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1.  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
2.  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
3.  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
4.  Prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) definition: findings from the Hertfordshire Cohort Study (HCS) 
Age and Ageing  2013;42(3):378-384.
Introduction: sarcopenia is associated with adverse health outcomes. The aim of this study was to describe the prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus definition.
Methods: we applied the EWGSOP definition to 103 community-dwelling men participating in the Hertfordshire Sarcopenia Study (HSS) using both the lowest third of dual-energy X-ray absorptiometry (DXA) lean mass (LM) and the lowest third of skin-fold-based fat-free mass (FFM) as markers of low muscle mass. We also used the FFM approach among 765 male and 1,022 female participants in the Hertfordshire Cohort Study (HCS). Body size, physical performance and self-reported health were compared in participants with and without sarcopenia.
Results: the prevalence of sarcopenia in HSS men (mean age 73 years) was 6.8% and 7.8% when using the lowest third of DXA LM and FFM, respectively. DXA LM and FFM were highly correlated (0.91, P < 0.001). The prevalence of sarcopenia among the HCS men and women (mean age 67 years) was 4.6% and 7.9%, respectively. HSS and HCS participants with sarcopenia were shorter, weighed less and had worse physical performance. HCS men and women with sarcopenia had poorer self-reported general health and physical functioning scores.
Conclusions: this is one of the first studies to describe the prevalence of sarcopenia in UK community-dwelling older people. The EWGSOP consensus definition was of practical use for sarcopenia case finding. The next step is to use this consensus definition in other ageing cohorts and among older people in a range of health-care settings.
doi:10.1093/ageing/afs197
PMCID: PMC3633365  PMID: 23384705
sarcopenia; prevalence; EWGSOP consensus definition; muscle mass; fat-free mass; grip strength; gait speed; older people
5.  Nutrition and Sarcopenia: A Review of the Evidence and Implications for Preventive Strategies 
Journal of Aging Research  2012;2012:510801.
Prevention of age-related losses in muscle mass and strength is key to protecting physical capability in older age and enabling independent living. To develop preventive strategies, a better understanding is needed of the lifestyle factors that influence sarcopenia and the mechanisms involved. Existing evidence indicates the potential importance of diets of adequate quality, to ensure sufficient intakes of protein, vitamin D, and antioxidant nutrients. Although much of this evidence is observational, the prevalence of low nutrient intakes and poor status among older adults make this a current concern. However, as muscle mass and strength in later life are a reflection of both the rate of muscle loss and the peak attained in early life, efforts to prevent sarcopenia also need to consider diet across the lifecourse and the potential effectiveness of early interventions. Optimising diet and nutrition throughout life may be key to preventing sarcopenia and promoting physical capability in older age.
doi:10.1155/2012/510801
PMCID: PMC3312288  PMID: 22506112
6.  Life Course Trajectories of Systolic Blood Pressure Using Longitudinal Data from Eight UK Cohorts 
PLoS Medicine  2011;8(6):e1000440.
Analysis of eight population-based and occupational cohorts from the UK reveals the patterns of change of blood pressure in the population through the life course.
Background
Much of our understanding of the age-related progression of systolic blood pressure (SBP) comes from cross-sectional data, which do not directly capture within-individual change. We estimated life course trajectories of SBP using longitudinal data from seven population-based cohorts and one predominantly white collar occupational cohort, each from the United Kingdom and with data covering different but overlapping age periods.
Methods and Findings
Data are from 30,372 individuals and comprise 102,583 SBP observations spanning from age 7 to 80+y. Multilevel models were fitted to each cohort. Four life course phases were evident in both sexes: a rapid increase in SBP coinciding with peak adolescent growth, a more gentle increase in early adulthood, a midlife acceleration beginning in the fourth decade, and a period of deceleration in late adulthood where increases in SBP slowed and SBP eventually declined. These phases were still present, although at lower levels, after adjusting for increases in body mass index though adulthood. The deceleration and decline in old age was less evident after excluding individuals who had taken antihypertensive medication. Compared to the population-based cohorts, the occupational cohort had a lower mean SBP, a shallower annual increase in midlife, and a later midlife acceleration. The maximum sex difference was found at age 26 (+8.2 mm Hg higher in men, 95% CI: 6.7, 9.8); women then experienced steeper rises and caught up by the seventh decade.
