nshd:approved2018onwards


The following table lists NSHD data access requests that have been approved.

Project IDDate SubmittedPrincipal ApplicantTitleSummary
AA022202020-02-18Andre AltmannValidation of a variant in the KLOTHO gene with cortical amyloid burdenIt has been reported in previous studies that heterozygous carriers of the variant rs9536314 in the KLOTHO gene enhances cognition [1]. 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.
Ab01202020-01-17Annie Britton Alcohol trajectories and mammographic density using data from MRC NSHDWe 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.
AB12192019-12-12Alexandra BaconAssessing 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.
AD11192019-11-14Dr Alex DreganMechanisms and consequences of depression-related multimorbidity over the life course: coordinated analysis of population and primary care dataMultimorbidity (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.
AE01212021-01-20Ahmed ElhakeemGenome-wide association study of age at peak height velocity and mendelian randomisation study of causal effects on adult height and body compositionThe 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).
AG01192019-01-09Anitha GeorgeBiological 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.
AG03232023-03-07Alice GoisisHarmonising partnership and fertility measures across British cohortsSince the end of the Second Word War Britain has witnessed significant societal change, including in relation to partnership and family formation. Main trends have showed postponement of marriage and childbearing, increases in non-marital cohabitation and childbearing, and rises in family dissolution and formation of blended families. Robust longitudinal and cross-cohort research requires data harmonisation to create comparable measures over time and across cohorts. Our aim is to enhance data from four British birth cohorts born between 1946 and 1990 through retrospective harmonisation of information on changing families (variables on partnerships and fertility), thereby enabling more cross-cohort research using these rich datasets. The four cohort studies included are: Next Steps born in 1989/90, the 1970 British Cohort Study (BCS70), the 1958 National Child Development Study (NCDS), and the National Survey of Health and Development (NSHD) born in 1947.
AG04192019-04-17Alice GoisisAre only children all right? A cross-cohort analysis on the well-being of only children in the UKDespite 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.
AG11202020-11-06Antoneta Granic 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?
AJ09192019-09-18Amber JohnLong-term mental ageing consequences of adolescent dyslexiaDyslexia, 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).
AJ10212021-10-20Amber JohnThe role of telomere shortening in the relationship between accumulation of affective symptoms and later life cognitionDepression 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.
AK02202020-01-27Almar KokThe role of cognitive functioning in explaining socioeconomic inequalities in perceived sense of controlHigher 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.
AK02222022-02-10Anika KnuppelPhysiological Resilience: CortisolCortisol 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.
AK03192019-03-19Praveetha PatalayClustering and trajectories of multimorbidity over the life courseMultimorbidity 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) 2. Investigate socio-economic inequalities in the incidence and consequences of multimorbidity and the clustering of diseases that constitute multimorbidity 3. Explore the role of substance use, obesity and psychological distress on the development of multimorbidity and its clustering.
AK03222022-03-11Ashvini KeshavanDeveloping blood based biomarkers to detect preclinical Alzheimer's disease and predict progressionThis 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
AK05192019-05-17Arti KaraFeto-Placental Origins of Cancer: An investigation of an association between birth-weight and future cancer riskDuring 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.
AK05202020-05-08Ashvini KeshavanLumipulse CSF vs amyloid PET cross validation studyIn order to validate the performance of the fully automated Lumipulse CSF testing platform, we undertook systematic comparisons of - Aβ42 measured by three CSF testing platforms (Lumipulse, MSD and Innotest), - Aβ40 measured by two platforms (Lumipulse and MSD), and - p-tau181 and t-tau measured by two platforms (Lumipulse and Innotest) in an interim dataset of CSF samples taken in phase 2 of the Insight 46 study. Individual biomarkers and ratios between biomarkers were examined for concordance with amyloid PET data from phase 2 of Insight 46.
AK11212021-11-25Anika KnueppelRisk factors for Covid-19 infection and long CovidThis 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.
AK12202020-12-03Ashvini KeshavanDeveloping blood based biomarkers to detect preclinical Alzheimer's disease and predict progressionThis 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.
AK12212021-12-06Anika KnuppelCOVID-19 serologyThe 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.
AKRH01212021-01-12Praveetha PatalayChildhood 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
AM05192019-05-01Andrew M McIntoshA longitudinal phenome-wide association analysis of genetic risk for major depressionDepression 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.
AMW02212021-02-22Alle Meije WinkMultimodal MRI networksThis project combines differnt MRI modalities to reconstruct multimodal brain networks and study their alteration in normal and pathological aging.
AR02222022-02-25Anenta RamakrishnanBlood Pressure IndexBlood 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.
AS07222022-05-19Alexandra SchmidtAffective symptoms trajectories from mid-life to older age and their predictors at age 53Worldwide, 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.
AS11182018-11-14Antoine SalzmannInsulin-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.
AS12192019-11-21Antoine SalzmannInvestigating 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.
AW09182018-09-17Adele WarrilowValidation of a risk score predictive of later life adversityNeurodevelopmental 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.
AW11192019-11-15Aaron WagenAnalysis and Predictors of 'Superaging' in the 1946 Cohort StudyThis 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.
BL09182018-09-26Bernadette W.A. van der LindenLife course social- and biomedical risk factors for cognitive and physical health in later lifeIn 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.
BW02202020-02-04Bozena WielgoszewskaThe Gender Wage Gap: evidence from the cohort studiesNearly 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
BW07192019-07-22Bozena WielgoszewskaHarmonising earnings and income within and across studiesThis 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.
CBS08192019-08-02Charis Bridger StaatzInvestigate the role of psychological factors in the changing association between socioeconomic position (SEP) and body mass index (BMI) in an increasingly obesogenic environmentLevels 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.
CC08182018-08-21Catherine CalvinAdult trajectories of inflammatory and cognitive change from mid to late life: A cross-cohort comparison studyThe 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.
CF12192019-12-10Charlotte Constable FernandezTo 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 NSHDThe 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. Exposures: Structural and functional aspects of social relationships will be considered: marital and cohabitation status, frequency of social contact and quality of social relationships. Outcomes: The primary outcome measure will the DASH-type diet score, generated from 5-day diet diaries of participants.
CK04182018-04-30Chi-Hun KimHave 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.
CS01232023-01-13Carole SudreImpact of WMH on GM measurements and association with blood pressure and cognitive measurementsWhite matter hyperintensities, a common staple of brain damage may impact the automated measurement of other brain tissues. We will investigate whether correcting for such lesions has an impact on downstream analyses and potentially affect findings of associations with risk factors and/or cognitive outcomes.
CS03232022-11-25Carole Sudre Patterns of cerebral small vessel disease markers and relationships with renal function and blood pressureMarkers of cerebral small vessel disease on brain MRI such as white matter hyperintensities (WMH) are very common in the ageing population. Damage to the function of small vessels in the brain are thought to explain partly the occurrence of these lesions. However, patterns of presentation vary greatly from one individual to another. Reasons for this variability are still unknown and may be explained by different etiologies. This project will look into the association between patterns of distribution of WMH across the brain and markers of small vessel disease in other organs (with a focus on kidneys) and with blood pressure whose association with overall CSVD burden is already established.
CS04222022-03-04Carole SudreValidation of a new biomarker characterising white matter lesion shapeWhile 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.
CS10192019-09-24Carole SudreCross-sectional and longitudinal diffusion imaging in white matter lesions and along tracts – link to cognitionOne 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.
DB10212021-10-26David BannInvestigating mental health inequalities across time and place, and the interplay between genes and environmentThe 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.
DB11202020-11-24david bannTitle How do ‘effects’ differ across time? Understanding health inequalities by triangulating across multiple data sources and empirical strategiesSocioeconomic circumstances such as our education or income are thought to have important effects on our health. On average, the more socioeconomically advantaged someone is, the better their health. Contrary to widely-held myth, these differences are not inevitable or unchangeable. Economic and health policies change across time, and are ultimately expected to either worsen (widen) or improve (narrow) these differences. Scientists, government departments, and voluntary organisations all agree that inequalities in health should be reduced. In order to do so, we need to have an evidence-based understanding of how these inequalities have changed across time to help us develop effective policies. 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. It is also possible that such causal effects differ across time, as society changes; and across age, as people get older. It will do this by using multiple data sources which follow many thousands of individuals across time. It will use information on the environment along with genetic information to attempt to address this. In addition, this project will investigate how the causal role of two other factors may have changed across time. The first is cognitive capability — this refers to how individuals think and process information. On average, those with higher cognitive capability seem to have better health across a range of health measures such as lower cardiovascular disease risk and lower body weight. Due to the increasingly complex nature of society (and potential future changes related to technological development), it is important to understand if the importance of this factor for health has changed across time. The second factor is genetic propensity to ill health. In recent decades our understanding of genetics has greatly improved. We all contain genetic propensity to common health measures, such as body weight and blood pressure, but some individuals have higher genetic propensity than others. These differences do not mean that they will definitively have worse health measures — genetic risk is considered ‘probabilistic’ rather than ‘deterministic’. The expression of these genes also depends on the environment. As such, this project will seek to understand if the links between genetic factors and body weight, blood pressure and mental health 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.
