 to 0.60 mmol/l), adjusted for age, gender, smoking, body mass index and heart rate, during the whole walking tour.
Conclusions
Walking the same distance faster improves HDL-c more, while LDL-c and total cholesterol decrease more with lower walking speed independent of changes in body weight in healthy middle-aged subjects.
Article summary
Article focus
Physical exercise has beneficial effects on cardiovascular risk factors; however, the knowledge about the effect of exercise intensity, specifically walking speed, on cardiovascular risk factors is limited.
We report the relationship between walking speed and changes in cardiovascular risk factors in participants of a 12-day walking tour to Santiago de Compostela.
Key messages
In subjects walking a 12-day walking tour to Santiago de Compostela, with long daily stages:walking the same distance with higher walking speed was related to a higher increase in HDL-c, while walking with lower walking speed was related to larger decreases in LDL-c and total cholesterol, adjusted for age, gender, smoking, body mass index and heart rate.there was no relationship between walking speed and changes in weight, waist circumference, blood pressure, triglycerides or glucose.
Strengths and limitations of this study
All subjects walked the same overall distance, walking speed was measured and measurements of cardiovascular risk factors were conducted every other day.
This is a small study with 29 participants walking 281 km in 12 days. Whether the results of this study can be extrapolated to less exercise, and other types of exercise is not known.
doi:10.1136/bmjopen-2012-000875
PMCID: PMC3353125  PMID: 22581795
12.  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
13.  Objectively measured physical capability levels and mortality: systematic review and meta-analysis 
Objective To do a quantitative systematic review, including published and unpublished data, examining the associations between individual objective measures of physical capability (grip strength, walking speed, chair rising, and standing balance times) and mortality in community dwelling populations.
Design Systematic review and meta-analysis.
Data sources Relevant studies published by May 2009 identified through literature searches using Embase (from 1980) and Medline (from 1950) and manual searching of reference lists; unpublished results were obtained from study investigators.
Study selection Eligible observational studies were those done in community dwelling people of any age that examined the association of at least one of the specified measures of physical capability (grip strength, walking speed, chair rises, or standing balance) with mortality.
Data synthesis Effect estimates obtained were pooled by using random effects meta-analysis models with heterogeneity between studies investigated.
Results Although heterogeneity was detected, consistent evidence was found of associations between all four measures of physical capability and mortality; those people who performed less well in these tests were found to be at higher risk of all cause mortality. For example, the summary hazard ratio for mortality comparing the weakest with the strongest quarter of grip strength (14 studies, 53 476 participants) was 1.67 (95% confidence interval 1.45 to 1.93) after adjustment for age, sex, and body size (I2=84.0%, 95% confidence interval 74% to 90%; P from Q statistic <0.001). The summary hazard ratio for mortality comparing the slowest with the fastest quarter of walking speed (five studies, 14 692 participants) was 2.87 (2.22 to 3.72) (I2=25.2%, 0% to 70%; P=0.25) after similar adjustments. Whereas studies of the associations of walking speed, chair rising, and standing balance with mortality have only been done in older populations (average age over 70 years), the association of grip strength with mortality was also found in younger populations (five studies had an average age under 60 years).
Conclusions Objective measures of physical capability are predictors of all cause mortality in older community dwelling populations. Such measures may therefore provide useful tools for identifying older people at higher risk of death.
doi:10.1136/bmj.c4467
PMCID: PMC2938886  PMID: 20829298
14.  Childhood Socioeconomic Position and Objectively Measured Physical Capability Levels in Adulthood: A Systematic Review and Meta-Analysis 
PLoS ONE  2011;6(1):e15564.
Background
Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.
Methods and Findings
Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.
Conclusions
Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.
doi:10.1371/journal.pone.0015564
PMCID: PMC3027621  PMID: 21297868
15.  Changes in Physical Performance in Older Women by Diabetes Presence and Treatment 
Journal of the American Geriatrics Society  2013;61(11):10.1111/jgs.12502.
