Joanna Wardlaw

Joanna Wardlaw
The University of Edinburgh | UoE · Division of Clinical Neurosciences

About

688
Publications
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Publications

Publications (688)
Article
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Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), i...
Article
Objectives To test whether Mediterranean-type Diet (MeDi) at age 70 years is associated with longitudinal trajectories of total brain MRI volume over a six-year period from age 73 to 79. Design Cohort study which uses a correlational design. Setting Participants residing in the Lothian region of Scotland and living independently in the community....
Preprint
Full-text available
Characterising associations between the epigenome, proteome and phenome may provide insight into molecular regulation of biological pathways governing health. However, epigenetic signatures for many neurologically-associated plasma protein markers remain uncharacterised. Here, we report an epigenome and phenome-wide association study of the circula...
Article
Full-text available
Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, however the precise nature of SVD-related cognitive deficits, and their associations with structural brain changes, remain unclear. We combined computational volumes and visually-rated MRI markers of SVD to quantify total SVD burden, using data from the Lothian...
Conference Paper
Full-text available
Introduction Cerebral small vessel disease (cSVD) causes stroke, with an increasing burden in the ageing population. cSVD develops due to a combination of environmental and genetic factors. A minority of individuals undergo genetic testing for a mutation in the NOTCH3 gene, which causes CADASIL. However, several other Mendelian cSVD genes have been...
Article
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Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian B...
Article
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Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical agein...
Article
BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute...
Article
Introduction Small vessel disease (SVD) commonly causes stroke and dementia. Early clinical predictors of disease progression are lacking. We aimed to determine whether informant reports of chronic cognitive/functional decline, prerequisites for dementia diagnosis, are associated with (a)baseline SVD burden, measured by Fazekas scores and (b)SVD ch...
Article
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Objective A study was undertaken to assess whether cerebral small vessel disease (SVD) computed tomographic (CT) biomarkers are associated with long‐term outcome after intracerebral hemorrhage. Methods We performed a prospective, community‐based cohort study of adults diagnosed with spontaneous intracerebral hemorrhage between June 1, 2010 and May...
Article
Background: Investigation of differential effects of early intensive versus guideline-recommended blood pressure (BP) lowering between lacunar and non-lacunar acute ischemic stroke (AIS) in the BP arm of Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: In 1632 participants classified as having definite or probab...
Article
Objective: To test the hypothesis that imaging signs of 'brain frailty' and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED). Methods: Blinded assessors...
Article
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Background Stroke commonly affects cognition and, by definition, much vascular dementia follows stroke. However, there are fundamental limitations in our understanding of vascular cognitive impairment, restricting understanding of prevalence, trajectories, mechanisms, prevention, treatment and patient-service needs. Aims Rates, Risks and Routes to...
Article
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Background: Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease. Aim: We designed the LACunar Intervention Trial-2 (LACI-2) to test fe...
Article
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Background Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but wh...
Article
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Introduction: We assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke. Patients and methods: In this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were r...
Article
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Aims Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age. Methods and results Associations...
Article
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Higher polygenic risk score for schizophrenia (szPGRS) has been associated with lower cognitive function and might be a predictor of decline in brain structure in apparently healthy populations. Age-related declines in structural brain connectivity-measured using white matter diffusion MRI -are evident from cross-sectional data. Yet, it remains unc...
Article
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Background: Carotid atherosclerosis is a significant risk factor for stroke and has been associated with cognitive decline and dementia. Methods: We assessed 554 community-dwelling subjects from the Lothian Birth Cohort of 1936 (LBC1936) who underwent brain MRI and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid...
Article
We aimed to explore the morphological evolution of recent small subcortical infarcts (RSSIs) over 15 months. Moreover, we hypothesized that quantitative lesion apparent diffusion coefficient (ADC) values and serum neurofilament light (NfL) levels predict subsequent lacunar cavitation. We prospectively studied 78 RSSI patients, who underwent pre-def...
Poster
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Can we use simple tests (CT and APOE genotype - The Edinburgh CT and genetic criteria for CAA-associated lobar ICH) in patients with lobar intracerebral haemorrhage to predict recurrent haemorrhage risk
Article
Objective To investigate brain structural connectivity in relation to cognitive abilities and systemic damage in systemic lupus erythematosus (SLE). Methods Structural and diffusion MRI data were acquired from 47 patients with SLE. Brains were segmented into 85 cortical and subcortical regions and combined with whole brain tractography to generate...
Article
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We aimed to assess whether and how changes in brain volume and increases in white matter hyperintensity (WMH) volume over three years predict gait speed and its change independently of demographics, vascular risk factors and physical status. We analyzed 443 individuals from the Lothian Birth Cohort 1936, at mean age 73 and 76 years. Gait speed at a...
Data
Voxel-by-voxel data. The data fields are described in the second row of the table. (CSV)
Conference Paper
Background Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Midlife vascular disease and adult socioeconomic status (SES) are established risk factors. Less is known about the effect of factors earlier in life. A recent meta-analysis found that lower levels of childhood IQ, childhood SES and education increased the risk...
Article
Background: Iodine deficiency is one of the three key micronutrient deficiencies highlighted as major public health issues by the World Health Organisation. Iodine deficiency is known to cause brain structural alterations likely to affect cognition. However, it is not known whether or how different (lifelong) levels of exposure to dietary iodine i...
Conference Paper
