Approved Projects from 2018 onwards
|ID||Project Title||Project Summary|
|KB0418||A qualitative exploration of older people’s views on influences on health, wellbeing and capability in older age||The qualitative data gathered from the participants in the National Study of Health and Development and the Hertfordshire Cohort Study provides a unique insight into individuals views on many aspects of ageing. There is no comparable data which I’m aware of which would provide an understanding of people’s perspectives on the influences on health and wellbeing in older age.|
|CK0418||Have we overestimated the impact of vascular factors on the declining incidence of dementia? DPUK-NIA cross-cohort collaboration||Research Question: What is the impact of vascular factors on the declining incidence of dementia?
To address these design issues of the previous studies, we propose 1) To identify all DUPK and NIA cohorts with mid-life (40+ years) vascular exposures and to conduct a pooled analysis. Preliminary scoping has identified 4 DPUK Portal cohorts and 4 NIA cohorts, over 80,000 participants that can be accessed through the DPUK-NIA partnership. Dr Chi-Hun Kim has been awarded an MRC-NIH partnering award (research visit costs only) and a DPUK Discovery Award to conduct this joint DPUK-NIA project with Dr Lenore Launer at NIA.
2) To harmonise data across the cohorts: Dr Launer has developed cross-cohort harmonisation procedures for the NIA cohorts. These will be adopted and applied to the DPUK cohorts. The developed harmonisation procedures will be made available to other researchers.
3) To develop longitudinal causal models: Causal inference from longitudinal observational data is challenging but critical to address our question. Formal causal models will be developed to account for non-random dropouts and death (e.g. joint models for longitudinal and survival data) and time-varying exposures (e.g. causal graphical models). The previous studies mainly focused on identifying the changing incidence of dementia using only older people. From our population-based mid-life cross-cohort project, we will be able to better estimate what has been the impact of vascular factors on the declining incidence of dementia than the previous single cohort studies did.
|VB0718||Violent victimisation and mortality in British Cohort Studies||Crime is important for society, public health, and for victims. The relevance of violent victimisation for later physical health is not well clarified, and would argue for investment in violence prevention programmes as a way of improving public health. This project will estimate the impact of crime prevention on population health using data from the NSHD, and assess the role of health-related behaviours(such as alcohol and smoking) in explaining any relationship.|
|DBMF0718||Socioeconomic inequalities in health: how have they changed in response to changing policy decisions and economic factors, and how may they be reduced?||This project aims to examine cross-cohort changes in health inequality, in birth cohorts initiated in 1946 (NSHD), 1958, 1970 and (where relevant) 2001. This project aims to builds on previous work which examined cross-cohort inequalities in adult BMI (Bann et al, PLOS Medicine 2017), and child-adolescent anthropometric outcomes (Bann et al, under review). It builds on this by examining other health outcomes (such as blood pressure at 43, and premature mortality; see below), other dimensions of socioeconomic circumstances (such as education, income; see below), and by examining the role of changing socioeconomic circumstances (eg, increases in income inequality) on population-wide health outcomes (eg, increases in body mass index).|
|SB0418||The effect of childhood adversity on adulthood behavioural, psychological, cognitive and health outcomes: A UK Biobank and DPUK cross-cohort investigation||Over the last decade there has been a substantial increase in the number of children presenting with mental health illnesses with the majority of these illnesses manifesting before the age of 14 (ONS, 2016). With suggestions that one in three of these illnesses are attributed to adverse childhood experiences which had a subsequent impact on their mental health, the importance of identifying and preventing, where possible, these, is of utmost importance. The difficulty with investigating childhood adversity presents both ethical and logistical difficulties, however, this proposed study uses existing adult population cohort data to investigate self-reported childhood sexual, physical and emotional trauma. The main aim of the study is to investigate associations between the aforementioned childhood adversities and adult behavioural, psychological, cognitive and health outcomes.
Item response theory (IRT) will be used to extract theta measures for mental health, lifestyle and scale data, and to harmonise these data across the cohorts (SB is a psychometric analyst). Multi-level modelling will be conducted as an initial exploratory procedure across variables of interest and thereafter, structural equation modelling will also be utilised to investigate the data.
|HH0818||Genomic analysis of spontaneous intracerebral haemorrhage; providing new insights into vascular integrity and amyloid deposition as causes of neurodegeneration||Spontaneous intracranial haemorrhage (ICH) is the most devastating form of stroke with 40% mortality. Survivors have a high rate of progressive dementia. Therefore, causes and mechanisms of ICH are important contributing factors to dementia. Moreover, small vessel disease in ICH is likely to influence neurodegeneration generally; in particular insights into cerebral amyloid angiopathy (CAA), which causes ICH via rupture of amyloid-laden vessel-walls, will improve understanding of vascular mechanisms in Alzheimer’s disease.
We hypothesise that novel genetic variants associated with ICH will reveal important information on overlapping causes of dementia, CAA and pathways involved in ICH. We collected clinical, imaging and DNA data on a UK cohort of 1,063 ICH patients, amongst them are 104 ICH families. We wish to investigate known genetic risk-factors for dementia and vascular disease, conduct a pilot genome-wide-association study for novel common variants combined with exome sequencing of familial ICH to identify overlapping highly penetrant.
|TN0818||How does growth in earlier life modify the relationship between adult BMI and cardio-metabolic outcomes all-cause mortality?||The majority of adults living in the United Kingdom (UK) are overweight or obese, which is a major public health concern as overweight/obese individuals are more likely (than normal weight individuals) to develop diseases representative of cardio-metabolic dysfunction (e.g. diabetes and hypertension).
However, becoming overweight or obese does not confer the same long-term health prospects across individuals, with some people appearing more resilient than others to the negative outcomes associated with overweight/obesity. The goal of this project is therefore to understand why the adverse effects of obesity on markers of cardio-metabolic disease and all-cause mortality (e.g. glucose levels, blood pressure and blood lipid levels) are less severe in some people than in others.
|CC0818||Adult trajectories of inflammatory and cognitive change from mid to late life: A cross-cohort comparison study||The principal aim of this study is to investigate whether within-individual change in the inflammatory biomarker C-reactive protein, in longitudinal follow-up, is predictive of later cognitive function, cognitive trajectories, and/or, dementia risk. Secondary aims are to test whether these associations are more present in particular age groups, and/or genetic risk groups (i.e. APOE e4 carriers). If the data allow, it may also be possible to test for causal inferences using CRP-relevant genotype data. CRP is a routinely collected measure in clinical practice, for screening and medication monitoring of a range of health outcomes in mid to late adulthood (i.e. cardiovascular disease, rheumatoid arthritis). If marked changes or sustained elevation in this biomarker over time, captured by existing routine testing, were shown to be helpful in risk prediction for cognitive-related outcomes and indeed for specific age groups (alongside other risk factors) this could be beneficial for preventative strategies targeted at reducing the population risk of dementia.|
|ME0918||The Non-Communicable Disease Risk Factor Collaboration (NCD-RisC): estimation of the global burden of cardio-metabolic risk factors||NCD-RisC is an international scientific collaboration working closely with the WHO through the WHO Collaborating Centre on NCD Surveillance and Epidemiology at Imperial College London, to estimate country/regional trends in major cardio- metabolic risk factors for non-communicable diseases (NCDs), globally. We are currently extending our work to estimate subnational risk factor trends for urban and rural populations worldwide. These risk factors include obesity, diabetes and blood pressure. Our results provide empirical evidence that inform the monitoring of progress towards global NCD targets.|
|PT0818||Transitions and Mobilities: Girls growing up in Britain 1954-76 and the implications for later-life experiences and identity.||This study addresses women born 1939-52 who became young adults in Britain 1954-76. The youth of this generation of women has immense historical and current significance but there has been no detailed study of it and its implications. Recent studies suggest young women were in the vanguard of postwar social change. They are now part of the largest group of over 60s in British history with unprecedented influence and are widely seen to be ageing differently from their predecessors partly due to their youth experiences. The research has 2 aims.  To investigate key events and transitions to adulthood of young women from different social backgrounds in Britain 1954-76, addressing related spatial mobilities. Youth is defined as 15 to 24 years, bridging the end of compulsory full-time education and the age by which most young women married.  To explore the relationship between the youth of these women and their current, later-life experiences and identities. The research employs a combination of quantitative and qualitative methods that include secondary analysis of the National Survey of Health and Development (NSHD) and qualitative study of the records of a sample of NSHD participants.|
|AW0918||Validation of a risk score predictive of later life adversity||Neurodevelopmental problems include a wide range of conditions including autism, attention deficit disorder and disorders of behaviour. Historically, they have been treated and studied as if distinct categories. In reality, they share symptoms and problems. I will study two large studies that have followed up members of the general population from birth to middle age. They provide information on a range of characteristics known to be more common in children with neurodevelopmental problems as well as their long-term prognosis. I intend to use this information to develop a risk score that can predict which children are most likely to have problems in the future. This risk score could then be used in clinical practice to identify those children who require further investigations, early intervention and follow-up.|
|RT0918||The multiple dimensions of ageing well: Characterising the health and well-being profiles of older adults using physical, psychological, cognitive, functional and social measures||The process of ageing involves many physiological and psychological changes. For example, many older adults are affected by multiple chronic diseases, changes in cognition as well as changes in everyday functioning. These changes often co-occur and may have a combined effect on later health outcomes, and there may be different patterns of health and well-being of older adults. Given that bidirectional associations between physical health, mental health and cognition have also been reported, the conventional approach of looking at health as a singular concept likely fails to capture the complexity of the multiple changes in ageing.
The objective of this study is to characterise the health and well-being profiles of older adults using a multidimensional approach with measures of physical health, mental health, cognition, everyday functioning and social engagement from existing cohort studies. It is hypothesised that there are qualitatively different profiles of health and well-being, and it will then be investigated whether demographic and lifestyle factors are associated with these profiles, and whether the profiles predict health outcomes such as chronic disease, dementia and death. Using such a multidimensional approach is expected to lead to a better understanding of the associations between chronic disease, health and well-being and everyday functioning in late life.
|BL0918||Life course social- and biomedical risk factors for cognitive and physical health in later life||In older age, health tends to decline with increasing age, however, the trajectory of decline seems to be slower among the socially advantaged groups compared to socially disadvantaged ones. This project aims to examine whether experiencing poorer physical and cognitive health in the second half of life is accelerated by specific life course trajectories, such as socioeconomic conditions during life. To our knowledge, there are limited studies which investigate life course influences on health in later life and the major limitation of the existing literature is the focus on health at a single time point rather than trajectories. However, health as well as its determinants are dynamic by nature. Our project will overcome this limitation by examining health outcomes measured at two or more timepoints within the same individuals.|
|EP1018||Meta-analysis of epigenome-wide association studies of carotid intima media thickness||Subclinical atherosclerosis is a major risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic risk variants for carotid intima media thickness (cIMT). However, the identified genes so far only explain a small part of the inter-individual variation in atherosclerosis. To identify further genes involved in atherosclerosis, we recently investigated the relation between whole blood gene expression and cIMT in a transcriptome-wide association study. This led to the identification of several genes implicated in atherosclerosis. An important epigenetic mechanism regulating gene expression and genome stability is DNA methylation. DNA methylation in relation to atherosclerosis has largely been unexplored. We therefore aim to conduct an epigenome-wide association study of cIMT.|
|HP1018||The value of aortic stiffness in predicting cardiovascular events in those at middle risk||Aortic stiffness has recently emerged as a novel cardiovascular risk factor. The addition of aPWV to standard risk prediction models also improved their performance, particularly in subjects at intermediate risk of CV events, specifically those with pre-hypertension or stage-1 hypertension.
The aim of this study is to assess whether aPWV improves risk prediction in individuals classified as having pre-hypertension or stage 1 hypertension beyond that provided by established cardiovascular risk factors.
|EM1018||CLOSER Mental Health and Cognitive Measures Harmonisation Project||The British birth cohorts contain a wealth of information on the cognitive ability and mental health of the population, and therefore represent a key resource in our attempts to understand changes in trends across generations. However, the specific instruments used to assess mental health and cognition vary substantially, both within and across, these cohort studies. This project has two main aims: i) document and harmonise the cognitive measures in the British birth cohorts, and ii) document the measurement properties and harmonise the various mental health measures in the British cohorts. By harmonising these measures (identifying comparable tests/items, or recoding variables to make them comparable), we will be able to explore the development of mental health difficulties and cognition across the life course, and compare trends across generations in order to determine whether difficulties are increasing or decreasing nationally. We will also explore the dynamic relationships between mental health and cognitive difficulties, and various established predictors of (e.g. socio-economic origins), and outcomes (e.g. socio-economic status in adulthood, educational attainment, physical health, wellbeing, employment), and compare these trends across cohorts. Moreover, this project will provide guidance for future researchers and will inform the development of future sweeps/studies.|
|EM181018||CLOSER Mental Health and Cognitive Measures Harmonisation Project||The British birth cohorts contain a wealth of information on the cognitive ability and mental health of the population, and therefore represent a key resource in our attempts to understand changes in trends across generations. However, the specific instruments used to assess mental health and cognition vary substantially, both within and across, these cohort studies. This project seeks to document existing cognitive and then harmonise both mental health and cognitive measures over the life course in five British birth cohorts: i) The National Survey of Health and Development (NSHD); ii) The National Child Development Study (NCDS); iii) The British Cohort Study – BCS70; iv) The Avon Longitudinal Study of Parents and Children (ALSPAC); v) the Millennium Cohort Study (MCS). By harmonising these measures (identifying comparable tests/items, or recoding variables to make them comparable), we will be able to explore the development of mental health difficulties and cognition across the life course, and compare trends across generations in order to determine whether difficulties are increasing or decreasing nationally. We will also explore the dynamic relationships between mental health and cognitive difficulties, and various established predictors of (e.g. socio-economic origins), and outcomes (e.g. socio-economic status in adulthood, educational attainment, physical health, wellbeing, employment), and compare these trends across cohorts. Moreover, this project will provide guidance for future researchers and will inform the development of future sweeps/studies.|
|EM301018||CLOSER Mental Health and Cognitive Measures Harmonisation Project||The British birth cohorts contain a wealth of information on the cognitive ability and mental health of the population, and therefore represent a key resource in our attempts to understand changes in trends across generations. However, the specific instruments used to assess mental health and cognition vary substantially, both within and across, these cohort studies. This project has two main aims: i) document and harmonise the cognitive measures in the British birth cohorts, and ii) document the measurement properties and harmonise the various mental health measures in the British cohorts. By harmonising these measures (identifying comparable tests/items, or recoding variables to make them comparable), we will be able to explore the development of mental health difficulties and cognition across the life course, and compare trends across generations in order to determine whether difficulties are increasing or decreasing nationally. We will also explore the dynamic relationships between mental health and cognitive difficulties, and various established predictors of (e.g. socio-economic origins), and outcomes (e.g. socio-economic status in adulthood, educational attainment, physical health, wellbeing, employment), and compare these trends across cohorts. Moreover, this project will provide guidance for future researchers and will inform the development of future sweeps/studies.|
|SB1108||Associations between childhood hormonal indicators, adult hormones, mental health and cognition: A UK Biobank and DPUK cross-cohort study||One in four people are affected by mental illness each year yet some areas of the UK have reached a crisis point with a severe shortage of mental health care services. With the promise of an injection of an extra £1.3 billion to be invested into mental health services by 2021, it is of utmost importance that a greater understanding about mental illness is part of this investment. This research proposes to use existing population cohorts to enhance understanding about the early hormonal indicators of adult mental health illness, and subsequent associations with cognition in later life. DPUK provides free access to over 600 000 participant records (at this current time but set to rise to over 2 million) affording the opportunity to exploring mental health predictors on a scale previously not possible. Identifying and understanding mental health predictors is of great public benefit for the treatment, monitoring and prevention of mental health illness and co-morbid disorders.|
|EB1018||Pharmacogenetics in Mental Health: 1946 Birth Cohort||A large number of drugs have a marketing authorisation in the UK for the treatment of psychiatric disorders, but the evidence guiding choice for an individual patient is limited. In clinical practice, the selection of drug is made by a trial and error approach. This can lead to several cycles of medications that fail until improvements are eventually reached, often several weeks or months later. In addition, standard doses are offered to all patients and doses are changed only in response to observed symptom changes and tolerability. Furthermore, many patients fail to show sufficient clinical improvement from psychotropic medication, and the side effect burden of these drugs is substantial. This contributes to the low levels of medication compliance seen in psychiatric conditions (e.g. depression, schizophrenia) and to the severe reduction in life expectancy among such patients.
Characterising the metabolic status of patients using genetic profiling could improve the prescribing of commonly used psychotropic medicines by helping clinicians to adjust the dose in an individualised, biologically-informed way. Such pharmacogenetic interventions have been successful in oncology and haematology, and testing is already in use for the management of some drugs such as tamoxifen and warfarin. However, although there has been extensive research on the pharmacogenetics of psychotropic drugs, there is very little evidence from clinical trials on this subject.
