This is a list of the current studies approved and undertaking research in the Data Portal. Studies listed below have all been through the DPUK application process, and are undertaking analysis to answer a wide-ranging variety of research questions.

The study list provides information on the study itself, as well as the PI and the cohorts involved in the study.

Study Reference Study Title  Study Summary  Principal Investigator  Lead Institution  Approved cohorts 

A001

Predictors of successful cognitive aging in European superagers (90+): a cross-platform investigation of research and real-world evidence The aim of this collaborative European cross-platform project is to construct a database of 85-90 + year olds to facilitate the understanding of successful ageing. The outcome of the creation of this database has extensive opportunities in creating prediction models not only in epidemiological dementia-related research but also for epidemiological health-related research across the entire lifespan. Sarah Bauermeister University of Oxford CFAS, ELSA, Generation Scotland, Whitehall II, CaPS.

A002

Developing risk stratification models for identifying sub-groups of individuals who are at high risk of short-to-long term cognitive decline or dementia The aim of this work is to develop and apply statistical methods to DPUK cohorts to identify subgroups of individuals that are at high risk of rapid future cognitive decline. Statistical models will be developed using measurements of cognitive functioning, biomarkers and genetic data, providing insight into disease processes and predicting an individual's risk of cognitive decline before symptoms have developed. Brian Tom University of Cambridge ELSA, Generation Scotland, CFAS, CaPS, Whitehall II.

A003

Using longitudinal data from multiple studies for predicting Alzheimer’s disease The project objective is to make use of multiple population studies in the MRC Dementias Platform to better predict, from the evidence of the database and individual characteristics, whether a specified individual will develop Alzheimer’s disease within a given future period. The primary goal of this analysis is to support the efficient design of clinical trials Terry Lyons University of Oxford ELSA, Generation Scotland.

A004

BMI and cognitive function: an investigation of its non linear association To identify the age at which the association between BMI and cognition changes direction. Knowing when the change occurs will be important for informing the development of accurate protocols for calculating dementia risk in different age groups. This is important for the development of intervention strategies focused on improvement/maintenance of cognitive function across different age groups. Catherine Calvin University of Edinburgh ELSA, Generation Scotland, Cam-CAN, Airwave.

A005

Validation of a model to predict MMSE in incident AD dementia cases The first objective of the study is to validate a simple natural disease progression model in people with AD. The study supports work packages 3 and 4 of the ROADMAP initiative. Objective of Use Case 1 of ROADMAP is to build a disease progression model that can be used, for example, for the health economic evaluation of the efficiency of different treatment pathways. The study is thus part of WP4’s effort of validating selected disease models which can be used to establish a sequence of disease stages. It additionally supports WP3’s pilot exercise of data extraction, harmonisation, integration and analysis. Christoph Jindra University of Oxford Whitehall II

A006

Integration and analysis of heterogeneous big data for precision medicine and suggested treatments for different types of patients (IASIS) The main objectives are to design a unified conceptual schema to represent diverse sources of available data; build an adaptive system able to manage data and content collected incrementally; provide actionable knowledge about disease diagnosis, prognosis, and treatment to policy makers; promote cooperation among clinicians and policy makers; define privacy- and trust-aware strategies. Eleftherios Samaras St. George's, University of London Cam-CAN, ELSA, ICICLE-PD.

3

Validation of a model of cognitive decline and time to first diagnosis of mild cognitive impairment or dementia due to Alzheimer’s disease (AD) in the elderly The main objective of the study is the validation of a model of cognitive decline and time to first diagnosis of mild cognitive impairment or dementia due to Alzheimer’s disease (AD) in elderly, cognitively normal individuals at risk to develop symptoms of AD. Christoph Jindra University of Oxford ELSA

132

The longitudinal relationships between mental health and cognitive change: a cross-cohort multivariate growth curve modelling approach This study proposes to use existing mental health and cognitive data in five existing cohorts which have at least three longitudinal waves of data. Individual mental health disorders (e.g., depression, anxiety and stress) will be examined and the associations with overall cognition and individual cognitive domains will be explored through latent cognitive and mental health constructs. Sarah Bauermeister University of Oxford ELSA, Whitehall II, CFAS.

133

Applying latent change score modelling to assess individual differences in cognitive change over time The aims of this study are: first, to assess different cognitive tasks as cognitive performance indicators of individual cognitive change and, second, to understand the other associative phenotypic indicators of cognitive change using latent change score modeling. Sarah Bauermeister University of Oxford ELSA, Whitehall II, CFAS.

