
Danielle NewbyUniversity of Oxford | OX · Department of Psychiatry
Danielle Newby
PhD Pharmacy - Computational Chemistry
Dementia prevention, Epidemiology, Real World Data, Causal Inference, Drug Repurposing
About
93
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Introduction
I am an early career dementia researcher with an interdisciplinary background in epidemiology, machine learning and pharmacology. Since April 2016, I have been working as a post-doctorate researcher in the informatics team of the Translational Neuroscience and Dementia Research Group jointly led by Sir Professor Simon Lovestone and Professor Noel Buckley.
My main areas of research within the team involve the analysis of real-world data such as medical electronic health records (EHR) datasets in order to characterise the role of certain diseases, their risk factors and drug treatments with dementia risk and cognitive decline. By understanding these relationships this will provide an evidence base to support public health intervention for dementia prevention.
Additional affiliations
September 2015 - March 2016
October 2014 - August 2015
September 2013 - September 2014
Education
September 2004 - June 2007
Publications
Publications (93)
Background
Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer’s disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aime...
The biopharmaceutical classification system (BCS) is now well established and utilised for the development and biowaivers of immediate oral dosage forms. The prediction of BCS class can be carried out using multi-label classification. Unlike single label classification, multi-label classification methods predict more than one class labels at the sa...
There are currently thousands of molecular descriptors that can be calculated to represent a chemical compound. Utilising all molecular descriptors in Quantitative Structure-Activity Relationships (QSAR) modelling can result in overfitting, decreased interpretability and thus reduced model performance. Feature selection methods can overcome some of...
Class imbalance occurs frequently in drug discovery datasets. In oral absorption datasets, in the literature, there are considerably more of highly-absorbed compounds compared with poorly-absorbed compounds. This produces models that are biased towards highly-absorbed compounds which lack generalization to industry settings where more early stage d...
This study presents regression and classification models to predict human intestinal absorption of 645 drug and drug like compounds using percentage human intestinal values from the published dataset by Hou et al. (2007c). The problem with this dataset and other datasets in the literature is there are more highly than poorly absorbed compounds. Any...
Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) G...
Augmenting traditional genome-wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce “genome-wide association neural networks (GWANN)” a novel approach that uses neural networks (NNs) to perform a gene-level association study with family history of Alzhei...
Importance: Incidence, prevalence, and survival are important measures to inform the management and provision of head and neck cancer care.
Objective To calculate the incidence, prevalence, and survival rates for head and neck cancers and subsites in the UK from 2000 to 2021.
Design, Setting, and Participants: This population-based cohort study use...
Introduction: While preclinical studies suggest that Phosphodiesterase 5 (PDE5) inhibition may reduce cognitive impairment, findings from observational studies on whether PDE5 inhibitors reduce Alzheimer's disease (AD) risk have been inconsistent.
Methods: A two-sample cis-Mendelian Randomisation (MR) analysis was conducted to estimate the causal e...
Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be us...
Background:
While summarized under the umbrella term "Parkinsonism", several subtypes with different etiologies exist, including Parkinson's Disease, Vascular Parkinsonism and Drug-induced Parkinsonism. However, evidence on their incidence and prevalence remains limited.
Objectives:
To evaluate secular trends of incidence and prevalence of parkinso...
Importance
Incidence, prevalence, and survival are pertinent measures to inform the management and provision of prostate cancer care.
Objective
To calculate the incidence, prevalence, and survival rates for prostate cancer in the UK from 2000 to 2021.
Design, Setting, and Participants
This population-based cohort study uses routinely collected pr...
Background
Lung cancer is the leading cause of cancer-associated mortality worldwide. In the United Kingdom (UK), there has been a major reduction in smoking, the leading risk factor for lung cancer. Therefore, an up-to-date assessment of the trends of lung cancer is required in the UK. This study aims to describe lung cancer burden and trends in t...
Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) G...
Background: Primary liver cancer (PLC) remains a global health challenge. Understanding trends in the disease burden and survival is crucial to inform decisions regarding screening, prevention and treatment.
Methods: Population-based cohort study using UK primary care data from the Clinical Practice Research Datalink (CPRD) GOLD (2000 to 2021), rep...
