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Richards M.,Medical Research Council Unit for Lifelong Health and Ageing
The journals of gerontology. Series B, Psychological sciences and social sciences | Year: 2011

A wide variety of factors across the life course jointly influence cognitive and emotional development. Indeed, research from a variety of disciplines strongly suggests that cognition and mental health are intertwined across the life course, by their common antecedents and underlying physiology in development and in their interplay across adult and later life. We suggest that cognitive and socioemotional function fuse to form skills for life supporting self-regulation, competence, and quality of life that persist into later life through linked reciprocal processes of genetic influence, nurturing, schooling, work, and lifestyle.

Ong K.K.,Medical Research Council Unit for Lifelong Health and Ageing | Ong K.K.,Addenbrookes Hospital | Kuh D.,Medical Research Council Unit for Lifelong Health and Ageing | Pierce M.,Medical Research Council Unit for Lifelong Health and Ageing | Franklyn J.A.,University of Birmingham
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Background: Complex bidirectional relationships have been described between body weight, thyroid function, and risk of thyroid disorders, includingthyroid autoimmunity. We used a life-course approach to examine the potential association of childhood or adult body weight with the risk of thyroid autoimmunity and otherthyroid disorders at age 60-64 years in a large population-based birth cohort study. Methods: In the UK Medical Research Council 1946 British Birth Cohort study, at age 60-64 years, 1277 women and 1185 men (78% of the target sample) respondedtoa postal questionnaire, which included questions on thyroid disease and thyroid medication. Circulating antithyroid peroxidase antibodies, free T4, and TSH concentrations were measured in 1057 women and 997 men at a subsequent clinic visit. Birth weight was recorded, and height and weight were measured at ages 2, 4, 6, 7, 11, 15 years and also repeatedly in adulthood. Results: At age 60-64 years, 10.9% of women (139 of 1277) and 2.3% of men (27 of 1185) reported they were taking T 4, and 11.5% of women (122 of 1057) and 3.3% of men (33 of 997) had positive anti-TPO antibodies (>100 IU/mL), consistent with thyroid autoimmunity. Among women, bothT4 use and positive anti-TPO antibodies at age 60-64 years were positively associated with childhood body weight, childhood overweight, and adult body mass index. Childhood weight gain between 0 and 14 years of age was positively associated with later T4 use (odds ratio 1.21, 95% confidence interval 1.03-1.42) and positive anti-TPO antibodies (1.21, 1.00-1.47). Women who were overweight or obese at age 14 years (127 of 972) had a higher risk of later positive anti-TPO antibodies (2.05, 1.12-3.76). In men and women without any thyroid disorders, serum freeT 4 concentrations were inversely associated with concurrent body mass index (P = .002). Conclusions: Childhood weight gain and childhood overweight conferred an increased susceptibility to later hypothyroidism and thyroid autoimmunity, particularly in women. Copyright © 2013 by The Endocrine Society.

Ong K.K.,Medical Research Council Unit for Lifelong Health and Ageing | Ong K.K.,Addenbrookes Hospital | Hardy R.,Medical Research Council Unit for Lifelong Health and Ageing | Shah I.,Medical Research Council Unit for Lifelong Health and Ageing | Kuh D.,Medical Research Council Unit for Lifelong Health and Ageing
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Background: Our aim was to examine the associations between childhood or adult height and adult mortality. Methods: In the prospective British 1946 Birth Cohort Study, childhood height was measured at 2, 4, 6, 7, 11, and 15 years, and adult height was measured at 36 years. Deaths were reported from the national health service register. Results: A total of 3877 study members (1963 male) contributed 106,333 person-years of follow-up; 391 deaths (228 male) were reported between the ages of 36 and 64 years. The strongest sex adjusted association between height and mortality between ages 36 and 64 years was seen for height at age 6 years. The association was nonlinear; only study members in the shortest quintile at 6 years had a higher relative risk of adult mortality compared with those in the tallest quintile. By contemporary growth standards, 5.7% (n = 188) had heights at 6 years less than the second percentile, and a further 15.0% (n = 490) had heights between the second to ninth percentiles; these groups had higher adult mortality than all other study members (hazard ratio, 2.18; 95% confidence interval, 1.52-3.13; P<.001; and hazard ratio, 1.42; 95% confidence interval, 1.08-1.88; P < .01, respectively). Several determinants of childhood stunting (height at 6 years less than the second percentile) were directly associated with adult mortality; these included shorter parental heights and adverse early life nutrition and housing. Conclusions: British men and women born in 1946 were relatively stunted as children by contemporary standards. Those who were short at age 6 years had substantially higher mortality 30 to 60 years later. Furthermore, they accounted for the well-recognized inverse association between adult height and mortality. Copyright © 2013 by The Endocrine Society.