136

DPUK Data Discovery Tools Categorisation and Coding Programme Dementias Platform UK (DPUK) proposes to develop its own Data Discovery Tools so that they become highly categorised, enabling researchers to more clearly identify cohorts which are applicable for their research proposals. This will be a data variable investigation, not an analytical investigation and no data will be analysed and no summary statistics will be computed. Sarah Bauermeister University of Oxford Airwave, Ample, BDR, Cam-CAN, CamPaIGn, CaPS, CFAS, CFAS II, DIAN, ELSA, EPIC Norfolk, Generation Scotland, GENFI, HWW, ICICLE-PD, Lewy Pro, Whitehall II, Track HD, SABRE, PROTECT, PRIME, PICNICS, OPDC Discovery, Nimrod, MRC NSHD.

137

The effectiveness of cholinesterase inhibitors in dementia due to Alzheimer's disease - Evidence from real world data The aim of the study is to enrich the evidence on all three acetylcholinesterase inhibitors (AcEIs) by looking at their effectiveness in more realistic settings. A number of real world data (RWD) and different outcome measures will be used to produce evidence on how effective the drugs are outside of the setting of clinical trials. Additionally, the effects, found in the RWD, will be compared to those of more homogenous populations of placebo arms of randomised control trials. Lastly, the study will explore between-person heterogeneity in trajectories and test which variables are predictive of response to the drugs. Christoph Jindra University of Oxford Whitehall II

140

Prevail Parkinson's Disease Natural History Prevail Therapeutics aims at developing gene therapy for Parkinson's disease. The current study aims at improving and refining our knowledge of the natural history of the disease, to design more efficient clinical trials and increase the odds of providing a cure for this disease. Hervé Rhinn Prevail Therapeutics, New York CamPaIGN, ICICLE-PD, PICNICS.

143

Associations between childhood hormonal indicators, adult hormones, mental health and cognition: A UK Biobank and DPUK cross-cohort study By using existing population cohorts with retrospective proxy measures of early childhood hormonal proxy indicators, this study will explore an extrapolated childhood hormone level, 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. Sarah Bauermeister University of Oxford MRC NSHD, UK Biobank, Whitehall II.

144

Effect of childhood adversity on adulthood behavioural, psychological, cognitive and health outcomes: The main aim of this study is to investigate associations between adverse childhood experiences and adult behavioural, psychological, cognitive and health outcomes, using self-report retrospective data across three population cohorts. This study will be followed by a birth-cohort study using ALSPAC data. Sarah Bauermeister University of Oxford ELSA, UK Biobank, MRC NSHD, Whitehall II. Substudy: Twins UK, ALSPAC.

145

Brains for Dementia Research - Curation, and analysis of data. We wish to "curate" the BDR data set, i.e. create usable datasets going forward for other researchers, as discussed in the BDR meeting in Cardiff. This will allow other users of the BDR dataset in the future to be able to access the data through the data portal in the best possible way. Georgina Menzies Cardiff University BDR

146

Investigating the longitudinal associations between earlier adult lifestyle activities, physical fitness, social engagement, biomedical health, mental wellness and later-life cognition: Investigating cognitive preserve and reserve in the ELSA population cohort. This study proposes to conduct multiple individual analyses to investigate associations between lifestyle activities, physical fitness, social engagement, biomedical measures, mental health on the longitudinal outcome of later life cognition in the population cohort, ELSA. Andrey Kormilitzin University of Oxford ELSA

147

Harmonising large-scale imaging databases to provide integrated assessments of the role of white matter hyperintensities in cognitive aging This study aims to develop and refine tools for harmonising measurements of white matter hyperintensities (WMH) in existing DPUK cohorts. This will permit an assessment of replicability of WMH measurements across studies, and an analysis of the relationship of WMH to demographic and cognitive variables. The harmonised WMH measures will be delivered back on the DPUK portal, and the harmonisation tools will be made available as a DPUK App. Ludovica Griffanti University of Oxford UK Biobank, Whitehall II - Imaging variables.

149

The role of metabolic and cardiovascular disease and treatments in cognitive decline The aim of this study is to investigate the role of Cardiovascular and metabolic diseases (M/C-D) and treatments on cognitive decline. It remains to be determined (1) Whether controlling M/C-D as a whole alters cognitive decline; (2) Whether known medications for M/C-D modify cognitive decline and (3) whether surrogate or proxies for M/C-D alters cognitive decline. Danielle Newby University of Oxford ELSA, CaPS, Whitehall II, Airwave.