We aim to use the data from the 1946 Birth Cohort to assess whether genetic variation in the enzymes known to metabolise the majority of psychotropic drugs correlates to treatment outcomes. We will look at a number of measures that could indicate that a patient experienced a known side effect of psychotropic medication, such as increases in BMI, HbA1c, lipid and prolactin levels and hospital admissions.
|EM141218||Assessment and harmonisation of cognitive measures in the British birth cohorts||The British birth cohorts contain a wealth of information about the cognitive ability of the population, and therefore represent a key resource in our attempts to understand changes in trends across generations. However, the specific instruments used to assess cognition vary substantially, both within and across, these cohort studies. This project has two main aims: i) document the existing cognitive measures in the British birth cohorts, and ii) harmonise these measures (identify comparable tests/items, or recode variables to make them comparable), so that we may explore the development of cognition across the life course, and compare trends across generations. We will also explore the dynamic relationships between cognitive ability, and various established predictors of (e.g. socio-economic origins), and outcomes (e.g. socio-economic status in adulthood, educational attainment, physical health, mental health and wellbeing, employment), and compare these trends across cohorts. Moreover, this project will provide guidance for future researchers and will inform the development of future sweeps/studies.|
|EM151218||Harmonisation of mental health measures in British birth cohorts||The British birth cohorts contain a wealth of information on the mental health of the population, and therefore represent a key resource in our attempts to understand changes in trends across generations. However, the specific instruments used to assess mental health vary substantially, both within and across, these cohort studies. This project has two main aims: i) document the measurement properties and ii) harmonise the various mental health measures in the British cohorts (i.e., identify comparable measures/items, or recode variables to make them comparable). By harmonising these measures, we will be able to explore the development of mental health difficulties across the life course, and compare trends across generations in order to determine whether difficulties are increasing or decreasing nationally. Moreover, this project will provide guidance for future researchers and will inform the development of future sweeps/studies.|
|AS1118||Insulin-like Growth factor-1 (IGF-1) and Cognition||IGF-1 and the somatotropic axis has been at the forefront of ageing research, in part due to their relationship with various diseases of ageing such as cancer and cardiovascular diseases. However, the relationship between IGF-1 and later life cognition, and cognitive decline remains uncertain. Thus, this study aims to examine and understand the relationship between IGF-1, its binding proteins, and cognition using the National Survey of Health and Development.|
|SB1218||Movement, activity, rest and neurodegeneration in the MRC National Survey of Health and Development (NSHD; 1946 birth cohort) at age 70-74.||Changes in the quality of movement and sleep are being explored as possible markers to predict the onset of dementia and Parkinson’s disease.|
|RK1118||The metabolome of obesity: a Consortium of Metabolomics Studies (COMETS) analysis||More than one third of US adults are obese 1. Obesity is associated with significant adverse health outcomes including cardiovascular disease, diabetes and many cancers, posing a huge public health burden 2,3. In the majority of cases, obesity emerges from a complex interaction between lifestyle, environmental factors and underlying genetic susceptibility with heritability estimates of up to 70% 4,5. The metabolome represents a dynamic functional readout of the state of a biological system; encompassing both genetic and environmental influences. Consequently, metabolomics is ideally suited to explore the drivers of BMI and the manifestation of obesity on a mechanistic and metabolic level.|
|SK1218||Inflammatory blood markers and their association with cerebral amyloid and brain volume in later life||Alzheimer’s disease (AD) is characterised by the presence of extracellular amyloid plaques and intracellular neurofibrillary tau tangles. Accumulation of these proteins is thought to lead to progressive neuronal loss, although the precise mechanism by which this occurs remains unclear. Emerging evidence suggests that the immune system may play an important role. The immune system usually has a protective function, but excessive inflammation over time may cause or contribute to neuronal damage and disease pathology. Several studies have found increased levels of inflammatory plasma markers in AD patients compared with controls, but results have been inconsistent. Longitudinal studies using prospectively collected data in cognitively normal individuals at risk of AD are scarce. This study aims to investigate whether greater systemic inflammation is associated with AD-related imaging changes in later life. It will also explore the interaction with APOE genetic status, which has previously been shown to modify the association between inflammation and AD risk.|
|AG0119||Biological mechanisms for inequalities in ageing: Does diet mediate the relationship between socio-economic position and DNA methylation?||Socioeconomic disparities in later life morbidity and mortality are well-established. However, the biological mechanisms that link socioeconomic position (SEP) to ageing outcomes remains unclear. Epigenetics processes are one potential mechanism, as they are known to be influenced by socially distributed external factors, such as diet, pollution and smoking. Additionally, the dysregulation of epigenetic processes has been associated with a number of non-communicable diseases (for example, cardiovascular diseases and cancer).
This PhD project aims to understand the influence of lifetime SEP and diet on later life epigenetic signals. The main hypothesis is that disadvantaged SEP is associated with more unhealthy epigenetic signals and that this association is, in part, mediated by diet. We will determine whether there are sensitive periods of disadvantage across the life course which influence epigenetics or whether accumulation of disadvantage is more important.
|YR0119||Genome-wide association analysis of intracranial aneurysms||Rupture of an intracranial aneurysm (IA) is the leading cause of subarachnoid haemorrhage. 40% of the risk to develop an IA can be explained by genetics.
We aim to identify which genetic variants contribute to the risk of IA. To investigate this, we will perform a genome-wide association analysis. The result from this analysis give us insight in the most important drivers of IA and will guide further genetic research.
|HS0219||Midlife lung function with later-life brain volumes and white matter hyperintensity||To test the hypothesis that reduced lung function in midlife would be associated with greater risk of cognitive decline in later life, shown by the presence of increased white matter lesions on the brain MRI|
|NF0219||Exploring the relationship between mid-Life Hyperglycaemia and later life-amyloid||Recent findings have shown that Type 2 diabetes (T2D) is associated with cognitive decline and an increased risk of developing Alzheimer’s disease (AD). Insulin is a hormone responsible for carrying glucose into cells and regulates sugar levels in the bloodstream. Individuals with T2D show a resistance to insulin, which makes it harder for glucose to reach muscle, fat and liver cells and in the process, results in elevated sugar levels in the bloodstream. Since insulin plays an important for the development and function of the brain, insulin insensitivity in T2D can affect brain health.
The project aims to look at the relationship between markers of T2D and those of AD in a British cohort. Using state of the arts brain imaging tools, we can look at whether individuals with T2D or at risk of T2D will display brain pathology similar to those at early stage of Alzheimer’s disease. We are particular interested in looking at whether blood sugar level during mid-life is related to how healthy the brain is at a later age.
|MD0219||Education, Marriage and Employment Across Generations||This project investigates the formation of life-long inequalities and how these have changed across generations in the UK. It looks at how different cohorts make some of the most crucial economic decisions of their lives, on education, marriage, divorce, fertility and employment, and studies how these decisions have responded to the changing economic environment that these cohorts faced.|
|KW0219||To understand the impact of modifiable environment on musculoskeletal ageing||Health behaviours such as diet and physical activity play an important role in not only current health but in how well an individual ages. For example previous research has shown links between greater levels of physical activity and the reduced risk of falls a number of years later. This body of work aims to further examine the link between changes in what an individual eats, types and duration of physical activity, and body composition in their midlife on the muscle strength and bone health of an individual in later life. Secondly, the growing years are very important for future health, identifying the impact of how weight and height trajectories translate to later-life fracture risk in this cohort will inform preventative strategies for healthy ageing.|
|AK0319||Clustering and trajectories of multimorbidity over the life course||Multimorbidity is the existence of two or more chronic conditions in an individual. It is increasing in prevalence, partly due to an ageing population, and increasingly common in both high- and low-income countries. It appears to disproportionately affect individuals from socioeconomically disadvantaged backgrounds. Our knowledge of multimorbidity including its epidemiology, causal risk factors and trends over time is limited and mainly derives from cross-sectional data. We aim to use the National Survey of Health and Development to:
1. Identify clusters and trajectories of multimorbidity across the lifecourse (including childhood, through adolescence, middle and older age)
|PTP0319||Association of midlife blood metabolites with Î²-amyloid deposition and MRI biomarkers in the Insight46 sub-study||Worldwide, about 47 million people are currently estimated to have dementia, the most common form of which is Alzheimer’s Disease (AD), and this number is projected to increase to 75.6 million by 2030. In the UK alone, there are currently 850,000 people with dementia, which costs the UK economy over Â£26 billion a year (http://www.alzheimersresearchuk.org). Dementias are a leading cause of death and a major cause of disability and as there are currently no effective treatments, they are one of the major public health challenges of the 21st century.
Most dementias have a long pre-symptomatic phase and there is evidence that the neuropathology, such as Î² amyloid deposition, predates symptoms. It is therefore important to identify the factors that lead to these changes and apply effective therapies at the earliest stage before significant irreversible damage occurs. This highlights the need to identify relevant and ideally modifiable disease markers for early diagnosis that will ultimately aid the identification of appropriate effective interventions.
Blood metabolites are small molecules, which are the intermediates or final products of biological processes in the body, and represent a more accurate approximation to the physiological state of an organism. They are therefore valuable as potentially modifiable markers of biological processes and disease states in dementia. We have previously identified blood metabolites measured at 60-64 years in the NSHD to be associated with cognitive function (60-64 years), and with cognitive decline (between 60 to 64 years and 69 years).
This project will use participants from Insight46, the NSHD neuroscience substudy, that aims to identify the prevalence of neuropathology at 69-70 years, before this is likely to have caused significant irreversible damage. The aims of this project are to 1) investigate whether blood metabolites measured at 60-64 years are associated with Î² – amyloid deposition and brain volume at 69-70 years and 2) whether metabolite levels at 69-70 years and change in metabolite levels between 60-64 years and 69-70 years is associated with Î² – amyloid deposition and brain volume at 69-70 years.
|LP0319||Education and Society in Scotland||Education is now the basis of social success in liberal societies, the key to occupational opportunity, civic participation and fulfilling leisure. Failure in education now greatly increases the risk of social marginalisation. The present project aims to explain how that role of education has come about using the uniquely rich set of educational surveys of Scotland that date back to 1932 and extend to the present century. Scotland pioneered the use of high-quality national surveys in education, often working in parallel to and interacting creatively with surveys such as the NSHD that covered the whole of Britain or the UK. The project brings together surveys of these diverse origins to seek to understand students’ learning, and the consequences of that learning, over a 70-year period of profound social change and of numerous radical policy interventions|
|RG0419||Linking blood metabolite levels to cognitive decline and subsequent dementia||Investigating whether late midlife peripheral metabolite levels are associated with cognitive decline and subsequent dementia and interrogating the causal nature of these associations.|
|AG0419||Are only children all right? A cross-cohort analysis on the well-being of only children in the UK||Despite fertility decline across advanced economies over the last few decades and the increasing numbers of only children families, little is known about the consequences of growing up without siblings. Previous research suggests that despite strong stereotypes of only children, on average, singletons do as well as children with few siblings and better than children from large families. But since existing evidence largely comes from U.S. research conducted during or before the 1980s, it is unclear whether it reflects current or past patterns in the U.K. since the selection process into only children families might vary over time and across geographical contexts. Moreover, little is known about the longer-term well-being of only children and whether and how growing up without siblings might affect their life chances. To address these gaps in knowledge, I propose an innovative program of research to analyze, for the first time, the effects of being an only child on both childhood and adulthood outcomes in the UK over time. Using rich data from the 1946 NSHD, the 1958 NCDS, the 1970 BCS and the Millennium Cohort Study, the project aims to 1) analyze the socio-demographic characteristics of only children families and whether/how the selection into only children families has changed over time 2) compare the (e.g. cognitive and socio-emotional) well-being of only children relative to the well-being of children growing up with siblings over time 3) focusing on the 1946, 1958 and 1970 cohort studies to analyze the social/demographic (e.g. education, employment, fertility, partnership trajectories) and health (e.g. mental and physical health) outcomes of only children over the life course 4) focusing on the 1946 and 1958 cohort studies to analyze the well-being (e.g. health, social support, loneliness) of only children in older age. The project will have important implications, as its findings will be immediately relevant to the demography/sociology literatures which have largely neglected this demographic group for the past 30 years, to family scholars who increasingly often rely on sibling fixed effects models which (by definition) exclude only children, to government bodies designing policies which might affect family size decisions and to only-children themselves and to their families.|
|DL0419||Apolipoprotein e genotype and healthy brain ageing: stratification, modification and outcomes.||With age, people on average cognitively decline to some degree. There are growing numbers of older people worldwide, and older people are living longer – making healthy ageing a key public health priority. The risk factors for healthy cognitive ageing are mostly the same risk factors for dementia in terms of healthy lifestyle, environment and genetics. The largest and most common genetic risk factor for accelerated brain ageing is in the apolipoprotein (APOE) locus, where people with e4 genotype – around 25% of the general population – have much-increased risk of accelerated brain ageing (i.e. worse cognitive abilities, or dementia; particularly Alzheimer’s disease [AD]). Despite being discovered nearly 30 years ago, we have little understanding of what mediates or moderates this link. Under what environmental and genetic conditions does APOE e4 exert its biggest effect on cognitive abilities; what biological and brain structure phenotypes underlie it; and how best can we integrate that information for clinical use?|
|EZ0419||Healthcare utilisation in early and late onset dementia||Early onset dementia, also known as young-onset dementia, accounts for approximately 5% of all dementia cases and is diagnosed in people less than 65 years old. In 2015, there were 42,000 people with early onset dementia in the United Kingdom. The common causes of EOD include Alzheimer’s disease, and vascular diseases. Genetic factors cause less than 1% of all EOD cases. Research in healthcare utilisation in all cases of dementia has shown that people with dementia are 50% more likely to be hospitalised, and 18% more likely to be re-hospitalised compared to people without dementia. With the current focus of healthcare services, such as hospitals and care homes, being on people with late onset dementia, there is a need to update policies and services in order to meet the needs of people with dementia who are less than 65 years old. The present study will explore the frequency and causes of health service use (hospitals, emergency departments, care home, day centres) by people with early and late onset dementia.|
|SB0419||The effect of childhood adversity on adult behavioural, psychological, cognitive and health: A DPUK cross-cohort multi-modality investigation – extension of DPUK study 0144||One in three adult mental and physical health conditions relate directly to adverse childhood experiences and trauma. Furthermore, adversity in younger life may lead to adverse adult behaviours and premature mortality. This study is of utmost public benefit, highlighting the importance of understanding the implications of childhood adversity on adult behavioural, psychological, cognitive and health outcomes. Only through understanding these implications can there be policy changes regarding funding distributions towards earlier interventions in preventing childhood adversity.