Almoosawi S.,Medical Research Council Human Nutrition Research | Prynne C.J.,Medical Research Council Human Nutrition Research | Hardy R.,Medical Research Council Unit for Lifelong Health and Ageing | Stephen A.M.,Medical Research Council Human Nutrition Research
Journal of Hypertension | Year: 2013

OBJECTIVES: The role of circadian rhythm of energy and macronutrient intake in influencing cardiometabolic risk factors is increasingly recognized. However, little is known of the association between time of energy intake and blood pressure. We examined the association between time-of-day of energy intake and subsequent hypertension and change in blood pressure. METHODS: The analysis included 517 men and 635 women from the 1946 British birth cohort. Diet was assessed using 5-day estimated diaries. Diaries were divided into seven meal slots: breakfast, mid-morning, lunch, mid-afternoon, dinner, late evening and extras. Time-of-day of energy intake at age 43 years was related to hypertension prevalence at 43 years and incidence at age 53 years and 10-year changes in SBP and DBP using logistic regression and censored regression controlling for medication use. RESULTS: Cohort members in the highest quintile of energy intake at breakfast at age 43 years had 30% lower odds of hypertension prevalence compared with those in the lowest. Cohort members in the highest quintile of energy intake at late evening had higher odds of incident hypertension at age 53 years [odds ratio = 1.55; 95% confidence interval (CI) 0.93-2.61; P for linear trend = 0.052]. Compared to the lowest quintile, the highest quintile of energy intake late in the evening was related to a greater rise in SBP (β = 5.09; 95% CI 1.25-8.93) and DBP (43-53 years) (β = 2.08; 95%CI 0.27-5.32). CONCLUSION: Higher energy intake at breakfast is associated with lower hypertension prevalence. Greater energy intake late in the evening is associated with higher hypertension prevalence, incidence and greater increases in blood pressure. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.

Dangour A.D.,London School of Hygiene and Tropical Medicine | Allen E.,London School of Hygiene and Tropical Medicine | Richards M.,Medical Research Council Unit for Lifelong Health and Ageing | Whitehouse P.,Case Western Reserve University | Uauy R.,London School of Hygiene and Tropical Medicine
Nutrition Reviews | Year: 2010

The results of randomized controlled trials of nutritional interventions aimed at preventing cognitive decline or dementia in older people have been largely disappointing. A reasonable argument can be made that this is at least in part because the design of primary prevention trials in older people is not straightforward and that the complexities of such trials are not readily apparent and commonly remain not fully recognized. This article analyzes some of the difficulties associated with identifying and enrolling study participants in long-term prevention trials, with available data from three large, recently published trials used as examples. This analysis also serves to identify examples of good practice and areas for further research. Randomized controlled trials remain the single most important tool in the epidemiological arsenal for identifying the effects of specific interventions, but consideration of critically important design features is essential. © 2010 ILSI Europe.

Tom S.E.,Group Health Research Institute | Cooper R.,Medical Research Council Unit for Lifelong Health and Ageing | Kuh D.,Medical Research Council Unit for Lifelong Health and Ageing | Guralnik J.M.,U.S. National Institute on Aging | And 2 more authors.
Human Reproduction | Year: 2010

Background: Early life development may influence the timing of natural menopause through association with size of the initial follicle pool or early follicular loss. This study examines the relationships of birthweight, gestational age and birthweight standardized by gestational age with early menopause in the 1958 British birth cohort study. Methods: Study participants were over 2900 women with data on birthweight, gestational age (obtained at birth), menopausal status at age 44-45 years and potential confounding factors. Logistic regression was used to study relationships of birthweight, gestational age and birthweight standardized by gestational age with post-menopausal status by 44-45 years, with and without adjustments for confounding factors. Results: There was a U-shaped association between birthweight and menopausal status at 44-45 years: women at either extremes of birthweight (<2.5 and ≥4.0 kg) had increased odds of post-menopausal status compared with those weighing 3.0-3.49 kg [odds ratio (OR) = 1.91, 95 confidence interval (CI) 1.08, 3.38; 1.81, 95 CI 1.11, 2.97, respectively]. Women with higher birthweight standardized by gestational age (which indicates faster fetal growth rate) also had increased odds of being post-menopausal by 44-45 years (OR for fastest quarter versus second fastest quarter = 1.80; 95 CI 1.16, 2.81). These associations persisted after adjustment for socioeconomic position at birth, adult smoking status and use of oral contraceptives. Conclusion: SThese findings suggest that variations in fetal environment may be associated with the timing of menopause. Given that extremes of birthweight and higher birthweight standardized by gestational age were associated with earlier age at menopause, mechanisms related to these characteristics that also regulate ovarian function should be investigated further.

Becares L.,University of Manchester | Shaw R.,University of Southampton | Nazroo J.,University of Manchester | Stafford M.,Medical Research Council Unit for Lifelong Health and Ageing | And 5 more authors.
American Journal of Public Health | Year: 2012

It has been suggested that people in racial/ethnic minority groups are healthier when they live in areas with a higher concentration of people from their own ethnic group, a so-called ethnic density effect. Ethnic density effects are still contested, and the pathways by which ethnic density operates are poorly understood. The aim of this study was to systematically review the literature examining the ethnic density effect on physical health, mortality, and health behaviors. Most studies report a null association between ethnic density and health. Protective ethnic density effects are more commonthanadverseassociations, particularly for health behaviors and among Hispanic people. Limitations of the literature include inadequate adjustment for area deprivation and limited statistical power across ethnic density measures and study samples.