Objectives
To determine if older, diabetic women have a greater longitudinal decline in physical performance and if these changes differ by insulin sensitizer use.
Design
Prospective cohort study.
Setting
Baltimore, Minneapolis, Portland and the Monongahela valley in Pennsylvania, USA.
Participants
2864 community-dwelling women (mean age 78.5±3.6 years) enrolled in the Study of Osteoporotic Fractures in 1997–1998 and re-studied 4.9 ± 0.6 years later.
Measurements
Women were categorized as having no diabetes (n=2680) or having diabetes (n=184). The prescription medication inventory was used to determine use of insulin sensitizers (metformin/thiazolidinedione). The outcomes were longitudinal changes in physical performance measures, including grip strength, usual walk speed, and rapid walk speed.
Results
Estimates from fully adjusted models showed that diabetic women had greater declines in usual walk speed (−0.16 m/s [95%CI −0.19, −0.14]) and rapid walk speed (−0.21 m/s [95%CI −0.24, −0.17]) compared to non-diabetic women (usual: −0.11 m/s [95%CI −0.12, −0.11], rapid: −0.15 m/s [95% CI −0.16, −0.14]), p<0.01 for both comparisons. Diabetic women on insulin sensitizers had an attenuated decline in the loss of usual walk speed compared to those not on insulin sensitizers, p<0.05. Declines in grip strength did not differ significantly by diabetes status or insulin sensitizer use.
Conclusion
Older women with diabetes have a greater decline in walk speed, but not grip strength compared to older women without diabetes. Clinical studies in older adults to determine whether diabetes treatments like insulin sensitizers can prevent the loss in walk speed and mobility are needed.
doi:10.1111/jgs.12502
PMCID: PMC3827698  PMID: 24219188
elderly; diabetes; insulin sensitizer; physical performance; walk speed
16.  Functional Decline in Cognitive Impairment – The Relationship between Physical and Cognitive Function 
Neuroepidemiology  2008;31(3):167-173.
Background
Physical function decline is associated with dementia, which might either be mediated by the coexisting sarcopenia or directly related to the impaired cognition. Our objectives are to examine the relationship between cognitive function and performance-based physical function and to test the hypothesis that cognitive function is related to poor physical function independent of muscle mass.
Methods
We measured muscle strength, performance-based physical function and muscle mass using dual-energy X-ray absorptiometry and cognitive function using the cognitive part of the Community Screening Instrument of Dementia (CSI-D) in 4,000 community-dwelling Chinese elderly aged >65 years. A CSI-D cognitive score of >28.40 was considered as cognitively impaired. The effect of cognitive impairment on muscle strength and physical function was analyzed by multivariate analysis with adjustment for age, appendicular skeletal mass (ASM), the Physical Activity Scale for the Elderly (PASE) and other comorbidities.
Results
In both genders, the cognitively impaired (CSI-D cognitive score >28.40) group had a weaker grip strength (–5.10 kg, p < 0.001 in men; −1.08 kg in women, p < 0.001) and performed worse in the two physical function tests (in men, 6-meter walk speed, −0.13 m/s, p < 0.001, chair stand test, 1.42 s, p < 0.001; in women, 6-meter walk speed, −0.08 m/s, p < 0.001, chair stand test, 1.48 s, p < 0.001). After adjustment for age, ASM, PASE and other comorbidities, significant differences in grip strength (–2.60 kg, p < 0.001 in men; −0.49 kg, p = 0.011 in women) and the two physical function tests persisted between the cognitively impaired and nonimpaired group (in men, 6-meter walk speed, −0.072 m/s, p < 0.001, chair stand test, 0.80 s, p = 0.045; in women, 6-meter walk speed, −0.049 m/s, p < 0.001, chair stand test, 0.98 s, p < 0.001).