Background: The management of colorectal cancer (CRC) is evolving, with advances in screening and treatment. We leveraged population-based data to generate up-to-date UK estimates of age and sex-specific incidence and prevalence and overall survival for the period 2000-2021.
Methods: We analysed nationally representative primary care records from C...
Purpose
The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreati...
Background
The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority.
Objectives
To examine how the changing social restrictions imposed by the pandemic affected i...
The explosion and abundance of digital data could facilitate large-scale research for psychiatry and mental health. Research using so-called “real world data”—such as electronic medical/health records—can be resource-efficient, facilitate rapid hypothesis generation and testing, complement existing evidence (e.g. from trials and evidence-synthesis)...
Background
An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data.
Setting
Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardise...
Introduction
The COVID-19 pandemic had collateral effects on many health systems. Cancer screening and diagnostic tests were postponed, resulting in delays in diagnosis and treatment. This study assessed the impact of the pandemic on screening, diagnostics and incidence of breast, colorectal, lung, and prostate cancer; and whether rates returned to...
Background
Use of personal sensing to predict mental health risk has sparked interest in adolescent psychiatry, offering a potential tool for targeted early intervention.
Objectives
We investigated the preferences and values of UK adolescents with regard to use of digital sensing information, including social media and internet searching behaviour...
Background: Lung cancer is the leading cause of cancer-associated mortality worldwide. In the UK, there has been a major reduction in smoking, the leading risk factor for lung cancer, as well as the introduction of the new screening in 2023. Therefore, an up-to-date assessment of the trends of lung cancer is required in the UK.
Methods: We performe...
Background
In India, anemia is widely researched in children and women of reproductive age, however, studies in older populations are lacking. Given the adverse effect of anemia on cognitive function and dementia this older population group warrants further study. The Longitudinal Ageing Study in India – Harmonized Diagnostic Assessment of Dementia...
Background
Iron dyshomeostasis is a feature of neurodegenerative disease. In circulating blood, changes in iron are associated with dementia disease phenotypes, while in brain tissue increased iron is associated with dementia progression. In UK Biobank, whole body imaging includes variables derived from the brain swMRI data which are indicative of...
Background
Epidemiological evidence has repeatedly demonstrated elevated systolic blood pressure (SBP) in midlife as a modifiable risk factor for Alzheimer’s Disease and Related Dementia (ADRD) later in life. Despite SBP being readily treatable with safe and inexpensive medications, no clinical intervention implementing a lower SBP goal (<120 mm Hg...
Background
Epidemiological evidence has repeatedly demonstrated elevated systolic blood pressure (SBP) in midlife as a modifiable risk factor for Alzheimer’s Disease and Related Dementia (ADRD) later in life. Despite SBP being readily treatable with safe and inexpensive medications, no clinical intervention implementing a lower SBP goal (<120 mm Hg...
Background: Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes UK secular trends in breast cancer from 2000-2021 for both sexes.
Methods: Population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD database...
Background: The COVID-19 pandemic affected cancer screening, diagnosis and treatment pathways. This study examined the impact of the pandemic on incidence and trends of endocrine treatments in patients with breast or prostate cancer; and endocrine treatment-related side-effects.
Methods: Population-based cohort study using UK primary care Clinical...
Purpose
Real‐world data (RWD) offers a valuable resource for generating population‐level disease epidemiology metrics. We aimed to develop a well‐tested and user‐friendly R package to compute incidence rates and prevalence in data mapped to the observational medical outcomes partnership (OMOP) common data model (CDM).
Materials and Methods
We crea...
Introduction:
Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia.
Methods:
We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases.
Results:
A total of 255 studies were identified. Most studies relied on the...
Current understanding of determinants for COVID-19-related cardiovascular and thromboembolic (CVE) complications primarily covers clinical aspects with limited knowledge on genetics and lifestyles. Here, we analysed a prospective cohort of 106,005 participants from UK Biobank with confirmed SARS-CoV-2 infection. We show that higher polygenic risk s...
Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis -Mendelian randomisation analysis to study the effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans. Public GWAS were used for study outc...