DBMF07182018-07-16David BannSocioeconomic 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).
DC01212021-01-08David M CashAssessing 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.
DD08192019-07-05Dr Declan Dudley Epidemiological Investigation into the Relationship between Analgesia, Pain and Cognitive function in later lifePain 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.
DG_08202020-08-03David GlahnLarge-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability - CNVs And Major Psychopathology (CAMP) studyCopy number variants (CNVs) are rare genetic variants where a section of DNA is duplicated or deleted. CNVs are strongly associated with neuropsychiatric symptoms, such as depression, autism, psychosis and intellectual deficits. However, current understanding of the impact of CNVs is limited because, due to their rarity, very large samples are needed to accurately test their effects. Moreover, previous studies have mostly focused on the most commonly recurring CNVs, leaving the majority unexamined. We aim to fill these knowledge gaps with a multisite, multidisciplinary, collaborative project that utilizes existing datasets to achieve a very large sample size. We will model the effect of rare CNVs on neuropsychiatric symptoms, such as depression, autism, psychosis and intellectual deficits. These models will be used to develop algorithms that can be utilized by researchers to formulate hypotheses, and by clinicians to estimate the contribution of CNVs in patients.
DL04192019-04-12Donald LyallApolipoprotein 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?
DMA05212021-05-19Darío Moreno AgostinoInequalities in mental health trajectories before and during the COVID pandemicThe 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.
DMSB03212021-02-17Donncha MullinThe relationship between walking speed and cognitive impairment: A multi-cohort study utilising Dementia Platforms UK infrastructureDementia 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.
DT05192019-05-01David ThompsonMedication adherence in the NSHD populationThe 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.
DW06192019-06-06Dylan WilliamsAssociations of circulating metabolites with cerebral small vessel pathology: a prospective study in Insight 46 with follow-up genetic analysesCerebral 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.
DW07202020-07-02Dylan WilliamsThe role of infectious disease burden in neurovascular healthAcute 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.
DW10212021-10-15Dylan WilliamsInvestigating the role of common pathogens in heart, brain and ageing healthIndividuals 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.
DW11192019-10-25Dylan WilliamsMetabolomic studies of white matter hyperintensities and microstructural properties of the brain: a meta-analysis in the NeuroCHARGE ConsortiumCerebral 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.
DW12192019-12-09Dylan WilliamsA METABOLOMIC STUDY OF BLOOD PRESSUREHigh 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.
DW2206072022-06-07Dylan WilliamsGWAS of age-related cognitive changeThe 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.
EB10182018-10-25Elvira BramonPharmacogenetics in Mental Health: 1946 Birth CohortA 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.
ED_12222022-12-13Eamon DhallSocial-inequalities, diet and cognition in early-life are linked to left ventricular diastolic dysfunction: A life-course environment-wide association study (EWAS) of the 1946 Birth CohortDiastolic heart failure increases with age and remains a major cause of mortality and morbidity. Left ventricular diastolic dysfunction (LVDD) is a key pathophysiological mechanism in diastolic heart failure but its environmental determinants are poorly understood. Environment-wide association studies (EWAS) provide a comprehensive method to test a variety of exposures across the human environment and life-course in a high-throughput, unbiased manner. The aim of this project is to carry out an EWAS using existing Medical Research Council (MRC) National Survey of Health and Development (NSHD) British 1946 birth cohort data. We will test and validate associations between environmental factors and echocardiography-derived categories of left ventricular diastolic dysfunction. The secondary aim is to construct and publish exposome correlation globes and matrices summarising the EWAS for diastolic dysfunction.
ELA10212021-10-15Emma Louise AndersonDoes 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.
EM10182018-10-30Eoin McElroyCLOSER Mental Health and Cognitive Measures Harmonisation ProjectThe 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.
EM1412182018-11-14Eoin McElroyAssessment and harmonisation of cognitive measures in the British birth cohortsThe 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.
EM1512182018-11-14Eoin McElroyHarmonisation of mental health measures in British birth cohortsThe 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.
EM1810182018-10-18Eoin McElroyCLOSER Mental Health and Cognitive Measures Harmonisation ProjectThe 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.
EM3010182018-10-30Eoin McElroy CLOSER Mental Health and Cognitive Measures Harmonisation ProjectThe 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.
EP06192019-06-03Elena PhilippouInvestigation of associations between the MIND diet and cognitive function in the 1946 birth cohortWe 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.
EP10182018-10-15Eliana PortillaMeta-analysis of epigenome-wide association studies of carotid intima media thicknessSubclinical 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.
EZ04192019-04-16Dr Evi ZafeiridiHealthcare utilisation in early and late onset dementiaEarly 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.
FP01222022-01-10Francisco Perez-RecheMetabolomics to identify the susceptibility to COVID-19 and long COVIDThe 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.
GC0210202020-10-14Gabriella Captur 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.
GC02222022-02-17Gabriella CapturPrognostic potential of 10-second resting Advanced ECG in NSHDThe electrocardiogram (ECG) is a common diagnostic tool in cardiology but in several cardiovascular diagnoses, including left ventricular hypertrophy (LVH), current conventional ECG measures and criteria have a poor diagnostic performance. LVH - a key pathological consequence of hypertension and diabetes, is often missed by the standard 12-lead ECG. Advanced-ECG (A-ECG) refers to the use of advanced ECG analysis methods to extract otherwise untapped ECG biomakers of adverse cardiac remodelling, including left ventricular electrical remodeling (LVER) measured as spatial QRS-T angles, using data and features encoded in the standard 12-lead ECG. We hypothesise that a multimarker A-ECG score of NSHD participants who underwent 10 second resting 12-lead ECG at age 60-64, will show superior prognostic ability in terms of mortality and cardiovascular outcomes when compared to traditional cardiovascular risk factors and to standard 12-lead ECG and echocardiography combined. The electrocardiogram (ECG) is one of the commonest and cheapest cardiac tests but we are not exploiting all the information contained inside an ECG. Using sophisticated mathematical methods we are now able to dig deeper into the ECG for a better understanding of heart health. We believe that using these sophisticated methods to look at the ECG will more accurately predict a person's risk of death and of developing heart disease in the future when compared to other currently available methods.
GC06192019-06-18Gabriella Captur 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.
GC10202020-10-13Gabriella CapturApolipoprotein-E (ApoE) and heart conduction defectsApolipoprotein 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.
GC11202020-10-29Gabriella Captur Associations between childhood and young-adulthood bradycardia and later-life cardiovascular dysfunction and mortality: a longitudinal birth cohort studyHeart 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.
GCCC11202020-11-02Gabriella Captur Relationship between Clinical Frailty Index across the Life-Course and Adult Cardiac Size and Function by Echocardiography in the NSHD British Birth CohortAbnormal 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.
GCCT01212021-01-16Gabriella CapturThe association between the frailty index and telomere length-a longitudinal studyAs 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.
GCCT09212021-09-15Dr Gabriella CapturThe phenotypic associations of ApoEApolipoprotein 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.
GCCT12192019-12-01Gabriella Captur Relationship between Clinical Frailty Index across the Life-Course and Adult Cardiac Size and Function by Echocardiography in the NSHD British Birth CohortFrailty 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.
GCED10192019-10-01Gabriella CapturEnvironment-wide association study to identify novel factors associated with left ventricular diastolic dysfunction–Results from the NSHD Birth CohortDiastolic 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.
GCMF11202020-11-02Gabriella CapturRelationship between Clinical Frailty Index across the Life-Course and Adult Cardiac Size and Function by Echocardiography in the NSHD British Birth CohortAbnormal 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.
GCMK12202020-12-05Gabriella CapturRelationship between Clinical Frailty Index across the Life-Course and Adult Cardiac Size and Function by Echocardiography in the NSHD British Birth CohortAbnormal 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.
GP06202020-06-23George PloubidisCovid web survey data analysisProduction 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. The following areas will be explored: 1) Prevalence of COVID 19, symptoms and testing 2) Time use and parenting 3) Education HE/ FE and apprenticeships (MCS mainly/ only) 4) Financial impacts and labour market outcomes 5) Changes in self-rated health and health behaviours 6) Loneliness, social isolation and mental health 7) Access to care and health services 8) Housing, local environment, and access to green space 9) In their own words – how study members described their experiences and expectations 10) Families, social support, and conflict 11) Attitudes, compliance and political trust.
