Joanna M. Wardlaw's research while affiliated with The University of Edinburgh and other places

Publications (694)

Article
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Background We aimed to assess the association of atrial fibrillation (AF) on outcomes in a post hoc analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) and how this association is modified by baseline imaging features. Methods Inverse probability of treatment weight was used to remove baseline imbalances betw...
Preprint
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Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, general rules may govern shared spatial fluctuations in expression across the genome. Such information would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive...
Article
Objectives: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antago...
Preprint
Background There is increasing interest in the concept of frailty in stroke, including both physical frailty and imaging-evidence of brain frailty. We aimed to 1)establish concurrent validity of a brain frailty measurement against traditional measures of physical and global frailty 2)establish prevalence of brain frailty in stroke survivors with an...
Article
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Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled tr...
Preprint
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Brain vascular health appears to be of critical importance for protection against the development of amyotrophic lateral sclerosis (ALS) as well as the slowing of disease progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in the small ce...
Article
Introduction: Endovascular treatment (EVT), in particular mechanical thrombectomy, has dramatically improved the clinical outcome of patients with large vessels occlusion (LVO) of the anterior circulation. In contrast, the benefits of EVT cannot be applied to lacunar strokes (LS). The absence of a LVO in LS has been historically associated with a m...
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Introduction: Cerebrovascular reactivity (CVR) measurements using blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) are commonly used to assess the health of cerebral blood vessels, including in patients with cerebrovascular diseases; however, evidence and consensus regarding reliability and optimal processing are lacking. We aim...
Article
Background: Treatment for ischemic stroke can be offered beyond conventional time limits for patients with favorable computed tomography perfusion (CTP), but this is not universally available. We sought a threshold for brain attenuation on nonenhanced computed tomography (NECT) to differentiate CTP-defined penumbra vs core, and correlated NECT fea...
Article
In preclinical Alzheimer’s disease (AD), amyloid accumulates in highly‐functionally connected brain regions. This selective vulnerability is related to the high neuronal fluctuations, typical of these regions. Dynamic functional connectivity (FC) was introduced to investigate network organization over time, with high network variations indicating r...
Article
Perivascular space (PVS) burden is an emerging MRI‐marker of cerebral small vessel disease (cSVD), a leading cause of stroke and dementia. Underlying mechanisms of PVS are unknown. PVS are thought to be related to the glymphatic system, involved in brain clearance of molecules such as amyloid beta. We aimed to decipher the genetic underpinnings of...
Article
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In preclinical Alzheimer’s disease (AD), amyloid accumulates in highly‐functionally connected brain regions. This selective vulnerability is related to the high neuronal fluctuations, typical of these regions. Dynamic functional connectivity (FC) was introduced to investigate network organization over time, with high network variations indicating r...
Presentation
Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging are markers of cerebral small vessel disease (cSVD), a major risk factor for Alzheimer’s disease and related dementia (ADRD). Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains...
Article
Background Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and w...
Preprint
Predicting the evolution of white matter hyperintensities (WMH) (i.e., whether WMH will grow, remain stable, or shrink with time) is important for personalised therapeutic interventions. However, this task is difficult mainly due to the myriad of vascular risk factors (VRF) and comorbidities that influence the evolution of WMH, and the low specific...
Article
Background: Conferences facilitate career advancement, but gender imbalances in public fora may negatively impact both women and men, and society. We aimed to describe the gender distribution of presenters at the UK’s 2014-2021 Royal College of Radiologists’ (RCR) Annual Scientific Meeting. Methods: We extracted data on presenter name, role and ses...
Article
Background: Neuropsychiatric symptoms could form part of an early cerebral small vessel disease prodrome that is detectable before stroke or dementia onset. We aimed to identify whether apathy, depression, anxiety, and subjective memory complaints associate with longitudinal white matter hyperintensity (WMH) progression. Methods: Community-dwell...
Article
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Cerebral small vessel disease (SVD) is a cause of stroke and dementia. Retinal capillary microvessels revealed by optical coherence tomography angiography (OCTA) are developmentally related to brain microvessels. We quantified retinal vessel density (VD) and branching complexity, investigating relationships with SVD lesions, white matter integrity...
Article
Background Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically-defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematicall...
Article
Objective: Cerebral small vessel diseases (cSVDs) are a major cause of stroke and dementia. We used cutting-edge 7T-MRI techniques in patients with CADASIL, to establish which aspects of cerebral small vessel function are affected by this monogenic form of cSVD. Methods: We recruited 23 CADASIL patients (age 51.1±10.1 years, 52% women) and 13 ag...
Article
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Background and purpose: Intracerebral haemorrhage volume (ICHV) is prognostically important but does not account for intracranial volume (ICV) and cerebral parenchymal volume (CPV). We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional outcomes. We al...
Article
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Background and objectives White matter hyperintensities (WMH) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, although the frequency and associated factors are unknown. This systematic review and meta-analysis aims...
Article
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Background Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD. Methods The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinde...
