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A Life Course Approach to Healthy Age investigates the lifetime determinants of healthy ageing and their implications for policy and practice, bringing together authorities in ageing research and knowledge transfer from across the world in one wide-ranging volume.

First published online: 21 July 2018 ; Attribution 4.0 International (CC BY 4.0) ; Frailty correlates with morbidity and is superior to chronological age in predicting mortality. Frailty of older migrants has important implications for the demands placed on healthcare systems. Examining 95,635 Europeans in the Survey of Health, Aging and Retirement in Europe, we investigated cross-sectional and longitudinal associations between migration and frailty at ages > 50 years. We examined whether associations differed by countries' level of healthcare coverage and access for migrants and tested mediation by home-ownership and citizenship. Cross-sectionally, first-generation migrants > 50 years old were, on average, 16.4% (95% confidence interval [CI]: 14.6, 18.2%) frailer than non-migrants after confounder-adjustment. This decreased to 12.1% (95% CI: 10.1, 14.1%) after adjustment for citizenship. The strength of association between migrant status and frailty was greater in migrants from low-or-middle-income countries, compared with mi-grants from high-income countries. Migrants into Northern, Western and Eastern Europe were 37.3% (95% CI:33.2, 41.5%), 12.2% (95% CI: 10.0, 14.6%) and 5.0% (95% CI: 0.5, 9.6%) frailer than non-migrants, respectively, but migrants into Southern Europe were no frailer than non-migrants. The strength of association between migrant status and frailty was greater in countries with lower healthcare coverage and access for migrants. However, citizenship attenuated this difference. Longitudinally, migrants were frailer than non-migrants at 50 years old and trajectories converged over time until migrants and non-migrants were equally frail by 80–90 years. Our work finds no evidence of the 'healthy migrant effect' outside of Southern Europe in older migrants and suggests that acculturation is a key determinant of migrant health. ; The project MiLifeStatus has received funding from the European Research Council (ERC) under the European Union's Horizon2020 research and innovation programme (grant agreement No 682626)

INTRODUCTION: In 2020 England moved to an opt‐out deceased donation law. We aimed to investigate the views of a mixed stakeholder group comprising people with kidney disease, family members and healthcare practitioners towards the change in legislation. We investigated the expected impacts of the new legislation on deceased‐donor and living‐donor transplantation, and views on media campaigns regarding the law change. METHODS: We undertook in‐depth qualitative interviews with people with kidney disease (n = 13), their family members (n = 4) and healthcare practitioners (n = 15). Purposive sampling was used to ensure diversity for patients and healthcare practitioners. Family members were recruited through snowball sampling and posters. Interviews were audio‐recorded and transcribed verbatim. Transcripts were analysed using thematic analysis. RESULTS: Three themes with six subthemes were identified: (i) Expectations of impact (Hopeful patients; Cautious healthcare professionals), (ii) Living‐donor transplantation (Divergent views; Unchanged clinical recommendations), (iii) Media campaigns (Single message; Highlighting recipient benefits). Patients expected the law change would result in more deceased‐donor transplant opportunities. CONCLUSIONS: Clinicians should ensure patients and families are aware of the current evidence regarding the impact of opt‐out consent: expectations of an increased likelihood of receiving a deceased‐donor transplant are not currently supported by the evidence. This may help to prevent a decline in living‐donor transplantation seen in other countries with similar legislation. Media campaigns should include a focus on the impact of organ receipt. PATIENT OR PUBLIC CONTRIBUTION: Two patient representatives from the Kidney Disease Health Integration Team, Primrose Granville and Soumeya Bouacida, contributed to the content and design of the study documents.

Introduction In 2020 England moved to an opt-out deceased donation law. We aimed to investigate the views of a mixed stakeholder group comprising people with kidney disease, family members and healthcare practitioners towards the change in legislation. We investigated the expected impacts of the new legislation on deceased-donor and living-donor transplantation, and views on media campaigns regarding the law change. Methods We undertook in-depth qualitative interviews with people with kidney disease (n = 13), their family members (n = 4) and healthcare practitioners (n = 15). Purposive sampling was used to ensure diversity for patients and healthcare practitioners. Family members were recruited through snowball sampling and posters. Interviews were audio-recorded and transcribed verbatim. Transcripts were analysed using thematic analysis. Results Three themes with six subthemes were identified: (i) Expectations of impact (Hopeful patients; Cautious healthcare professionals), (ii) Living-donor transplantation (Divergent views; Unchanged clinical recommendations), (iii) Media campaigns (Single message; Highlighting recipient benefits). Patients expected the law change would result in more deceased-donor transplant opportunities. Conclusions Clinicians should ensure patients and families are aware of the current evidence regarding the impact of opt-out consent: expectations of an increased likelihood of receiving a deceased-donor transplant are not currently supported by the evidence. This may help to prevent a decline in living-donor transplantation seen in other countries with similar legislation. Media campaigns should include a focus on the impact of organ receipt.

In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants' LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)(2); mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (β = -0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a "programming" effect of early nutrition supplementation on adult LBM and muscle strength.

BACKGROUND: Drugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease. METHODS: In this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012-003641-15), and is completed. FINDINGS: Between July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was -2·29 mL (95% CI -6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group. INTERPRETATION: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods. FUNDING: Efficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research).

BACKGROUND: Drugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease. METHODS: In this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012–003641–15), and is completed. FINDINGS: Between July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or ...

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson's disease.

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson's disease.

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success. Government agencies included EMA, FDA, NINDS/NIH and IMI (Innovative Medicines Initiative). Emerging discoveries in new biomarkers and genetic endophenotypes are contributing to our understanding of the underlying pathophysiology of PD. In parallel there is growing recognition that early intervention will be key for successful treatments aimed at disease modification. At present, there is a lack of a comprehensive understanding of disease progression and the many factors that contribute to disease progression heterogeneity. Novel therapeutic targets and trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination are required. The integration of robust clinical data sets is viewed as a powerful approach to hasten medical discovery and therapies, as is being realized across diverse disease conditions employing big data analytics for healthcare. The application of lessons learned from parallel efforts is critical to identify barriers and enable a viable path forward. A roadmap is presented for a regulatory, academic, industry and advocacy driven integrated initiative that aims to facilitate and streamline new drug trials and registrations in Parkinson's disease.

The lifecourse perspective on adult health and on health inequalities in particular, is one of the most important recent developments in epidemiology and public health. This book brings together, in a single volume, the work of one of the most distinguished academics in the field. It is the first to specifically take a lifecourse approach to health inequalities and will be essential reading for academics, students and policy makers with an interest in public health, epidemiology, health promotion and social policy

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

This volume and its companion, The new dynamics of ageing volume 2, provide comprehensive multi-disciplinary overviews of the very latest research on ageing. It reports the outcomes of the most concerted investigation ever undertaken into both the influence shaping the changing nature of ageing and its consequences for individuals and society. This book concentrates on three major themes: active ageing, design for ageing well and the relationship between ageing and socio-economic development. Each chapter provides a state of the art topic summary as well as reporting the essential research findings from New Dynamics of Ageing research projects. There is a strong emphasis on the practical implications of ageing and how evidence-based policies, practices and new products can produce individual and societal benefits

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.