GP12212021-11-08Grace Marion PowerNovel applications of genetic and observational methods to lifecourse epidemiologyOften 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.
HH08182018-08-15Henry HouldenGenomic analysis of spontaneous intracerebral haemorrhage; providing new insights into vascular integrity and amyloid deposition as causes of neurodegenerationSpontaneous 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.
HJ07192019-07-16Hannah JongsmaCalibration of Mental Health MeasuresA 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.
HM04202020-04-28Henk MutsaertsInsight46 ASL analysisCardiovascular 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.
HP10182018-09-20Holly Pavey 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.
HS02192019-02-07Han Sang SeoMidlife lung function with later-life brain volumes and white matter hyperintensityTo 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
HS10192019-09-24Han Sang SeoAge 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
HSS05202020-05-07Han Sang SeoClustering and trajectories of multimorbidity over the life courseMultimorbidity 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 2.. Explore the role of substance use, obesity and psychological distress on the development of multimorbidity and its clustering. This PhD project will be an expansion to the previous multimorbidity project started by Dr Amal Khanolkar and Dr Praveetha Patalay
IB06212021-06-01Ioannis Bakolis Air pollution and mental health and cognition over the life courseAir 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.
IP01202019-12-13Ivanna Pavisic 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).
IS10212021-10-26Inga SteinbergA study of elite mobility in BritainThis 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.
JB01212020-12-17Jo BarnesRadiomics of WMHThis 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.
JB03232023-03-29Dr Joanna BlodgettExploring the importance of physical activity and physical activity contexts on cognition and cognitive decline.Even for those individuals who live long, healthy lives, gradual decline in memory reasoning and thinking does occur as we get older. But for some individuals, more rapid and substantive declines in these mental abilities may occur which risk impeding their daily lives and progressing to dementia; a point where even ordinary daily tasks become unmanageable as a direct consequence of impairment to one’s memory and reasoning. One possible therapy for slowing this decline may be our movement habits. Experiments testing individuals cognitive functioning over a few months in response to an exercise regime have linked more intense movements to improvements in memory and reasoning. Larger studies tracking the movement habits of thousands of people over many years, have showed similar benefits of purposeful exercise for reducing our risk of dementia. However, these studies are primarily performed in individuals in the second half of life, so it is not well understood how our earlier life behaviour may impact on our cognitive health in later life (i.e. whether we ought to prioritise or increase our exercise levels as we get older, rather than maintaining a steady state of exercising throughout adulthood). Further, physical activity can be a highly varied behaviour encompassing walking alone, cycling with friends, or even playing sports in groups. Activities vary in their degree of socialising as well as degree of physical and mental exertion. This study seeks to use data from the National Survey of Health and Development to address the question of how our movement habits, including how much, and what types of exercise we perform in adulthood, may influence our cognition and the natural decline in cognitive abilities in mid and later life.
JB10192019-10-16Dr Jordana BellEpigenetic responses to social and environmental cues in early life and over the life course: impact on healthy ageing in UK population-based cohortsThe 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).
JBK07212021-07-27John BakerInvestigating 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 DevelopmentVitamin 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.
JBYX12202020-07-06Dr Jordana BellAssociation between DNA methylation, diet and cardiovascular disease riskDNA 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.
JC09222022-05-04Dr James ColeConnectomics in people at risk of Alzheimer’s diseaseThe 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.
JD07202020-07-06Dr Jordana BellAssociation between DNA methylation, diet and cardiovascular disease riskDNA 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.
JD09212021-09-28Dr JD CarpentieriCONVALESCENCE 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.
JF02202020-01-28Jana FehrVisualizing health riskIn 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.
JG04232023-04-04James GrovesImproving the identification accelerated brain ageing through neuroimaging: A population-based studyWorldwide, the number of people suffering from Dementia is due to triple by 2050, to a total of 150 million. Individuals whose brains appear to be disproportionately ‘old’ for their age on standard T1 MRI Brain scans have been shown to have a greater risk of subsequently developing Dementia. If such individuals in the general population can be more reliably and practically identified, the prevention of Dementias may become an increasingly possible, providing an early opportunity for lifestyle modifications or drug-based treatments. Although advances in the last decade have allowed the brain’s age to be estimated using MRI scans, much of the rich information contained within the full set of brain images captured in each scanning session remains underutilised and underexplored. Understanding more about how the lesser-studied types of MR images, such as Diffusion Weighted Imaging, relate to aging may help to fill some of the gaps in knowledge that currently exist, and allow more precise and complete estimates of brain aging to be made. Similarly, newer and more sophisticated methods for calculating brain age have been trialled in recent years, some of which are based on ‘Deep Learning’. It is thought that these may produce more accurate and valuable estimates of Brain Age than less sophisticated methods. Our project will use the data from the 1946 British Birth Cohort to address these issues. We aim to determine in this cohort of population-representative people which method produces the most accurate estimates of Brain Age, and, in doing so, hoping to uncover some of the causes and pathological consequences of accelerated brain aging. Alongside this, we will seek to understand the information each different type of MR image contributes in mapping the brain aging process. Answering such questions will improve our ability to predict those who are most at risk for developing Dementia, which may enhance our ability to stop the exponential rise in cases predicted in the coming years.
JHT02232023-02-06Johan Hilge ThygesenPredicting mental health conditions from longitudinal data using machine learningMachine learning has shown promise for early prediction of mental health conditions and risk factors can be used to identify individuals who could benefit from targeted prevention. The National Study of Health and Development (NHSD) 1946 dataset offers an opportunity to train a machine learning model on data collected over a participant's lifetime to identify individuals with mental illness, describe common disease trajectories, and train prediction models to determine mental illness. We will (A) develop machine learning algorithms to predict mental illness and (B) evaluate model performance and (C) see if we can improve the models by incorporating disease knowledge from external data sources.
JKR08222022-08-08Josh King-RobsonInsight 46 SleepSleep 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.
JLFG02232023-02-13Jose Luis Flores GuerreroHRV and cardiovascular outcomesHeart rate variability is the variance in time between the beats of the heart. This variability heavily depends on the balance between the sympathetic and parasympathetic nervous systems. The current evidence suggests that a decreased heart rate variability is associated with better health outcomes. The aim of the project is to identify which circulating concentrations of plasma biomarkers are associated with high HRV is associated.
JLFG12222022-12-01Jose Luis Flores GuerreroAutonomic nervous system and hormone biomarkersThe potential role of individual plasma biomarkers in the prediction of chronic disease has been broadly studied, but the impact of biomarkers interaction remains underexplored. Recently, the Mahalanobis distance (MD), biomarker-based metric of physiological dysregulation has been proposed as an alternative to integrate the information of several circulating biomarkers. (1) In this project we aim to investigate whether the MD calculated from circulating biomarkers is prospectively associated with development of autonomic dysregulation, and its potential effect in brain changes, defined by white matter hyperintensities. Various metrics of comorbidity, multimorbidity and frailty have been proposed in the literature (2), though most of them show limited variation among healthy younger and middle-aged adults because they are based on elements that only occur late in life. There are biomarker-based metrics that attempt to integrate the signal of multiple aspects of health. Perhaps the best-known of these is allostatic load (3). Allostatic load is based on the theory that chronic stress can leave physiological sequalae that can be measured by creating a metric of common biomarkers linked to appropriate physiological systems: neuro-endocrine stress (cortisol, epinephrine, norepinephrine), metabolic markers (blood pressure, lipid profiles, glucose metabolism, obesity metrics), as well as a few additional biomarkers (inflammatory markers, DHEA-S, IGF-1, etc.) (4,5). However, allostatic load is challenging because it is conceptualized based on circular reasoning: the proxy metrics are chosen because of their known association with health and aging, so it is unsurprising the sum does as well (6). Because it is often operationalized as a count of how many of the factors exceed clinical bounds, measures of allostatic load end up resembling comorbidity metrics in many ways, though the latter are generally not biomarker based. Recently, it has been developed an alternative biomarker-based metric of physiological dysregulation based on Mahalanobis distance among biomarkers (7). The idea is that a population average is an approximation of a homeostatic state, and that deviations from this multivariate biomarker average represent dysregulation and thus should increase with age and predict poor health state. It has been shown that homeostasis loss rates increase with age within individuals, and predict multiple health outcomes (mortality, frailty, various chronic diseases) after controlling for age (8). Nevertheless, whether the Mahalanobis distance is associated with autonomic dysregulation and its complications remains unknow. Proposed output. Scientific article depicting for first time the association between Mahalanobis distance and autonomic dysregulation. References 1. Flores-Guerrero JL, Grzegorczyk MA, Connelly MA, Garcia E, Navis G, Dullaart RPF, Bakker SJL. Mahalanobis distance, a novel statistical proxy of homeostasis loss is longitudinally associated with risk of type 2 diabetes. EBioMedicine. 2021 Sep;71:103550. doi: 10.1016/j.ebiom.2021.103550. 2. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–51. 3. McEwen BS. Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci. 1998;840:33–44. 4. Seeman TE, McEwen BS, Rowe JW, Singer BH. Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. Proc Natl Acad Sci USA. 2001;98:4770–5. 5. Seplaki CL, Goldman N, Glei D, Weinstein M. A comparative analysis of measurement approaches for physiological dysregulation in an older population. Exp Gerontol. 2005;40:438–49. 6. Singer BH, Ryff CD, Seeman T. Operationalizing allostatic load. In: Schuli J, editor. Allostasis, homeostasis, and the costs of physiological adaptation. New York: Cambridge University Press; 2004. p. 113–49. 7. Cohen AA, Milot E, Yong J, Seplaki CL, Fülöp T, Bandeen-Roche K, et al. A nove
JLS08192019-08-19Jessica Lasky-SuMetabolomics of Asthma, Lung Function, and Immunoglobulin E (IgE): a Consortium of Metabolomics Studies (COMETS) analysisAsthma 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.