Introduction:
The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as "deep phenotyping" cohorts with multi-omics health data become available.
Methods:
This narrative review synthesizes understanding of applied models and digital health technologies, in te...
Background:
Current dementia risk scores have had limited success in consistently identifying at-risk individuals across different ages and geographical locations.
Objective:
We aimed to develop and validate a novel dementia risk score for a midlife UK population, using two cohorts: the UK Biobank, and UK Whitehall II study.
Methods:
We divide...
Background
Hypertension is a well‐established risk factor for dementia and antihypertensive treatments could be important for disease prevention. Observational and animal studies suggest Angiotensin‐Converting Enzyme Inhibitors (ACEIs) are associated with reduced dementia risk whereas genetic studies show these drugs increase risk. One plausible ex...
Background
Anemia is a condition characterised by low haemoglobin concentration, which is common in elderly populations. In India, anemia is widely researched in childhood development and women of reproductive age, although studies in older populations are lacking. The Longitudinal Ageing Study India ‐ Diagnosis of Dementia (LASI‐DAD) dataset is an...
Importance:
Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression.
Objective:
To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian rando...
Progress in dementia research has been limited, with substantial gaps in our knowledge of targets for prevention, mechanisms for disease progression, and disease-modifying treatments. The growing availability of multimodal data sets opens possibilities for the application of machine learning and artificial intelligence (AI) to help answer key quest...
Background:
The increasing availability of large high-dimensional data from experimental medicine, population-based and clinical cohorts, clinical trials, and electronic health records has the potential to transform dementia research. Our ability to make best use of this rich data will depend on utilisation of advanced machine learning and artific...
The pathogenesis of dementia and depression is complex involving the interplay of genetic and environmental risk factors including diet, life‐style and the gut microbiome. Dementia and depression co‐occur and metabolomics studies may shed light on the interplay of the various risk factors. We have studied the metabolome of 118,466 individuals inclu...
The increasing availability of large high‐dimensional data from experimental medicine, population‐based and clinical cohorts, clinical trials, and electronic health records has the potential to transform dementia research. Our ability to make best use of this rich data will depend on utilisation of advanced machine learning and artificial intellige...
Clinical determinants for cardiovascular and thromboembolic (CVE) complications of COVID-19 are well-understood, but the roles of genetics and lifestyle remain unknown. We performed a prospective cohort study using UK Biobank, including 25,335 participants with confirmed SARS-CoV-2 infection between March 1, 2020, and September 3, 2021. Outcomes we...
Clinical determinants for cardiovascular and thromboembolic (CVE) complications of COVID-19 are well-understood, but the roles of genetics and lifestyle remain unknown. We performed a prospective cohort study using UK Biobank, including 25,335 participants with confirmed SARS-CoV-2 infection between March 1, 2020, and September 3, 2021. Outcomes we...
Dementia is caused by an acquired, sustained decline in brain function, leading to difficulty with everyday activities. With multiple aetiologies, clinical presentation varies, typically including problems with memory, cognition, and communication. Dementia research aims to identify risk factors, disease mechanisms and treatments. However, progress...
Introduction
Type 2 diabetes is a risk factor for dementia and Parkinson’s disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subt...
Introduction: Type 2 diabetes is a risk factor for dementia and Parkinson's disease (PD). Drug treatments for diabetes, such as metformin, could be used as potential novel treatments for these neurological conditions. Using medical records from the USA (OPTUM) we aimed to assess the association of metformin with all cause dementia, dementia subtype...
The pathogenesis of depression is complex involving the interplay of genetic and environmental risk factors including diet, lifestyle and the gut microbiome. Metabolomics studies may shed light on the interplay of these factors. We study over 63,000 individuals including 8462 cases with a lifetime major depression and 5403 cases with recurrent majo...
Augmenting traditional genome wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce "Genome wide association neural networks (GWANN)", a novel approach that uses neural networks (NNs) to account for nonlinear and SNP-SNP interaction effects. We applied G...
Background
Hypertension is a well‐established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertensions, such as isolated hypertension on brain health and its comparison to systolic‐diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown....