Conclusions
Our investigation shows a general pattern of SBP progression from childhood in the UK, and suggests possible differences in this pattern during adulthood between a general population and an occupational population.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About a third of US and UK adults have high blood pressure (hypertension). Although hypertension has no obvious symptoms, it can lead to life-threatening heart attacks, stroke, and other forms of cardiovascular disease (CVD). It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic blood pressure [SBP]) and lowest when the heart is re-filling with blood (diastolic blood pressure [DBP]). Normal adult blood pressure is defined as an SBP of less than 130 millimeters of mercury (mm Hg) and a DBP of less than 85 mm Hg (a blood pressure of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat fatty or salty food are at high risk of developing hypertension. Moreover, blood pressure tends to increase with age. Mild hypertension can often be corrected by making lifestyle changes, but many people take antihypertensive drugs to reduce their blood pressure.
Why Was This Study Done?
Several trials have indicated that SBP is an important, modifiable risk factor for CVD. But, to determine the best way to prevent CVD, it is important to understand how SBP changes through life and how lifestyle factors affect this age-related progression. Textbook descriptions of age-related changes in SBP are based on studies that measured SBP at a single time point in groups (cohorts) of people of different ages. However, such “cross-sectional” studies do not capture within-individual changes in SBP and may be affected by environmental effects related to specific historical periods. The best way to measure age-related changes in SBP is through longitudinal studies in which SBP is repeatedly measured over many years in a single cohort. Such studies are underway, but it will be some decades before individuals in these studies reach old age. In this study, therefore, the researchers use data from multiple UK cohorts that had repeated SBP measurements taken over different but overlapping periods of life to investigate the life course trajectory of SBP.
What Did the Researchers Do and Find?
The researchers used statistical models to analyze data from longitudinal studies of SBP in seven population-based cohorts (the participants were randomly chosen from the general population) and in one occupational cohort (civil servants). SBP measurements were available for 30,372 individuals with ages spanning from seven years to more than 80 years. The researchers' analysis revealed four phases of SBP change in both sexes: a rapid increase in SBP during adolescent growth, a gentler increase in early adulthood, a midlife acceleration beginning in the fourth decade of life, and a period in late adulthood when SBP increases slowed and then reversed. This last phase was less marked when people taking antihypertensive drugs were excluded from the analysis. After adjusting for increases in body mass index (a measure of body fat) during adulthood, the magnitude of the SBP age-related changes was similar but the average SBP at each age was lower. Compared to the population-based cohorts, the occupational cohort had a lower average SBP, a shallower annual increase in SBP, and a later midlife acceleration, possibly because of socially determined modifiable SBP-related factors such as diet and lifestyle. Finally, although women had lower SBPs in early adulthood than men, they experienced steeper midlife SBP rises (probably because of a menopause-related effect on salt sensitivity) so that by the seventh decade of life, men and women had similar average SBPs.
What Do These Findings Mean?
These findings describe the general pattern of age-related progression of SBP from early childhood in the UK. The findings may not be generalizable because other populations may be exposed to different distributions of modifiable factors. In addition, their accuracy may be affected by differences between cohorts in how SBP was measured. Nevertheless, these findings—in particular, the slower midlife increase in SBP in the occupational cohort than in the population-based cohorts—suggest that the key determinants of age-related increases in blood pressure are modifiable and could be targeted for CVD prevention. Further research is now needed to identify exactly which factors affect the life course trajectory of SBP and to discover when these factors have their greatest influence on SBP.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000440.