Conclusions
Poor physical function and muscle strength coexisted with cognitive impairment. This relationship was independent of muscle mass. It is likely therefore that the functional decline in dementia might be related directly to factors resulting in cognitive impairment independently of the coexisting sarcopenia.
doi:10.1159/000154929
PMCID: PMC2824577  PMID: 18784415
Sarcopenia; Dementia; Cognition; Chinese elderly; Physical function; Muscle
17.  Physical capability in mid-life and survival over 13 years of follow-up: British birth cohort study 
Objectives To examine associations between three commonly used objective measures of physical capability assessed at age 53 and a composite score of these measures and all cause mortality; to investigate whether being unable to perform these tests is associated with mortality.
Design Cohort study.
Setting MRC National Survey of Health and Development in England, Scotland, and Wales.
Participants 1355 men and 1411 women with data on physical capability at age 53 who were linked to the National Health Service (NHS) central register for death notification.
Main outcome measure All cause mortality between ages 53 (1999) and 66 (2012).
Results For each of the three measures of physical capability (grip strength, chair rise speed, and standing balance time) those participants unable to perform the test and those in the lowest performing fifth were found to have higher mortality rates than those in the highest fifth. Adjustment for baseline covariates partially attenuated associations but in fully adjusted models the main associations remained. For example, the fully adjusted hazard ratio of all cause mortality for the lowest compared with the highest fifth of a composite score of physical capability was 3.68 (95% confidence interval 2.03 to 6.68). Those people who could not perform any of the tests had considerably higher rates of death compared with those people able to perform all three tests (8.40, 4.35 to 16.23). When a series of models including different combinations of the measures were compared by using likelihood ratio tests, all three measures of physical capability were found to improve model fit, and a model including all three measures produced the highest estimate of predictive ability (Harrell’s C index 0.71, 95% confidence interval 0.65 to 0.77). There was some evidence that standing balance time was more strongly associated with mortality than the other two measures.
Conclusions Lower levels of physical capability at age 53 and inability to perform capability tests are associated with higher rates of mortality. Even at this relatively young age these measures identify groups of people who are less likely than others to achieve a long and healthy life.
doi:10.1136/bmj.g2219
PMCID: PMC4004787  PMID: 24787359
18.  Lifetime occupation and physical function: a prospective cohort study on persons aged 80 years and older living in a community 
Background
Several studies have reported predictors for loss of mobility and impairments of physical performance among frail elderly people.
Aim
To evaluate the relationship between lifetime occupation and physical function in persons aged 80 years or older.
Methods
Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study (a prospective cohort study performed in a mountain community in Central Italy). Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-metre walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. Lifetime occupation was categorised as manual or non-manual work.
Results
Mean age of participants was 85.9 (SD 4.9) years. Of the total sample, 273 subjects (75%) had a history of manual work and 91 subjects (25%) a history of non-manual work. Manual workers had significant lower grip strength and physical performance battery score (indicating worse performance) than non-manual workers. After adjustment for potential confounders (including age, gender, education, depression, cognitive performance scale score, physical activity, number of diseases, hearing impairment, history of alcohol abuse, smoking habit, and haemoglobin level), manual workers had significantly worse physical function (hand grip strength: non-manual workers 32.5 kg, SE 1.4, manual workers 28.2 kg, SE 0.8; physical performance battery score: non-manual workers 7.1, SE 0.4, manual workers 6.1, SE 0.2).
Conclusions
A history of manual work, especially when associated with high physical stress, is independently associated with low physical function and muscle strength in older persons.
doi:10.1136/oem.2005.023549
PMCID: PMC2092516  PMID: 16782827
19.  Lifetime occupation and physical function: a prospective cohort study on persons aged 80 years and older living in a community 
Background
Several studies have reported predictors for loss of mobility and impairments of physical performance among frail elderly people.
Aim
To evaluate the relationship between lifetime occupation and physical function in persons aged 80 years or older.
Methods
Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study (a prospective cohort study performed in a mountain community in Central Italy). Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4‐metre walking speed, balance, and chair stand tests. Muscle strength was measured by hand grip strength. Lifetime occupation was categorised as manual or non‐manual work.
