Tim Wilkinson

• PhD
• Fellow at University of Edinburgh

Background and objectives: Plasma biomarkers of Alzheimer disease (AD), neuroinflammation, and neurodegeneration are increasingly being used in clinical trials for diagnosis and monitoring of dementia. However, their association with longitudinal structural brain MRI changes, an important outcome measure across neurodegenerative and cerebrovascula...

Background Functional cognitive disorder (FCD) poses a diagnostic challenge due to its resemblance to other neurocognitive disorders and limited biomarker accuracy. We aimed to develop a new diagnostic checklist to identify FCD versus other neurocognitive disorders. Methods The clinical checklist was developed through mixed methods: (1) a literatu...

Objective To investigate the use of sodium valproate in England and Wales, including during pregnancy, compared with other antiseizure drug treatments, based on national level electronic health records. Design Quantitative analysis of nationwide linked electronic health records. Setting Individual level, population scale data from NHS England's S...

Cognitive symptoms are prevalent across neuropsychiatric disorders, increase distress and impair quality of life. Self-guided digital interventions offer accessibility, scalability, and may overcome the research-to-practice treatment gap. Seventy-six trials with 5214 participants were identified. A random-effects meta-analysis investigated the effe...

Alzheimer’s disease is a neurodegenerative disorder marked by cognitive decline and brain pathology involving amyloid plaques and neurofibrillary tangles. Current drug development focuses on disease-modifying therapies, primarily antibodies targeting amyloid or tau. However, the blood-brain barrier (BBB) poses a challenge for drug delivery to the b...

Background Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. Methods International experts in cognitive disorders were invited to assess s...

Background Due to low success rates in clinical trials for Alzheimer’s disease (AD), there is a need to apply precision medicine approaches, such as stratifying based on APOE genotype, in order to assess its effects on outcome measures. Herein, we aim to better understand how plasma biomarkers of AD and neurodegenerative pathology are associated wi...

Background It is critical to better understand the value of plasma biomarkers in predicting cognitive deficits before widespread use as diagnostic and prognostic tools in specialized clinics and as markers of neurodegenerative disease progression in trials. Herein, we investigate their association with five cognitive domains across three common neu...

Background It is necessary to better understand the value of plasma biomarkers in reflecting ongoing neurodegenerative processes before widespread use as diagnostic and prognostic tools in specialized clinics and as markers of disease progression in trials. Herein, we investigate their association with imaging markers of brain atrophy and white mat...

INTRODUCTION We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p‐tau)181 and amyloid beta (Aβ)42...

Background: Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to in...

Background: Antipsychotic drugs have been associated with increased mortality, stroke and myocardial infarction in people with dementia. Concerns have been raised that antipsychotic prescribing may have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of the virus. We used multisource, routinely-collecte...

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...

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 summarise the cerebral phenotypes associated with these more recent cSVD genes. Me...

Background Previous studies have suggested that some medications may influence dementia risk. We conducted a hypothesis-generating medication-wide association study to investigate systematically the association between all prescription medications and incident dementia. Methods We used a population-based cohort within the Secure Anonymised Informa...

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...

Introduction Research can often be slow to start and require duplication of effort which in lots of cases has previously been completed to generate research-ready-data-assets (RRDA). Within the UK, two programmes: Dementias Platform UK (DPUK) that brings together over 50 different dementia-related cohorts and Secure Anonymised Information Linkage (...

Objectives Limited research has shown that people with dementia (PwD) from lower socio‐economic backgrounds can face difficulties in accessing the right care at the right time. This study examined whether socio‐economic status (SES) and rural versus urban living location are associated with the time between diagnosis and care home admission in PwD...

Background and Purpose An important minority of cerebral small vessel disease (cSVD) is monogenic. Many monogenic cSVD genes are recognized to be associated with extracerebral phenotypes. We assessed the frequency of these phenotypes in existing literature. Methods We performed a systematic review following the PRISMA guidelines (Preferred Reporti...

Objective: To determine the association of epilepsy with incident dementia we conducted a nation-wide retrospective data-linkage, cohort study, to examine whether the association varies according to dementia subtypes and investigate whether risk factors modify the association. Methods: We used linked health data from hospitalisation, mortality rec...

Objective In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes. Methods In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 co...