JM01202020-01-21Jane MaddockSocial 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.
JM01212021-01-18Jane MaddockGlobal PWV CollaborationThis 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.
JM11202020-11-02Jane MaddockCOVID National Cohorts Study This project aims to examine the wider social, economic and health effects of the covid-19 pandemic response in the UK.
JSAW11202020-11-12Jonathan SchottStructural connectomics in Insight 46This 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.
JZ11212021-11-05Jiaxiang Zhang Individual differences in information processing speedInformation 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.
KB04182018-04-02Kate BirrellA qualitative exploration of older people's views on influences on health, wellbeing and capability in older ageThe 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.
KC02222022-02-21Mei Chung, Ph.D. and M.P.H.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.
KD06232023-01-10Kenan DirekNSHD Data on the UK Biobank PlatformThe current data discovery platform for the NSHD cohort, Skylark, has been in use for over a decade, it is increasingly showing its age, in appearance and functionality compared to other platforms, and frequently (typically once per fortnight) requires actions by the DMG for it to function correctly. Therefore, we were faced with two options; to replace Skylark with a modern alternative or to identify an existing platform that meets our user needs. We opted for the latter due to (1) UKB’s interest in making their platform available to the research community, (2) it is widely used and respected internationally for epidemiological research, and (3) has a dedicated infrastructure support team. The migration work will be broken down by wave of data collection, starting with the 2006-2010 wave. Within each wave there will be a series of milestones such that the progress of the project can be monitored. Where metrics can be identified, these will be tracked alongside associated tasks and overall progress, to ensure task are completed on time and according to project requirements (set out by UKB). Out of scope data includes raw imaging and -omic datasets that have a different set of requirements to those set out here and will be delt with separately.
KK06232023-05-02Kaisa KoivunenExploring the concepts of intrinsic capacity and fatigability using data from the MRC National Survey of Health and DevelopmentIntrinsic capacity (IC), as defined by the WHO, encompasses an individual's physical and mental capacities an individual can draw upon. When interacting with the environment and social factors, IC defines a person’s functional ability. The five key domains of IC are locomotion, psychology, sensory, cognitive, and vitality which together contribute to functional reserve (1). Preventing decline in these capacities is an important goal when promoting healthy ageing. Imbalance between energy availability and demand for daily functioning is potentially an important driver of decline in IC during ageing. Fatigability, meaning perceived fatigue while performing a standardized activity (2), may reflect energy imbalance. Individuals with higher fatigability may start adapting their behaviour to save energy, which may lead to decreased physical activity and intrinsic capacity. Previous research has provided evidence that physical fatigability may precede declines in observed functional capacities, such as walking ability (2). In addition, higher BMI and inflammation have been associated with higher perceived physical fatigability (3), suggesting that fatigability may manifest the underlying chronic low-grade inflammation, which partly contributes to the exhaustion of functional reserves. Several factors may contribute to exacerbated fatigability including poor sleep quality (4). There is evidence that the associations between sleep and physical activity are bidirectional – physical activity can improve sleep and well rested individuals have more energy to be physically active. Increased fatigability is plausibly one of the main pathways by which poor sleep may affect physical activity levels in older age. While our pilot analyses, using data from the Finnish AGNES study, suggest that the association between poor sleep quality and poor perceived opportunities for physical activity in old age can be explained by higher fatigability, this has not been systematically studied. Furthermore, although fatigability can be subdivided into mental and physical domains, it has been suggested that these domains can cross borders (4). This is supported by our previous findings showing that a simple walking task considered predominantly as physically demanding, was considered mentally fatiguing by one third of community-dwelling older participants (5). By utilising the NSHD data, we aim to investigate the complex relationships between the domains of IC, fatigability, sleep quality and physical activity, and to publish two original articles. The data offers a good opportunity to do this, as important aspects of IC and physical activity has been monitored over several time points, and the 2014-2016 data collection also includes the Pittsburgh Fatigability Scale. First, we aim to investigate the relationships between IC, fatigability and physical activity by applying network analysis, which allows to investigate simultaneous interactions between multiple variables within complex systems. Second, we aim to focus more closely on the relationships between sleep and physical activity and investigate whether physical and mental fatigability explain their association. References: (1) Cesari et al. (2018). Evidence for the Domains Supporting the Construct of Intrinsic Capacity. J. Gerontol., 73(12), 1653–1660. (2) Simonsick et al. (2016). Fatigued, but Not Frail: Perceived Fatigability as a Marker of Impending Decline in Mobility-Intact Older Adults. JAGS, 64(6), 1287–1292. (3) Cooper et al. (2019). Are BMI and inflammatory markers independently associated with physical fatigability in old age? IJO, 43(4), 832–841. (4) Kratz et al. (2019). Development of a person-centered conceptual model of perceived fatigability. Qual. Life Res., 1–11. (5) Palmberg et al. (2020). The associations of activity fragmentation with physical and mental fatigability among community-dwelling 75-, 80-, and 85-year-old people. J. Gerontol., 75(9), e103–e110.
KL03202020-03-03Kirsty LuCognition and its associations with biomarkers of Alzheimer’s disease in Insight 46, a sub-study of the MRC National Survey of Health and DevelopmentAlzheimer’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.
KM06192019-06-12Kyriaki MengoudiExploring 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.
KP05192019-05-07Kai-Wen, PaiHow 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.
KS12202020-09-25Katherine StainesAre 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. Osteoarthritic joints, most often knees and hips, undergo structural deterioration, characterised by loss of the joint cartilage which covers the bone and normally allows pain-free joint movement. Current osteoarthritis treatments are limited and largely consist of the use of pain-killers and physiotherapy. In some individuals, osteoarthritis progresses to the extent that total joint replacement is required. Currently we are unable to identify those at risk of developing osteoarthritis. We are also unable to treat those at early disease stages. This proposal will change this by examining in the NSHD whether growth during childhood and adolescence, changes how joints adapt to the huge loads placed upon them, and is associated with osteoarthritis in later life.
KSZ04212021-04-15Dr. Kaspar StaubLife course trajectories of height and later health outcomes in the 1946 UK birth cohortHuman 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.
KT04232023-04-04Kate TimminsConsortium Against Pain InEquality (CAPE) – The impact of adverse childhood experiences on chronic pain and responses to treatmentHaving a traumatic experience as a child – for example, abuse, or deprivation – can have a lifelong impact. People who report having several adverse childhood experiences, or ACEs, are more likely to have health problems later in life. The Consortium Against Pain InEquality (CAPE) aims to further understand how ACEs might lead to chronic pain in adulthood. We want to consider how other factors (such as mental health or support from friends or family) contribute to pain vulnerability. Our main question is: Do ACEs cause an increased risk of chronic pain in later life, and, if so, what roles do other factors play? Using existing data from several cohorts, of which the MRC National Survey of Health and Development is one, we will conduct analyses to better understand the factors that may contribute to, or protect against, developing chronic pain, trying to describe the different ways ACEs (of different types, number and characteristics) may be linked to chronic pain (‘causal pathways’).
KW02192019-02-27Kate WardTo 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.
KW08192019-08-07Kate WardTo 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.
LB11192019-11-07Liam BurkeMachine 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.
LC03202020-03-12Laura CarterSecondary education and social change in the United Kingdom since 1945The 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.
LHG06212021-06-08Dr Lisanne A Horvat-GitselsTrends in the impact of childhood visual function on health and social outcomes in adult life across 3 UK birth cohortsThe 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.
LL04202020-04-15Luigi lorenziniResting-state Functional Connectivity: Cross-sectional and Longitudnal analysis of functional brain networks in patients at risk of Alzheimer's DementiaThe 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.