This study will explore multi-modalities (genetic, imaging and phenotypic) datatypes across four populations cohorts to extract multiple variable characteristics to explore associations between childhood adversity and adult outcomes. By utilising a multi-methodological and multi-modality approach, triangulation of both methods and analyses will strengthen the outcomes and publication opportunities this project affords. Furthermore, the overall aim of this project is to utilise advanced datascience methodologies such as machine learning alongside multi-modality data to understand the mechanisms underlying causal effects where they exist.
|AM0519||A longitudinal phenome-wide association analysis of genetic risk for major depression||Depression frequently presents for treatment during adolescence or young adulthood, yet we have little idea when more subtle changes may first be observed and how we might better predict the onset of future depression in vulnerable individuals. Using the NSHD, we will use recent results from genetic studies of depression to estimate indivudal genetic propensity to depression – and then relate that measure to changes in cogntion, behaviour and other phsical and blood based measures throughout the lifecourse.|
|DT0519||Medication adherence in the NSHD population||The project will quantify medication usage in NSHD and compare self-reported medication adherence with objectively-measured medication adherence using HPLC t-MS of the 2009 visit serum samples (Metabolon).We will explore predictors of poor adherence from the patients’ known socioeconomic and behavioural phenotypes and whether medication adherence predicts health outcomes.|
|AK0519||Feto-Placental Origins of Cancer: An investigation of an association between birth-weight and future cancer risk||During pregnancy, the placenta acts like an invasive cancer. It uses the same strategies as a tumour to evade maternal immunity and promote its own growth. The usual consequence of a successful placenta is a well-grown baby with a high birth-weight. Birth cohorts like the NSHD 1946 cohort, have shown an association between high birthweight and increased risk of some cancers. Now that the 1946 cohort are older and about to be studied again, we wish to investigate this association more closely by studying the link between birthweight and all cancers. In particular, for women we will study the association between birthweight and pre and post-menopausal breast cancer. Furthermore, the mechanism through which this association exists has not been discovered. We suspect that the genes that promote growth of the placenta might also promote tumour growth. We will investigate if genetic analyses of DNA already sequenced from the 1946 cohort can be linked to genes that have the dual effect of promoting placental and tumour growth.|
|KP0519||How Dietary Approaches to Stop Hypertension (Dash) affects heart failure measurements, using the British Birth Cohort 1946||Heart failure is a common yet complicated syndrome that affects more than half million patients in the UK. It is formed as multiple culmination of cardiovascular risks: age, hypertension, obesity and type 2 diabetes mellitus etc Dietary approaches have been proved to be the most cost-effective intervention on preventing of Heart failure in previous studies. Our study using 1946 British Birth Cohort has proven long term DASH-style dietary to be associated with lower CVD risk, hypertension and better blood vessel function. Yet, long-term adherence of DASH hasn’t been studied to be relevant with heart failure. Our aim is to understand the association between long term adherence of DASH and Heart failure.|
|SB0518||Using MRI imaging to investigate how health lifestyle effect dementia-associated brain lesions and what genes and health factors underlie these changes.||Advanced psychometric methodologies using mathematical estimation models (IRT) provide an efficient method of analysing scale data. We propose that advanced psychometric methodologies which use mathematical estimation models, such as item response theory (IRT) provide a more efficient method of analysing scale data over CTT. With origins in educational testing whereby the field required the ability to differentiate between respondents obtaining the same score, IRT addresses many of the limitations of CTT (e.g., de Ayala, 2009). The application of CAT to health scales addresses psychometric inefficiency, increases precision in measurement and reduces participant burden, important aspects to consider when considering designing epidemiological studies.|
|DW0619||Associations of circulating metabolites with cerebral small vessel pathology: a prospective study in Insight 46 with follow-up genetic analyses||Cerebral small vessel disease (SVD) is the predominant cause of vascular dementia, and also underlies substantial proportions of stroke cases. Moreover, SVD-related brain damage is present in the majority of individuals aged 60 years or older, and this is likely to contribute to cognitive decline and other physical and psychiatric diagnoses, such as walking problems and depression. Delaying or stopping the progression of SVD could therefore provide multiple health benefits to ageing individuals. However, the causes and physiological processes underlying SVD are not well established, which has limited the development of ways to prevent or treat the disease. Large-scale metabolomics measurements provide scans of hundreds or thousands of small products of bodily processes (metabolites) present in the blood or other tissues. These measures are a promising tool for furthering our understanding of SVD and developing ways to treat the disease. In this study, we will examine whether any of approximately 1200 known metabolites measured in blood sampled from NSHD participants aged 60-64 years are associated with markers of SVD identified with brain scans 7-11 years later. Promising findings arising from the study will be further interrogated with genetic analyses.|
|EP0619||Investigation of associations between the MIND diet and cognitive function in the 1946 birth cohort||We aim to investigate whether a particular diet rich in whole grains, fruit and vegetables and especially green leafy vegetables and berries as well as low in animal fat, referred to as the “MIND” diet is protective against cognitive decline in participants of the 1946 British birth cohort taking into consideration among other factors their cognitive abilities or IQ when they were young, something that is rarely measured or considered in other studies since this information is not usually available.|
|LOK0619||Sex differences in cardiovascular risk factors in NSHD from 36 to 69 years and the role of BMI in sex differences in cardiovascular risk factors and metabolites from NMR spectroscopy at age 60-64 and 69 years||The aims of this project are 1. To model trajectories of blood pressure, body mass index (BMI), waist circumference, lipids and glycated haemoglobin (HBA1C) in male and female participants of NHSD. 2. To examine the association of age at menopause or hysterectomy with repeated measures of cardiometabolic risk factors, as modelled above (such as blood pressure, BMI and lipids) in NHSD. 3. To examine the association of age at menopause or hysterectomy with measures of cardiovascular structure and function outcomes in NHSD 4. To examine sex differences in the association between BMI and >200 metabolites available at 60-64 and 69 years from NMR spectroscopy.|
|GC0619||MyoFit46: Multi-Morbidity Life-Course Approach To Myocardial Health – A Cardiac Sub-Study of the MRC National Survey of Health and Development (NSHD)||Using the most advanced heart imaging technologies currently available, we will study the structure and function of the heart muscle in 75-year old participants of the world’s longest running birth cohort. The information we obtain will help us understand how air pollution, childhood infections and the accumulation of heart disease risk factors throughout life, impact on the well being of the heart in older age.|
|KM0619||Exploring the relationship between eye-movement patterns and later life-amyloid||Eye movements provide several important advantages as a measure of cognitive processing during everyday tasks such as reading. Technological advancements have permitted the use of devices that track people’s gaze with a plethora of generated data. Using the Insight 46 cohort, we aim to investigate unobserved characteristics of eye-movement during complex tasks associated with cognitive decline. By doing so, we intent to evaluate whether the eye could be a window to dementia.|
|MS0619||Investigating the imaging and genetic differences between posterior cortical atrophy and the amnestic presentation of Alzheimer’s disease|
|SVS0719||How strongly is family socioeconomic status associated with children’s cognitive and scholastic performance during the years of attending primary school?||Family background influences children’s cognitive and scholastic performance, which have important long-term effects on children’s lifespan development, but the strength of this association is unknown in the National Survey of Health & Development. The project’s key research question is: What is the strength of the association between family SES and children’s differences in cognitive and scholastic performance during the years of attending primary school?|
|BW0719||Harmonising earnings and income within and across studies||This project investigates how families transfer wealth and advantage across generations by harmonising measures of earnings and income in four CLOSER studies, to allow comparisons within the same study over time and comparisons between different studies. Different surveys have adopted very different approaches to measuring individual or household income, making it difficult to compare different generations. The project team uses the harmonised measures to assess the relationship between net family income across the cohort studies. This dataset can provide evidence about intergenerational income persistence, and help to show how social mobility is changing over time.|
|HJ0719||Calibration of Mental Health Measures||A widely-used feature of the British birth cohorts is the wealth of mental health measures collected throughout the life course. Nevertheless, measures used vary widely, both within and between cohorts. The extent to which they are comparable is not known, which currently limits cross-cohort comparative research. In this project, we will calibrate existing adult mental health measures across national birth cohorts with each other and (where possible) with external up-to-date measures using innovative survey design and statistical modelling. The proposed work complements the existing CLOSER harmonisation project on mental health which is, where possible, creating harmonised variables using existing cohort data. In combination with findings from the current project they will increase the usability of the studies, particularly from disciplines that haven’t traditionally done so. Moreover, this project will provide guidance for future researchers and will inform the development of further sweeps/studies.|
|CBS0819||Investigate the role of psychological factors in the changing association between socioeconomic position (SEP) and body mass index (BMI) in an increasingly obesogenic environment||Levels of obesity have been increasing over time, with more recent generations experiencing increasingly obesogenic environments. Both psychological characteristics and socioeconomic position (SEP) are associated with obesity. Therefore the aim of the project is to test the hypothesis that increasingly obesogenic environments (Assumed to increase with year and differ by SEP) result in greater levels of obesity, through greater variance in the way psychological characteristics are expressed or manifest into behaviours.|
|DD0819||Epidemiological Investigation into the Relationship between Analgesia, Pain and Cognitive function in later life||Pain related illnesses affect an increasing number of adults in the general population and are often treated with many types of pain-killing drugs (analgesics) to a varying degree of success. These pain killers are often started after an operation and continue to be prescribed over time, or may be started by your GP or other hospital specialist. Whilst it is important that these conditions are treated appropriately, we do not fully understand the long term impact that many pain killers might have- particularly on aspects of function like our memory; and some research has suggested that long term use may contribute towards decline in memory and cognitive function. Using data collected over the life-course, we hope to try to better understand the impact that chronic pain and associated analgesic drugs might have on cognition. Improving understanding of later life outcomes is a key driver to changing current practice in healthcare both in the UK and elsewhere.|
|KW0819||To understand the impact of modifiable environment on musculoskeletal ageing||Health behaviours such as diet and physical activity play an important role in not only current health but in how well an individual ages. For example previous research has shown links between greater levels of physical activity and the reduced risk of falls a number of years later. This body of work aims to further examine the link between changes in what an individual eats, types and duration of physical activity, and body composition in their midlife on the muscle strength and bone health of an individual in later life. Secondly, the growing years are very important for future health, identifying the impact of how weight and height trajectories translate to later-life fracture risk in this cohort will inform preventative strategies for healthy ageing.|
|RD0819||The prevalence of probable sarcopenia in early old age||The loss of muscle strength and mass as we age is increasingly recognised as an important medical condition called sarcopenia. Sarcopenia is relevant as those who lose muscle rapidly are at risk of a range of health problems including disability. At the same time there are a range of effective treatments including exercise training.
A recent meeting of European experts has proposed a new approach to testing for sarcopenia. Using data from the 1946 British birth cohort, we plan to examine how this approach would work in practice and look at whether certain groups of people (such as those living with long-term conditions) are at greater risk of sarcopenia.
|SS0819||The creation and validation of birth cohort frailty indices and life course risks of frailty||At any given age, there are some individuals, who as a result of ageing differently have accumulated health problems that make them more at risk for having poor health outcomes. This is frailty (or robustness) and is quantified by a frailty index. We plan to create a frailty index for the last three waves of the 1946 Birth Cohort. Due to the uniqueness of this cohort, we will be able to identify life course events, health issues and social factors from birth that lead to both the development and trajectory of frailty in those aged in their 50s-60s.|
|JLS0819||Metabolomics of Asthma, Lung Function, and Immunoglobulin E (IgE): a Consortium of Metabolomics Studies (COMETS) analysis||Asthma is a common chronic disease that imparts a significant public health burden worldwide. In most cases this condition arises from interactions between both genes and the environment. Metabolomics is a technology which allows us to measure all the downstream small molecules, or metabolites, in a biological system that are the products of these interactions.
In this study, we propose to combine the results of 47 studies including the MRC NSHD, to identify metabolites that are associated with asthma and its symptoms including lung function and measures of allergy. The identification of these metabolites will allow us to better understand the mechanisms of asthma and to identify novel therapeutic targets.
|RC0919||Socioeconomic adversity across life and its implications for musculoskeletal ageing||This project aims to investigate how different indicators of socioeconomic position across life relate to:
i) trajectories of functional limitations from ages 43 to 69 years
ii) clusters of musculoskeletal symptoms at age 69 years
iii) different patterns of change in physical capability from age 53 to 69 years
|MS0919||Postponement of Childbearing and Mental Health in midlife: Evidence from three British Birth Cohorts||Existing studies haven’t investigated how postponement of childbearing and the changes in the distribution of age at first birth over time are associated with mental health. Using data from three British Cohort Studies (the National Survey of Health and Development – NSHD, the National Child Development Study – NCDS, The British Cohort Study – BCS70), we aim to fill this gap by examining the relationship between age at childbearing and psychological distress among men and women in midlife and early old age, born in 1946, 1958 and 1970, respectively. The mechanisms that link age at first birth and mental health seem to suggest that people who postpone their parenthood tend to have later and better first marriages, higher educational level, lower risk of economic strain, and better physical health. However, the implications for mental health of the general shift in the distribution of age at first birth (to later ages) are not clear and need to be addressed.|
|SM0819||Relationship between cardiac function and neurovascular coupling in an ageing population||The aim of this project is to investigate the relationship between cardiovascular and neurodegenerative diseases and the cerebral haemodynamic response during various cognitive and motor tasks. Vascular disruption/pathology may be an early indicator of cognitive decline, making it a promising biomarker for dementia. The objective of our work is to compare functional near infrared spectroscopy (fNIRS) measurements during various tasks (specifically the Stroop test, the finger tapping test, and the trail-making test) between participants in the INSIGHT 46 trial (a) with and without cardiovascular disease and (b) against brain morphology (i.e. brain volume, amyloid plaque status, etc.) to see whether there is a difference in the haemodynamic response between groups. We will also determine whether there is a relationship between the kinetics of the neuronal haemodynamic response (i.e. the shape of the fNIRS curve) and cognitive performance. A better understanding of the relationship between cardiovascular disease and cardiovascular disorders and dementia could help with early diagnosis, treatment, and potential prevention in the future.|
|AJ0919||Long-term mental ageing consequences of adolescent dyslexia||Dyslexia, defined as a focal reading impairment in the face of general cognitive ability within the normal age-appropriate range, was ascertained in NSHD at age 11; and was shown to be associated with slower milestone attainment (Gaysina et al. Developmental Medicine and Child Neurology 2010; 52: 680-1). However, the long term consequences of dyslexia have not been investigated in this cohort. This project will investigate associations between dyslexia in NSHD and mental health and cognitive function in early old age, and the extent to which any associations are mediated by educational attainment and socioeconomic circumstances. At a later stage this work will be extended to include problems with numeracy (dyscalculia).|
|GCED1019||Environment-wide association study to identify novel factors associated with left ventricular diastolic dysfunction – Results from the NSHD Birth Cohort||Diastolic heart failure increases with age and remains a major cause of mortality and morbidity. Whilst some of its causes are know there are still major knowledge gaps surrounding the environmental risk factors for this condition. We will use exposome correlation globes to identify environmental factors throughout the life-course that associate with left ventricular diastolic dysfunction in older age. This information will improve our efforts to maintain heart health for longer.|
|HS1019||Age related changes in cognitive and neuroimaging profile in relation to lung function||To test the hypothesis that reduced lung function in midlife would be associated with greater risk of cognitive decline in later life, shown by the presence of increased white matter lesions on the brain MRI|
|SR0919||NSHD Diet and CVD – Continuation of ongoing study||Longitudinal analyses of dietary patterns and vascular function in the 1946 British birth cohort or National Survey of Health and Development (NSHD), including derivation of novel intermediates from stored samples..|
|CS1019||Cross-sectional and longitudinal diffusion imaging in white matter lesions and along tracts – link to cognition||One of the main hypotheses to explain the variety of symptoms associated with white matter lesions is their location with respect to white matter bundles connecting different part of the brain. This project aims at investigating how the lesion load and damage to the tracts measured through diffusion weighted imaging relates to cognition and how analysis of diffusion imaging can help predict the longitudinal development of the pathology.|
|JB1019||Epigenetic responses to social and environmental cues in early life and over the life course: impact on healthy ageing in UK population-based cohorts||The NSHD is the oldest of the British birth cohort studies, with data on health and life
circumstances collected at 23 follow-ups from birth so far to age 68 years on 5,362 British men and women (www.nshd.mrc.ac.uk) born in mainland Britain in March 1946. The strength of this study for epigenetic, early life and ageing research is the intensive phenotyping of the cohort that recently took place at 60-64 years (36), together with the range and depth of prospective data across life. The first biological samples (blood and buccal) were collected in 1999 (n=2,700), with a repeat blood sample collection in 2006-10. The current NSHD genetics resource includes genotype data (n=2,500 with Illumina CardioMetabochip Beadchip), metabolomic (n=1,800) and lipidomic profiling (n=1,800), and genome-wide methylation in a subsample (39). NSHD will contribute existing Illumina 450k data on 800 females, with 154 blood (n=154 age 53 and n=30 age 60-64) and 800 buccal samples (age 53). There is funding in place to increase the NSHD methylation dataset in 2015, resulting in n=188 females with blood methylation from two time points (age 53 and 60-64) and methylation in men (n = 800 buccal and n=46 blood samples).
|AMTEST||Adam’s test project – to be used to link datasets not for any particular project, or general dataset-building||Adam’s test project – to be used to link datasets not for any particular project, or general dataset-building|
|DW1119||Metabolomic studies of white matter hyperintensities and microstructural properties of the brain: a meta-analysis in the NeuroCHARGE Consortium||Cerebral small vessel disease (SVD) is the predominant cause of vascular dementia, and also underlies substantial proportions of stroke cases. Moreover, SVD-related brain damage is present in the majority of individuals aged 60 years or older, and this is likely to contribute to cognitive decline and other physical and psychiatric diagnoses, such as walking problems and depression. Delaying or stopping the progression of SVD could therefore provide multiple health benefits to ageing individuals. However, the causes and physiological processes underlying SVD are not well established, which has limited the development of ways to prevent or treat the disease.