152

Characterizing associations between apolipoprotein (APOE) e4 genotype and accelerated brain aging The central research question of this study is whether new tools developed by the study Principal Investigator for measuring brain structure can improve understanding of links between brain structure and the APOE e4 allele, using the Lothian Birth Cohort 1936 (LBC1936) dataset. Christopher Madan Nottingham University LBC1936

156

Identifying reliable change using cognitive tests in ageing and dementias research. The primary aim of this study is to more accurately characterize individual level change in cognitive functions. This study proposes to apply IRT methods from the field of psychometrics to cognitive functioning and ability data from cohort studies of dementia. The methodologies proposed are uniquely suited to the study of reliable individual level change. Tom Booth University of Edinburgh CamPaIGN, ELSA, ICICLE-PD, CFAS, CFAS II, LBC 1936, CaPS.

157

Exploring the associations between Mediterranean diet adherence and cognitive function, brain imaging parameters, and dementia incidence in a UK cohort This research will further DPUK’s aims of identifying dementia prevention strategies by helping understand if a Mediterranean diet, or individual food components of this diet, improve cognition function and reduce dementia risk. Moreover, the research findings will assist the design of future intervention studies that target healthy brain ageing by identifying specific MedDiet components to prioritise. Mario Siervo Newcastle University Whitehall II

158

Have we overestimated the impact of vascular factors on the declining incidence of dementia? DPUK-NIA cross-cohort collaboration This proposal aims to investigate how much impact vascular factors have had on the current declining trend of dementia incidence in the UK and US. Chi-Hun Kim University of Oxford ELSA, Whitehall II, CaPS.

159

Effects of mental health status on putative biomarkers of cognitive decline It is well established that psychiatric symptoms are associated with cognitive decline and neural degeneration in older age. This study aims to evaluate this association by looking at the associations between mental health status, biological indicators of stress reactivity, cognitive status, cognitive function and brain structure and function. Delia Alexandra Gheorghe University of Oxford Whitehall II

162

Socioeconomic inequalities, cognitive reserve and dementia (SICRAD) – Dementia Platform UK (DPUK) This project intends to investigate the socioeconomic inequalities influencing cognitive reserve and apply recent methodological and statistical advancements to reach two distinct objectives in a large-scale data through DPUK. Dorina Cadar University College London ELSA

169

Using Item Response Theory (IRT) and Computer Adaptive Testing (CAT) to process and analyse DPUK scale data: Improving the efficiency of self-report scale analysis and delivery in epidemiological research Using self-report scales (mental health, lifestyle, mood and quality-of-life scales) for detection of longitudinal change in epidemiological research is an effective and widely used method of data collection. However, few scales are designed for epidemiological use and are psychometrically inefficient. Using CTT to analyse scales has some limitations such as providing only a single metric, total score. This study proposes to use IRT to scale data. Sarah Bauermeister University of Oxford Whitehall II, Airwave, MRC NSHD.

170

Adult trajectories of inflammatory and cognitive change from mid to late life: A cross-cohort comparison study The principal aim of this study is to investigate whether within-individual change in the inflammatory biomarker C-reactive protein, in longitudinal follow-up, helps to predict later cognitive function, cognitive trajectories, and, 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). Catherine Calvin University of Oxford ELSA, MRC NSHD, Whitehall II, UK Biobank, CaPS.

174

Parkinson's Disease ACE Simulator (3) The goal of this study is to develop multivariate equations that characterize the risk and rate of long-term disease progression. The equations developed by analyzing the datasets, and inputs obtained from other data sources, will then be used to support the development of an individual patient simulation that simulates the clinical progression of Parkinson's Disease, accounts for quality of life, and can predict long term (e.g., lifetime) health outcomes and costs. Alex Ward Evidera Pharamaceuticals, Bethseda, MD, USA. ICICLE-PD

179

Thromboembolic Events The aim is to quantify the attributable risk of Ig independent of, and in interaction with, traditional risk factors. Once this is completed, the aim is to create a simple scoring system that allows clinicians to summarise the overall risk of myocardial infarction, stroke, and transient ischaemic attacks in neurology outpatients, similar to the CHADSVASC2 score widely used. Mahima Kapoor University College London OPDC Discovery

181

The multiple dimensions of ageing well: Characterising the health and well-being profiles of older adults using physical, psychological, cognitive, functional, and social measures The objective of this study is to characterise the health and well-being profiles of older adults using physical health, functional status, mental health, cognition and social engagement data from three existing cohorts. It will then be investigated whether these profiles are differentially associated with sociodemographic and lifestyle factors, and whether they predict health outcomes such as incident dementia, chronic disease and mortality. Ruby Tsang University of Oxford ELSA