LLC00152022-06-27Olivia HamiltonSocio-demographic determinants of COVID-19Research has shown that some people are more at risk of COVID-19 than others because of personal factors, such as sex, ethnicity, or financial situation. In this study, we aim to understand whether differences in peoples’ personal factors increase their risk of COVID-19. To do this, we will link data from 10 research studies with data on COVID-19 infection status from NHS health records. We will use statistical modelling to look at the relationship between personal factors and COVID-19. We will also look at whether certain combinations of personal factors increase someone’s risk of COVID-19 further. For example, are Ethnic Minority women without a university degree more likely to report having had COVID-19 than others? Our findings will identify groups of individuals who had the highest risk of COVID-19 in the early waves of the pandemic. We will share the results with policy makers to help with decisions on how to support and protect these people.
LLC00252022-06-27Francisco Perez-RecheUsing metabolomics to better understand COVID-19 symptomsThe effects of COVID depend on each patient and range from no symptoms to fatal cases. COVID complications are more common in older patients or those who already have health conditions. However, COVID can also be severe for healthy middle-aged individuals. We need to better understand why some patients have severe COVID symptoms. In this study, we will use detailed blood tests to see if there are differences between patients with severe symptoms and those that were mostly fine. NHS healthcare information and study questionnaires are needed to know if patients had COVID and what their symptoms were. The findings of the project will allow us to better identify individuals that could be at risk of severe COVID. This is beneficial for the entire population since we are all at risk of catching COVID. Our findings will allow individuals that may develop serious symptoms to be better identified. This will then help putting measures in place to protect them against the virus.
LN04202020-03-30Louisa NeedhamIdentifying which cognitive domains, measured in late adulthood, most strongly associated with age and type of menopause in a British Birth CohortAlzheimer’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.
LN04232023-04-05Louisa NeedhamSex differences in cognition and brain healthThis work will test whether males and females differed in their cognitive abilities measured throughout life - from age 8 into their seventies - and in their brain health measured using brain scans at age 70. The aim is to describe how sex differences (and similarities) might vary throughout life among individuals born in 1946, while considering how environmental factors (like education and smoking behaviours) might explain any sex differences.
LN06222022-06-10Sarah-Naomi JamesThe association between systolic blood pressure across the life course and later-life depressive symptoms in the 1946 British Birth CohortPoor 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.
LN12192019-12-06Louisa NeedhamInvestigating associations of childhood infections with Alzheimer's Disease neuropathology in later life, using the Insight-46 sub-study of the NSHD 1946 Birth Cohortβ-amyloid plaques are one of the neuropathological hallmarks of Alzheimer’s Disease. The Antimicrobial Protection Hypothesis suggests that β-amyloid has a normal function as part of the body’s innate immune system, whereby β-amyloid traps invading pathogens. A bi-directional relationship exists in which β-amyloid induces neuroinflammation but neuroinflammation also drives β-amyloid deposition. When this pathway becomes overactive, β-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.
LOK06192019-06-05Linda O’KeeffeSex 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 yearsThe 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.
LP03192019-03-27Lindsay Paterson Education and Society in ScotlandEducation 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
LS06222022-06-10Alun Hughes 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.
MA03212021-03-12Melis AnatürkModelling brain and cognitive age to study cognitive reserve and resilienceAgeing 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.
MB06222022-06-07Bettina MoltrechtAdolescent mental health as a risk factor for adult COVID-19 infection and long COVID – evidence from three British Cohort StudiesCOVID-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.
MC03222022-03-01Molly CartlidgeLife course exposure to neighbourhood deprivation and cognition in later lifeThere 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.
MD02192019-02-20Monica Costa DiasEducation, Marriage and Employment Across GenerationsThis 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.
MD03202020-03-16Madelaine DaviesNumber 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.
ME09182018-08-18Majid Ezzati The Non-Communicable Disease Risk Factor Collaboration (NCD-RisC): estimation of the global burden of cardio-metabolic risk factorsNCD-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.
MEG03202020-03-23Maria del Mar Estarellas GarciaData-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.
MK02222022-02-14Michail KatsoulisBMI trajectories chronic diseasesIn 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.
MM09222022-07-25Megan MarronA metabolomic characterization of APOE genotype using the COsortium of METaboloics StudiesThe 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 ε2, ε3, and ε4. The ε4 variant is associated with a higher risk and ε2 variant is associated with a lower risk of Alzheimer’s disease when compared to ε3 homozygotes. Allele frequencies in the U.S. are 7%, 78%, and 15% for ε2, ε3, and ε4, respectively, with a higher likelihood of the ε4 “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 ε4 allele causes apolipoprotein E to have a higher affinity for larger very low-density lipoprotein particles rich in triglycerides, whereas ε2 and ε3 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 ε2 and ε4 carriers. For example, the ε4 variant was associated with higher levels of triglycerides and low-density lipoprotein cholesterol, whereas the ε2 variant was associated with lower levels of low-density lipoprotein cholesterol, but higher levels of triglycerides when compared to ε3. 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.
MM11192019-11-13Mark MiodownikTasting spoons: gustatory qualities of different metalsMany 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.
MN04232023-04-20Martina NarayananHarmonising physical health measures across the British birth cohorts Robust longitudinal and cross-cohort research requires data harmonisation to create comparable measures over time and across cohorts. Our aim is to enhance data from five British birth cohorts through retrospective harmonisation of physical health variables, thereby enabling more cross-cohort research using these rich datasets. The five cohort studies included are: the Millennium Cohort Study (MCS, 2000-02), Next Steps (1989-90), the 1970 British Cohort Study (BCS70), the 1958 National Child Development Study (NCDS), and the 1946 MRC National Survey of Health and Development (NSHD). We will focus on major chronic conditions and their timing, bringing together self-reported measures of health collected through surveys, and linked data from electronic health records.
MO09212021-09-21Michele OriniLongitudinal 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.
MR10212022-01-25Mark James RawleAssociations 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.
MS01232023-01-17Muhammad Saad SalmanThe influence of Sodium and Potassium on Cardiovascular Structure and Function in Adult lifeMultiple publications have demonstrated a relationship between high salt intake and high blood pressure. Additionally, it is also well known that potassium could have an important role in lowering blood pressure and maintaining cardiac rhythms. However, the exact relationship between sodium and potassium on cardiac remodelling is less well understood. I aim to use the data from NSHD and other literatures in this project is to investigate the relationship between Sodium and cardiovascular outcomes in the NSHD cohort. I also aim to look at the effects of potassium on the same outcomes to identify whether it has any potential beneficial effects in improving cardiovascular health. The proposed research questions that I would like to investigate is: 1) Does increased levels of sodium result in structural changes in the heart? 2) Does increased levels of sodium affect systolic and diastolic function? 3) Does this relationship change after accounting for mediators like blood pressure/other co- founders? Secondary 4) Does increased levels of potassium result in improvement in these structural measures? 5) Does potassium affect the systolic and diastolic measures in the echocardiogram? 6) Same as 3 but for Potassium
MS06192019-06-18Marzia Antonella ScelsiInvestigating the imaging and genetic differences between posterior cortical atrophy and the amnestic presentation of Alzheimer’s disease
MS09192019-08-05Maria SironiPostponement 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.
MS11192019-11-01Dr Maryam ShoaiDeriving and validating of polygenic risk scores for Alzheimer’s diseaseAlzheimer'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.
MS11212021-11-07Manas SoniAssociation of early-life air pollution exposure with cardiovascular and mortality outcomes across the lifecourseAssociation of early-life air pollution exposure with cardiovascular and mortality outcomes across the lifecourse
MTH03222022-03-08Monica Truelove-HillValidation of the ACE-III for remote administrationThe 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.
NF02192019-02-13Nasri FatihExploring 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.
NFSJ04212021-04-14NASRTULLAH FATIHthe relationship between markers of diabetes during life and later-life white matter outcomes in the brainThis 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.
NM06212021-06-01Natalie MarchantRepetitive negative thinking across the life course and its association with cognition and brain healthRepetitive 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.
NO01232023-01-23Neil OxtobyEarly Detection of Alzheimer's Disease SubtypesAlzheimer'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: 1. Is an individual's genetic and environmental profile predictive of Alzheimer's disease subtype at an early stage (mid-life) and does it increase confidence in subtype assignment? 2. Are subtype disease models useful in clinical practice? Including for optimising treatment and prevention strategies.
NO11212021-11-10Neil OxtobyEarly Detection of Alzheimer's Disease SubtypesAlzheimer'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: 1. Is an individual's genetic and environmental profile predictive of Alzheimer's disease subtype at an early stage (mid-life) and does it increase confidence in subtype assignment? 2. Are subtype disease models useful in clinical practice? Including for optimising treatment and prevention strategies.
NR06222022-10-06Nicole RobinsonAssociation 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.