Article
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Objective: To test e-ASPECTS software in patients with stroke. Marketed as a decision-support tool, e-ASPECTS may detect features of ischemia or hemorrhage on computed tomography (CT) imaging and quantify ischemic extent using ASPECTS (Alberta Stroke Program Early CT Score). Methods: Using CT from nine stroke studies, we compared software with m...
Article
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Post-stroke cognitive impairment is common and can have major impact on life after stroke. Peak-width of Skeletonized Mean Diffusivity (PSMD) is a diffusion imaging marker of white matter microstructure and is also associated with cognition. Here, we examined associations between PSMD and post-stroke global cognition in an ongoing study of mild isc...
Article
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Vast quantities of Magnetic Resonance Images (MRI) are routinely acquired in clinical practice but, to speed up acquisition, these scans are typically of a quality that is sufficient for clinical diagnosis but sub-optimal for large-scale precision medicine, computational diagnostics, and large-scale neuroimaging collaborative research. Here, we pre...
Article
Full-text available
Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH) are features of cerebral small vessel disease which can be seen in brain magnetic resonance imaging (MRI). Given the associations and proposed mechanistic link between PVS and WMH, they are hypothesized to also have topological proximity. However, this and the influence of t...
Article
Importance Cerebral small vessel disease (SVD) causes a quarter of strokes and is the most common pathology underlying vascular cognitive impairment and dementia. An important step to developing new treatments is better trial methodology. Disease mechanisms in SVD differ from other stroke etiologies; therefore, treatments need to be evaluated in co...
Article
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Background The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or...
Article
Full-text available
Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA meth...
Article
Background: Stroke survivors are at an increased risk of developing post-stroke cognitive impairment and post-stroke dementia; those at risk could be identified by brain imaging routinely performed at stroke onset. Aim: This systematic review aimed to identify features which are associated with post-stroke cognitive impairment (including dementia),...
Preprint
Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational frame...
Article
Full-text available
Cerebral small vessel disease (SVD) is the leading cause of vascular dementia, causes a quarter of strokes, and worsens stroke outcomes. The disease is characterised by patchy cerebral small vessel and white matter pathology, but the underlying mechanisms are poorly understood. This microvascular and tissue damage has been classically considered se...
Article
Background Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report...
Article
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Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational frame...
Article
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The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer’s Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimo...
Article
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Background Cerebral small‐vessel disease (cSVD) is an important cause of stroke and vascular dementia. Most cases are multifactorial, but an emerging minority have a monogenic cause. While NOTCH3 is the best‐known gene, several others have been reported. We aimed to summarize the cerebral phenotypes associated with these more recent cSVD genes. Me...
Article
One of the most common causes of dementia is cerebral small vessel disease (SVD), which is associated with enlarged perivascular spaces (PVS). Clinically, PVS are visible as hyperintensities on T2-weighted (T2w) magnetic resonance images (MRI). While rodent SVD models exhibit arteriolosclerosis, PVS have not been robustly documented by MRI casting...
Article
Background MRI and fluorine 18-labeled sodium fluoride (18F-NaF) PET can be used to identify features of plaque instability, rupture, and disease activity, but large studies have not been performed. Purpose To evaluate the association between 18F-NaF activity and culprit carotid plaque in acute neurovascular syndrome. Materials and Methods In this...
Article
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Background and AimsThe visibility of ischaemic brain lesions on non-enhanced CT increases with time. Obviously hypoattenuating lesions likely represent infarction. Conversely, viable ischaemic brain lesions may be non-visible on CT. We tested whether patients with normal appearing ischaemic brain tissue (NAIBT) on their initial CT are identifiable,...
Preprint
Background Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD. Methods The LACunar Intervention Trial-2 (LACI-2) is an investigator-initiated prospective randomised open-lab...
Article
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Background Magnetic resonance susceptibility-weighted imaging (SWI) can identify small brain blood vessels that contain deoxygenated blood due to its induced magnetic field disturbance. We observed focal clusters of possible dilated small vessels on SWI in white matter in severe small vessel disease (SVD). We assessed their prevalence, associations...
Poster
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Background: Long-term exposure to cardiovascular risk factors can harm cerebral micro-vessels, causing endothelial dysfunction and damaging the brain parenchyma. Visibility of perivascular spaces (PVS) on MRI is thought to be an early feature. Here, we investigate whether common cardiovascular risk factors (BP, smoking, diabetes) predict PVS burde...
Article
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Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cer...
Article
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Lateral ventricles might increase due to generalized tissue loss related to brain atrophy. Alternatively, they may expand into areas of tissue loss related to white matter hyperintensities (WMH). We assessed longitudinal associations between lateral ventricle and WMH volumes, accounting for total brain volume, blood pressure, history of stroke, car...
Article
There is increasing interest in computer applications, using artificial intelligence methodologies, to perform health care tasks previously performed by humans, particularly in medical imaging for diagnosis. In stroke, there are now commercial artificial intelligence software for use with computed tomography or MR imaging to identify acute ischemic...
