David J Llewellyn

David J Llewellyn
University of Exeter | UoE · Medical School

PhD

About

209
Publications
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Introduction
David is a Professor at the University of Exeter Medical School and a Fellow at the Alan Turing Institute. He also holds an honorary contract with Devon Partnership NHS Trust. He moved to Exeter in 2009 having received advanced training in epidemiology and data science as a Research Associate at the University of Cambridge. He leads the DEMON Network (http://demondementia.com/) the national network for data science and AI applied to dementia research. Follow on Twitter: @DrDJLlewellyn

Publications

Publications (209)
Article
Sporadic Creutzfeldt-Jakob disease, the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to increased c...
Article
Background: Observational studies have found an association between attention-deficit/hyperactivity disorder (ADHD) and ischemic stroke. Aims: The purpose of this study was to investigate whether genetic liability to ADHD has a causal effect on ischemic stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, ge...
Article
Background: Individual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated...
Article
Background: Higher vitamin D status has been suggested to have beneficial effects on the brain. Objective: To investigate the association between 25-hydroxyvitamin D [25(OH)D], neuroimaging features and the risk of dementia and stroke. Design: We used prospective data from the UK Biobank (37-73 years at baseline) to examine the association bet...
Preprint
Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to incr...
Article
Full-text available
Background and Objectives There is an urgent need to better understand frailty and it’s predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies...
Article
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Objective: To optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics. Methods: We explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission...
Article
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GWASs have identified numerous genetic variants associated with a wide variety of diseases, yet despite the wide availability of genetic testing the insights that would enhance the interpretability of these results are not widely available to members of the public. As a proof of concept and demonstration of technological feasibility, we developed P...
Preprint
GWASs have identified numerous genetic variants associated with a wide variety of diseases, yet despite the wide availability of genetic testing the insights that would enhance the interpretability of these results are not widely available to members of the public. As a proof of concept and demonstration of technological feasibility, we developed P...
Article
Full-text available
We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disea...
Article
Full-text available
Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting sev...
Article
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Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence s...
Article
Full-text available
We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disea...
Article
Background Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. The aim was to examine whether habitual coffee consumption is associated with differences in brain volumes or the risk odds of dementia or stroke. Methods Prospective analyses of habitual coffee consumption were conducted in 3...
Article
Background: Visual impairment and eye diseases have been associated with dementia, though with mixed findings and often in cross-sectional studies. Objective: To identify prospective studies investigating associations between visual impairment or common eye diseases and risk of all-cause dementia or key dementia subtypes. Methods: We searched...
Article
Background Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. Objectives We examined whether habitual coffee consumption is associated with differences in brain volumes or the odds of dementia or stroke. Methods We conducted prospective analyses of habitual coffee consumption on 398,646...
Preprint
Full-text available
We conducted a population-based retrospective cohort study to evaluate whether the association between cigarette smoking and dementia risk is modified by genetic predisposition including apolipoprotein E (APOE) genotype and polygenic risk (without APOE gene). We included 193,198 UK Biobank participants aged 60 to 73 years without dementia at baseli...
Article
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Despite strong evidence for a socioeconomic gradient in many health outcomes, including cognition, substantial gaps remain in understanding these disparities. We investigated the biopsychosocial mechanisms underlying the associations between socioeconomic status (SES) and later-life cognitive health using the Harmonised Cognitive Assessment Protoco...
Article
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Functional disability might be related to an increased risk of dementia or could represent a prodromal stage. We examined the occurrence of functional impairments over eight years follow-up and their association with dementia incidence in 1,666 participants aged 65+ from the English Longitudinal Study of Ageing. Growth models with distal outcome we...
Article
Previous work using data from the UK Biobank has shown that both unfavorable lifestyle and genetic risk are associated with higher dementia risk; however, it is not known whether these results transfer to more representative samples and across country. Data come from the Health and Retirement Study (HRS), a cohort study of Americans 65 years of age...
Article
Collaborative interdisciplinary research will be key to advances in dementia prevention, identification and treatment. We established the DEMON Network to revolutionise dementia research by bringing innovators together to harness the power of data science and artificial intelligence with funding from Alzheimer’s Research UK and the Alan Turing Inst...
Article
There is evidence that educational attainment increases cognitive reserve, and may prevent or delay the development of dementia. However, the extent to which education offsets or interacts with genetic risk is unknown. We therefore investigated the relationship between education and genetic risk for dementia. In this cohort study, we used data from...