OR05202020-05-26Oliver RobinsonMetabolomic age acceleration and its determinants: A multi-cohort analysisBoth 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
OR12162016-12-06Oliver RobinsonThe association of socio-economic status and the metabolomeIt has long been known that socio-economic status (SES), whether assessed by income, education level or occupation, is a strong determinant of healthy aging and life expectancy. For instance, we have recently shown in an analysis of 1.7 million individuals as part of the LIFEPATH project, that participants with low SES had higher mortality compared to those with high SES (hazard ratio 1.42; 95%CI: 1.38,1.45, Stringini et al 2016. The Lancet. Accepted). This suggests that SES, as a potentially modifiable risk factor, should be given similar consideration in public health interventions to other established risk factors such the “25x25 risk factors” targeted by The World Health Organisation Global Action Plan for the Prevention and Control of Non-Communicable Diseases. The 25 x 25 risk factors include the harmful use of alcohol, insufficient physical activity, current tobacco use and raised blood pressure, intake of salt/sodium, and diabetes and obesity. While the distribution of these risk factors varies by SES, they do not account for the total effect on mortality observed with SES, with models additionally adjusted for these risk factors still demonstrating an independent association between SES and mortality (hazard ratio 1.34, 95%CI: 1.20,1.48, Stringini et al 2016. The Lancet. Accepted).
OT01232023-01-14Oliver ThomasSalt intake and brain health: insights from the NSHD study.The negative health effects of salt (sodium) are well established. High dietary salt intake is linked to the development of high blood pressure, which has been shown to be associated with several indicators of poor cardiovascular health. Furthermore, a link between salt intake blood pressure, and poor brain health and cognitive function has been proposed, suggesting not only that high blood pressure has a role in vascular dementia, but also that sodium may play a direct role in dementia pathology. However, the evidence concerning sodium’s role in brain health and cognitive function is conflicting, with some studies suggesting an adverse effect of sodium, while others observed that low levels of sodium in the blood (hyponatraemia) were associated with poorer cognitive function, suggesting that sodium is important for normal cognitive function. We aim to contribute to the literature on this topic by examining the effect of sodium intake over a lifetime on brain health and cognitive function using data from the 1946 NHSD study, which will allow us to adjust for confounders (such as childhood cognition) which are rarely measured. The research questions of this project are: 1) Is higher sodium intake associated with indicators of cognitive function and brain health? 2) Does this association remain after adjustment for blood pressure? 3) Does this association remain after adjustment for other potential confounders?
PA01222022-01-14Pamela Almeida-MezaA life-course study of cognitive reserve and cognitive state in older ageThe 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.
PA02202020-02-17Pamela Almeida-MezaA life-course study of cognitive reserve and cognitive state in older ageThe 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.
PA02222022-01-14Pamela Almeida-MezaA life-course study of cognitive reserve and cognitive state in older ageThe 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.
PT08182018-08-31Penny TinklerTransitions 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. [1] 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. [2] 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.
PTP03192019-03-15Petroula ProitsiAssociation of midlife blood metabolites with β-amyloid deposition and MRI biomarkers in the Insight46 sub-studyWorldwide, 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 £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 β–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 β–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 β–amyloid deposition and brain volume at 69-70 years.
PW03232023-01-06Philip WestonAssociations between tau deposition and cortical microstructureThe project uses advanced Brain scanning (MRI and PET) to examine the association between amyloid and tau protein - the pathological hallmarks of Alzheimer's disease - and downstream loss of neurons, in individuals who have yet to develop any cognitive symptoms. By addressing these questions, the study will help us to better understand the mechanisms by which Alzheimer''s disease leads to loss of brain cells and cognitive decline.
QD05202020-05-01Quentin DerconAssociations between physical function across adulthood and late-life brain health in the 1946 British birth cohortWorse 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?
RA03232023-03-18RAYAN ANBAR THE IMPACT OF CAROTID ARTERY PLAQUE ON COGNITIVE FUNCTION FOR THE MRC NATIONAL SURVEY OF HEALTH AND DEVELOPMENT: IN THE BRITISH 1946 BIRTH COHORT: PROSPECTIVE COHORT STUDYThis project aims to investigate the association between carotid artery plaque and cognitive function in a British birth cohort using imaging techniques and cognitive function tests. The study aims to shed light on the potential long-term effects of carotid artery plaque on brain health and cognitive ability, and to identify any gaps in the current evidence regarding this relationship. The output of the project will be an article that contributes to the scientific understanding of the link between carotid artery plaque and cognitive function, and provides insights that can inform clinical practice and public health policy. The findings of the study have the potential to improve the diagnosis and treatment of individuals with carotid artery plaque and cognitive impairment, and to promote strategies that can prevent or delay the onset of cognitive decline.
RC09192019-09-04Rachel CooperSocioeconomic adversity across life and its implications for musculoskeletal ageingThis 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
RD06222022-06-20Ucci MarcellaAssociation between indoor temperature in housing and self-reported sleep qualityOptimal 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.
RD08192019-08-21Richard DoddsThe prevalence of probable sarcopenia in early old ageThe 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.
RG04192019-04-02REBECCA GREENLinking blood metabolite levels to cognitive decline and subsequent dementiaInvestigating whether late midlife peripheral metabolite levels are associated with cognitive decline and subsequent dementia and interrogating the causal nature of these associations.
RK11182018-11-12Rachel KellyThe metabolome of obesity: a Consortium of Metabolomics Studies (COMETS) analysisMore 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.
RM02212021-02-03Dr Rosie MansfieldSocial Isolation, Loneliness and Wellbeing across the Life Course and between Five British Birth CohortsWe 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.
RS06202020-06-09Richard SilverwoodCovid-19 web survey non-response weight derivationThe 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.
RS12212021-12-15Rebecca Street Longitudinal trajectories of self-reported subjective cognitive decline in relation to objective cognitive performance, in a population-based cohortSubjective 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.
RT09182018-09-21Ruby TsangThe multiple dimensions of ageing well: Characterising the health and well-being profiles of older adults using physical, psychological, cognitive, functional and social measuresThe 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.
SB04182018-04-12Sarah BauermeisterThe effect of childhood adversity on adulthood behavioural, psychological, cognitive and health outcomes: A UK Biobank and DPUK cross-cohort investigationOver 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.
SB04192019-04-18Sarah BauermeisterThe effect of childhood adversity on adult behavioural, psychological, cognitive and health: A DPUK cross-cohort multi-modality investigation – extension of DPUK study 0144One 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.
SB05182018-05-29Sarah BauermeisterUsing 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. IRT provides two metrics, item ‘difficulty’ and item ‘discrimination’ – difficulty is the probability of endorsement and discrimination is the amount of information an item possesses about the latent trait measured whereas CTT only provides item difficulty information. • The SE is computed at the item level rather than across the whole scale. • It is possible to predict the probability of the response of any individual performance at a given level of the trait, at any point along an incremental scale of -4 to +4. Item difficulty and person trait-level are placed along the same scale, scored as theta (θ). • Statistical assumptions which are computed during the IRT procedure may be used to identify redundant scale items. • IRT is sample independent with invariance of item parameters by population and the item difficulty is invariant across populations up to a linear transformation • CTT provides only a single metric, which is the probability of endorsement (scoring). • Sample dependency – CTT scores always depend on the population completing the scale as it is impossible to separate the two. • Item equivalence – CTT does not provide information about the contribution of each item to the test score, implying that each item contributes an equivalent value to the score of the latent trait in other words, the distance between each cut-off point is equivalent. • Assumption of the standard error (SE) – The SE in CTT is computed across the whole scale - if the data are not normally distributed, the SE will be larger at the extreme ends of the distribution and smaller towards the middle of the distribution. • Equating test scores – Using CTT makes it difficult to equate scores a person receives on one test with those they receive on another, although test scores are often standardised (z-scores), this then assumes the scores are normally distributed. 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.
