2011/02/01 by D Kuh, M. Pierce, J.E. Adams +14 · 2 citations
Medicine · Social Sciences · Health Professions · #Birth, Development, and Health #Health disparities and outcomes #Global Health Care Issues #Cohort #Cohort study #Medicine #Data collection #Gerontology #Ageing #Pathology #Internal medicine #Sociology #Social science
paper · pdf · doi:10.1093/ije/dyq231
openalex publication_date 2011/02/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
In a previously published cohort profile,1 we showed how the MRC National Survey of Health and Development (NSHD), the oldest of the British birth cohort studies, has played an important role in identifying the early origins of adult health and function. The study has a wealth of existing prospective data from birth; and with study members now in their early sixties and approaching conventional retirement age, the NSHD offers the opportunity to investigate how lifetime experience and exposures affect the chance of healthy ageing and reduction of functional decline and chronic disease in later life. Ageing populations, and the heterogeneity observed among ageing individuals, pose a grand challenge to society. We need to understand better how factors acting across the whole of life can affect the chance of living a long, healthy and independent life.2,3 The NSHD, one of the UK’s rich set of longitudinal cohort resources, facilitates a life course approach to the study of ageing, a strategic priority of the Medical Research Council4 and the other UK research councils and funders.5–7 Evidence is accumulating from the NSHD and from other cohort studies with information from birth, infancy or childhood that adult function and age-related chronic disease have their origins in early life experience and environment and share common risk factors operating across the life course.8–13 There is a growing consensus that biological ageing (a progressive, generalized impairment of function resulting in a loss of adaptive response to life challenges) is caused by the rate of accumulation of molecular and cellular damage from the beginning of life.14 Modifiable factors (such as nutrition and physical activity) and non-modifiable or random factors acting across the life course can alter exposure to sources of damage, and the effectiveness of body systems for maintenance and repair. The MRC Unit for Lifelong Health and Ageing (LHA) was established in 2008 to maximize the scientific potential of the NSHD and develop it into an interdisciplinary study of ageing. The LHA research team and their scientific collaborators secured MRC funding to invite study members to take part in their first adult clinic-based data collection to obtain new ageing outcomes, as well as repeat measures of health, function and life circumstances, previously collected by research nurses at home visits. Collection of data took place in 2006–07 in a feasibility study on 10% of the NSHD sample living near the Wellcome Trust Clinical Research Facility (CRF) Manchester, and since 2008 has been taking place on the remainder of the sample at five other UK CRFs (due for completion March 2011). The ageing outcomes in the latest NSHD follow-up were chosen to facilitate the testing of life course hypotheses that capitalized on the existing study data, and because they represented important public health problems or intermediate markers of such problems thought to be potentially modifiable. Quantitative ageing traits were preferred over binary outcomes as they provide greater power for analysis, which is important given that the sample contains less than 3500 study members still alive and living in Britain. The choice of outcomes also took into consideration whether the measures would be sufficiently attractive to induce study members in their early sixties to travel a considerable distance for a clinical assessment. For this data collection between ages 60 and 64 years, we chose to focus on physical and cognitive capability, the capacity to undertake the physical and mental tasks of daily living, as measured by physical performance tests (such as grip strength, chair rises, standing balance) and cognitive performance tests (such as verbal memory and information processing). These tests reflect underlying ageing processes rather than specific diseases per se; are the foundation for continued independence and quality of life, as we grow older; and predict future risk of disability, disease, morbidity and mortality.15–18 We also chose to study the structure and function of musculoskeletal and cardiovascular (CV) body systems because age-related changes in these systems threaten capability and account for a major proportion of the disease burden in the ageing population and because there may be opportunities to delay, if not reverse, adverse biological changes. We hypothesize that together these ageing outcomes co-vary in ways that have important practical implications for daily living, and for understanding the ageing process, the development of frailty, disease and longevity. The existing life course prospective data make this cohort particularly suited to test several hypotheses, namely: (i) early as well as adult life exposures and risks impact on these aspects of ageing; and (ii) exposure to earlier sources of risk (from gestation to early adulthood) adds substantially to, or is dependent on, the burden of mid-life risk. Our conceptual framework is that NSHD data on earlier life characteristics (such as physical growth and cognitive development, adolescent behaviour and temperament and lifetime socio-economic environment) and on adult functional trajectories (such as changes in blood pressure, lung function and body size) and repeat measures of health behaviours (such as diet, smoking and physical activity) relate to these ageing outcomes via various biological, psychological and social pathways. The study has a wealth of life course data to elucidate psychological