Neighbourhood tractography aims to automatically segment equivalent brain white matter tracts from diffusion magnetic resonance imaging (dMRI) data in different subjects by using a “reference tract” as a prior for the shape and length of each tract of interest. In the current work we present a means of improving the technique by using references tr...
Article
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Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker...
Article
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Gait and balance impairment is highly prevalent in older people. We aimed to assess whether and how single markers of small vessel disease (SVD) or a combination thereof explain gait and balance function in the elderly. We analysed 678 community-dwelling healthy subjects from the Lothian Birth Cohort 1936 at the age of 71–74 years who had undergone...
Article
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Background: Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. Methods: In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and sys...
Article
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Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegen...
Conference Paper
White matter hyperintensities (WMH) seen on FLAIR images are established as a key indicator of Vascular Dementia (VD) and other pathologies. We propose a novel modality transformation technique to generate a subject-specific pathology-free synthetic FLAIR image from a T\(_1\) -weighted image. WMH are then accurately segmented by comparing this synt...
Article
Full-text available
Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegen...
Article
Full-text available
Background and purpose: Several studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visib...
Article
White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyp...
Article
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Objectives: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). Methods: Polygenic risk scores for i...
Article
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Incidental findings of imaging research studies can turn healthy individuals into anxious patients, while putting an extra burden on primary care. J M Wardlaw and colleagues argue that doctors should ensure that the personal, ethical, healthcare, and cost implications of these common findings are managed proportionately, sensitively, and economical...
Article
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Rationale Cerebral small vessel disease (SVD) is common in ageing and patients with dementia and stroke. Its manifestations on magnetic resonance imaging (MRI) include white matter hyperintensities, lacunes, microbleeds, perivascular spaces, small subcortical infarcts, and brain atrophy. Many studies focus only on one of these manifestations. A pro...
Article
Purpose: present and assess clinical protocols and associated automated workflow for pre-surgical functional magnetic resonance imaging in brain tumor patients. Methods: Protocols were validated using a single-subject reliability approach based on 10 healthy control subjects. Results from the automated workflow were evaluated in 9 patients with br...
Article
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There is evidence that subtle breakdown of the blood-brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body t...
Article
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Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygen...
Article
Background and purpose: We sought to establish whether the presence (versus absence) of a lesion on magnetic resonance imaging (MRI) with diffusion weighting (DWI-MRI) at presentation with acute stroke is associated with worse clinical outcomes at 1 year. Methods: We recruited consecutive patients with a nondisabling ischemic stroke and performe...
Article
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Purpose: Perivascular spaces (PVS) are associated with ageing, cerebral small vessel disease, inflammation and increased blood brain barrier permeability. Most studies to date use visual rating scales to assess PVS, but these are prone to observer variation. Methods: We developed a semi-automatic computational method that extracts PVS on bilater...
Article
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Several studies have reported associations between brain iron deposits and cognitive status, and cardiovascular and neurodegenerative diseases in older individuals, but the mechanisms underlying these associations remain unclear. We explored the associations between regional brain iron deposits and different factors of cognitive ability (fluid inte...
Article
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Non-pathological, age-related cognitive decline varies markedly between individuals andplaces significant financial and emotional strain on people, their families and society as a whole.Understanding the differential age-related decline in brain function is critical not only for the development oftherapeutics to prolong cognitive health into old ag...
Article
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Later-life changes in brain tissue volumes—decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)—are strong candidates to explain some of the variation in ageing-related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structura...
Article
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People with larger brains tend to score higher on tests of general intelligence (g). It is unclear, however, how much variance in intelligence other brain measurements would account for if included together with brain volume in a multivariable model. We examined a large sample of individuals in their seventies (n = 672) who were administered a comp...
Article
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Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease. To test for independent associations between two Alzheimer's disease-susceptibility gene loci - APOE ε and the TOMM40 '523' poly-T repeat - and white matter hyperintensities/cerebral micro...
Article
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Background: Spontaneous intracerebral haemorrhage is a devastating form of stroke and its incidence increases with age. Obtaining brain tissue following intracerebral haemorrhage helps to understand its cause. Given declining autopsy rates worldwide, the feasibility of establishing an autopsy-based collection and its generalisability are uncertain...
Article
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Examining the dynamics of stroke ischemia is limited by the standard use of 2D-volume or voxel-based analysis techniques. Recently developed spatiotemporal models such as the 4D metamorphosis model showed promise for capturing ischemia dynamics. We used a 4D metamorphosis model to evaluate acute ischemic stroke lesion morphology from the acute diff...
Article
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Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI...
Article
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Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies w...
Article
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The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It...
Article
Intracranial internal carotid artery calcification is associated with cerebrovascular risk factors and stroke, but few quantification methods are available. We tested the reliability of visual scoring, semiautomated Agatston score, and calcium volume measurement in patients with recent stroke. We used scans from a prospective hospital stroke regist...