SB11082018-11-08Sarah BauermeisterAssociations between childhood hormonal indicators, adult hormones, mental health and cognition: A UK Biobank and DPUK cross-cohort studyOne 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. 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. The sex-hormones testosterone and oestrogen are implicated in psychological behaviour and as such, also in psychiatric disorders. Specifically, the sex-hormones, testosterone and oestrogen are implicated in mood and mental health stability. An increase in testosterone and oestrogen accompany physical and psychological changes during puberty and the age at which this begins may vary from aged 10 to 15 for girls and aged 11 to 16 for boys, rising gradually until reaching a peak just after adulthood. If children have indications of early higher levels of sex hormones through signs of early puberty, the associative link with later-life adult mental health and cognition would be difficult to assess unless a longitudinal birth cohort study was conducted. By using existing population cohorts with retrospective proxy measures of early childhood hormonal proxy indicators, this study will explore an extrapolated childhood hormone level (e.g., age of menarche, early beard growth), adult mental health, adult hormone level and cognitive performance to investigate the associations and interactions between these variables whilst controlling for co-variates such as social deprivation, age and medications. The main aim of the study therefore is to utilise the power of DPUK cohorts to assess early-life predictors and, interactions of the sex-hormones, mental health and cognition. Our objective is to investigate whether adult mental health is associated with both childhood and adult hormone levels and, whether the associative hormone levels are predictive of mental health and cognition, or independent. For example, it is suggested that early puberty is associated with earlier menopause in women and this in turn, is also associated with increased levels of depression (e.g., Bromberger et al., 2010). Furthermore, a decrease in testosterone is implicated in both an onset of depression and decreased cognitive function in men (e.g., Matsumoto, 2002). Moreover, it is well established that poor mental health in has a deleterious effect on cognition (e.g., Bauermeister and Bunce, 2006) and as such, therefore, the mediating relationship between hormonal level, mental health and cognition is important to understand in the context of understanding cognitive decline in older age. Through comprehensive exploratory analyses we will explore both predictive and associative models with the data aiming to follow this study up using a comprehensive birth cohort, e.g., ALSPAC. Analysis Plan Item response theory (IRT) will be used to extract theta measures for mental health and to harmonise mental health scale variables within and across the cohorts (SB is a psychometric analyst). Childhood ‘hormone’ data will be extracted from self-report retrospective biographical data. Multiple regression analyses will be conducted as an initial exploratory procedure and thereafter, structural equation modelling will be utilised to investigate the longitudinal (childhood to adulthood) and mediation model data using latent constructs.
SB12182018-12-05Dr Sarah BuchananMovement, 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.
SBMB03212021-03-16Dr Sarah D BauermeisterSensory deficits and longitudinal cognitive and dementia outcomesSensory 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.
SC05232023-04-27Sujay ChakrabartyHyperglycaemia and White Matter Hyperintensity patterns in later-life – Insights from Insight46WMH, with the presence of WMH attributed to an increased risk in developing neurological conditions such as vascular dementia. Little is currently known however about the effect from hyperglycaemia on the shape and location of WMH. Our study aims to address how hyperglycaemia across adulthood is predictive of later-life location and shape of WMHV. De Bresser et al., are one of the few groups to have considered WMH shape and location in diabetic patients considering shape as a range of features such as eccentricity, diameter, and volume (de Bresser et al., 2018). The key findings were that most WMH presented in the frontal and parietal lobes and eccentricity was greater in these locations. We do this by analysing coalescence and gradient, two previously unused variables, in association to the location of the ventricles, with hyperglycaemia as an exposure variable; the exposure is measured at three time points with data being sourced from Insight-46, a sub-study of the 1946 NHSD study. Coalescence is measured as a summary score on a 0-4 scale weighted by volume. The score is calculated by measuring morphological erosion from neuroimages with 4 representing highest coalescence. Gradient is measured as WMH volume relative to location to the ventricles. By accounting for confounding factors such as occupational social class, we aim to answer two research questions: 1) Does hyperglycaemia affect the shape and/or location of WMH in adults? 2) Is this association still present after adjusting for other potential confounders. References: de Bresser, J. et al. (2018) “White matter hyperintensity shape and location feature analysis on brain MRI; proof of principle study in patients with diabetes,” Scientific Reports, 8(1). Available at: https://doi.org/10.1038/s41598-018-20084-y.
SC11222022-11-29Scott ChiesaCumulative exposure to BMI in early-life and mid-life cognitive function: a longitudinal analysis across three British cohortsA limited number of recent studies carried out in the early decades of the life-course have suggested that exposure to high BMI in adolescence / young adulthood may already impact cognitive function by the time an individual reaches middle-age, thereby potentially increasing risk of later-life dementia. Many of these studies are limited however by the absence of important childhood measures which may confound these associations, in particular childhood cognitive ability which is known to remain relatively consistent across the lifecourse, and also to increase risk of obesity as people age. Using data from three large British birth cohorts which contain 1) repeated measures of BMI across the first 50 years of life, 2) measures of cognitive ability in both childhood and middle-age, and 3) detailed information of a wide-range of oter factors that may affect any potential relationships between BMI and cognitive ability; this project aims to test associations between cumulative exposure to BMI across the early lifecourse and cognitive function in midlife.
SDZA11212021-11-07Surani De Zoysa AnthonyHeart rate variability to predict neuropsychological dysfunction in older ageAn 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.
SEL04202020-04-22Sara Evans-LackoLong term economic impact of childhood emotional and behavioural problems4. Brief description of project (no more than 1-2 sides A4 with up to 10 key references. 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. Specific objectives 1) To estimate the economic impact in mid and later life of mental health problems experienced by children and young people linked to health service use, educational attainment, criminal justice system contact (not available for NSHD), relationship breakdown, unemployment, productivity losses, and welfare benefits. 2) To examine how economic impacts related to having a mental health problem early in life change over the life course, overall and by sociodemographic characteristics and type and severity of mental health problem. 3) To understand how changes in educational, health and social care structures and policies (across cohorts) might influence these life course patterns in economic impacts. 4) To estimate the potential for long-term economic benefits of early interventions for mental health problems for children and young people, and to assess the scale of impact needed for such interventions to be cost-saving in the long-run. 5) To use our findings as a platform for future work which would investigate further how economic impact is affected by trajectories of persistence and onset of mental health problems in adulthood; and mediators of those trajectories with regard to potential targets for intervention. METHODOLOGY Economic and statistical analysis plans The sequence of analyses will be as follows: 1) For each cohort and each time point we will identify all variables that represent potential economic impacts in adulthood (from age 16 onwards). 2) Where cohort data are insufficiently detailed – such as when contact with a health service is recorded but not the frequency of contact – making it hard to calculate the associated cost, we will apply the closest estimates available based on other relevant UK studies, such as data from a relevant general population sample, such as the General Household Survey (1974), OPCS Survey of Disabled Adults in Private Households (1985) or Adult Psychiatric Morbidity Surveys (2000, 2007). 3) Costs associated with economic impacts will be estimated for all individuals over the periods spanned by the cohort datasets. Service-related costs will be estimated by combining data on service use with unit costs that pertained at the time the cohort data were collected, which we will subsequently adjust to a common price base (2015 levels). We will draw on contemporaneous sources where possible, and will use (e.g.) the annual PSSRU Unit Costs volume for health and care costs. We will estimate productivity losses under a human capital approach, based on unemployment (occupational status) and weekly earnings, adjusting for national contemporaneous unemployment rates. We will combine responses to questions about criminal justice contacts with data from the National Audit Office and Home Office to determine the costs of arrests and prison sentences. We will also link data on contacts with the criminal justice system to other studies which estimate the long-term costs of offending for specific groups such as young offenders and adults receiving prison sentences.1–3 Costs of welfare benefits will be based on data from the Department of Work and Pensions. 4) We will conduct sensitivity analyses that will show how our estimates of economic impact vary under different assumptions about (for example) simulated frequency measures, unit costs, productivity losses, price inflation and choice of discount rate. 5) Generalised linear models will be used to examine the relationships between presence of mental health problems during childhood and adolescence (occurring before age 16) and subsequent costs. At each assessment point, we will calculate economic impacts for each cost domain separately (e.g. health service use, criminal justice contacts, relationship breakdown, unemployment/productivity losses, welfare benefits) before looking at the aggregate impact weighted by monetary values. We will examine the association with mental health problems, overall and by subtype, adjusting for all relevant covariates. Issues with skewness often arise when dealing with cost data and we will attend to this in our analysis. A modified Park test, as proposed by Manning and Mullahy,4 will be used to select the most appropriate distribution to optimise the robustness of our estimates. 6) We will then investigate which sociodemographic and clinical characteristics (e.g., mild, moderate and severe conduct and emotional problems, relative to no problems based on established cut points5,6) are associated with adulthood economic impacts. We will also investigate the additional impact of individuals who have comorbid learning disabilities as we know this is associated with marked disadvantage in adulthood.7 Where measures differ between datasets or across time points, we will use standardised values so that the comparisons can be made. Based on previous analysis of the three cohorts, we will plan to adjust for socioeconomic background (assessed by occupational class of the father or mother if this was unknown) to remove potential confounding of these variable.6 We will be alert to the potential for selection bias when conducting our analyses. To address sample attrition, models will incorporate inverse probability weights derived from logistic regression analyses predicting availability of complete data on child mental health problems at the latest follow-up time point. We will also perform further sensitivity analyses and repeat key analyses unweighted, in order to examine the extent of the bias. Other studies examining similar outcomes in these cohorts have found no difference in the findings.8 List of references 1. Knapp M, et al. Economic outcomes in adulthood and their associations with antisocial conduct, attention deficit and anxiety problems in childhood. J Ment Health Policy Econ 2011; 14: 137–47. 2. Matrix Knowledge Group. The economic case for and against prison. London, UK, 2007. 3. National Audit Office. The cost of a cohort of young offenders to the criminal justice system. London, UK, 2011. 4. Manning WG, Mullahy J. Estimating log models: to transform or not to transform? J Health Econ 2001; 20: 461–94. 5. Colman I, et al. Outcomes of conduct problems in adolescence: 40 year follow-up of national cohort. BMJ 2009; 338: a2981. 6. Richards MAR. Childhood mental health and life chances in post-war Britain. Insights from three national birth cohort studies. 2009. 7. Maughan B, et al. Mild mental retardation: psychosocial functioning in adulthood. Psychol Med 1999; 29: 351–66. 8. Maughan B, et al. Pregnancy smoking and childhood conduct problems: a causal association? J Child Psychol Psychiatry 2001; 42: 1021–8. 9. Ferri, E, et al. Changing Britain Changing Lives. Three generations at the turn of the century. London: Institute of Education, University of London, 2003.