and social pathways. A priority of this data collection was to obtain new assessments of well-being and quality of life at an age when social roles may be rapidly changing (for example, the supervision of grandchildren), and when retirement, an important life transition, is taking place. A previous study of this cohort at age 53 years collected blood biomarker information on aspects of metabolic function (HbA1c, total and high-density lipoprotein, triglycerides), and extracted DNA to be used for genotyping and measures of telomere length. Another priority was, therefore, to collect fasting blood and overnight urine samples to facilitate further study of biological pathways linking lifetime risk factors to our ageing outcomes. Of particular interest are markers of dysregulation of homoeostatic equilibrium hypothesized to underlie musculoskeletal, CV and cognitive ageing and other aspects of functional decline. They include markers of chronic inflammation, adipocyte, renal and hepatic function and neuro-endocrine function (such as insulin growth factors, cortisol, thyroid function and heart rate variability). The new data collection was designed to allow LHA scientists and their expert collaborators to meet the objectives of LHA’s integrated research programmes (www.nshd.mrc.ac.uk). It also enhances the NSHD resource for the wider scientific community (see below). The MRC NSHD is the oldest of the UK national birth cohort studies and is based on a nationally representative sample of 5362 births out of all the single, legitimate births that took place in 1 week in March 1946 in England, Scotland and Wales.19 The whole sample has been followed up 23 times previously, and, at the last visit in 1999, the sample remained broadly representative of native born British men and women.19 For the new data collection, the initial target sample at the age of 60 years was 3116, excluding 337 who remained untraced despite attempts to trace study members through the health authorities in 2005. Of the remainder of the original cohort of 5362, 636 had died, 604 had emigrated and 669 were prior refusals. To accommodate our scattered geographical sample, we chose the CRFs in Manchester, Edinburgh, Birmingham and Cardiff, as well as two CRFs in London, and allocated the target sample to the nearest facility. These CRFs offer high-quality research environments within or close to acute hospital facilities. The NSHD data collection was the first co-ordinated data collection across these clinical facilities. A 10% sample (n = 348) of traced and untraced study members was selected for a feasibility study. This was a stratified random sample selected from all target study members whose last known address was closest to the Wellcome Trust Clinical Research Facility (WTCRF) Manchester. The target sample was stratified into those living ≤40 miles from the WTCRF Manchester and those living further away with equal numbers being sampled from each group. The main aims of the feasibility study at the WTCRF Manchester were to test: (i) what proportion of the sample would be successfully contacted; (ii) whether study members were prepared to come to a clinic for an assessment and to estimate the overall clinic response rate to within ±5%; (iii) whether distance from the clinic was a deterrent to attendance; and (iv) satisfaction with the clinic visit and compliance with the various tests. The feasibility study, therefore, had to involve study members who have a lifelong experience of being part of the study as their response was likely to be different from other members of the population. An invitation to attend a clinic at 08.00 h on a specific day was sent out by CRF staff with an accompanying information brochure. Before the visit, a trained research nurse contacted the study member by telephone to discuss any concerns (health, regular medication, fasting etc.). Instructions about the visit and how to collect the overnight urine sample, along with urine collection equipment and a pre-assessment questionnaire, were posted to the study members before the visit. Study members unwilling or unable to travel to the CRF were offered an alternative home visit, which had fewer assessments. Collection of other information was achieved by an initial postal questionnaire to update socio-demographic, socio-economic and medical information, sent ∼2 months before the CRF visits began; a pre-assessment questionnaire to capture information on everyday function, attitudes and life events, sent ahead and collected on the day of the visit; and through dietary diaries and activity monitors in the days following the visit. The measures collected are shown in Table 1. The supplementary data available at IJE online describe the main fieldwork processes and the data acquisition and duty of care protocols. A 4-day training programme and 60-page training manual for the research nurses and the technicians were designed and implemented by the MRC LHA and Human Nutrition Research (HNR) fieldwork teams and their key collaborators. Measurements taken in the NSHD at the age of 60–64 years Vascular structure and function: carotid intima-medial thickness (IMT) and arterial distensibility (GE Vivid-I), carotid/femoral pulse wave velocity (Vicorder) and central blood pressure and pulse wave analysis (Sphygmocor) Cardiac structure and function: echocardiography (GE Vivid-I). Images from parasternal long axis and short axis views, apical 5-chamber, 4-chamber, 3-chamber, 2-chamber and aortic views (plus conventional and tissue Doppler in 4-chamber view). Brachial blood pressure (Omron HEM-705), 12 lead ECG (Burdick Eclipse 850i), including 6 min heart rate and respiration recordings by ECG for heart rate variability measurements. DXA (Hologic QDR 4500 Discovery): hip (total, femoral neck, trochanter, Ward’s), lumbar spine (L1-4), whole body and region BMD, fat and lean mass, vertebral fracture assessment, aortic calcification