182

Genetic characterisation of neuropsychiatric symptoms in Alzheimer's disease The overall aim of this project is to identify and characterise genetic risk for neuropsychiatric symptoms using the largest data set in the world. Specifically, the study aims to: Determine the genetic overlap between AD-P and other clinical and non-clinical putative associated phenotypes; Identify novel loci associated with AD-P by conducting the largest ever GWAS in a total sample of over 10,000. Byron Creese University of Exeter BDR

184

Assessment of the role of common genetic variants for Alzheimer’s disease on clinical characteristics within the Brains for Dementia Research cohort The overarching aim of this proposal is to explore the clinical and neuropathological outcomes of a high genetic burden for dementia in the Brains for Dementia Research (BDR) cohort. The results of this study will provide further information regarding the complex interplay of genetic risk, clinical presentation and neuropathological burden. Eilis Hannon University of Exeter BDR

185

Life course social- and biomedical risk factors for cognitive and physical health in later life 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. Bernadette van der Linden University of Geneva MRC NSHD, Whitehall II, UK Biobank.

186

Stratifying Resilience and Depression Longitudinally Progress in understanding the pathophysiology of depression has been severely restricted by its aetiological heterogeneity. Our contention is that longitudinal and quantitative assessment of individuals stratified by key exposures and course modifiers will reduce dilution across diverse aetiologies, measurement error and capture more of the biological variation. It will thus enable the genetic and neurobiological mechanisms underlying enduring resilience, depressive symptoms and depression to be determined. Andrew McIntosh University of Edinburgh Airwave

188

The temporal inversion of cardiovascular risk factors for cognitive impairment and dementia There is an extensive literature indicating that classical cardiovascular risk factors (hypertension, overweight and hypercholesterolaemia) in midlife are associated with cognitive impairment and dementia in later life. On the other hand a smaller but interesting literature suggests that the direction of these risk factors inverts over time, as they become proximal to the cognitive outcomes.; for example hypertension to hypotension, overweight to underweight. This study will investigate the possibility of this temporal inversion of blood pressure, body size and shape, and blood lipid profiles, in DPUK cohorts that span midlife and later life. Marcus Richards University College London MRC NSHD, SABRE

189

The Airwave Health Monitoring Study (AHMS) of the British Police Forces The objectives of this study are both to extend the follow-up of the Airwave Health Monitoring Study (AHMS) to Scotland and Wales, and to provide a resource for studying how gender, lifestyle, and occupational exposures interact with genetic and metabolic factors in relation to physical and mental health. Martie van Tongeren University of Manchester Airwave

191

Predicting different risk subgroups of developing dementia and cognitive impairment in longitudinal cohorts – doubly robust survival trees method The current project plans to apply doubly robust survival trees method to predict subgroups with different risk of developing dementia and to identify predictors for each subgroups. Public health policies can prioritise high-risk groups for resource allocation and risk management. Scientists can conduct further studies to investigate biological and social mechanisms clustering the different risk subgroups. Chi-Hun Kim University of Oxford ELSA

192

Cognitive reserve as a protective factor in Parkinson's and Huntington's disease The aim of the current project is to examine the effect of cognitive reserve on cognitive impairment in both Huntington’s (HD) and Parkinson’s disease (PD). More specifically, we will test whether cognitive reserve has a neuroprotective role in cognitive impairment and whether this can be generalised across two different types of dementia. Marina Papoutsi University College London TRACK HD

194

The Airwave Health Monitoring Study (AHMS). An Occupational Cohort Study of the British Police Forces. The Aim of the present proposal is to greatly enhance the Airwave Health Monitoring Study (AHMS) occupational cohort of police officers and staff as a major resource for studying the health and well-being of the British police forces. Evangelia Demou University of Glasgow Airwave

195

How does alcohol intake influence diet quality and contribute to cardio metabolic risk in a UK population? The aims of this study are: to explore the association between dietary pattern and risk factors of CVD in a large UK population cohort; capture alcohol consumption in a large UK population cohort; explore the association between diet quality and alcohol consumption; within measures of alcohol consumption, explore the relationship between alcohol consumption and risk factors of CVD; explore the association between alcohol consumption, diet quality and variance in the genome in a large UK cohort. Jennifer Griffin Imperial College London Airwave

197

The association of diet quality, body composition and cardiometabolic risk in UK population This PHD project will explore the correlation between diet quality, body composition (across different ranges of body mass index) and future cardiometabolic risk.. Diet quality will be studied using 7-day diaries and will be defined using DASH score. Future risk of CMS will be mainly defined using metabolic syndrome severity score. Body composition independent of BMI will be associated with future risk of cardiometabolic syndrome in order to have a better understanding of the effect of waist circumference and the total percentage of body fat on the future risk of cardiometabolic syndrome development. Dana Hajjar Imperial College London Airwave