Large-scale metabolomics measurements provide scans of hundreds or thousands of small products of bodily processes (metabolites) present in the blood or other tissues. These measures are a promising tool for furthering our understanding of SVD and developing ways to treat the disease. In this study, we will examine whether any of 1000+ metabolites measured in blood samples are associated with markers of SVD identified with brain scans. This will combine data from the NSHD alongside similar measures from other studies an international consortium of neurological researchers.
|SWJ1119||Blood metabolomics and lung cancer risk||Lung cancer is the leading cause of cancer mortality in the world, accounting for 1.6 million deaths in 2012. Metabolomics is the rapid, high-throughput detection and quantification of small-molecules found in an organism. The relationship between these metabolites and lung cancer risk is still largely unknown. We propose to identify the associations between metabolite levels and lung cancer risk within the Consortium of Metabolomics Studies (COMETS) cohorts that measured pre-diagnostic blood metabolite levels.|
|TC1119||Automated assessment of figure drawings in Insight 46||This project aims to develop machine-learning techniques to score drawings of a complex figure. These drawings have been completed by Insight 46 participants as part of a memory test. An automated method for accurately scoring these drawings would enhance our ability to measure subtle changes in memory that occur with ageing and in the early stages of neurodegenerative disease.|
|LB1119||Machine learning of echocardiography to gain new insight into disease||The aim of this project is to apply machine learning (ML) techniques to echocardiography, providing insight into physiological and pathological processes as well as improving disease diagnosis. In particular we will analyse tissue doppler imaging (TDI) from the NSHD birth cohort, which provides quantitative measures of cardiac function with high temporal resolution. Currently, only several simple scalar variables (e.g. s’, e’ and a’ velocities) are routinely extracted from these high-dimensional vectors. Whilst the use of these variables provides some insight into myocardial function, and can be used to aid diagnosis and prognosis, this dismisses most of the information contained within the data. We hypothesise that there are insightful features contained within the rest of the velocity trace that can be extracted using a variety of ML techniques, such as unsupervised and supervised learning. Ultimately, we aim to examine how machine learning may be of use for the automatic analysis and interpretation of echocardiographic images.|
|AD1119||Mechanisms and consequences of depression-related multimorbidity over the life course: coordinated analysis of population and primary care data||Multimorbidity (MM), defined as the co-existence of two or more mental and/or physical chronic conditions, represents a complex challenge for clinicians, participants, and their families. Current preventive efforts have partly failed because they have focused on one disease at a time and too late in life. For this reason, there is a critical need to identify groups of individuals at risk of MM earlier in life, and to develop interventions to prevent MM and its adverse health outcomes.
Several surveys have shown that not only clinical depression the most common illness in any MM cluster, it also is the most important for harming a patient’s quality of life. Compared with most diseases that occur (and begin to cluster) in later years, depression tends to begin much earlier in adult life. As most existing research on MM has focused on older adults (over 60 years), this means an important component has been relatively ignored. What exactly is the relationship between the onset of depression in early adult years and later MM clusters? A life course approach that follows groups of people over many years is the best way of addressing this question.
In the proposed study we will analyse three of the world largest birth cohorts (all based in the UK) that contain around 40,000 participants who have been regularly studied in the decades since their birth. We will identify those participants with a record of depression in young and mid-adult years (20 to 64 years of age) and examine how their early onset psychological difficulties interacted with later illnesses, both physical and mental. In particular, we will explore these relationships across time and within different subgroups, defined by gender and socioeconomic background.
|AW1119||Analysis and Predictors of ‘Superaging’ in the 1946 Cohort Study||This project aims to identify those characteristics associated with those participants who age exceptionally well, incorporating data collected from neuroimaging and genetic studies, as well as previous longitudinally collected lifestyle data.|
|MM1119||Tasting spoons: gustatory qualities of different metals||Many different materials come into contact with our food and taste buds every day. Tastes are received through our taste buds, which are located on the upper surface of the tongue. There are five basic tastes: bitter, salty, sour, sweet, and umami. These formal tastes are not the only component of the sensations associated with the overall experience of flavour. Other important factors include smell, detected by the olfactory system, texture detected by mechanoreceptors, and temperature, detected by thermoreceptors.
The perception of flavour in relation to the cutlery used to eat the food is less appreciated and understood. In this research project we aim to perform a systematic investigation of the relation between perceived taste and the physical or chemical properties of cutlery material. In other words we set out to determine how the taste of materials affects the experience and perception of them.
|MS1119||Deriving and validating of polygenic risk scores for Alzheimer’s disease||Alzheimer’s Disease (AD) has been proven to be a multigenic disorder, in which several genes play a role in the outcome. This project will aim to utilise the biggest genetic studies on AD, to identify the risk of getting AD using a combination of genetic factors.|
|AS1219||Investigating the relationship between midlife IGF-1 and structural brain measures using data from the INSIGHT 46 study||Epidemiological studies have investigated the relationship between IGF-1 and cognition in a number of populations. However, not many have looked at the relationship of IGF-1 with neuroimaging values or studied how these compare with changes in cognition values. Through the use of the INSIGHT 46 data, we aim to better understand the relationship between IGF-1, cognition and brain structure.|
|LN1219||Investigating associations of childhood infections with Alzheimer’s Disease neuropathology in later life, using the Insight-46 sub-study of the NSHD 1946 Birth Cohort||Î²-amyloid plaques are one of the neuropathological hallmarks of Alzheimer’s Disease. The Antimicrobial Protection Hypothesis suggests that Î²-amyloid has a normal function as part of the body’s innate immune system, whereby Î²-amyloid traps invading pathogens. A bi-directional relationship exists in which Î²-amyloid induces neuroinflammation but neuroinflammation also drives Î²-amyloid deposition. When this pathway becomes overactive, Î²-amyloid may become dysfunctional as it accumulates, forms plaques and induces a chronic inflammatory response. The Antimicrobial Protection Hypothesis is based on evidence that Alzheimer’s Disease is associated with various infections experienced in adulthood (e.g. Herpes Simplex Virus 1). However, no research to date has investigated whether childhood infections are associated with amyloid burden or Alzheimer’s Disease risk in later life. Given that childhood infections can have detrimental impacts on neurodevelopment, that some pathogens can remain dormant in the body for decades after initial infection (e.g. Tuberculosis) and that childhood infections can be associated with complications affecting the Central Nervous System (e.g. Encephalitis, Meningitis), it is important to consider whether childhood infections have adverse outcomes in later life. Using the Insight-46 cohort, this project proposes to investigate whether experience of infections in childhood (Measles, Scarlet Fever, Mumps, Tuberculosis, Whooping Cough and other respiratory infections) relates to amyloid burden and other Alzheimer’s Disease neuropathologies (White Matter Hyperintensity Volumes, Hippocampal Volumes) in late adulthood.|
|CF1219||To investigate whether social connectedness is associated with diet quality, captured by measuring adherence to the DASH-type diet, in adults aged 60-64 years using the NSHD||The overall aim is to investigate whether social connectedness is associated with diet quality, captured by measuring adherence to the DASH-type diet, in adults aged 60-64 years. It is hypothesised that good social connectedness is associated with better diet quality. Social connectedness, i.e. the quality and quantity of social relationships, has been shown to influence mortality to the same extent as other well-established risk factors such as alcohol consumption and smoking (Holt-Lunstad, Smith, Layton, 2010). Dietary behaviour is a possible pathway through which social relationships exert their influence on health outcomes.
The project will analyse data collected in the MRC NSHD cohort at age 60-64 years.
|DW1219||A METABOLOMIC STUDY OF BLOOD PRESSURE||High blood pressure (BP) is a major risk factor for cardiovascular as well as non-cardiovascular diseases. Genome-wide association studies have identified hundreds of loci related to BP levels and hypertension. Underlying molecular pathways related to BP regulation are not fully understood. To help characterise these pathways relating to blood pressure, the CHARGE consortium is conducting a meta-analysis of cross-sectional associations of circulating metabolites (measured by Broad or Metabolon metabolomics platforms) with blood pressure.|
|AB1219||Assessing the prevalence of secondary nocturnal enuresis in senior adults||We are aiming to see if adults experiencing ‘bedwetting’ are also suffering with a brain disease and/or have experienced this since they were a child. In order to do this we are asking individuals to fill in a short questionnaire about their bladder. We hope, if we see any link, we can provide better support to patients and improve their care.|
|GCCT1219||Relationship between Clinical Frailty Index across the Life-Course and Adult Cardiac Size and Function by Echocardiography in the NSHD British Birth Cohort||Frailty refers to a multidimensional syndrome of loss of reserves (energy, physical ability, cognition, health) that gives rise to vulnerability. Clinical frailty predicts outcomes but little is known about the life-course trajectories of frailty from early life to older age and how these patterns relate to heart size and function as we grow older. Understanding how frailty across life impacts the heart in older age has the potential to inspire public health interventions aimed at preserved heart health for longer.|
|IP0120||Subjective memory complaints in two “at risk” populations: familial Alzheimer’s disease and Insight 46||Understanding early changes in Alzheimer’s disease is important for intervention. Familial Alzheimer’s disease gives the possibility to study individuals over this period as mutation carriers have relatively predictable ages of symptom onset.
The Insight46 study aims to identify preclinical AD and investigate life course and genetic influences on symptom onset and progression. Research increasingly suggests that subjective memory complaints, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. This project aims to compare memory complaints in these two different populations who have the commonality of being “at risk” of AD (either due to ageing or family history).
|Ab0120||Alcohol trajectories and mammographic density using data from MRC NSHD||We will exploit the unique opportunity provided by the MRC National Survey of Health and Development, to investigate whether alcohol trajectories throughout adult life are related to women’s breast density in midlife.|
|JM0120||Social Health And Reserve in the Dementia patient journey (SHARED)||The role of social health in the onset, disease course and prognosis of dementia remains underexplored. Social health has been conceptualized as the influence of social resources in finding a balance between capacities and limitations. Moreover, social health affects and is affected by biological processes that underlie the dementia syndrome. This bidirectional link between social health and cognitive health acts across the entire trajectory from cognitive health to severe dementia and manifests itself differently during various phases of disease. Firstly, social health can impact an individual’s capacity to withstand brain pathology. As such, social health may influence brain reserve and cognitive reserve, both of which play a role in the discrepancy between neuropathology and clinical symptoms. Secondly, accumulating brain pathology leading to clinical manifestation of cognitive deficits can reciprocally impact social health and need for social care and support. This mixed methods project aims to unravel the interplay between social health and biological and psychological factors on the trajectory through dementia and to develop a framework for developing health and social care interventions. There will be a specific focus on the bidirectional link before and after dementia develops, the biological substrate on imaging, and the modifying role of brain and cognitive reserve. We bring together >40 studies totaling nearly 150,000 individuals that together capture the whole life course and the entire population from cognitively healthy to severe dementia, and that have longitudinal data available on social, cognitive and brain reserve, brain imaging, environmental, clinical, physical and mental factors, and cognitive decline and onset of dementia. We will perform qualitative studies to probe additional relevant social factors and relations with cognitive reserve and function. Further, we will perform quantitative analyses that will leverage the vast amount of data available in these studies, including repeated and multi-level measurements. Knowledge generated across these various disciplines and work packages will be integrated into a system dynamics model on the role of social health during the entire patient journey. In turn, this will inform about modifiable pathways and targets for preventive interventions at both the population and individual level.|
|AK0220||The role of cognitive functioning in explaining socioeconomic inequalities in perceived sense of control||Higher educated older adults tend to experience more control over their lives. This sense of control is in turn related to various favourable outcomes, such as better health and wellbeing. However, it is unknown why exactly these differences in sense of control between higher and lower educated older adults exist. In this research project, we examine whether differences in cognitive functioning – particularly those functions related to planning, regulation, and control (so-called ‘executive functions’) partly explain the relationship between education and sense of control. If this is the case, interventions aiming at improving executive cognitive functions in older adults with a low socioeconomic position might reduce socioeconomic inequalities the sense of control, which may possibly contribute to more equality in health and wellbeing in old age.|
|JF0220||Visualizing health risk||In order to provide benefits for participants to attend cohort studies longitudinally, we aim at developing an app-based data exploration tool empowering participants about their own health status. Based on their donated data and compared to the average population, we aim at developing explorative scenarios to depict the effect of lifestyle changes, such as quitting smoking behavior or losing weight, on future cardiovascular risk trajectories. Here, we want to use the longitudinal MRC dataset to explore risk modelling under life-style changes and subsequently, how these trajecectories can be comprehensively visualised to a study participant.|
|BW0220||The Gender Wage Gap: evidence from the cohort studies||Nearly half a century after the Equal Pay Act, women still earn less than men and convergence is slow.
The gap grows with family formation, as mothers spend time out of the labour market and face lower pay than previously on returning to employment, particularly part-time. One view is that the GWG reflects conventional norms about the division of domestic labour, while others point to discriminatory practices in the workplace. Growing concern about the persistence of the GWG and the way it evolves over the life course and across cohorts prompted the team to start examining
the reasons for the GWG
|PA0220||A life-course study of cognitive reserve and cognitive state in older age||The extent of neuropathology required to cause cognitive impairment consistent with dementia varies among individuals (Stern 2013). Cognitive reserve theory postulates that the knowledge and experiences individuals accumulate through their lives provide an increased resilience against cognitive ageing or cognitive disorders (Stern et al., 2018). It is hypothesised that cognitive reserve originates from the interaction of various markers through the lifespan, which accumulates over time and modifies the risk of cognitive impairment (Richards Deary, 2005). The aim of this study is to create a life-course model to evaluate how dynamic changes in cognitive reserve markers relate to the cognitive state during older age.|
|AA02220||Validation of a variant in the KLOTHO gene with cortical amyloid burden||It has been reported in previous studies that heterozygous carriers of the variant rs9536314 in the KLOTHO gene enhances cognition . The variant rs9536314 tags a haplotype where the wild-type amino acids at positions 352 and 370 in the KLOTHO gene are replaced with valine (V) and serine (S), respectively. Thus, the haplotype is referred to as KLOTHO-VS. In this project, using the INISGHT46 study sample and available genotyping data, we aim to test whether heterozygous carriers of KLOTHO-VS exhibit reduced cortical amyloid burden.|
|KL0320||Cognition and its associations with biomarkers of Alzheimer’s disease in Insight 46, a sub-study of the MRC National Survey of Health and Development||Alzheimer’s disease (AD) has a long preclinical stage beginning several decades before the onset of symptoms, during which pathology accumulates in the brain. My research aims to identify the earliest changes in memory and thinking that occur during this preclinical stage, and to find out what are the most sensitive cognitive tests to measure these changes.|
|LC0320||Secondary education and social change in the United Kingdom since 1945||The 1944 Education (Butler) Act overhauled the structure of British education. For the first time secondary schooling became a mass experience, which would have an impact upon the life course of successive generations growing-up in late 20th century Britain. By 1961 3.2 million pupils were being educated in state funded secondary schools, and over 600,000 in the independent sector. Over the ensuing 50 years, educational reform has repeatedly divided political and popular opinion as successive governments have attempted to remodel the system. Yet while this narrative of political meddling has been exhaustively told, we know very little about what pupils and parents thought mass education was for after 1945. Reform of the system occurred against a backdrop of profound social and economic transformation across British society. Traditional social structures appeared to fragment as processes including affluence, social mobility, a decline in deference, individualism and consumerism reconfigured how individuals understood their position within wider society.
Drawing on an innovative range of sources, this project provides a new social and cultural history of postwar secondary education, embedding education in the experience of rapid social and cultural change in late 20th century Britain. This represents an indispensable contribution to the existing picture of post-1945 education by moving beyond entrenched historiographical positions, which too often treat education as a proxy for other concerns, such as national decline or class realignment. Rather than relying entirely on ‘expert voices’ – politicians, commentators or teachers – we ask how the everyday experience of education shapes and reflects pupils’ and parents’ aspirations, expectations, and sense of self, across their lives from youth to employment to parenthood. Our project draws on original data and interview transcripts from postwar longitudinal studies and post-1950 social surveys, regional archival material from Local Education Authorities and schools, and new oral histories and social media research. We explore the intersection of national, regional, local and individual histories of education, charting how these differed across the UK and changed over time. Our findings will combine a broad national overview with a series of local case-studies to root the experience of education within specific contexts. Unlike previous studies, our research looks beyond England and Wales to consider the whole of the UK and the complete spectrum of schools (secondary modern, grammar, comprehensive and independent). We will deliver a diverse range of outputs, including two academic monographs and 5 journal articles, as well as resources aimed at a wide public audience.
|LN0420||Identifying which cognitive domains, measured in late adulthood, most strongly associated with age and type of menopause in a British Birth Cohort||Alzheimer’s Disease (AD) is more common in women than in men. This sex difference cannot solely be attributed to the fact that women have a greater life expectancy than men. Evidence shows that dementia is more common in women shortly after menopause, whilst the risk for men and women becomes more equal after age 70 years. Menopause could therefore serve as a mechanism for increased dementia risk in post-menopausal women.