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with t...

The Dementias Platform UK (DPUK) Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations...

IntroductionThe rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owi...

Introduction: Incidental findings are common in presumed healthy volunteers but are infrequently studied in patients in a clinical context. Objective: To determine the prevalence, nature, and management implications of incidental findings on head MRI in patients presenting with cognitive symptoms, and to quantify and describe unexpected MRI abno...

Background The Secure Anonymised Information Linkage Dementia e-Cohort (SAIL-DeC) is composed of anonymised, linked, routinely-collected healthcare datasets for the population of Wales. We used this population-based e-cohort to investigate dementia mortality. Methods SAIL-DeC uses a validated algorithm to identify allcause dementia cases from coded...

Introduction Dementia Platform UK (DPUK) brings together over 50 different dementia-related cohorts. Most studies have restricted follow-up times and all are based on information from people who volunteer time and data for research. Participants are therefore often not representative of the 'wider population' and generalization of results is compl...

Introduction: Prospective studies reporting associations between cognitive performance and subsequent incident dementia have been subject to attrition bias. Furthermore, the extent to which established risk factors account for such associations requires further elucidation. Methods: We used UK Biobank baseline cognitive data (n ≤ 488,130) and el...

Background People with epilepsy (PWE) are reported to have higher risk of dementia. However, the magnitude of this association, whether it varies according to dementia subtypes and whether there are factors that modify the association is uncertain. We investigated the apparent association in a large population-based retrospective cohort study using...

Background Recent studies have reported conflicting associations between drug prescriptions and incident dementia. Any association between drug and dementia could be due to the drugs directly causing or preventing dementia; the drugs being associated with a risk factor for dementia; or the drugs being prescribed as a consequence of prodromal dement...

Prospective, population-based studies that recruit participants in mid-life are valuable resources for dementia research. Follow-up in these studies is often through linkage to routinely-collected healthcare datasets. We investigated the accuracy of these datasets for dementia case ascertainment in a validation study using data from UK Biobank—an o...

Objective To identify and quantify cerebral phenotypes as-sociated with Mendelian cerebral small vessel diseases(CSVD) in order to improve our understanding of thesedisorders. Background CSVD is a major cause of morbidityin the developed world. The majority of cases are sporadic butMendelian forms account for a significant minority and mayoffer ins...

Background Population-based, prospective studies can provide important insights into Parkinson’s disease (PD) and other parkinsonian disorders. Participant follow-up in such studies is often achieved through linkage to routinely collected healthcare datasets. We systematically reviewed the published literature on the accuracy of these datasets for...

Objectives Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR. Methods and findings A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [C...

Background: Population-based, prospective studies can provide important insights into Parkinson's disease (PD) and other parkinsonian disorders. Participant follow-up in such studies is often achieved through linkage to routinely-collected healthcare datasets. We systematically reviewed the published literature on the accuracy of these datasets for...

INTRODUCTION: Prospective, population-based studies can be rich resources for dementia research. Follow-up in many such studies is through linkage to routinely-collected, coded healthcare datasets. We evaluated the accuracy of these datasets for dementia case identification. METHODS: We systematically reviewed the literature for studies comparing d...

Introduction: Prospective, population-based studies can be rich resources for dementia research. Follow-up in many such studies is through linkage to routinely collected, coded health-care data sets. We evaluated the accuracy of these data sets for dementia case identification. Methods: We systematically reviewed the literature for studies compa...

Background It is unclear whether the risk of bleeding from brain arteriovenous malformations is higher during pregnancy, delivery, or puerperium. We compared occurrence of brain arteriovenous malformation hemorrhage in women during this period with occurrence of hemorrhage outside this period during their fertile years. Methods We included all wom...

Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essentia...

Objectives Dementia is a major public health concern worldwide and consequently there is an urgent need to expedite research into its causes so that preventative strategies can be sought. Given that dementia is likely to be the result of a complex interplay of many factors, large study populations are required in order to detect effects reliably. U...

Background Motor neurone disease (MND) is a rare neurodegenerative condition, with poorly understood aetiology. Large, population-based, prospective cohorts will enable powerful studies of the determinants of MND, provided identification of disease cases is sufficiently accurate. Follow-up in many such studies relies on linkage to routinely-collect...