199

Can diet influence genetic risk in abdominal adiposity and the risk of hyperglycemia This study will measure the effect of diet on gene translation regarding central obesity and the risk of IGT and T2D. In addition to introducing new methods in diabetes care and early detection and prediction of populations under high risk, aiming to reduce the incidence and the burden of diabetes and its complication. Anwar AlBaloul Imperial College London Airwave

201

Healthcare utilisation in early and late onset dementia The current focus of healthcare services, such as hospitals and care homes, being on people with Late Onset Dementia. This study aims to expand on these findings and assess the frequency and reasons for health service use (hospitals, emergency departments, care home, day centres) by people with Early Onset Dementia. Paraskevi Zafeiridi Queens University Belfast BDR, PRIME, Whitehall II.

202

Clinical and neuropathological diagnosis mismatch The aim of the study is perform a comprehensive clinicopathological study of BDR donations to investigate the agreement between clinical and neuropathological diagnosis and the sensitivity differences in different disease subtypes. Kirsty McAleese Newcastle University BDR

205

Depression and Cardiometabolic Abnormalities as Potential Risk Factors for Dementia The project investigates the prospective relationship of depression and cardiometabolic abnormalities (central obesity, raised triglycerides, low HDL cholesterol, hypertension, hyperglycemia, type 2 diabetes and increased inflammation) with risk of dementia. The study also includes investigation of potentially modifiable risk factors for dementia and design of a holistic risk prediction model for dementia. Panagiota Kontari University of Surrey Whitehall II, CaPS, UK Biobank, Generation Scotland.

206

Cross-sectional investigation of diurnal eating patterns and cardiometabolic health This research will define diurnal eating patterns (i.e., based on energy distribution recorded in pre-defined eating occasions) in the Airwave Health Monitoring Study using 7-dietary records, and determine whether, and to what extent, specific diet patterns show associations health by relating the patterns to cardiometabolic biomarkers (incl. HbA1c, LDL, HDL, CRP), blood pressure, and body composition (% body fat from bio-electrical impedance). Rachel Gibson King's College London Airwave

207

The Influence of Polyphenol Consumption and Metabolism on Measures of Brain Structure and Function Associated with Cognitive Decline We intend to investigate the impact of varied dietary consumption of polyphenols, and subsequent polyphenol metabolism, on measures of cognitive health (including mental health descriptors such as depression) derived from cognitive tests and magnetic resonance imaging (MRI)-derived structural/functional phenotypes related to dementia. Elliott Dryer-Beers Imperial College London Airwave

208

Refining risk factors for depression during Alzheimer's Disease This study proposes to: 1) Characterise individuals in the BDR cohort who develop depression during AD by examining known risk factors for depression in the general population e.g socioeconomic status, stressful life events, use of alcohol/illicit drugs, concomitant physical illness and history of mental health problems. 2) Calculate the odds ratio of developing depression during AD for the lowest and highest quartile of polygenic risk score for depression. Lindsey Sinclair University of Bristol BDR

209

Stressors, wellbeing and mental health: an empirical economic approach The overall objective of this study is to provide the economic literature with empirical evidence on the relationship between stressful events and mental health and wellbeing. The Whitehall II data are the best available dataset to identify these relationships, as they collect all the variables we are interested in: stressful events, cortisol hormone levels, individuals’ personality traits, attitudes towards stress, early exposure to stressful life experience, and mental health and wellbeing. Veruska Oppedisano University of Westminster Whitehall II

210

Cortical diffusion investigation in Dementias In this proposal, we want to study the neural architecture changes across a range of stages of Dementia, using an MRI index of microstructural change in the brain tissue, obtained by a novel Diffusion tensor imaging (DTI) analysis. This new MRI DTI method is applied to Grey Matter in order to investigate the regularities in cortical organization that are linked to the arrangement of cells and neurites. Mario Torso University of Oxford NIMROD, Cam-CAN.

212

Robust training of recurrent neural networks to test the mental comorbid disorders of cognition: a UK Biobank and DPUK cross-cohort investigation The aim of the study is to examine the role of anxiety and depression as comorbid disorders of cognition. This study will apply a sequence learning based machine learning techniques to jointly model the longitudinal data and offer an alternative continuous, non-parametric test of mental comorbid disorders. Chenlu Li University of Oxford ELSA

213

Associations between coffee, coffee (poly)phenols and cardiovascular disease risk factors The aim of this research is to investigate the associations between coffee and coffee (poly)phenols and CVD risk factors. It is hypothesised that consumption of coffee (poly)phenols will be inversely associated with CVD risk factors. The objectives are to 1) to estimate coffee intake and hence coffee chlorogenic acid intake and 2) to associate coffee and coffee chlorogenic acids with CVD and its risk factors in this cohort. Charlotte Mills University of Reading Airwave