Menopause is subjectively associated with cognitive decline (often called ‘brain fog’), frequently manifesting as increased forgetfulness and attention problems. Subjective reports have been corroborated through objective measurements. Additionally, cognition has been associated with age of menopause, whereby later menopause is believed to have a beneficial effect on long-term cognition post-menopause. Women in the National Survey of Health and Development (NSHD) 1946 British Birth Cohort who had later natural menopause maintained better verbal memory through to age 69 years, compared with women who experienced earlier natural menopause. The proposed research aims to further investigate whether menopause associates with different cognitive domains in later life. We will explore a range of cognitive measures to delineate which cognitive domains most strongly correlate with age and type of menopause. Unpicking the relationship between menopause and cognition in later life is important to help us to understand the mechanisms through which menopause may influence risk of cognitive decline and dementia.
|MD0320||Number of children and cardiovascular health – social or biological pathway?||Having a greater number of children has been linked to a higher risk of cardiovascular disease. However, it is not yet clear to what extent this association is explained by the biological effects of pregnancy, or whether it may be attributable to social or behavioural factors related to child-rearing. This study aims to investigate the association between parity and cardiovascular health using measurements of pulse wave velocity and carotid intima-media thickness at age 60-64. By assessing the associations in men and women, we aim to assess the role of biological and social/behavioural factors in this association.|
|MEG0320||Data-driven models of AD initiation and progression using Insight46.||This project uses machine-learning techniques to construct models of normal and pathological ageing with the goal of helping facilitate early detection and personalised treatment options for dementia.|
|LL0420||Resting-state Functional Connectivity: Cross-sectional and Longitudnal analysis of functional brain networks in patients at risk of Alzheimer’s Dementia||The project aims to investigate how functional connectivity in resting-state fMRI relates to a variety of concurrent conditions and future outcomes and whether this can be predictive of Alzheimer’s Disease progression.|
|SEL0420||Long term economic impact of childhood emotional and behavioural problems||This study will evaluate the economic impacts in adulthood of mental health problems experienced by children and young people. Mental health problems are common among children and young people and it is known that they can have long lasting effects into adulthood. These effects have economic consequences, both in the short term (e.g., through the costs of health care and educational support) and into adulthood and across the life course (e.g. service use in adulthood due to continued difficulties, loss of earnings and unemployment). There is only limited information on the relationship between early difficulties and economic impacts in adulthood. Existing studies only look at short-term impacts, or focus on specific communities or types of mental disorder.
Overarching aim: To analyse the long-term economic impacts of mental health problems experienced by children and young people and implications for policy and service provision. Although this application focuses on the 1946 British birth cohort, we will also use data from the 1958 and 1970 cohorts.
|SM0420||Examination of the relationship between sodium and potassium intake with cardiovascular health and blood pressure trajectories||The relationship of sodium and potassium consumption with blood pressure
and cardiovascular health will investigated using data from a British
This will help verify advice given regarding salt intake.
|AK0520||Lumipulse CSF vs amyloid PET cross validation study||In order to validate the performance of the fully automated Lumipulse CSF testing platform|
|HSS0520||Clustering and trajectories of multimorbidity over the life course||Multimorbidity is the existence of two or more chronic conditions in an individual. It is increasing in prevalence, partly due to an ageing population, and increasingly common in both high- and low-income countries. It appears to disproportionately affect individuals from socioeconomically disadvantaged backgrounds. Our knowledge of multimorbidity including its epidemiology, causal risk factors and trends over time is limited and mainly derives from cross-sectional data. We aim to use the National Survey of Health and Development to:
1. Identify clusters and trajectories of multimorbidity across the lifecourse and predict mortality and ADL outcomes
This PhD project will be an expansion to the previous multimorbidity project
|HM0420||Insight46 ASL analysis||Cardiovascular health can have a large effect on the cerebrovascular health, and subsequently affect the chances of a person getting cognitive decline. We have developed a new MRI biomarker that allows to charter the cerebrovascular health. In this study, we will use cardiovascular data of the British Birth Cohort, as collected over the lifespan, and investigate whether these are associated with the cerebrovascular health as measured on the recent MRI scans of the brain.|
|OR0520||Metabolomic age acceleration and its determinants: A multi-cohort analysis||Both genetic and environmental factors affect the ageing process, leading to differences in ageing rates. Therefore, a person’s “biological age”, or overall physiological state, may differ from what is expected given their chronological age, and may provide common pathway underlying multiple age-associated diseases. Metabolomics may provide a more cost effective ‘omic platform and complementary assessment of biological ageing.The metage project aims to understand metabolomic age acceleration and its determinants by utilising and pooling data from multiple cohort|
|RS0620||Covid-19 web survey non-response weight derivation||The National Survey of Health and Development (NSHD), alongside the four longitudinal cohort studies run by the UCL Centre for Longitudinal Studies (CLS), has recently completed a Covid-19 web survey. Data for a limited number of pre-specified NSHD variables are requested in order to derive non-response weights for the NSHD web survey. These weights will be used in subsequent analyses, by researchers at the MRC Unit for Lifelong Health and Ageing at UCL, CLS, and beyond, to ensure that the findings are population-representative.|
|QD0520||Associations between physical function across adulthood and late-life brain health in the 1946 British birth cohort||Worse physical function in adults, such as lower hand strength, has been linked to worse performance on assessments of memory and other aspects of cognition. However, the exact nature of this relationship is unclear, especially in terms of whether declines in physical function might lead to declines in cognition and if so, how this might happen. This project aims to look at this question to investigate whether declines in physical function in mid-life lead to lower cognition and differences on brain scans in later life.
To do so, we will use data from participants in the National Survey of Health and Development (NSHD) on mid-life physical measures, such as grip strength, and link these to cognitive and brain imaging data collected on a subset of the study participants at age 70. In this way, we will be able to look at the links between brain function and cognition in later life and physical function that was measured many years before. We hope through this work to be able to shed some light on the overarching question: are changes in physical function predictive of subsequent cognitive decline and is this because of differences observed in the brain?
|GP0620||Covid web survey data analysis||Production of Report on Initial findings of the Covid web survey.
Short document with high-level descriptive statistics containing cross-cohort comparisons involving all the following cohorts: NSHD, NCDS, BCS70, the Millennium Cohort Study and Next Steps.
|YJC0620||Life course physical activity on later-life cognition and brain health||Using Insight 46, a neuroscience sub-study embedded in the rich population-based age-homogenous birth cohort NSHD (1946 British Birth cohort), we can now extend on previous research to assess the effects of physical activity across the life course on later-life cognitive functon and global white matter hyperintensity volume and amyloid load in later-life, whilst adjusting for a range of potential confounders.|
|DW0720||The role of infectious disease burden in neurovascular health||Acute and chronic infections may affect the risk of many cardiovascular diseases. For instance, varicella zoster vasculopathy (following shingles bouts) substantially increase short-term ischaemic stroke risk. Whether cerebral small vessel disease (SVD) – a determinant of vascular dementia and ischaemic stroke – is affected by specific pathogens and/or overall pathogen burden is unknown. In particular, long-term exposure to cumulative chronic infections may be of key relevance for sustained and progressive damage to the cerebral vasculature. Addressing this crucial question, this epidemiological research will study prospective and longitudinal associations of multiple infections with markers of SVD and other neurodegenerative traits. Findings from this project might establish infectious agents as novel (and often preventable) risk factors for vascular dementia and stroke risk.|
|JD0720||Association between DNA methylation, diet and cardiovascular disease risk||DNA methylation is the most common and stable epigenetic mark, which has been shown to be associated with different diets and the development of cardiovascular disease. This project aims to further explore the epigenome-wide association between dietary intakes, risk of cardiovascular disease and DNA methylation in UK cohorts, in order to expand the understanding of how DNA methylation changes from diet may be related to cardiovascular disease development.|
|GC1020||Apolipoprotein-E (ApoE) and heart conduction defects||Apolipoprotein E has been shown to increase the LDL (“bad cholesterol) levels. This can affect both large vessels (leading to strokes and heart attacks) and small vessels (such the ones in kidneys). However, it is unknown whether small vessel disease can affect the heart conduction system predisposing to abnormal heart rhythms. Exploring this association would provide a better understanding of the pathology underlying certain abnormal heart rhythms. This would open the way to better targeted approach of such conditions.|
|GC021020||Impact of lockdown on key workers – Findings from the COVID-19 survey in five UK national longitudinal studies||Key workers played a pivotal role during the national lockdown in the UK’s response to the COVID-19 pandemic. Although protective measures have been taken, the impact of the pandemic on key workers is yet to be fully elucidated. To answer this question, we used electronic survey data captured at the peak of the UK national lockdown (May 2020) from participants of five UK longitudinal studies spanning multiple generations (18 to 74 years old). We investigated whether being a key worker during lockdown was associated with a set of neegative health and socio-economic outcomes. This should inform policy makers on the impact of lockdown on keyworkers in anticipation of second COVID-19 wave.|
|GC1120||Associations between childhood and young-adulthood bradycardia and later-life cardiovascular dysfunction and mortality: a longitudinal birth cohort study||Heart rate refers to the rate at which the heart beats. Heart rate in general has been associated with negative health outcomes such as heart disease. Interestingly, a fast heart rate during childhood has been associated with premature death. However, the consequences of a low heart rate are yet to be elucidated.|
|AG1120||Lifelong milk intake and muscle function decline in the 1946 British birth cohort|| Older adults are at an increased risk of loss of muscle strength and mass, a muscle disorder termed sarcopenia. Physical activity and healthy diet throughout one’s life may help in preserving healthy muscle and reduce the risk of sarcopenia in later life.
Bovine milk is a part of healthy diet, and a source of several essential nutrients and non-nutrients, potentially relevant for muscle function across the life course. Investigations into national dietary and consumer preferences surveys have shown that the type and amount of milk intake has changed in the UK population, showing an overall lower consumption and an increased preference for reduced fat milk.
Using the longitudinal data from the MRC National Survey of Health and Development (NSHD, the 1946 British cohort), we aim to investigate the relationship between lifelong milk intake and change in skeletal muscle function by asking: (a) does milk intake from age 36 to 60-64 years influence change in muscle strength (grip strength) from midlife to old age (53 to 69 years)? (b) does lifelong milk intake influence muscle function in older men and women differently?
|GCCC1120||Relationship between Clinical Frailty Index across the Life-Course and Adult Cardiac Size and Function by Echocardiography in the NSHD British Birth Cohort||Abnormal control of basic nervous system functions required to maintain a constant blood pressure and heart rate, develops with advancing age and complicates a number of diseases. Children and adolescents with diabetes have previously been shown to have heart rhythm abnormalities because of a loss of this normal nervous system function. We hypothesize that the reduction in carotid artery wall elasticity related to ageing can lead to similar changes in heart rhythm detectable on the standard ECG. Such ECG abnormalities are associated with sudden cardiac death so identifying potential risk factors is of major importance.|
|GCMF1120||Relationship between Clinical Frailty Index across the Life-Course and Adult Cardiac Size and Function by Echocardiography in the NSHD British Birth Cohort||Abnormal control of basic nervous system functions required to maintain a constant blood pressure and heart rate, develops with advancing age and complicates a number of diseases. The normal variability of one’s resting heart rate can be lost with advancing age. We hypothesize that disease in the carotid artery wall related to ageing is one of the factors leading to abnormal heart rate variability. Such ECG abnormalities are associated with premature death so identifying potential risk factors is of the utmost importance.|
|JM1120||COVID National Cohorts Study||This project aims to examine the wider social, economic and health effects of the covid-19 pandemic response in the UK.|
|JSAW1120||Structural connectomics in Insight 46||This project aims to apply new imaging techniques to explore the white matter tracts of the participants in the Insight 46 cohort. White matter tracts are the connecting parts of the brain, linking the nerves cells to each other. These imaging techniques allow greater ability to explore the complex arrangement of these white matter tracts in a way not possible with prevailing approaches. This might help detect early breakdown in global or specific brain networks in Insight 46 participants who develop Alzheimer’s Disease, as well as uncover mechanisms of this decline. Regional changes in these networks can be mapped to specific genes that are expressed in these regions using the Allen Brain Atlas.|
|KS1220||Are altered growth trajectories associated with hip shape and OA?||Throughout life, our joints change continuously and adapt to the varying and often huge loads placed upon them as we walk, run, lift and jump. However, as we get older our joints undergo structural changes that may lead to the aching and stiffness that is often associated with ageing.
Osteoarthritis is the most important ageing-related disease affecting almost 9 million people in the UK. It is estimated that more than 33% of the UK population aged over 45 have sought treatment for osteoarthritis. For this reason, osteoarthritis is a major financial, social and healthcare burden.
|TP1120||The genetics of telomere attrition rate||The UK Office for National Statistics estimates that in 50 years’ time, there will be an additional 8.6 million people aged 65 years and over. Longer lifespan has clear benefits, but when it is associated with an increased proportion of the population suffering from age-related diseases, it can pose a burden to individual sufferers and to the economy.
Telomeres are ‘DNA tails’ at the end of chromosomes that shorten as we age, in accordance with the number of cell divisions. Premature telomere shortening is hypothesized to predispose to age-related diseases, like coronary artery disease. Within this project we will be determining which genetic factors affect the rate of telomere shortening by studying ~1000 individuals within the MRC National Survey of Health Development Study. We will then combine results from this study with those generated from an additional 21,000 individuals.
|DB1120||How do ‘effects’ differ across time? Understanding health inequalities by triangulating across multiple data sources and empirical strategies||Socioeconomic circumstances such as our education or income are thought to have important effects on our health. This project seeks to generate this evidence. First, it will bring together multiple datasets to investigate how these health inequalities have changed across time in the UK. In the past, researchers have tended to use these studies separately – analysing them together is a very powerful way of understanding how inequalities have changed across time.
It will then seek to understand whether these correlations reflect causal relationships. While it is possible that social circumstances are correlated with health, there are other explanations for such correlations. In addition, this project will investigate how the causal role of two other factors may have changed across time. Taken together, this project seeks to advance scientific understanding and provide evidence which can ultimately be used to inform national policies related to public health inequalities in the UK.
|GCMK1220||Abnormal control of basic nervous system functions required to maintain a constant blood pressure and heart rate, develops with advancing age and complicates a number of diseases. The normal variability of one’s resting heart rate can be lost with advancing age. We hypothesize that disease in the carotid artery wall related to ageing is one of the factors leading to abnormal heart rate variability. Such ECG abnormalities are associated with premature death so identifying potential risk factors is of the utmost importance.|
|AK1220||Developing blood based biomarkers to detect preclinical Alzheimer’s disease and predict progression||This project is part of the funding for the Insight 46 study; involving the investigation of blood and cerebrospinal fluid biomarkers of Alzheimer’s disease both cross sectionally and longitudinally in this cohort in relation to cross sectional and longitudinal amyloid PET, brain volumes, white matter hyperintensity burden, diffusion tensor imaging metrics, and cognition.|
|JBYX1220||Association between DNA methylation, diet and cardiovascular disease risk||DNA methylation is the most common and stable epigenetic mark, which has been shown to be associated with different diets and the development of cardiovascular disease. This project aims to further explore the epigenome-wide association between dietary intakes, risk of cardiovascular disease and DNA methylation in UK cohorts, in order to expand the understanding of how DNA methylation changes from diet may be related to cardiovascular disease development.|
|JB0121||Radiomics of WMH||This project will investigate whether other features of white matter lesions besides volumes, extracted directly from the brain scans, are related to one of the proteins that gets deposited in the brain in Alzheimer’s disease.|
|SR0121||Causal pathways linking diet and cardiometabolic diseases||Cardiovascular diseases (CVD), including coronary heart diseases and stroke, cause millions of deaths every year across the world. Improvements in identification and treatment of well-established risk factors for CVD such as hypertension, diabetes, dyslipidemias, obesity and smoking have reduced CVD occurrence and deaths, but still fail to prevent CVD in many people. Risk factors for CVD, such as hypertension, diabetes, dyslipidemias, obesity and smoking, are interconnected, meaning that one of
them (or treatment for it) can cause conditions that magnify or lead to others. For instance, obesity is associated with increased blood pressure, insulin resistance and bad cholesterol levels, all of which contribute to CVD risk.
|TB0121||DNA methylation early-warning biomarkers for head and neck squamous cell carcinoma||Cancer survival rates are dramatically increased when the disease is caught early. This motivates us to search for biomarkers that can give early warning of cancer. Fanconi Anemia (FA) is a rare genetic disorder that leads to cancer in 75% of sufferers by the age of 45, and so there is a specific need for early-warning cancer biomarkers for this population. FA sufferers are particularly likely to be diagnosed with head and neck cancer. We will study large public data-repositories of healthy and cancerous samples from studies of head and neck cancer, that include carriers of genetic mutations present in FA sufferers. This will enable us to identify potential biomarkers of genomic changes present before the onset of disease. The data from the NSHD repository will be vital for validating these findings in data from the wider population, in non-invasive samples.|
|GCCT0121||The association between the frailty index and telomere length-a longitudinal study||As people age, they accumulate more health deficits which are counted by a frailty index (FI) . However, evidence has emerged that people do not age at the same rate. The chronological age (i.e., how old a person is) and the biological age (i.e., how old a person appears to be) are not regarded as different concepts. Humans are the product of the genetical material known as DNA. The ends of the DNA are known as telomeres. In older age, the frailty index has been associated with the length of telomeres. In this study, we want to look at this association throughout life-course to provide insight into ageing patterns.|
|WC0121||Rates of cerebral beta-amyloid accumulation in preclinical AD||Alzheimer’s disease (AD) is the most common cause of dementia and there is currently no disease modifying treatment available. The pathological characteristics of AD include the build-up of cerebral amyloid-beta plaques and tau neurofibrillary tangles followed by neurodegeneration and cognitive decline. Beta-amyloid plaques can be detected in vivo using positron emission tomography (PET) decades before symptom onset.