Experimental models shows that bioenergetic homeostasis changes with increasing age based on apolipoprotein E (APOE) gene. However, such link with dementia remains unclear in population. We used H1-NMR metabolome in blood from 118,021 random-selected participants in UK Biobank (n=118,021 individuals), and identified 56 metabolites associated with t...
UK Biobank (UKB) is widely employed to investigate mental health disorders and related exposures; however, its applicability and relevance in a clinical setting and the assumptions required have not been sufficiently and systematically investigated. Here, we present the first validation study using secondary care mental health data with linkage to...
Background
Globally, up to 40% of dementia cases may be prevented if several key risk factors, such as low education and obesity, are targeted. This has motivated interest into the development of risk scores that aim to quantify an individual’s risk of developing dementia within a given time frame. However, translation to a clinical setting has bee...
Background
Hypertension is a well‐established risk factor for cognitive impairment, brain atrophy and dementia. Isolated hypertension is where either systolic or diastolic blood pressure is high and the other measure is normal. It is unknown the impact of isolated hypertension on brain atrophy and how it compares to non isolated hypertension (NIH)....
Background
There is increasing interest in early metabolic changes in dementia, which may reflect the effects of genetic determinants of dementia, medical history and co‐morbidity, environmental risk factors, and aging. We studied the relation of blood‐based metabolites to the risk of dementia.
Method
The analyses are conducted in 121,389 particip...
Background:
Mid-life hypertension is an established risk factor for cognitive impairment and dementia and related to greater brain atrophy and poorer cognitive performance. Previous studies often have small sample sizes from older populations that lack utilizing multiple measures to define hypertension such as blood pressure, self-report informati...
Hypertension is a well-established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertension, such as, isolated hypertension on brain health and its comparison to systolic-diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its...
Background: Globally, up to 40% of dementia cases may be prevented if several key risk factors, such as low education and obesity, are targeted. This has motivated interest into the development of risk scores that aim to quantify an individual’s risk of developing dementia within a given
time frame. However, translation to a clinical setting has be...
Background:
Understanding adolescents' mental health during lockdown and identifying those most at risk is an urgent public health challenge. This study surveyed school pupils across Southern England during the first COVID-19 school lockdown to investigate situational factors associated with mental health difficulties and how they relate to pupils...
The multiple layers of exclusion that can be experienced by a child at school and the relationship of this to mental well-being is the focus of this paper. The relationship between specific mental health problems and school exclusion is discussed. Data gathered from 1648 English school-aged students in 2019 who participated in the OxWell school men...
INTRODUCTION: Current prognostic models of dementia have had limited success in consistently identifying at-risk individuals. We aimed to develop and validate a novel dementia risk score (DRS) using the UK Biobank cohort.METHODS: After randomly dividing the sample into a training (n=166,487, 80%) and test set (n=41,621, 20%), logistic LASSO regress...
Objectives
Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA.
Methods
We performed a...
Background
Cardiovascular disease affects multiple organs beyond those of the cardiovascular system including the brain. However, the mechanisms linking cardiovascular disease and cognitive decline are still poorly understood. Studies suggest specific cardiovascular medications targeting different mechanisms may slow cognitive decline and reduce de...
BACKGROUND
Findings from randomized controlled trials have yielded conflicting results on the association between blood pressure (BP) and Dementia traits. We tested the hypothesis that a causal relationship exists between systolic (SBP) and/or diastolic (DBP) blood pressure and risk of Alzheimer’s Disease (AD).
METHODS
We performed a Generalized S...
Background
Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the...
Objectives Concern has been raised in the rheumatological community regarding recent regulatory warnings that hydroxychloroquine used in the COVID-19 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation, or psychosis associated with hydroxychloroquine as used for rheumatoid...
Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin.
Methods: New user cohort studies were conducted including 16 severe adverse events (...
Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (...
Background:
Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk.
Methods:
A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 6...
Inflammatory processes have been shown to play a role in dementia. To understand this role we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk.METHODS A retrospective matched case-control study, of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) were...
Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer’s disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) Aβ and tau tests.
Objective: To discover a plasma proteomic signature associated with CSF and PET measures of...