Peterzan M.A.,Imperial College London | Hardy R.,Medical Research Council Unit for Lifelong Health and Ageing | Chaturvedi N.,Imperial College London | Hughes A.D.,Imperial College London
Hypertension | Year: 2012

Thiazide and thiazide-like diuretics are widely used in the management of hypertension, but recently the equivalence of hydrochlorothiazide and chlorthalidone for blood pressure (BP) lowering and prevention of cardiovascular disease has been questioned. We performed a meta-analysis to characterize the dose-response relationships for 3 commonly prescribed thiazide diuretics, hydrochlorothiazide, chlorthalidone, and bendroflumethiazide, on BP, serum potassium, and urate. Randomized, double-blind, parallel placebo-controlled trials meeting the following criteria, ≥2 different monotherapy dose arms, follow-up duration ≥4 weeks, and baseline washout of medication ≥2 weeks, were identified using Embase (1980-2010 week 50), Medline (1950-2010 November week 3), metaRegister of Controlled Trials, and Cochrane Central. A total of 26 trials examined hydrochlorothiazide, 3 examined chlorthalidone, and 1 examined bendroflumethiazide. Studies included a total of 4683 subjects in >53 comparison arms. Meta-regression of the effect of thiazides on systolic BP showed a log-linear relationship with a potency series: bendroflumethiazide> chlorthalidone>hydrochlorothiazide. The estimated dose of each drug predicted to reduce systolic BP by 10 mm Hg was 1.4, 8.6, and 26.4 mg, respectively, and there was no evidence of a difference in maximum reduction of systolic BP by high doses of different thiazides. Potency series for diastolic BP, serum potassium, and urate were similar to those seen for systolic BP. Hydrochlorothiazide, chlorthalidone, and bendroflumethiazide have markedly different potency. This may account for differences in the antihypertensive effect between hydrochlorothiazide and chlorthalidone using standard dose ranges. © 2012 American Heart Association, Inc.

Dangour A.D.,London School of Hygiene and Tropical Medicine | Allen E.,London School of Hygiene and Tropical Medicine | Elbourne D.,London School of Hygiene and Tropical Medicine | Fasey N.,Medical Research Council General Practice Research Framework | And 7 more authors.
American Journal of Clinical Nutrition | Year: 2010

Background: Increased consumption of n-3 (omega-3) long-chain polyunsaturated fatty acids (LC PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may maintain cognitive function in later life. Objective: We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people. Design: At total of 867 cognitively healthy adults, aged 70-79 y, from 20 general practices in England and Wales were randomly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo. Treatment-allocation codes were obtained from a central computerized randomization service. Trained research nurses administered a battery of cognitive tests, including the primary outcome, the California Verbal Learning Test (CVLT), at baseline and 24 mo. Intention-to-treat analysis of covariance, with adjustment for baseline cognitive scores, age, sex, and age at leaving full-time education, included 748 (86%) individuals who completed the study. Results: The mean age of participants was 75 y; 55% of the participants were men. Withdrawals and deaths were similar in active (n = 49 and n = 9, respectively) and placebo (n = 53 and n = 8, respectively) arms. Mean (±SD) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo (49.9 ± 2.7 mg EPA/L in the active arm compared with 39.1 ± 3.1 mg EPA/L in the placebo arm; 95.6 ± 3.1 mg DHA/L in the active arm compared with 70.7 ± 2.9 mg DHA/L in the placebo arm). There was no change in cognitive function scores over 24 mo, and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome. Conclusions: Cognitive function did not decline in either study arm over 24 mo. The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study. The Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) Study was registered at www.controlled- trials.com as ISRCTN 72331636. © 2010 American Society for Nutrition.

PubMed | Medical Research Council Unit for Lifelong Health and Ageing and Imperial College London
Type: Journal Article | Journal: Journal of cardiology and therapeutics | Year: 2016

Clinical practice evaluates cardiovascular risk based on current risk factor (RF) levels [Blood pressure (BP), body mass index (BMI) and glycaemic control] largely disregarding previous risk-factor history over the totality of the life course. RFs are related to contemporaneous echocardiographic measures of cardiac structure and function which in turn are independently related to cardiovascular morbidity and mortality in cross-sectional studies. However, the effect of lifetime or earlier RF history on future echocardiographic changes has never been systematically examined.A systematic review of the published literature identified 24 studies relating either earlier BP, BMI, glycaemic control or a combination to future cardiac structure and/or function.The majority of studies showed that elevated BP and BMI in earlier life and greater cumulative burden of these factors resulted in worse cardiac structure up to 24 years later. Studies examining glycaemic control as RF were few, but poorer glycaemic control in young adults was associated with increased future left ventricular mass. While only 5 papers related RFs to future cardiac function, all RFs were positively associated with worse future diastolic function.BP, BMI and glycaemic control measures in childhood, adolescence and early adulthood and subsequent longitudinal trajectories of BP and BMI are predictive of future abnormalities in cardiac structure and function. Lifetime RF history should be used to inform clinical practice. Further research is required to enable the identification of any sensitive periods in the life course to enable prevention when it is most likely to be effective.

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