The standard uptake value ratio (SUVR) is a common semi-quantitative method for analysing static PET images. Differences in SUVR processing have a large effect on the outcome and there is no consensus on the optimal methodology. Measurement of the rate of amyloid change requires additional considerations about the longitudinal stability of the processing pipeline. More accurate and precise measurement of amyloid accumulation would improve our ability to detect subtle early changes in beta-amyloid, track progression and reduce sample sizes needed for future prevention trials. Additionally, standardising results using the Centiloid scale would improve our ability to interpret results from different methodologies and aid our understanding of preclinical AD.
This PhD will explore the effect of processing methods on beta-amyloid positivity and accumulation rates using longitudinal 18F-florbetapir data, all acquired on a combined PET-MR scanner, from participants in Insight 46, a large community sample of individuals born in the same week in 1946.
|AE0121||Genome-wide association study of age at peak height velocity and mendelian randomisation study of causal effects on adult height and body composition||The aim of this project is to perform a genome-wide association study to identify genetic variants that are associated with the timing of puberty, and to use these findings in a mendelian randomisation analysis to provide evidence on the causal effects of puberty timing on adult height and body composition (body mass index, fat mass, and muscle mass).|
|DC0121||Assessing the variability of SUVr due to changes in perfusion and its impact on longitudinal studies||Amyloid plaques in the brain are one of the earliest signs of Alzheimer’s disease, and they are present many years before memory problems begin to occur. These plaques can be detected in images acquired using Positron Emission Tomography (PET). This project will investigate how to best measure the change in the amyloid plaques over time and how to account for changes in blood flow to the brain, which can affect the results from these images.|
|JM0121||Global PWV Collaboration||This is project will be part of a comprehensive high-quality meta-analysis. Results based on the collaboration’s data will be published on behalf of the Global PWV Collaboration Group, which includes all collaborators. The aim is for for publication of the meta-analysis in one of the major clinical journals.|
|RM0221||Social Isolation, Loneliness and Wellbeing across the Life Course and between Five British Birth Cohorts||We know that tackling social isolation and loneliness is important for wellbeing, and there has been increased policy interest in recent years. However, previous research is predominantly cross-sectional and focused on later life stages. Using large scale, population based, and representative data, this project aims to develop a conceptual and empirical understanding of social isolation across the life course. We will apply our conceptualisation of social isolation to five British birth cohort studies, identifying all relevant items across cohorts and sweeps. Items that are conceptually similar will be grouped to create comparable measures of social isolation across the life course and cohorts. These harmonised variables will be made available to researchers, laying the groundwork for future social isolation research with the British cohorts.
Life course trajectories of social isolation and cross-generational differences in trends will be explored, offering insights into at risk groups to inform prevention efforts. The association between social isolation and wellbeing will also be documented with a life course and cross-generational perspective.
Social isolation and loneliness are related but independent constructs. We will therefore also investigate the relative association of social isolation and loneliness on wellbeing at different ages across the life course.
|VEP0121||DPUK/DRI Genetic Consortium||Dementia is a global threat that requires a coordinated, global response. Strengthening efforts by
research collaboration and transdisciplinary partnership is the way forward to meet this challenge. UKDRI (Dementia Research Institute) is a national group of experts in different, complementary fields. DPUK (Dementia Platforms UK) is a national data portal which is designed to enable researchers to have rapid online access to unprecedented amounts of cohort data including genetics, imaging and medical records of over 3 million participants. The present project will focus on cohorts with genetic data to address the genetic variability of dementia. In particular, we will link genetic information with clinical presentation at different stages of Alzheimer’s disease (AD) and integrate additional factors, such as geographical and ethnic diversity, in order to fully capture AD heterogeneity. In that context, establishing a technological platform and best practices for national collaboration between clinicians, geneticists, biostatisticians, data scientists and wet lab scientists will be a huge step forward. As such, DRI is a living laboratory, developing and testing a novel way of addressing treatment and care for AD. By designing an innovative solution in a strategic national partnership between UKDRI and DPUK, our ambition is to initiate a change that will stimulate further public and private investment and pave the way to a precision medicine approach of AD
|AKRH0121||Childhood Adversity and multimorbidity across the lifecourse (this project is an extension of a previous application titled: Clustering and trajectories of multimorbidity over the life course’)||Multimorbidity is the existence of two or more chronic conditions in an individual. It is increasing in prevalence, partly due to an ageing population, and increasingly common in both high- and low-income countries. It appears to disproportionately affect individuals from socioeconomically disadvantaged backgrounds. Our knowledge of multimorbidity including its epidemiology, causal risk factors and trends over time is limited and mainly derives from cross-sectional data. We aim to use the National Survey of Health and Development to: 1. We will develop appropriate measures of childhood adversity in the NSHD 2. Examine associations between childhood adversity and multimorbidity development across the lifecourse 3. Examine whether the above associations differ by socioeconomic position and sex|
|MA0321||Modelling brain and cognitive age to study cognitive reserve and resilience||Ageing is associated with changes in the brain’s structure as well as in specific cognitive abilities, such as memory. Yet, neuroimaging studies suggest that there is substantial variability in the extent to which these age-related changes emerge between individuals. The application of machine learning to MRI data offers an avenue to capture this variability in the population, by computing each individual’s unique ‘brain age’. The difference between an individual’s chronological age and brain age is then used to quantify how much ‘older’ or ‘younger’ their brain is, relative to what is expected for their age. While ‘older-looking’ brains have been linked to an increased risk of dementia and mortality, certain health behaviours (abstaining from smoking, physical activity, lower alcohol intake) may play a role in maintaining the brain’s health. Recently, we have demonstrated that machine learning can also be applied to cognitive test scores in order estimate a person’s ‘cognitive age’. As brain age and cognitive age are potentially sensitive to mechanisms that support cognitive function in old age (i.e., brain maintenance and cognitive reserve), the present study aims to validate these markers within the Insight 46 cohort. Specifically, we aim to evaluate how changes in brain age and cognitive age over time relate to education, premorbid IQ and lifestyle measures. Overall, the findings of this study may highlight two complementary markers that may be of interest to future studies of ageing.|
|SG0221||The dynamic relationship between cardiovascular predictors of mental health and autonomic neuroscience||How we feel is influenced by the dynamic integration of brain and body. Autonomic variations, such as resting heart rate and heart rate variability, are often found in altered mood states and in conditions such as depression and anxiety. Individual differences, such neuroticism and propensity to ruminate, as well as early exposure to adversity, are also associated with depressive and anxiety symptoms. Autonomic areas in the brain are associated with depressive and anxious symptomatology, however, limited work integrates cardiovascular measures, neural autonomic centres and mental health, especially from a longitudinal perspective. The aim of this project is to analyse the dynamic relationships between autonomic variables, individual differences, and depression and anxiety symptoms across the lifespan. How brain dynamics in later years are predicted by measures obtained across the life course, with a particular focus on the heart, individual differences and depression/anxiety, will also be examined.|
|DMSB0321||The relationship between walking speed and cognitive impairment: A multi-cohort study utilising Dementia Platforms UK infrastructure||Dementia is an enormous public health issue but there is still no effective drug treatment. Preventing even a small number of cases will reduce both many people’s suffering and its huge cost to society. Dementia is a condition with a collection of symptoms including memory loss, thinking difficulties, problems with language and behavioural changes. Most experts agree that the origins of dementia lie many years, even decades, before people notice these overt symptoms thus making early detection of dementia important. However, a reduction in walking speed is often detectable in these early years. Measuring walking speed can help predict who will go on to develop dementia years later.|
|SBMB0321||Sensory deficits and longitudinal cognitive and dementia outcomes||Sensory and cognitive deficits have been found to be consistently associated across multiple studies. Sensory deficits may precede cognitive decline and the onset of dementia symptoms by a number of years. These deficits are not isolated to vision and hearing alone, although both of these are associated with longitudinal cognitive decline and dementia outcomes. It is of utmost importance that AD and dementia are diagnosed early to facilitate pharmaceutical and behavioural interventions, to improve quality-of-life and disease progression outcomes. If sensory deficits can be identified as early predictors of this decline, interventions may be implemented. This project is of great public benefit/interest as early detection of sensory disturbances (i.e., visual and auditory tests, and behavioural interventions) will have a positive impact on disease progression and quality-of-life.|
|ULSB0221||Sleep as a risk factor for dementia: collecting evidence from multiple cohort studies||Sleep is crucially involved in brain development and ageing. Impaired sleep may precede dementia but the precise relationships between sleep and other risk factors of dementia remain to be elucidated. This study will collect information on sleep from different cohort studies to enable detailed investigations of sleep’s role in ageing and dementia. The identification of early risk factors may reduce the incidence of dementia in the general population through appropriate prevention, thus is of significant public interest.|
|NFSJ0421||the relationship between markers of diabetes during life and later-life white matter outcomes in the brain||This is an opportunity to explore the relationship between two of the biggest conditions that affect society. Previous studies have shown that diabetes is associated with poorer problem solving and decision making skills. There is therefore important interest in looking at how diabetes affects the brain. There appears to be a precedent that suggests that white matter, one of the two major type of tissues in the brain, is more at risk of being affected. This study will see whether different features of diabetes (e.g. hyperglycemia) is associated with subtle damage in white matter tissue.|
|VMLB0521||Analysis of dietary and lifestyle factors predicting vascular risk||This analysis will compare different aspects of diet and exercise, compared to blood tests and imaging measures of blood vessel risk factors for diseases such as cardiovascular disease.|
|AMW0221||Multimodal MRI networks||This project combines differnt MRI modalities to reconstruct multimodal brain networks and study their alteration in normal and pathological aging.|
|IB0621||Air pollution and mental health and cognition over the life course||Air pollution is a key threat to human health. The World Health Organization (WHO) recently estimated that air pollution causes 482,000 premature deaths per year within the WHO European Region. Previous studies have concentrated on heart and lung disease, but recent research has demonstrated that air pollution, particularly emissions from traffic may also reach the brain and potentially affect mental health and wellbeing. Individuals from low income backgrounds and residentsof more socially disadvantaged areas tend to be exposed to higher levels of air pollution and may be more vulnerable to effects of air pollution on mental health. The aim of our project is to investigate the link between air pollution and mental health. We will address four key questions: What are the effects of air pollution on mental health from adult life to later life? Do these effects depend on individual’s socioeconomic characteristics or neighbourhood’s quality? What are the pathways between air pollution and mental health. To answer these questions, we use existing linkage of air pollution metrics with mental health Heatlh with the NHSD. We will then analyse the links between air pollution exposure at different periods of life and mental health using cutting edge statistical methods. New and
ground-breaking aspects of our work are the use of over three decades of air pollution and mental health data to explore links between air pollution and mental health from midlife to 60+ years of age, to identify potential critical periods in life where these effects are more pronounced and to elucidate potential pathways via individual’s socioeconomic status and neighbourhood’s quality Establishing the true associations between air pollution with mental health outcomes, with cutting-edge modelling approaches to estimate the exposures of an individual across their life course has the potential to inform our understanding of the contribution of environmental factors to mental health from early life to adulthood and to identify particular populations at risk. This work with provide information for the development of policy recommendations for appropriate
interventions and will inform policy makers with the ultimate goal of reducing the substantial costs to the NHS arising from poor mental health.
|NM0621||Repetitive negative thinking across the life course and its association with cognition and brain health||Repetitive negative thinking (RNT) is a cognitive process that encompasses worry (i.e., future-directed negative thoughts) and rumination (i.e., past-directed negative thoughts). Recent evidence suggests that higher levels of RNT are associated with an increased risk of Alzheimer’s disease. This project aims to further our understanding of the association between RNT and Alzheimer’s disease by (i) exploring the association between RNT and cognition and brain health and (ii) investigating whether late-life or persistent RNT over the life course has a stronger relationship with cognition and brain health.|
|LHG0621||Trends in the impact of childhood visual function on health and social outcomes in adult life across 3 UK birth cohorts||The adverse impact of visual impairment on health and social outcomes are well known, with a gradient in the magnitude of the association reported across the spectrum from mild visual impairment affecting only one eye through to severe bilateral impairment. Cross-cohort comparisons allow investigation of these associations longitudinally through the life course, over different time periods, to help understand the pathways to such inequalities. We will extend our previous investigation of visual function in childhood and early-life social position in the 1946, 1958, and 1970 British birth cohorts, and we will now investigate whether the temporal decline in visual function in childhood we previously observed leads to a widening of health and social inequalities in adult life in the same individuals. The findings will be informative for ophthalmic health services and public health policies tackling inequalities.|
|DMA0521||Inequalities in mental health trajectories before and during the COVID pandemic||The study of the trajectories of mental health in the population is crucial to monitor and understand the differential impact of relevant events such as the COVID pandemic in different population groups. This project aims to i) analyse the potential heterogeneity in mental health trajectories in the UK population by birth sex, childhood socioeconomic position, and adult socioeconomic status; ii) to study the impact of the COVID pandemic in those trajectories; iii) to explore differential effects of the pandemic on the mental health of different relevant demographic and socioeconomic groups. This project will provide evidence on potential pre-existing inequalities in mental health in the population, and on how these may have changed during the COVID pandemic.|
|KSZ0421||Life course trajectories of height and later health outcomes in the 1946 UK birth cohort||Human body height is known to be associated with various consequences. This begins with the influence of the parents’ height and living conditions on the child in utero and then at birth, and continues through all stages of body growth during the first ca. 20 years of life, when deviations from the normal growth pattern are associated with negative consequences. Adult height also has well established consequences for health, for example in terms of morbidity and mortality, but also in terms of income, happiness, occupational success, or success in the partnership market. Other studies have also shown that height loss with age is associated with negative health consequences. In addition to genetics, socioeconomic status (SES) plays an important role for body size throughout life, as do lifestyle factors (diet, exercise, etc.). So far, studies have dealt separately with either growth, adult height, or height loss in old age. Few attempts have been made to describe individual patterns of change and trajectories in height over a lifetime, and to look at the influence of SES at different ages and the associations of these cross-life height patterns with health outcomes. This is mainly due to the fact that data sets that would allow such questions to be asked are very rare. One of the few possibilities is the The Medical Research Council (MRC) National Survey of Health and Development (NSHD), which is the oldest and longest running of the British birth cohort studies; it is a nationally representative sample (N=5,362) of men and women born in England, Scotland or Wales in March 1946. Currently, there is information on the height of the parents and then height measurements of the study participants at the ages of 0, 2, 4, 6, 7, 11, 15, 26, 36, 43, 53 and 63 years. In addition, the health status, especially in the second half of life, the SES from birth, and especially questions about nutrition were extensively documented. In addition, there is linked data to mortality, emigration, cancer registrations and Hospital Episodes Statistics (HES) data.|
|JBK0721||Investigating the association between vitamin D levels and cognition in later life in Insight 46, a sub-study of the MRC National Survey of Health and Development||Vitamin D is a widely taken supplement with evidence of benefits for bone health and reducing the risk of fractures following falls. Most of our requirement for Vitamin D is obtained through sun exposure and deficiency is common in the UK. As a result, the National Institute of Health and Care Excellence (NICE) recommends vitamin D supplementation for all adults in the UK. Some research evidence has suggested that low vitamin D levels are also associated with an increased risk of dementia. In my study we aim to examine whether there is an association between vitamin D levels, measured at age 63 and performance on tests of memory and thinking in later life, and whether the use of vitamin D supplements has an effect on this.|
|VG0821||Type-2 diabetes and brain health in a nationwide birth cohort: the mediating role of hypertension||This study will use NSHD data from early mid-life to later life with the aim of understanding whether diabetes causes worse brain and cognitive health, via its mediating effects on high blood pressure.|
|GCCT0921||The phenotypic associations of ApoE||Apolipoprotein E has been shown to increase the LDL (“bad cholesterol) levels. This can affect both large vessels (leading to strokes and heart attacks) and small vessels (such the ones in kidneys). In addition, it has also been associated with progressive brain disorders such as dementia. However, the full extent of the implications for the heart and the brain of having an Apolipoprotein E mutation is yet to be elucidated. A better understanding of the implications of having a faulty Apoliprotein E gene, would pave the way to develop novel therapies and provide better support to the individuals who have this mutation.|
|MO0921||Longitudinal study on heart rate and physical activity||This project will study the interaction between heart rate and physical activity and its relation to clinical and subclinical outcome.|
|YL1021||Pathways from early adversity to mental ageing: A life course approach||Depression and cognitive impairment are intertwined across the life course and are major causes of disability in later life. This project will investigate how mental ageing (emotional and cognitive) is associated with adversity across the life course. Exposure to childhood adversity has been consistently associated with psychological functioning such as the onset of psychopathology (e.g. Copeland et al., 2018; Hughes et al., 2017; McKay et al., 2021) and poorer cognitive development (e.g. Platt et al., 2018; Richards Wadsworth, 2004). However, there is relatively little research on how mental ageing is affected by the continuity of these adverse events into early, middle, and later adulthood. Early adversity may also increase risk of exposure to further adversity, leading to a cascade of risks cumulating in disease in older age (e.g. O’Connor, 2016; Power et al., 2013); and adverse events may layer on top of older ones even if non-associated. Adopting this life course approach allows the investigation of processes underlying the association between adversity and adult function in later life.|
|AJ1021||The role of telomere shortening in the relationship between accumulation of affective symptoms and later life cognition||Depression and anxiety earlier in life are linked to worse memory and thinking skills later on in life. Some people with depression and anxiety are also more likely to develop dementia when they are older. At the moment we are not sure how these things are linked. Recent research has shown that the two may be linked via biological mechanisms. One of these biological mechanisms that scientists are investigating is telomeres or telomere shortening.