216

Understanding the role of mutation burden in human lifespan and healthspan We aim to analyze whole exome sequencing data accompanied by individual lifespan to improve our understanding how mutation burden shape human longevity and age-related diseases. Our preliminary data suggests that effect of same mutation on phenotype may change across human lifespan, most likely due to age-related transcriptomic and epigenetic changes. Also, some variant categories have higher association with lifespan than others. We anticipate that by targeting pathways causing age-related increase in detrimental effect of mutation, we can extend human lifespan and delay age-related disease. Anastasia Shindyapina Harvard University BDR

221

Electrophysiological phenotyping for complex arrhythmogenesis Cardiometabolic and chronic inflammatory phenotypes, such as obesity, insulin resistance and arthritis, are known to induce electrophysiological changes which may confer increased risk of arrhythmia. Changes in clinical biomarkers, for example waist:hip ratio (WHR), glycosylated haemoglobin (HbA1c) and C-reactive protein (CRP), inform clinical treatment but may also reflect electrophysiological remodelling to predict arrhythmogenesis. To investigate this hypothesis, we intend to determine if there are any specific identifiable differences in 12-lead ECGs between participants with (1) high vs low WHR (2) high vs low HbA1c (3) high vs low CRP, to determine if obesity, diabetes and chronic inflammatory, respectively, are important factors in electrophysiological remodelling. Identifying biomarkers in this manner at a population level will inform focused, deeper phenotyping of patients at higher risk of cardiac arrhythmia in our intended prospective clinical studies Fu Siong Ng Imperial College London Airwave

223

Decomposing health inequalities in cognitive ageing Previous research has shown that one’s socio-economic status can explain differences in cognition (for example Cermakova, 2018) and is associated with differential risks of developing dementia (for example. Cadar, 2018). However, we do not know which factors and group characteristics are behind these differences across levels of social status and how important they are. The present study contributes to the closing of this research gap by looking at the importance of socio-economic status from a different perspective. Instead of trying to estimate the potential effect of the socio-economic status, the study uses Oaxaca-Blinder type decompositions to find differences in group characteristics between high and low socio-economic status that contribute to the observed differences between groups. The study looks particularly at lifestyle factors and comorbidities. Christoph Jindra University of Oxford ELSA

233

0144 Substudy focussing on Genomic and Imaging data. The effect of childhood adversity on adulthood behavioural, psychological, cognitive and health outcomes: A UK Biobank and DPUK cross-cohort investigation This study is a bridging study to DPUK project 0144 and is a multi-modality study utilising gentic and imaging data in the MRC NSHD and UK Biobank cohorts to investigate APOE status and structural brain outcome outcome/mediation effects. UK Biobank application 15008 will be utilised for this study. Sarah Bauermeister University of Oxford MRC NSHD, UK Biobank.

234

Apolipoprotein e genotype and healthy brain ageing: stratification, modification and outcomes. This project will make use of Dementia’s Platform UK: including several unrelated ageing cohorts with varying demographic and phenotypic characteristics, to understand under what conditions modify the APOE e4 effect, and via what mechanisms. Donald Lyall University of Glasgow ELSA, CFAS, Generation Scotland, GERAD, NICOLA

235

Deciphering the effect of lifestyle exposures on immune-cell compositions via -omics data integration In this project, we propose a novel approach for the integration of data already available such as those of Airwave Health Monitoring Study to highlight a mechanism poorly understood at the base of differential methylation derived by EWASs. In particular, we want to investigate whether the shift in cell-type composition and/or the DNA methylation signatures associated with an exposure, like tobacco smoking known for affecting the cell-type composition, are shared by other exposures or whether they are exposure-specific. EWASs are usually conducted on DNA derived from whole blood and the variation in leukocyte proportions may confound true epigenetic associations between methylation and the outcome of interest. Paolo Vineis Imperial College London Airwave

236

APOE status, cognition, mental health, sleep patterns and cortical atrophy in Parkinson’s disease: A multi-modal study utilising DPUK infrastructure PD is a multi-faceted disease that warrants a multi-disciplinary research approach. Although primarily classified as a neurological movement disorder, PD presents itself with co-morbid symptoms such as poor mental health, sleep disorders and cognitive impairment. We propose to investigate multiple mechanistic pathways through a multi-modality approach using phenotypic, genetic and imaging data across four DPUK datasets: UK Biobank, the Deep and Frequent Phenotyping (DFP) study, Generation Scotland and ICICLE-PD. We will conduct a cross-cohort analyses within the DPUK Data Portal investigating associative and predictive pathways using machine learning and structural equation modeling. Furthermore, we will also conduct imaging analyses of structural brain images to assess brain atrophy and reorganisation of structural networks. Sarah Bauermeister University of Oxford Generation Scotland, ICICLE PD, UK Biobank