Results
Mean age of participants was 85.9 (SD 4.9) years. Of the total sample, 273 subjects (75%) had a history of manual work and 91 subjects (25%) a history of non‐manual work. Manual workers had significant lower grip strength and physical performance battery score (indicating worse performance) than non‐manual workers. After adjustment for potential confounders (including age, gender, education, depression, cognitive performance scale score, physical activity, number of diseases, hearing impairment, history of alcohol abuse, smoking habit, and haemoglobin level), manual workers had significantly worse physical function (hand grip strength: non‐manual workers 32.5 kg, SE 1.4, manual workers 28.2 kg, SE 0.8; physical performance battery score: non‐manual workers 7.1, SE 0.4, manual workers 6.1, SE 0.2).
Conclusions
A history of manual work, especially when associated with high physical stress, is independently associated with low physical function and muscle strength in older persons.
doi:10.1136/oem.2005.023549
PMCID: PMC2092516  PMID: 16782827
lifetime occupation; physical performance; aging;  ilSIRENTE study
20.  Are they half as strong as they used to be? An experiment testing whether age-related social comparisons impair older people's hand grip strength and persistence 
BMJ Open  2012;2(3):e001064.
Objective
To assess how age-related social comparisons, which are likely to arise inadvertently or deliberately during assessments, may affect older people's performance on tests that are used to assess their needs and capability.
Design
The study randomly assigned participants to a comparison with younger people or a no comparison condition and assessed hand grip strength and persistence. Gender, education, type of residence, arthritis and age were also recorded.
Setting
Age UK centres and senior's lunches in the South of England.
Participants
An opportunity sample of 56 adults, with a mean age of 82.25 years.
Main outcomes measures
Hand grip strength measured using a manual hand dynamometer and persistence of grip measured using a stopwatch.
Results
Comparison caused significantly worse performance measured by both strength (comparison =6.85 kg, 95% CI 4.19 kg to 9.5 kg, control group =11.07 kg, 95% CI 8.47 kg to 13.68 kg, OR =0.51, p=0.027) and persistence (comparison =8.36 s, 95% CI 5.44 s to 11.29 s; control group =12.57 s, 95% CI 9.7 s to 15.45 s, OR =0.49, p=0.045). These effects remained significant after accounting for differences in arthritis, gender, education and adjusting for population age norms.
Conclusions
Due to the potential for age comparisons and negative stereotype activation during assessment of older people, such assessments may underestimate physical capability by up to 50%. Because age comparisons are endemic, this means that assessment tests may sometimes seriously underestimate older people's capacity and prognosis, which has implications for the way healthcare professionals treat them in terms of autonomy and dependency.
Article summary
Article focus
What is the relationship between ageing and physical strength, measured by hand grip?
Does stereotype threat affect older people's physical capacities?
Substantial variability in diagnosis of physical strength could be caused by inadvertent invocation of age stereotypes during assessment.
Key messages
Psychosocial factors may influence how strongly physical effects of ageing manifest themselves.
Age comparison creates a stereotype threat, which can reduce older people's hand grip strength by up to 50%—as large as the normal range from middle to old age.
Healthcare professionals should be aware of the potential for age comparison and stereotypes to affect outcomes of assessments of older people.
Strengths and limitations of this study
Hand grip is an ‘objective measure’ of physical capability among older people. It is predictive of frailty, morbidity, disability and mortality.
This first experimental test of the impact of age comparison on older people's hand grip strength demonstrates that it is impaired by comparison with younger people.
This research was conducted in a non-medical setting and involved participants in good health with a small convenience sample. However the effects remain significant even when age, gender, education, degree of arthritis in the hands, type of residence and location of testing are accounted for.
Further research is needed to evaluate the prevalence of age comparisons in clinical testing settings, and effects on people of different ages.
doi:10.1136/bmjopen-2012-001064
PMCID: PMC3364452  PMID: 22619267
21.  ACTN3 Genotype, Athletic Status, and Life Course Physical Capability: Meta-Analysis of the Published Literature and Findings from Nine Studies 
Human Mutation  2011;32(9):1008-1018.