Telomeres are protein structures found inside our cells at the ends of DNA strands. The DNA strands are wound tightly together, and the telomeres are a bit like the protective tips found at the end of shoelaces that stop the shoelace from unrevealing and becoming unusable. Telomeres act in the same way for our DNA. Telomeres are small sections of DNA on the ends of the DNA strands making sure the DNA does not unravel and stop working. As the cell ages these telomere sections get shorter and shorter until finally the cell stops working and dies. Telomere length, specifically shorter telomeres is found to be linked to depression, anxiety as well as dementia. Because all of these things are linked the question we are seeking to answer in this piece of research is: does depression and anxiety earlier in life have an impact on telomere length or how quickly telomeres are becoming shorter which in turn impacts on how likely a person is to get dementia? We aim to test this theory in the 1946 birth cohort data which has data on telomere length, depression and anxiety as well as memory and thinking skills later on in life.
|DB1021||Investigating mental health inequalities across time and place, and the interplay between genes and environment||The overarching aim of this study is to better understand differences in mental health across context and time through the lens of social and genetic determinants of health.|
|DW1021||Investigating the role of common pathogens in heart, brain and ageing health||Individuals in the UK are exposed to many germs that cause infections. These are often benign or have only minor health consequences in childhood and early adulthood, but may play a more insidious role in ill health as people age and their immune systems weaken. In particular, researchers are concerned that common viruses and bacteria may cause harm to the heart and brain tissues over long periods of time through a variety of mechanisms. However, these links are not concrete, and require further investigation. In this study, we will use recently developed blood tests to identify whether members of the NHSD had been exposed to at least 13 common infectious agents by their early 60s, and use this information to investigate whether these infections might (individually or in combination) be having detrimental effects on the heart, brain and overall health of individuals as they age.|
|ELA1021||Does social isolation/loneliness mediate the effect of educational attainment on indicators of Alzheimer’s disease in the 1946 NSHD birth cohort?||In our study, we aim to examine if the effects of educational attainment on indicators of Alzheimer’s disease (e.g. cognitive decline) are mediated through differences in isolation or loneliness in 1946 birth cohort. Firstly, we will investigate this question in the full 1946 sample (N~5,000), using change in cognitive ability from age 53 to 60 years as the outcome or cognitive ability at a single timepoint. Furthermore, to examine markers that are more specific to Alzheimer’s disease and Alzheimer’s-related pathology, we will use measures such as the Preclinical Alzheimer’s Cognitive Composite, plasma amyloid and tau levels, and hippocampal volume at age 70 years in the smaller NSHD sub-sample, Insight 46 (age 70 years, N~500). Examining pathological outcomes such as plasma amyloid levels and hippocampal volume may also provide insight into the mechanisms by through which social isolation and loneliness influence differences in Alzheimer’s disease-related outcomes. Results from our study may provide additional modifiable factors as targets for the prevention of cognitive decline and Alzheimer’s disease.|
|IS1021||A study of elite mobility in Britain||This project investigates the lack of social mobility into Britain’s elites. The study will be ground-breaking in several ways: properly defining who our elites are; establishing their social origins more reliably than in existing studies; tracing links between different elites; determining whether British elites are more closed than elites in other countries; and investigating the actual mechanisms through which British elites reproduce themselves. We aim to offer insights into how elites may be opened up to people from a broader range of backgrounds.|
|JD0921||CONVALESCENCE study: long Covid longitudinal qualitative project||This project is part of the CONVALESCENCE study, a large NIHR-UKRI funded project employing a mixed method approach to gain interdisciplinary understandings of long Covid in the UK. In our longitudinal qualitative project, we will conduct in-depth interviews with long Covid sufferers identified from five UCL based population cohort studies at three points between 2021 and 2023. In so doing, we will investigate long-Covid sufferers’ experiences of and perspectives on the condition; the impacts that long-Covid has had on their lives and sense of self; and their perspectives on the treatment and support they have or have not received from the healthcare system. More particularly, through a longitudinal lens, our project aims to draw on the rich narratives from long Covid sufferers to understand the lived experience of long Covid as a chronic and often fluctuating experience over time, further seeking to improve practice and policy for more adequately and continuously support long Covid sufferers.|
|MS1121||Association of early-life air pollution exposure with cardiovascular and mortality outcomes across the lifecourse||Association of early-life air pollution exposure with cardiovascular and mortality outcomes across the lifecourse|
|NO1121||Early Detection of Alzheimer’s Disease Subtypes||Alzheimer’s disease (AD) is a global health burden. There are currently no treatments that prevent AD or modify the course of the disease. Recent work has identified several subtypes of Alzheimer’s disease that become apparent once clinical symptoms appear. These subtypes can guide improved treatment and care decisions. Here we aim to predict which subtype of Alzheimer’s disease an individual will develop late in life from earlier life risk factors. This is important for developing and trialling new treatments because Alzheimer’s disease pathology starts decades before clinical symptoms appear.
We will develop and apply novel statistical methods to achieve this, including combining results from multiple existing medical datasets, which are publicly available or are maintained by our partners. Data sets include anonymised demographics, genetics, clinical assessments of function and cognition, features from biological samples (measures from the fluid surrounding the brain), and features extracted from medical images including magnetic resonance imaging (MRI) and positron emission tomography (PET) data.
The statistical models we employ were designed to detect subgroups of patients that follow different disease trajectories and link those to existing co-morbidities, genetics or life-style choices. We will explore various technical refinements to existing methods (many developed by us and project partners) to improve their predictive performance.
Using this methodology, we will investigate the following main questions:
|SDZA1121||Heart rate variability to predict neuropsychological dysfunction in older age||An investigation into whether a reduction in heart rate variability is an early marker of neuropsychological dysfunction in older age. Statistical analysis of mental health and cognitive trajectories up to the time of the HRV assessment period and the decade subsequent to the assessment, will examine whether HRV-components at 60-64 years can predict future neuropsychological trajectories after adjustment for demographic characteristics and traditional cardio/cerebrovascular risk factors.|
|AK1121||Risk factors for Covid-19 infection and long Covid||This study aims to find out why some people are more likely to get a Covid-19 infection than others, and why after a Covid-19 infection some are suffering from long-lasting symptoms (long COVID). We will use pre-pandemic data to identify factors that may be associated , such as diabetes, blood pressure and blood measures. The Covid-19 questionnaires will allow us to identify those with a Covid-19 infection or long Covid. The findings will be combined with those from other UK studies to clarify if they are similar for example across different ages.|
|GP1221||Novel applications of genetic and observational methods to lifecourse epidemiology||Often diseases diagnosed in adulthood have physiological antecedents that begin in early life. Gaining a better understanding of how the timing of exposures at different stages in the lifecourse influence health outcomes is key to identifying when the effects of risk factors driving health inequalities may be reversed through lifestyle or environmental modifications. A lifecourse approach crucially investigates the contribution of early and later life exposures together, to identify risk and protective mechanisms across the lifespan. Separating the effects of risk factors at different stages of the lifecourse is challenging, particularly due to the influence of confounding factors; variables that influences both the exposure and outcome of interest, causing a spurious association.
It has previously been shown that genetic associations may arise from the direct effects of the same inherited genetic variants at different stages of the lifecourse. Mendelian randomisation (MR) exploits the random assortment of genetic variants, independent of other traits, to enable analyses that largely mitigate against distortions resulting from confounding and reverse causality, which afflict epidemiological observational research. However, there are only a handful of studies that have incorporate a lifecourse approach using MR. For example, a recent study successfully used genetic variation to separate the effects of early and late life body size on several diseases and metabolites. The instruments used in this investigation have since been validated and applied to investigate mechanistic links and other disease endpoints. Furthermore, studies have utilised non-transmitted maternal alleles as a valid genetic instrument for maternal phenotypic effects on foetal and offspring outcomes whilst others have highlighted genetic contributions to lifecourse associations between birthweight and late-onset diseases using a multi-ancestry approach.
Contributing to the development of this field will help to elucidate modifiable pathways at high-risk periods in the lifecourse to decipher potential intervention targets as well as identify important translatable messages that have the capacity to impact evidence-driven social policy. The more we understand about causal risk factors across the lifecourse, the more effective our interventions will be.
|TP1221||Head injury and hearing loss – predictors of longitudinal change in Insight 46||Preventing dementia is one of the most important health challenges of the 21st century. One potential approach of preventing dementia that has been proposed is to aim to improve brain health by addressing a number of factors that are felt to increase risk of subsequent dementia. Two examples of such factors include hearing loss and head injury. However, the precise nature of the relationship between hearing loss/head injury and brain health and how this could increase the chances of someone developing dementia is unclear. The aim of this project would be to investigate whether hearing ability (measured using a series of tests of hearing), or head injury, lead to changes in detailed measurements of brain structure (using advanced techniques that analyse brain scans) or changes in performance on detailed tests of memory and thinking in older adults.
This research would aim to improve understanding of how hearing loss and head injury may lead to dementia, with the hope that his will guide further research and inform strategies for preventing dementia in the future.
|MR1021||Associations between lifelong exposure to anticholinergic medication, later life cognition and amyloid burden.||The project will look into lifelong exposure to anticholinergic medications, and their associations with later life cognitive outcomes. A key outcome studied will be the amyloid burden seen on neuroimaging from the Insight46 substudy; an important proponent of Alzheimer’s dementia risk.|
|JZ1121||Individual differences in information processing speed||Information processing speed (IPS) has been related to intelligence, various cognitive abilities, education, and lifestyle. It is measured through reaction time tasks or the accuracy of a simple task during a limited period of time. Previous studies with the Lothian Birth Cohort measuring childhood intelligence and IPS, as well as other cognitive functions throughout the aging process (70-82) gave insights into the development of IPS decrease and its association to general cognitive abilities. Structural neuroimaging studies also showed the association of white matter microstructure with IPS and heritability studies point to genetic factors that might influence IPS. Thus, the aim of our project is to model individual differences in IPS in the MRC NSHD cohort considering demographic factors, education, cognitive abilities, and neuroimaging measurements, as well as studying the aging process of IPS throughout the adult lifetime.|
|RS1221||Longitudinal trajectories of self-reported subjective cognitive decline in relation to objective cognitive performance, in a population-based cohort||Subjective cognitive decline (SCD) is the self-reported worsening of cognitive abilities despite seemingly performing normally on objective cognitive tests. Evidence suggests that self-reported concerns are one of the earliest symptoms of Alzheimer’s Disease (AD) and therefore may represent subtle cognitive decline before impairment can be detected on standard cognitive tests. However, this exact nature of the relationship between self-report decline and performance on objective cognitive tests is unclear. This project aims to understanding the relationship between SCD and AD by exploring the longitudinal association between SCD, cognition and brain health.|
|FP0122||Metabolomics to identify the susceptibility to COVID-19 and long COVID||The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide increase in hospitalisations and deaths since it emerged in December 2019. The effects of COVID-19 depend very much on each patient and range from asymptomatic to fatal cases. The duration of symptoms is also very heterogeneous, lasting between a few days for some patients and several weeks for others that develop the so-called ‘long COVID’. Older age is a well-known risk factor for both severe and long COVID. This has been associated with a debilitated immune response caused by ageing processes. Pre-existing diseases such as hypertension, diabetes, cardiovascular disease, or cancer also increase the risk of severe infection in patients with COVID-19. However, severe COVID-19 has also been observed for many seemingly healthy middle-aged individuals. Understanding of the risk factors for severe COVID-19 remains limited and the reasons why susceptibility to the virus varies so widely in the population are poorly understood. More research is needed to unveil the biological mechanisms of severity so that highly susceptible individuals and pathways to novel treatments can be identified.
Recent studies have shown that the molecules in biofluids such as blood, urine or faeces are altered in people with cardiovascular disease, diabetes, or chronic inflammation. These conditions represent risk factors for severe COVID-19 and we hypothesise that biofluid molecules can be used as metabolic biomarkers to predict whether a patient infected by SARS-CoV-2 is likely to be seriously affected.
The central idea of the proposed research is to use metabolic biomarkers to predict the severity of COVID-19 and the likelihood of long COVID for individuals that have not necessarily been diagnosis with a pre-existing health condition. To this end, we will use pre-pandemic data from several cohort studies which, in addition to basic information on age, sex, ethnicity, etc, contain hundreds of metabolic biomarkers for thousands of individuals. To understand the link between these characteristics and the impact of COVID-19, we will use symptoms data for those individuals in the cohort studies that had COVID-19. The data will be analysed with statistical methods to identify associations between the characteristics of individuals before the pandemic and the severity of the disease. This analysis will be complemented with computer programs developed to predict if the infection of an individual will have serious effects based on his/her characteristics before the pandemic. Machine learning techniques will be used to train computer programs to automatically recognise metabolic features that represent a risk for severe COVID-19.
The project can be beneficial both in terms of basic science and applications. Indeed, the proposed research will enhance our understanding of how metabolic biomarkers may explain the susceptibility to severe COVID-19. From an applied viewpoint, using the information encoded by numerous metabolic biomarkers to train machine learning models can improve our ability to identify individuals for whom COVID-19 may have serious consequences.
|MK0222||BMI trajectories chronic diseases||In this project, I will study BMI trajectories over the life course. First, I will investigate within individual BMI change in different sociodemographic groups. Second, I will focus on early determinants of adult obesity in childhood and adolescence. Third, I will estimate the direct effects of physical activity and diet on chronic diseases (e.g. cardiovascular disease, cancer etc), as well as the indirect through body mass index. Forth, I aim to use the trial emulation framework to study whether hypothetical BMI change interventions have impact on different chronic diseases.|
|TN1221||Life course predictors of distinct grip strength trajectories from mid-life onwards||This project aims to: i) identify whether distinct grip strength patterns exist from mid-life onwards and if so; ii) identify earlier life predictors of these patterns.|
|PA0122||A life-course study of cognitive reserve and cognitive state in older age||The extent of neuropathology required to cause cognitive impairment consistent with dementia varies among individuals (Stern 2013). Cognitive reserve theory postulates that the knowledge and experiences individuals accumulate through their lives provide an increased resilience against cognitive ageing or cognitive disorders (Stern et al., 2018). It is hypothesised that cognitive reserve originates from the interaction of various markers through the lifespan, which accumulates over time and modifies the risk of cognitive impairment (Richards Deary, 2005). The aim of this study is to create a life-course model to evaluate how dynamic changes in cognitive reserve markers relate to the cognitive state during older age.|
|PA0222||A life-course study of cognitive reserve and cognitive state in older age||The extent of neuropathology required to cause cognitive impairment consistent with dementia varies among individuals (Stern 2013). Cognitive reserve theory postulates that the knowledge and experiences individuals accumulate through their lives provide an increased resilience against cognitive ageing or cognitive disorders (Stern et al., 2018). It is hypothesised that cognitive reserve originates from the interaction of various markers through the lifespan, which accumulates over time and modifies the risk of cognitive impairment (Richards Deary, 2005). The aim of this study is to create a life-course model to evaluate how dynamic changes in cognitive reserve markers relate to the cognitive state during older age.|
|AK0222||Physiological Resilience: Cortisol||Cortisol is a hormone that is secreted in response to stress and has a pattern throughout the day. The regulation of cortisol is affected in old age and can be considered a sign of biological aging. In this project we will investigate how cortisol regulation relates to heart health, cardiovascular diseases and death. We will further examine other systems of biological ageing and their interplay.|
|AK1221||COVID-19 serology||The immune system uses proteins called antibodies to identify and neutralise foreign objects such as viruses. Vaccination can induce the production of such antibodies without having had to have been infected by a virus. We will investigate whether who has lower antibody levels and whether there are certain factors such as health associated with this. The findings will be combined with those from other UK studies to clarify if they are similar for example across different ages.|
|AK0322||Developing blood based biomarkers to detect preclinical Alzheimer’s disease and predict progression||This project is part of the funding for the Insight 46 study; involving the investigation of blood and cerebrospinal fluid biomarkers of Alzheimer’s disease both cross sectionally and longitudinally in this cohort in relation to
1. cross sectional and longitudinal amyloid PET, brain volumes, white matter hyperintensity burden, diffusion tensor imaging metrics, and cognition.