The US National Heart Lung and Blood Institute has patient information about high blood pressure (in English and Spanish)
The American Heart Association provides information on high blood pressure and on cardiovascular diseases (in several languages)
The UK National Health Service Choices Web site also provides detailed information for patients about hypertension and about cardiovascular disease
MedlinePlus provides links to further information about high blood pressure, heart disease, and stroke (in English and Spanish)
doi:10.1371/journal.pmed.1000440
PMCID: PMC3114857  PMID: 21695075
7.  Liver fat accumulation is associated with reduced hepatic insulin extraction and beta cell dysfunction in healthy older individuals 
Background
There is a well-established association between type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) secondary to excess accumulation of intrahepatic lipid (IHL), but the mechanistic basis for this association is unclear. Emerging evidence suggests that in addition to being associated with insulin resistance, NAFLD may be associated with relative beta-cell dysfunction. We sought to determine the influence of liver fat on hepatic insulin extraction and indices of beta-cell function in a cohort of apparently healthy older white adults.
Methods
We performed a cross-sectional analysis of 70 healthy participants in the Hertfordshire Physical Activity Trial (39 males, age 71.3 ± 2.4 years) who underwent oral glucose tolerance testing with glucose, insulin and C-Peptide levels measured every 30 minutes over two hours. The areas under the concentration curve for glucose, insulin and C-Peptide were used to quantify hepatic insulin extraction (HIE), the insulinogenic index (IGI), the C-Peptide increment (CGI), the Disposition Index (DI) and Adaptation Index (AI). Visceral fat was quantified with magnetic resonance (MR) imaging and IHL with MR spectroscopy. Insulin sensitivity was measured with the Oral Glucose Insulin Sensitivity (OGIS) model.
Results
29 of 70 participants (41%) exceeded our arbitrary threshold for NAFLD, i.e. IHL >5.5%. Compared to those with normal IHL, those with NAFLD had higher weight, BMI, waist and MR visceral fat, with lower insulin sensitivity and hepatic insulin extraction. Alcohol consumption, age, HbA1c and alanine aminotransferase (ALT) levels were similar in both groups. Insulin and C-Peptide excursions after oral glucose loading were higher in the NAFLD group, but the CGI and AI were significantly lower, indicating a relative defect in beta-cell function that is only apparent when C-Peptide is measured and when dynamic changes in glucose levels and also insulin sensitivity are taken into account. There was no difference in IGI or DI between the groups.
Conclusions
Although increased IHL was associated with greater insulin secretion, modelled parameters suggested relative beta-cell dysfunction with NAFLD in apparently healthy older adults, which may be obscured by reduced hepatic insulin extraction. Further studies quantifying pancreatic fat content directly and its influence on beta cell function are warranted.
Trial registration
ISRCTN60986572
doi:10.1186/1758-5996-6-43
PMCID: PMC3974597  PMID: 24669786
Adaptation index; Beta cell dysfunction; C-peptide-genic index; Disposition index; Hepatic insulin extraction; Insulinogenic index; Intrahepatic lipid; Non-alcoholic fatty liver disease
8.  Age and Gender Differences in Physical Capability Levels from Mid-Life Onwards: The Harmonisation and Meta-Analysis of Data from Eight UK Cohort Studies 
PLoS ONE  2011;6(11):e27899.
Using data from eight UK cohorts participating in the Healthy Ageing across the Life Course (HALCyon) research programme, with ages at physical capability assessment ranging from 50 to 90+ years, we harmonised data on objective measures of physical capability (i.e. grip strength, chair rising ability, walking speed, timed get up and go, and standing balance performance) and investigated the cross-sectional age and gender differences in these measures. Levels of physical capability were generally lower in study participants of older ages, and men performed better than women (for example, results from meta-analyses (N = 14,213 (5 studies)), found that men had 12.62 kg (11.34, 13.90) higher grip strength than women after adjustment for age and body size), although for walking speed, this gender difference was attenuated after adjustment for body size. There was also evidence that the gender difference in grip strength diminished with increasing age,whereas the gender difference in walking speed widened (p<0.01 for interactions between age and gender in both cases). This study highlights not only the presence of age and gender differences in objective measures of physical capability but provides a demonstration that harmonisation of data from several large cohort studies is possible. These harmonised data are now being used within HALCyon to understand the lifetime social and biological determinants of physical capability and its changes with age.
doi:10.1371/journal.pone.0027899
PMCID: PMC3218057  PMID: 22114723

Results 1-8 (8)