239

Mediterranean dietary patterns in British population and their association with 10-year cardiovascular disease risk The aim of this cross-sectional study (Master of Research project) is to provide information on whether and how a Mediterranean-style diet is associated with a smaller cardiovascular disease risk in adult UK population. Kris Elomaa Imperial College London Airwave

240

Prediction of real-world clinical utility of PET Amyloid scanning using routinely available cognitive and genetic information The NHS currently does not routinely commission PET-amyloid scans. Given the numbers of patients presenting annually to UK memory assessment services (MAS), the introduction of amyloid-PET imaging as routine in MCI may be prohibitively expensive. We wish to examine if we can develop a clinically relevant prediction tool to help clinicians detect patients in whom PET-Amyloid scanning would give the greatest information gain (and therefore clinical utility). We aim to use data that is clinically available currently, including the Samsung cohort. We envisage that this will increase the ability of leading clinicians to prove to commissioners that targeted use of PET amyloid imaging is possible, useful and cost-efficient. Ross Dunne University of Manchester SMC Amyloid PET

243

Understanding the Contributions of Multiple Pathologies to Dementia in the BDR Programme This proposal is for a PhD student to study valuable data from these >800 study participant brain donations in the BDR cohort (all available at the time of the PhD) and to examine the relationship between the clinical measures in life and these different underlying pathologies using sophisticated statistical methods. This will include weighing up which diseases or disease combinations are the most important in causing dementia. Dementia treatments so far aimed at treating Alzheimer’s disease have failed in part because most people have other diseases causing their dementia. Therefore, future dementia treatments will need to be treatment combinations which target the different underlying diseases and which are informed by knowledge of the diseases that are more important to treat because they have larger effects. Alan J Thomas Newcastle University BDR

244

Effects of APOE e2 on Hippocampi Shape This proposal aims to determine the extent to which the Apolipoprotein E (APOE) ε2 allele protects the left and right hippocampus from atrophy in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. We propose to aggregate MRI structural scans of APOE ε2/ε2, ε2/ε3, and ε3/ε3 subjects, segment hippocampi, and compute shape metrics. Using either clinical diagnoses of cognitively normal, MCI, and AD or inferred diagnositic categories derived from cognitive measures, we will investigate whether or not dosage of APOE ε2 is correlated with shape differences across diagnostic categories. Scott Neu University of Southern California Generation Scotland, ICICLE PD, DFP

246

Identifying predictors of reversion across the dementia spectrum The aim is to identify what predicts if a patient will show improvement in their cognitive status over time. Although the majority of people diagnosed with mild cognitive impairment will stay impaired over time, or get worse, a subset of patients (20-30%) show improvement. Because these patients get better, and not worse, the study will also help clarify which factors give patients a lower risk of developing dementia in the long-term. Michele Veldsman University of Oxford ELSA, GERAD

247

PETRUSHKA: Prescribing the Right Antidepressant for Depression in Adults. Our study aims to extract data in parallel from randomized clinical trials and observational studies.We will then use both an epidemiological approach and a machine learning approach to combine randomised and observational data to build a treatment algorithm. Andrea Cipriani University of Oxford ELSA, CFAS, CFAS II

248

Is Neuroinflammation the missing link between depression and Alzheimer’s disease? We propose to examine the relationship between depression and Alzheimer's disease by examining whether anti-inflammatory medications affect the effect of depression on performance on cognitive tests. Lindsey Sinclair University of Bristol ELSA, Generation Scotand, Whitehall II

249

GWAS of Epigenetic Clocks The study will perform a GWAS analysis of 'age acceleration' calculated from various DNA methylation based 'epigenetic clocks'. Oliver Robinson Imperial College London Airwave

250

On the relationship between depression and cognitive function Depression has often been linked to poor cognitive function and higher risk of dementia. However, the relationship is still not well understood and different hypotheses are being postulated linking depression and cognition (Bennett and Thomas 2014; Byers and Yaffe 2011; John et al. 2019). For the present research, we will focus on testing three specific hypotheses that can be found in the literature. We will specifically look at the aetiological risk factor hypothesis, the reversed causality hypothesis and lastly the possibility that depression and cognition are in fact two separate processes and any association between the two is due to earlier confounders. Christoph Jindra University of Oxford ELSA