2. life course variables focused on vascular and other comorbidities from age 36 onward
|MTH0322||Validation of the ACE-III for remote administration||The Addenbrooke’s Cognitive Examination-III (ACE-III), a brief assessment for the detection of dementia or mild cognitive impairment, is among the most used cognitive assessments in the United Kingdom (UK). However, the COVID-19 pandemic has necessitated its administration through video calls, a method that has yet to be validated. In this study, we aim to investigate the validity of the ACE-III for remote use. Remote data was previously collected by administering the assessment to neurotypical participants through a video call. The proposed analysis aims to compare ACE-III scores and subscores of the remote sample to those collected through in-person testing. While it is expected that the setting will not affect test administration in neurotypical participants, if significant differences are noted, there may be issues to identify and consider before remote ACE-III scores may be considered valid.|
|YL0322||The impact of persistent financial adversity across adulthood on cognitive decline and neurological changes in older adulthood||Financial adversity – commonly defined as having a lack of money or resources to provide basic household necessities for themselves and their families (Mirowsky Ross, 2001) – is consistently associated with adverse health outcomes, including impaired cognitive functioning in older adults (Masud Hamid, 2017; Mani et al., 2013). However, there is little research on the long-term impact of persistent financial adversity on cognitive decline in older age. According to the neo-materialistic model of health inequalities, income inequalities resulting from political and economic environments can lead to differences in the accumulation of individual resources and access to community services, which can result in different health outcomes (Lynch et al., 2000; Ploubidis et al., 2011). Therefore, persistent experiences of financial adversity across adulthood may also be associated with greater age-related cognitive decline in later life. The overall aim of this project is to examine the accumulation of financial adversity across adulthood and cognitive decline as well as neurological changes in older age in the NSHD cohort. Three research questions are proposed: 1) Is the accumulation of financial adversity (indicated by low income and financial hardships) across adulthood associated with cognitive decline and neurological changes in older age? 2) Does this association hold after adjusting for the confounding effect of covariates? 3) Is there a moderating effect of sex, childhood SES and APOE-4?|
|MC0322||Life course exposure to neighbourhood deprivation and cognition in later life||There is a growing field of research investigating the impact of life course exposure to neighbourhood deprivation on health and wellbeing later in life (Jivraj et al., 2020). Residence in more deprived neighbourhoods has been shown to be associated with poorer cognitive performance in older adults, this association holds after adjusting for individual socioeconomic status and level of education (Basta et al., 2008; Lang et al., 2008; Clarke et al., 2012). Cumulative exposure to neighbourhood deprivation has also been shown to increase the odds of both functional decline and mortality over time (Clarke et al., 2014). However, there is little research on the cumulative effect of neighbourhood deprivation on cognitive performance in older adults. This project seeks to investigate the influence of exposure to neighbourhood deprivation across the life course on cognitive performance and neurological correlates at age 69.|
|TB0322||WMH changes and relationships with amyloid load, brain atrophy and diffusion metrics||In this study, we will conduct longitudinal analysis of phase 1 and 2 Insight46 PET and MRI scans to determine if there are significant changes in WMH load and volume from baseline to follow up, and determine if PET amyloid status at baseline influences progression of white matter pathology. Amyloid status will be factored in using defined positive/negative cut-off values, as well as by establishing if there is a linear relationship between amyloid tracer SUVR and changes in WMH volume.
We will then aim to determine if there is a relationship between WMH and brain atrophy while again factoring in amyloid status as well as life-course predictors of white matter disease, and establish if there is a linear relationship between increased amyloid tracer SUVR and loss of brain volume from baseline to follow-up.
Finally, we will analyse diffusion weighted images for the comparison of WMH growth, stable WMH and normal appearing white matter, and determine if early life-course measures influence changes in WMH appearance over time.
|AR0222||Blood Pressure Index||Blood pressure varies with each heart beat in a wave-like pattern. We know if a person has high peak blood pressure, then they are at a higher risk of experiencing a stroke or heart attack. However, currently we do not know which part of the wave-like pattern of blood pressure gives us the most accurate prediction of whether a patient is at higher risk. We aim to study this using machine learning approaches.|
|KC0222||Effect of dietary patterns on cognitive ability, cognitive reserve, and Alzheimer’s Disease and related dementias: A life course approach|| Healthy dietary patterns, especially those rich in plant sources of food, can improve cognitive outcomes and prevent, delay, or slow the progression of age-related degenerative brain disease, such as Alzheimer’s disease and related dementias (ADRD). Age-related cognitive decline is also thought to be buffered by higher levels of cognitive reserve (CR), which is an unexplained difference in individuals’ cognitive ability despite equally severe brain disease pathology. CR is generally thought to be determined by innate intelligence and cognitively stimulating or challenging activities throughout life; however, other factors such as health behaviors and lifestyle may also influence CR. With no known cure for ADRD, evidence for the role of modifiable lifestyle risk factors, like diet, is urgently needed but currently scarce. Furthermore, the effect of diet on CR is not yet known.
Using data from the 1946 British Birth Cohort, we plan to examine if dietary patterns followed in the early part of life (i.e., childhood up to middle age) that are high quality, rich in plants, and lower in animal foods will be associated with greater cognitive ability and slower rates of subsequent decline, greater CR, and lower incidence of ADRD than low quality dietary patterns with fewer plants and more animal foods. Our findings may suggest that establishing a healthy dietary pattern before middle age is vital for healthy cognition in later life and may fortify resilience against natural cognitive decline.
|JC0922||Connectomics in people at risk of Alzheimer’s disease||The neurodegenerative process in Alzheimer’s disease (AD) predates symptoms by many years and involves increasing disruption to the network of communicating brain regions, which are fundamental to normal brain functioning. Connectomics, the in vivo study of brain networks, uses diffusion-weighted magnetic resonance imaging (MRI) to characterise structural connectivity of the brain and studies have shown that the presence of amyloid-beta (AB) plaques, a key pathological hallmark of Alzheimer’s, may exacerbate AD-related network disruption. This project will use a machine learning pipeline to classify structural connectomes in older adults with or without amyloid deposition from the Insight46 study. This will help clarify the role of amyloid in brain networks disruption before AD symptoms develop, which in turn could help improve detection of those of greatest risk of AD.|
|MB0622||Adolescent mental health as a risk factor for adult COVID-19 infection and long COVID – evidence from three British Cohort Studies||COVID-19 infections have led to increased mortality rates and prolonged physical and mental health complications across the UK population. Specific concerns have been expressed for adults with pre-existing mental health conditions who seem to be at an increased risk of contracting SARS-CoV-2 and to suffer from worse physical and mental health outcomes following COVID-19 infection (Yao et al, 2020; Wang, Xu Volkow, 2021). Numerous factors, including poor living and working conditions, as well as the impact of continuous psychological distress on the immune system, have been suggested to explain the links between mental ill-health and increased COVID-19 infection risk and severity (Shinn et al, 2020). However, evidence highlighting specific pathways has been missing. Internalizing (e.g., anxiety and depression symptoms) and externalizing symptoms (e.g., conduct problems or hyperactivity) are common mental health conditions seen in children and adolescents, and both have been linked to increased psychological distress and poorer social, economical and health outcomes in adulthood (Colman et al., 2009, Oerlemans et al., 2020). Past research suggests that individuals with both early internalizing or externalizing symptoms are more likely to suffer from chronic physical health and infection conditions later in life than those without past mental health difficulties (Ploubidis et al., 2021; Scott et al. 2016; Winning et al., 2015). In line with that, we expect that during the COVID-19 pandemic, individuals with previous mental health problems were more likely to experience long COVID-19 symptoms. Internalizing and externalizing symptoms tend to co-exist in younger age groups, yet both have been shown to follow distinct life trajectories, thereby leading to different risk exposures and outcomes (Ning et al., 2021; Richards et al., 2009; Veldman et al., 2015). Despite differing trajectories, researchers have highlighted the importance of investigating the long-term effects of internalizing and externalizing symptoms together (Papachristou Flouri, 2020), as the two conditions are highly comorbid and mutually reinforcing.
The present research investigates the association between adult COVID-19 infection risks and adolescent internalizing and externalizing problems in three UK cohort studies. We consider both adolescent internalizing and externalizing symptoms as risk factors for experiencing long COVID-19 symptoms in adulthood but hypothesize that individuals with past externalizing symptoms are at greater risk of contracting SARS-CoV-2 due to their known tendencies to engage in risky health behaviors (Laukkanen et al, 2002, Richards et al. 2009). On the other hand, we hypothesize the reverse for internalizing problems since these tend to be associated with risk avoidance.
|LS0622||Adiposity gain and diabetes duration over the adult life course and its implications for cardiac structure and function in later life||Obesity, as assessed by either body mass index (BMI) or waist hip ratio (WHR) and associated insulin resistance/hyperglycaemia, culminating in type 2 diabetes mellitus (T2DM) are associated with adverse cardiac function and elevated left ventricular mass index (LVMI) (i.e., LV structure) in cross-sectional studies. There is some evidence for a causal relationship between obesity and T2DM and cardiac disease including left ventricular hypertrophy. However, the importance of the time of onset and duration of excessive adiposity and T2DM over the adult life course on future cardiac structure and function is unknown. We will study the consequences of earlier age of first overweight and diabetes duration over the adult life course on subsequent cardiac structure and function. Findings from this project could be beneficial for both designing and implementing targeted interventions against obesity and prevention strategies against DM at an appropriate stage for individuals at risk.|
|LN0622||The association between systolic blood pressure across the life course and later-life depressive symptoms in the 1946 British Birth Cohort||Poor cardiovascular health and depression are highly prevalent among the elderly population and are associated with increased risk for morbidity and mortality. The proposed ‘vascular depression hypothesis’ states that vascular disease may predispose, precipitate or perpetuate depressive syndromes among older adults (Aizenstein et al 2016). However, as most studies investigating this association are cross-sectional in nature or have limited follow-up periods, the nature of the relationship and directionality is unclear (Ravona-Springer et al., 2017). Using the rich population-based age-homogenous 1946 British Birth Cohort, the National Survey of Health and Development (NSHD), we can now extend on previous research to assess the effects of systolic blood pressure throughout the life course and later-life depressive symptoms, whilst adjusting for a range of potential confounders.|
|NR0622||Association between mid-life lung function and later-life cognitive state||Multiple studies have attempted to analyse the factors that increase risk of cognitive dysfunction in later adulthood. Lung function has increasingly come under scrutiny as a possible factor that is associated with cognitive state. Impaired cognitive function has been observed in patients with respiratory illness, such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). However, additional studies are necessary to determine whether lung function during specific stages in the life course influences cognitive outcomes in later life. While an association between midlife lung function and certain indicators of cognitive function at the same age was shown in a previous study, there is a dearth of research on the potential link between midlife lung function and cognitive outcomes at older ages. Such research is necessary to bring focus to lung function as a potential risk factor for cognitive impairment that may be intervened upon before cognitive decline occurs at older ages.
In addition, it is necessary to examine whether the potential association between lung function and cognition differs depending on the indicator of cognition that is analysed. Cognition may be measured by a range of indicators, including attention, verbal memory, visuospatial function, concentration and language. Data from the National Survey of Health and Development (NSHD) 1946 Birth Cohort has shown that certain cognitive measures, such as verbal memory and concentration, may show a stronger correlation with lung function compared to other measures of cognition. The objective of this research is to analyse the association between lung function at ages 43, 53, and 60-64 and cognitive state at age 69 as indicated by a range of cognitive measures. This research may further our understanding of the potential link between lung function and cognitive state, which may in turn help to uncover the mechanism by which lung function influences cognition. Moreover, on the basis of the evidence provided by the study outcomes, better preventative strategies for minimizing the risk of cognitive deficits in later life may be elucidated.
|DW220607||GWAS of age-related cognitive change||The causes of the deterioration in mental abilities (cognitive decline) in old age are not fully understood, and are likely to be complex and numerous. Genetic factors probably have some role in determining different rates of age-related cognitive decline, but precisely which genetic variations have the largest impact remains to be discovered. By combining genetic information with repeated measures of cognition collected from NSHD participants between ages 43 and 69 years, we will contribute to a large international study which aims to identify the genetics underlying cognitive decline in more detail.|
|CS0422||Validation of a new biomarker characterising white matter lesion shape||While white matter hyperintensity lesion volumes have been for long shown to be associated with markers of cardiovascular health, little interest has been given to the shapes and patterns of these lesions. The variability of these patterns may however reflect different disease mechanisms. In this project we aim at validating a new way of characterising the lesion shapes and assess whether shape is indeed associated with some known risk factors for white matter hyperintensity lesions.|
|AS0722||Affective symptoms trajectories from mid-life to older age and their predictors at age 53||Worldwide, the population is ageing and life expectancy increases. However, time spent in poor health has also increased and common mental health problems such as depression and anxiety are highly prevalent in older adults. In this study, we want to investigate potential risk and protective factors for development of mental health problems from mid to later adulthood. Knowing factors that may impact the development of mental health problems in later life can inform new or personalised treatments and preventative strategies.|
|RD0622||Association between indoor temperature in housing and self-reported sleep quality||Optimal sleep is integral to human health. Inadequate or inappropriate sleep contributes to a range of health conditions, and sleep disorders are risk factors for a number of chronic diseases. Sleep is affected by complex arrays of factors such as physical, social and environmental factors, and thermal environment is one of the most important sleep contributing factors. Sleep should be provided with thermally comfortable environment, either too hot or too cold. However, sleeping thermal environment is still a largely neglect topic in thermal comfort research and further empirical research is warranted on to what extent temperatures affect human sleep. Based on cross-sectional data from NSHD (1989), the proposed analysis aims to investigate associations between indoor air temperatures in residential settings and self-reported sleep quality.|
|MM0922||A metabolomic characterization of APOE genotype using the COsortium of METaboloics Studies||The glycoprotein, apolipoprotein E regulates lipid metabolism in the brain and periphery. The structure and function of apolipoprotein E is impacted by allelic variation in apolipoprotein E (APOE) genotype. The APOE common alleles are Îµ2, Îµ3, and Îµ4. The Îµ4 variant is associated with a higher risk and Îµ2 variant is associated with a lower risk of Alzheimer’s disease when compared to Îµ3 homozygotes. Allele frequencies in the U.S. are 7%, 78%, and 15% for Îµ2, Îµ3, and Îµ4, respectively, with a higher likelihood of the Îµ4 “risk” allele among black versus white Americans ages 18+. In addition, U.S. black older adults are more likely to have Alzheimer’s disease when compared to white older adults (14% vs. 10%, respectively). A better understanding of metabolic differences that occur as a result of APOE genotype may help reduce racial disparities in dementia.
The Îµ4 allele causes apolipoprotein E to have a higher affinity for larger very low-density lipoprotein particles rich in triglycerides, whereas Îµ2 and Îµ3 alleles cause a preference for smaller high-density lipoprotein particles rich in phospholipids. Altered profiles of plasma lipids and lipoproteins have been reported in both Îµ2 and Îµ4 carriers. For example, the Îµ4 variant was associated with higher levels of triglycerides and low-density lipoprotein cholesterol, whereas the Îµ2 variant was associated with lower levels of low-density lipoprotein cholesterol, but higher levels of triglycerides when compared to Îµ3. However, it is unknown which specific triacylglycerol and cholesterol molecules make up these observed altered profiles of overall triglycerides and cholesterol. Metabolomics can provide a more detailed description of specific plasma triglycerides and cholesterols, as well as metabolites of other chemical taxonomy classes that differ by APOE genotype. Thus, we seek to use metabolomics through the COsortium of METaboloics Studies (COMETS) to provide a better metabolic characterization of APOE genotype to potentially shed light on novel biological pathways to target in interventions aimed at mitigating the APOE-associated higher risk of disease.
|JKR0822||Insight 46 Sleep||Sleep is an essential requirement of all animal life, including humans, who spend around a third of their life asleep. We do not understand why humans need to sleep, however it is becoming clear that sleep is linked to cognition (brain functions such as thinking and memory). Even short periods of sleep deprivation result in worse cognitive function and signs of damage to the brain. Evidence is emerging that disrupted sleep may be part of the cause of Alzheimer’s disease.
We do not know how or when abnormal sleep patterns emerge, how they change over time, or how they relate to cognition in the long term. It is unclear if disturbed sleep patterns are early signs of disease, or if they precede and cause neurodegenerative diseases. To answer these questions we must analyse sleep in detail.
We plan to examine sleep in relation to cognition and neurodegeneration in the NSHD. Unpicking these relationships is essential to improving our understand neurodegenerative diseases, and has important implications for their diagnosis and treatment.