Article
Stroke is a strong, independent and modifiable risk factor for all‐cause dementia. However, the extent to which stroke adds to or moderates genetic risk is unknown. In this cohort study, we used data from UK Biobank including adults aged 60 years and older of European ancestry without cognitive impairment or dementia at baseline. Participants joine...
Article
Diagnosing dementia is clinically challenging due to substantial heterogeneity in presenting symptoms and underlying pathologies. However, machine learning provides a powerful approach to uncover hidden patterns in complex data that may in turn inform clinical practice. We used patient data from the National Alzheimer’s Coordinating Center Uniform...
Article
Being in hospital can be particularly confusing and challenging not only for people living with dementia, but also for their carers and the staff that care for them. We undertook three systematic reviews of quantitative and qualitative evidence according to best practice guidelines. The reviews explored: 1) experience of care in hospital; 2) experi...
Article
Background Being in hospital can be particularly confusing and challenging not only for people living with dementia, but also for their carers and the staff who care for them. Improving the experience of care for people living with dementia in hospital has been recognised as a priority. Objectives To understand the experience of care in hospital f...
Article
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Objective: Vitamin D is involved in brain health and function. Our objective was to determine whether the serum 25-hydroxyvitamin D (25OHD) concentration was associated with delirium in a case-control study of geriatric inpatients. Methods: Sixty cases with delirium (mean ± SD, 84.8 ± 5.7years; 58.3% female) and 180 age- and gender-matched controls...
Article
Background Systolic inter-arm difference in blood pressure (IAD) and cognitive decline are both associated with cardiovascular disease; therefore, it was hypothesised that IAD may be predictive of cognitive decline. Aim To examine associations of IAD with cognitive decline in a community population. Design and setting A prospective study of older...
Article
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Aims and objectives To systematically review and synthesise qualitative data from studies exploring the experiences of hospital staff who care for people living with dementia (Plwd). Background In hospital, the number of Plwd continues to rise; however, their experiences of care remain problematic. Negative experiences of care are likely to contri...
Article
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Background: An increasingly high number of patients admitted to hospital have dementia. Hospital environments can be particularly confusing and challenging for people living with dementia (Plwd) impacting their wellbeing and the ability to optimize their care. Improving the experience of care in hospital has been recognized as a priority, and non-...
Article
Objective: We investigated two hypotheses: First, incident CHD, defined as myocardial infarction or definite angina, leads to faster long-term cognitive decline. Second, among those with CHD, treatment with CABG surgery or PCI leads to slower long-term cognitive decline. Methods: The Cardiovascular Health Study is a cohort of US adults aged 65+. Gl...
Article
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Biological and psychosocial risk factors, particularly those that are malleable across the life course, are important determinants of neurocognitive health in later life. We investigated several determinants of cognitive impairment using the Mini-Mental Status Examination (MMSE), as part of the Harmonised Cognitive Assessment Protocol in 1,200 indi...
Article
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Globally the numbers of older people who live alone and those who may experience certain risk factors have risen. In this study, we aim to examine associations between social isolation and loneliness with different domains of cognitive impairment. Data are from the English Longitudinal Study of Ageing (ELSA). Social isolation and loneliness were me...
Article
The 16-item Vitamin D Status Diagnosticator (VDSD) tool was built to diagnose, without resorting to a blood test, hypovitaminosis D among healthy seniors living at home. The objective of this study was to determine the feasibility of the VDSD by general practitioners (GPs), the acceptability to outpatients, and the diagnostic accuracy of the VDSD i...
Preprint
Full-text available
The increasing global prevalence of dementia and the lack of disease-modifying treatments give rise to the need for early detection of dementia-causing diseases to enable the development and targeted administration of preventative interventions. However, current methods that have potential for the early detection of dementia-causing diseases, such...
Article
Background: Apolipoprotein E (APOE) genotype affects the risk of Alzheimer's disease (AD) with inconclusive evidence on the opportunity to mitigate related adverse effects by lifestyle changes. Objective: To examine the individual and interactive associations of APOE and objectively-measured physical activity (PA) and sedentary activity with cog...
Article
https://deepblue.lib.umich.edu/bitstream/2027.42/152906/1/alzjjalz2019064649.pdf
Article
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In recent years, extreme sport-related pursuits including climbing have emerged not only as recreational activities but as competitive sports. Today, sport climbing is a rapidly developing, competitive sport included in the 2020 Olympic Games official program. Given recent developments, the understanding of which factors may influence actual climbi...
Article
Objective: The AHA Life’s Simple 7 (LS7) defines cardiovascular health with smoking, physical activity, diet quality, body mass index (BMI), blood pressure, total cholesterol, and blood glucose. We examined changes in LS7 score and its components in older adults over seven years of follow-up. Methods: We analyzed 2,234 adults aged 65+ in the Cardio...
Article