253

Effects of APOE e2 on Hippocampi Shape (Addition) This study is an amended version of Study 0244 that forms part of a cross-platform interoperability pilot study using multi-modal data Scott Neu University of Southern California Generation Scotland, ICICLE PD, DFP

257

Stratified medicine approaches to drug repurposing for Alzheimer’s disease The specific aims of this study include: - Integration the multiple categories of data from the Alzheimer’s disease cohorts for the identification of subgroups among the patients, and the key biomarkers for such stratification. - Characterization of Alzheimer’s diseases in terms of clinical and molecular biomarkers, and associate some major subgroups with clinical outcome. - Pilot research into drug repurposing for the identified sub-groups of Alzheimer’s disease. This research may help to generate preliminary data and new hypotheses regarding the pathogenesis and progression of the disease, and also provide effective prevention and treatment options for Alzheimer’s disease. It has the potential to ultimately benefit AD patients, their families and the wider public. Shu-Dong Zhang Ulster University GERAD

261

Alzheimer's Disease Inter-operability Pilot Project The objective of this project is to develop a data platform interoperability infrastructure and toolset to support AD research through a federated interrogation of disparate AD datasets and on-demand access to datasets, tools and services across data platforms.It is envisioned that this initiative will help to promote and accelerate the sharing of AD research data and lead to breakthroughs in the research of novel AD treatments as well as other related dementias. Amanda Borens C-Path Institute ELSA, GERAD

263

Metabolomics of Asthma, Lung Function, and Immunoglobulin E (IgE): a Consortium of Metabolomics Studies (COMETS) analysis The aim of this study is to better understand the biology of asthma. This aim is rooted in the hypothesis that asthma, is a function of both genetics and the environment, and the interactions between them, and that therefore metabolomics, which captures the downstream products of gene-environment interactions, is the ideal tool with which to study asthma. Elucidating the pathogenesis of asthma lays the ground work for the development of novel preventative and therapeutic strategies for asthma- a condition that imparts a substantial morbidity and mortality burden globally. The use of metabolomics in particular, provides a unique opportunity for the development of novel biomarkers that could be useful in diagnosis and monitoring this prevalent condition. Jessica Lasky-Su Harvard University Airwave

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Cognitive reserve and dementia incidence The overall aim of this study is to investigate the association between a rich assessment of cognitive reserve and its subcomponents (education, work, and leisure) in relation to subsequent dementia incidence in various longitudinal studies of ageing as well as in a harmonised dataset from the studies. Pamela Almeida University College London ELSA

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Replication in AIRWAVE of metabolome-genome cross-links related to blood pressure from INTERMAP We have previously found in the INTERMAP cohort 31 associations of urinary metabolites with blood pressure. These metabolites relate to a variety of metabolic pathways by which these can affect blood pressure. A number of metabolites point to a dietary origin, whereas others relate to gut microbial metabolism. We now want to replicate in AIRWAVE these associations between urinary metabolites and blood pressure previously found in INTERMAP and in addition test whether these associations are causal or remain after we control for genetic factors associated with metabolic syndrome. This analysis allows for studying in greater detail the pathways that are perturbed in hypertension that may point to potential treatment or prevention strategies. Joram Matthias Posma Imperial College London Airwave

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Study Name: Component-Specific Air pollutant Drivers of Disease Risk in Early to Midlife: a pathway approach (DREaM) The causal pathways linking early environmental exposures to poor long-term health remains unclear. The DREaM study will use AIRWAVE data to identify the most health relevant components of the air pollution mixture, by establishing whether exposure to pollutant components is associated with increased CVD risk, including differential patterns of gene methylation, and with pre-existing biomarkers of increase CDV risk. We aim to focus on early to mid-life exposures, as potential predictors of poor health outcomes in later life, by linking air pollution exposures to known pre-clinical risk factors in adults and examining epigenetic changes to DNA, triggered by environment stress. Daniela Fecht Imperial College London Airwave

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Exploration of the rate of progression in Alzheimer's disease The objectives of this project are 1) to establish a valid measure of disease progression in AD, 2) to run genome-wide association analyses on the most robust measure of AD progression, 3) to run additional genetic analyses, including AD and AD progression PRS. We aim to combine the data requested with a large and well-phenotyped in-house cohort (N ~ 1,200) as well as the publicly available Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). Valentina Escott-Price Cardiff University Whitehall II

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The impact of vision-enhancing interventions on the onset and progression of dementia This study explores the effect of the use of corrective lenses on the cognitive decline of individuals with MCI and dementia. We examine if vision-enhancing interventions, that can optimize visual function in elderly patients, can reduce the risk of dementia onset and slow dementia progression. Magda Bucholc Ulster University ELSA