Preprint
Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods is still unclear. Here, we propose an open-source computational model generating three-d...
Article
Full-text available
Background: Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction. Aims: To determine if the network impact scor...
Article
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Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association...
Preprint
Full-text available
White matter hyperintensities (WMH) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, although the frequency and associated factors are unknown. This systematic review and meta-analysis aims to assess longitudinal in...
Article
Full-text available
Preterm birth is associated with dysconnectivity of structural brain networks and is a leading cause of neurocognitive impairment in childhood. Variation in DNA methylation is associated with early exposure to extrauterine life but there has been little research exploring its relationship with brain development. Using genome-wide DNA methylation da...
Article
Cerebral small vessel disease (SVD) is highly prevalent and a common cause of ischemic and hemorrhagic stroke and dementia, yet the pathophysiology is poorly understood. Its clinical expression is highly varied, and prognostic implications are frequently overlooked in clinics; thus, treatment is currently confined to vascular risk factor management...
Article
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Background and Objectives The severity of white matter hyperintensities (WMH) at presentation with stroke associates with post-stroke dementia and dependency. However, WMH can decrease or increase after stroke, prediction of cognitive decline is imprecise, and there are few data assessing longitudinal interrelationships between changing WMH, cognit...
Article
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Background Metrics derived from the human eye are increasingly used as biomarkers and endpoints in studies of cardiovascular, cerebrovascular and neurological disease. In this context, it is important to account for potential confounding that can arise from differences in ocular dimensions between individuals, for example, differences in globe size...
Article
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Background It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. Methods We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of st...
Article
Vascular dysfunction is frequently observed in disorders associated with cognitive impairment, dementia and Alzheimer’s disease (AD). Recent advances in neuroimaging and fluid biomarkers suggest that vascular dysfunction is not an innocent bystander only accompanying neuronal dysfunction. Loss of cerebrovascular integrity, often referred to as brea...
Article
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Objectives The purpose of this study was to investigate whether thoracic ¹⁸F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke. Background Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aorti...
Preprint
Full-text available
A bstract Vast quantities of Magnetic Resonance Images (MRI) are routinely acquired in clinical practice but, to speed up acquisition, these scans are typically of a quality that is sufficient for clinical diagnosis but sub-optimal for large-scale precision medicine, computational diagnostics, and large-scale neuroimaging research. Here, we present...
Article
Background: White matter hyperintensities (WMH) are identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness; WMH are a major risk factor of stroke, dementia, and death. Currently, there are no large-scale studies testing associations between WMH and circulating metabolites. Methods: We studied up to 9,...
Article
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Background Neuropsychiatric symptoms associate cross-sectionally with cerebral small vessel disease but it is not clear whether these symptoms could act as early clinical markers of small vessel disease progression. We investigated whether longitudinal change in Neuropsychiatric Inventory (NPI) scores associated with white matter hyperintensity (WM...
Article
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Background Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia. Results Using blood-based epigenome-wide analyses of general cognitive function, we show that individual differences in DNA methylation (DNAm) explain 35.0% o...
Article
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Background Prehospital stroke trials will inevitably recruit patients with non-stroke conditions, so called stroke mimics. We undertook a pre-specified analysis to determine outcomes in patients with mimics in the second Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT-2). Methods RIGHT-2 was a prospective, multicent...
Article
Objective Whether perivascular space (PVS) visible on magnetic resonance imaging (MRI) represents glymphatic dysfunction and whether this imaging marker is pathologic in Parkinson's disease (PD) have been controversial. The objective was to determine whether PVS visible on MRI is independently associated with cognitive decline in patients with PD,...
Preprint
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Background: Major Depressive Disorder (MDD) is associated with accelerated ageing trajectories including functional markers of ageing, cellular ageing and markers of poor brain health. The biological mechanisms underlying these associations remain poorly understood. Chronic inflammation is also associated with advanced ageing; however, the degree t...
Article
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Background Accessible tools to efficiently detect and segment diffusion abnormalities in acute strokes are highly anticipated by the clinical and research communities. Methods We developed a tool with deep learning networks trained and tested on a large dataset of 2,348 clinical diffusion weighted MRIs of patients with acute and sub-acute ischemic...
Preprint
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Small Vessel Disease (SVD) is the leading cause of vascular dementia, causes a quarter of strokes, and worsens stroke outcomes(1, 2). The disease is characterised by cerebral small vessel and white matter pathology, but the underlying mechanisms are poorly understood. Classically, the microvascular and tissue damage has been considered secondary to...
Article
Structural MRI measurements can contribute to the prediction of amyloid pathology in cognitively unimpaired (CU) individuals. In this work, we aimed at studying the predictive capacity, robustness, and generalizability of ML techniques to predict amyloid‐β pathology in CU individuals, as well as identifying key brain regions contributing to this pr...
Article
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Background and Purpose Cerebral small vessel disease—a major cause of stroke and dementia—is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging–measured cerebrovascular function in patients with lacunar ischemic st...