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.
doi:10.1002/humu.21526
PMCID: PMC3174315  PMID: 21542061
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
22.  Evaluation of Factors Influencing Grip Strength in Elderly Koreans 
Journal of Bone Metabolism  2012;19(2):103-110.
Objectives
Grip strength has been used as a measure of function in various health-related conditions. Although grip strength is known to be affected by both physical and psychological factors, few studies have looked at those factors comprehensively in a population-based cohort regarding elderly Koreans. The aim of this study was to evaluate potential factors influencing grip strength in elderly Koreans.
Methods
We evaluated dominant hand grip strengths in 143 men and 123 women older than 65 years who participated in a population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA). Individuals who had a history of surgery for musculoskeletal disease or trauma in the upper extremity were excluded. Factors assessed for potential association with grip strength were; 1) demographics such as age and gender, 2) body constructs such as height, body mass index (BMI), and bone mineral density (BMD), 3) upper extremity functional status using disabilities of the arm, shoulder and hand (DASH) scores, and 4) mental health status using a depression scale and the short form-36 (SF36) mental health score. Multivariate analyses were performed in order to identify factors independently associated with grip strength.
Results
Grip strengths of dominant hands in elderly Koreans were found to generally decrease with aging, and were significantly different between men and women, as expected. Multivariate analyses indicated that grip strength was independently associated with age, height and BMI in men (R2 = 21.3%), and age and height (R2 = 19.7%) in women. BMD, upper extremity functional status, or mental health status were not found to be associated with grip strength.
Conclusions
This study demonstrates that in elderly Koreans, grip strength is mainly influenced by age and height in both men and women, and additionally by BMI in men. BMD or self-reported physical or mental health status was not found to influence grip strength in elderly Koreans. This information may be helpful in future studies using grip strength as a measure of function in elderly Koreans.
doi:10.11005/jbm.2012.19.2.103
PMCID: PMC3780925  PMID: 24524040
Factors; Grip strength; Influence; Koreans
23.  ACTN3 genotype, athletic status and lifecourse physical capability: meta-analysis of the published literature and findings from nine studies 
Human mutation  2011;32(9):1008-1018.
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.
doi:10.1002/humu.21526
PMCID: PMC3174315  PMID: 21542061
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
24.  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
25.  Limitations in physical functioning among older people as a predictor of subsequent disability in instrumental activities of daily living 
Age and Ageing  2011;40(4):463-469.
Background: physical functioning describes the underlying abilities that make activities necessary for independent living in the community possible.
Objective: to test self-reported and objective measures of physical functioning in predicting subsequent disability in cooking, shopping and housework.
Design: we used data from the first and second waves of the Survey of Health, Ageing and Retirement in Europe. The respondents were asked about physical functioning (climbing, pulling/pushing, stooping/crouching/kneeling, lifting/carrying and reaching/extending were comparable) and they had their grip strength and walking speed measured.
Participants: men and women aged 65 years or over who reported no disability in cooking, shopping and housework at baseline were included in the analysis. There were 6,841 individuals for whom data on disability status at follow-up were available.
Methods: Poisson regression was used to calculate relative risks for the associations between self-reported and objective measures of physical functioning with disability at 2 years, adjusting for age, gender, educational level, cognitive function and chronic conditions.
Results: those with limitations in physical functioning at baseline more frequently reported subsequent disability. Walking ability was most strongly associated with disability; climbing, pulling/pushing, lifting/carrying and reaching/extending were comparable (picking was non-significant). Similar results were obtained with grip strength and walking speed.
Conclusions: both self-reports and objective measures capture information on the functional ability of older people that can be used to predict disability onset. Objective measures offer little to the development of intervention strategies, whereas self-reports provide some insight into the demands of the environment, being more amenable to interventions.
doi:10.1093/ageing/afr054
PMCID: PMC3114622  PMID: 21609999
physical functioning; disability; instrumental activities of daily living; elderly

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