Objective: The AHA Life’s Simple 7 (LS7) defines cardiovascular health with smoking, physical activity, diet quality, body mass index (BMI), blood pressure, total cholesterol, and blood glucose. We examined associations of LS7 score and its components with cognitive decline in older adults. Methods: The Cardiovascular Heart Study is a longitudinal...
Article
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Objectives: Poor social connections may be associated with poor cognition in older people who are not experiencing mental health problems, and the trajectory of this association may be moderated by cognitive reserve. However, it is unclear whether this relationship is the same for older people with symptoms of depression and anxiety. This paper aim...
Article
Older adults often complain about their memory ability, but it is not clear to what extent subjective memory complaints accurately reflect objective cognitive dysfunctions. The concordance between objective and subjective cognitive performance may be affected by depressive symptoms and by declining insight into cognitive deficits. This study aims t...
Article
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Background: Living alone may be associated with greater risk for social isolation and loneliness. Living alone, social isolation, loneliness, and limited engagement in social activity have all been associated with poorer cognitive function in later life. Hence, if individuals who live alone are also at greater risk of isolation and loneliness, thi...
Article
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Background Brief cognitive assessments can result in false-positive and false-negative dementia misclassification. We aimed to identify predictors of misclassification by 3 brief cognitive assessments; the Mini-Mental State Examination (MMSE), Memory Impairment Screen (MIS) and animal naming (AN). Methods Participants were 824 older adults in the...
Article
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We evaluated the associations between allostatic load (AL), with subsequent coronary heart disease (CHD) and dementia during 12-year follow-up in the English Longitudinal Study of Ageing. Participants (N= 4,335) were aged ≥50 years at baseline. The AL index included five biomarker risk groups covering neuroendocrine (Insulin growth factor 1), cardi...
Article
Full-text available
The relationship between trajectories of functional impairments or depressive symptoms and future dementia is poorly understood. We employed Growth Mixture Modelling with a categorical distal outcome to identify independent group-based trajectories of activities of daily living (ADL); instrumental activities of daily living (IADL) or depressive sym...
Conference Paper
The relationship between trajectories of functional impairments or depressive symptoms and future dementia is poorly understood. We employed Growth Mixture Modelling with a categorical distal outcome to identify independent group-based trajectories of activities of daily living (ADL); instrumental activities of daily living (IADL) or depressive sym...
Article
Full-text available
There is evidence to suggest that social isolation is associated with poor cognitive health, although findings are contradictory. One reason for inconsistency in reported findings may be a lack of consideration of underlying mechanisms that could influence this relationship. Cognitive reserve is a theoretical concept that may account for the role o...
Data
Longitudinal association between social isolation and sub-domains of cognition assessed by the CAMCOG. We conducted further regression analyses to determine whether social isolation was more associated with any specific cognitive domains assessed by the CAMCOG using longitudinal data (see “S4 Table”). Social isolation was significantly associated w...
Data
Cross-sectional association between social isolation and sub-domains of cognition assessed by the CAMCOG. We conducted further regression analyses to determine whether social isolation was more associated with any specific cognitive domains assessed by the CAMCOG (see “S2 Table”). Social isolation was significantly associated with orientation (adju...
Data
Comparison of included and excluded participants at two year follow-up. S1 Table provides a comparison of participants who were included and excluded at follow-up. Excluded participants were significantly older, had a significantly lower baseline CAMCOG score, fewer years of education, lower scores for cognitive activity, lower occupational complex...
Data
Longitudinal association between social isolation and cognitive change. A sensitivity analysis was conducted to determine the reliability of the regression analysis assessing the relationship between social isolation and cognitive change score. As there was little cognitive change across the sample over two years, a binary variable was created to d...
Article
Introduction: Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk. Methods: We searched Medline, PsycINFO, and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to po...
Article
Full-text available
Earlier diagnosis of dementia is increasingly being recognized as a public health priority. As screening is not generally recommended, case-finding in clinical practice is encouraged as an alternative dementia identification strategy. The approaches of screening and case-finding are often confused, with uncertainty about what case-finding should in...
Data
eAppendix. Supplementary materials description. eFigure 1. Flowchart of the individuals included in the competing risk hazard model analyses. eFigure 2. Stacked cumulative incidence plots for dementia and death as competing risks within each age cohort. eTable 1. Dementia incidence rates per 1,000 person-years and 95% confidence intervals (CI), acc...
Article
Full-text available
Background: Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear. Objective: To systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia. Methods: We searched five databases from...
Article
Full-text available
Importance Lower educational attainment is associated with a higher risk of dementia. However, less clear is the extent to which other socioeconomic markers contribute to dementia risk. Objective To examine the relationship of education, wealth, and area-based deprivation with the incidence of dementia over the last decade in England and investiga...
Article
Full-text available
Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from...