score. pQCT (Stratec XCT 2000) radius: 4% site (trabecular, cortical and subcortical BMD), 50% site (endosteal/periosteal circumference, cortical CS area and thickness, BMC and BMD, CS muscle and fat area, stress strain index, moment of inertia). Verbal and and choice standing grip strength, chair rises, up and and and hip days by heart rate and with rate response to an total total total capacity blood DNA and and at and at and sample was collected at the visit and a further the following h day and min and test for disease, functional fracture and regular medication, hospital day and assessment physical activity assessment the life events, life for and and of and and Vascular structure and function: carotid intima-medial thickness (IMT) and arterial distensibility (GE Vivid-I), carotid/femoral pulse wave velocity (Vicorder) and central blood pressure and pulse wave analysis (Sphygmocor) Cardiac structure and function: echocardiography (GE Vivid-I). Images from parasternal long axis and short axis views, apical 5-chamber, 4-chamber, 3-chamber, 2-chamber and aortic views (plus conventional and tissue Doppler in 4-chamber view). Brachial blood pressure (Omron HEM-705), 12 lead ECG (Burdick Eclipse 850i), including 6 min heart rate and respiration recordings by ECG for heart rate variability measurements. DXA (Hologic QDR 4500 Discovery): hip (total, femoral neck, trochanter, Ward’s), lumbar spine (L1-4), whole body and region BMD, fat and lean mass, vertebral fracture assessment, aortic calcification score. pQCT (Stratec XCT 2000) radius: 4% site (trabecular, cortical and subcortical BMD), 50% site (endosteal/periosteal circumference, cortical CS area and thickness, BMC and BMD, CS muscle and fat area, stress strain index, moment of inertia). Verbal and and choice standing grip strength, chair rises, up and and and hip days by heart rate and with rate response to an total total total capacity blood DNA and and at and at and sample was collected at the visit and a further the following h day and min and test for disease, functional fracture and regular medication, hospital day and assessment physical activity assessment the life events, life for and and of and and Measurements taken in the NSHD at the age of 60–64 years Vascular structure and function: carotid intima-medial thickness (IMT) and arterial distensibility (GE Vivid-I), carotid/femoral pulse wave velocity (Vicorder) and central blood pressure and pulse wave analysis (Sphygmocor) Cardiac structure and function: echocardiography (GE Vivid-I). Images from parasternal long axis and short axis views, apical 5-chamber, 4-chamber, 3-chamber, 2-chamber and aortic views (plus conventional and tissue Doppler in 4-chamber view). Brachial blood pressure (Omron HEM-705), 12 lead ECG (Burdick Eclipse 850i), including 6 min heart rate and respiration recordings by ECG for heart rate variability measurements. DXA (Hologic QDR 4500 Discovery): hip (total, femoral neck, trochanter, Ward’s), lumbar spine (L1-4), whole body and region BMD, fat and lean mass, vertebral fracture assessment, aortic calcification score. pQCT (Stratec XCT 2000) radius: 4% site (trabecular, cortical and subcortical BMD), 50% site (endosteal/periosteal circumference, cortical CS area and thickness, BMC and BMD, CS muscle and fat area, stress strain index, moment of inertia). Verbal and and choice standing grip strength, chair rises, up and and and hip days by heart rate and with rate response to an total total total capacity blood DNA and and at and at and sample was collected at the visit and a further the following h day and min and test for disease, functional fracture and regular medication, hospital day and assessment physical activity assessment the life events, life for and and of and and Vascular structure and function: carotid intima-medial thickness (IMT) and arterial distensibility (GE Vivid-I), carotid/femoral pulse wave velocity (Vicorder) and central blood pressure and pulse wave analysis (Sphygmocor) Cardiac structure and function: echocardiography (GE Vivid-I). Images from parasternal long axis and short axis views, apical 5-chamber, 4-chamber, 3-chamber, 2-chamber and aortic views (plus conventional and tissue Doppler in 4-chamber view). Brachial blood pressure (Omron HEM-705), 12 lead ECG (Burdick Eclipse 850i), including 6 min heart rate and respiration recordings by ECG for heart rate variability measurements. DXA (Hologic QDR 4500 Discovery): hip (total, femoral neck, trochanter, Ward’s), lumbar spine (L1-4), whole body and region BMD, fat and lean mass, vertebral fracture assessment, aortic calcification score. pQCT (Stratec XCT 2000) radius: 4% site (trabecular, cortical and subcortical BMD), 50% site (endosteal/periosteal circumference, cortical CS area and thickness, BMC and BMD, CS muscle and fat area, stress strain index, moment of inertia). Verbal and and choice standing grip strength, chair rises, up and and and hip days by heart rate and with rate response to an total total total capacity blood DNA and and at and at and sample was collected at the visit and a further the following h day and min and test for disease, functional fracture and regular medication, hospital day and assessment physical activity assessment the life events, life for and and of and and to and their about is in Table and in the supplementary data available at IJE to and to with not given and not to have blood samples are not as to which at blood sample = as as BMC = = = blood = CS = DXA = ECG = = health = to and to with not given and not to have blood samples are not as to which at blood sample = as as BMC = = = blood = CS = DXA = ECG = = health = was given by the Manchester Research for the data collection taking place in Manchester, and was given by the A Research for the data collection taking place in These the duty of care that were because of the clinical from the assessments. 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