SG02212021-02-25Sarah GarfinkelThe dynamic relationship between cardiovascular predictors of mental health and autonomic neuroscienceHow 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.
SK12182018-12-17Sarah KeussInflammatory 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.
SM04202020-04-08Steven MorrisseyExamination of the relationship between sodium and potassium intake with cardiovascular health and blood pressure trajectoriesThe relationship of sodium and potassium consumption with blood pressure and cardiovascular health will investigated using data from a British birth cohort. This will help verify advice given regarding salt intake.
SM08192019-09-13Sarah MasonRelationship 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.
SR01212020-12-01Sumantra RayCausal pathways linking diet and cardiometabolic diseasesCardiovascular 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. Diet is another important factor in CVD prevention and management. Similar to other conditions, nutrientsconsumedasapartofindividual’sdietsinteractamongthemselvesandalsowithdifferent processes in the body that contribute to CVD risk. For example, consumption of diets that are rich fibre positively influence the management of glucose and bad cholesterol levels. Understanding which nutrients or particular diets are the cause of changes observed in CVD risk is essential to inform guidelines and practices in CVD prevention and management. Establishing a causal relationships between diet and CVD risk would traditionally require researchers to use experimental designs, such as randomized controlled trials. However, RCTs are not always feasible or practical in nutrition research, particularly in the CVD domain. For instance, it can take several years before CVD outcomes can be directly measured. Using observational designs is not without limitations, as unmeasured variables and other factors can create errors in estimations of effects of nutrients and diets on CVD risk. There are tools borrowed from causal inference thinking that can help to address some of the limitations in traditional methods used to analyse observational research, such as the development of causal diagrams. As such, the overall aim of this project is use tools from causal inference to disentangle the relative importance of particular dietary factors on CVD risk, but also the interconnections (pathways) between nutrients and diets and CVD risk.
SR09192019-09-12Sumantra RayNSHD Diet and CVD – Continuation of ongoing studyLongitudinal 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..
SS08192019-08-21Samuel SearleThe creation and validation of birth cohort frailty indices and life course risks of frailtyAt 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.
SS10222022-10-09Sivaniya SubramaniapillaiSex differences in the association between cardiometabolic and brain age: a longitudinal investigationGlobally, there are greater numbers of women than men with Alzheimer’s disease (AD). Although AD is complex, it is recognized that sex-specific factors (e.g., age at menopause) and cardiovascular risk (e.g., obesity) may contribute to accelerated brain aging and subsequent AD risk. Importantly, lifestyle factors such as increased physical activity could mitigate detrimental brain aging, although it is unclear how risk and lifestyle factors interact to influence brain aging processes. Our project will therefore investigate the influence of cardiometabolic risk in brain aging and AD risk over time and determine whether these relationships depend on i) sex, ii) sex-unique factors (e.g., menopause), and iii) lifestyle factors. Importantly, a greater understanding of how risk and lifestyle factors contribute to aging pathways separately in women and men can inform sex-/gender-specific healthy aging interventions.
ST03232023-03-28Stella TsoliUnderstanding the trajectory of frailty across the life course.Frailty refers to a person’s mental and physical ability to bounce back and recover from illness or injury. Frailty is widely used to guide the clinical care of older people. However, its relevance in people aged under 65 is not clear. This research will examine different approaches to frailty measurement in younger people. We will see if we can apply these measurements across the NHS. The aim is to identify the risk of future poor outcomes, such as changes in physical health or quality of life to direct earlier care and treatment. We will use national studies which have followed people since birth, to make a ‘frailty index’. This is a way of measuring the level of frailty and it can be applied to different groups of people over time. These work by identifying common factors associated with frailty and determining how many are present in any given individual. This results in a frailty index, higher scores of which are linked to adverse outcomes in older people. The birth cohorts allow us to look at factors from across people’s lives (e.g. socioeconomic position), which may influence frailty at any age. At the same time, we will test a Hospital Frailty Risk Score (HFRS), created automatically from NHS electronic records for people admitted to hospital in England. We will examine if this risk score is related to hospital outcomes such as long stays and survival. The frailty index and the HFRS will be linked to NHS electronic records in the same people. We can then see how the two different approaches to frailty measurement compare, for the available outcomes. Once we understand the factors associated with frailty in younger adults, we can think about polices or interventions that could be applied during a person’s life to slow or prevent the development of frailty. To inform and support this work, we will engage with lay and professional stakeholders with an interest in frailty in younger ages. Together, we will consider which changes in health or quality of life are meaningful to younger people with a range of long-term conditions. Using their perspectives on experiencing frailty earlier in adulthood, we will ensure our research is capturing what’s important, and that it will be useful. There will be widespread communication of the findings through lay briefings, a YouTube video, podcasts, and academic papers. In addition, we have strong links to national networks (including the NHS director for health inequalities) that are well placed to put the results of this work into practice.
SV07222022-07-04James ColeInsight_normative_modelApplying normative modelling techniques to map neuroanatomical heterogeneity
SVS07192019-06-28Sophie von StummHow 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?
SWJ11192019-10-29Dr Seow Wei JieBlood metabolomics and lung cancer riskLung 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.
TB01212020-12-17Thomas BartlettDNA methylation early-warning biomarkers for head and neck squamous cell carcinomaCancer 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.
TB03222022-03-15Thomas BrownWMH changes and relationships with amyloid load, brain atrophy and diffusion metricsIn 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.
TC11192019-10-29Thomas CollyerAutomated assessment of figure drawings in Insight 46This 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.
TESTMay20232023-04-05Louisa NeedhamSex differences in cognition and brain healthThis work will test whether males and females differed in their cognitive abilities measured throughout life - from age 8 into their seventies - and in their brain health measured using brain scans at age 70. The aim is to describe how sex differences (and similarities) might vary throughout life among individuals born in 1946, while considering how environmental factors (like education and smoking behaviours) might explain any sex differences.
TN08182018-08-15Tom NorrisHow 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.
TN12212021-12-10Tom NorrisLife course predictors of distinct grip strength trajectories from mid-life onwardsThis 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.
TP11202020-11-14Timothy PowellThe genetics of telomere attrition rateThe 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.
TP12212021-11-18Dr Thomas ParkerHead injury and hearing loss - predictors of longitudinal change in Insight 46Preventing 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.
ULSB02212021-02-04Ullrich Bartsch Sleep as a risk factor for dementia: collecting evidence from multiple cohort studiesSleep 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.
VB07182018-07-01Vishal BhavsarViolent victimisation and mortality in British Cohort StudiesCrime 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.
VEP01212021-01-22Valentina Escott-PriceDPUK/DRI Genetic ConsortiumDementia 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
VG08212021-08-31Victoria GarfieldType-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.
VMLB05212021-05-11Vidya Mohamed AliAnalysis of dietary and lifestyle factors predicting vascular riskThis 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.
WC01212021-01-04David CashRates of cerebral beta-amyloid accumulation in preclinical ADAlzheimer’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.
YFC07222022-07-31Zhou Juan, HelenStaging co-evolution of amyloid, tau and white matter hyperintensitiesIn this project, we aim to use data-driven machine learning techniques to stage the progression of neuroimaging biomarkers in Alzheimer's disease: amyloid PET, tau PET, and cerebrovascular disease.
YJC06202020-06-25Yu-Jie ChiouLife course physical activity on later-life cognition and brain healthUsing 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.
YL03222022-03-11Dr Yiwen LiuThe impact of persistent financial adversity across adulthood on cognitive decline and neurological changes in older adulthoodFinancial 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?
YL10212021-10-07Dr Yiwen LiuPathways from early adversity to mental ageing: A life course approachDepression 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.
YR01192019-01-24Y.M. RuigrokGenome-wide association analysis of intracranial aneurysmsRupture 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.

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