R4VaD
Research type
Research Study
Full title
Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD)
IRAS ID
239109
Contact name
Joanna Wardlaw
Contact email
Duration of Study in the UK
4 years, 8 months, 0 days
Research summary
Summary of Research
Stroke commonly affects cognition and, by definition, vascular dementia is driven by stroke disease in some way. However, fundamental knowledge about risk factors is widely acknowledged to be missing, restricting mechanistic understanding, prevention, treatment, and design of patient services.
We aim to recruit a wide range of patients with stroke, presenting to geographically diverse UK hospitals, into a longitudinal study to determine rates of, and risk factors for, cognitive and related impairments after stroke, to assess mechanisms and improve prediction models.
We will recruit about 2000 patients within a few weeks of stroke, collect patient, stroke, socioeconomic, lifestyle, cognitive (plus fatigue, mood) and informant data using streamlined methods appropriate to the stroke stage. We will obtain more detailed assessments at 6+/- 2 weeks post baseline assessment and follow-up by phone and post yearly to at least 2 years. We will assess diagnostic neuroimaging, vascular function, high-sensitivity inflammatory markers and genetic associations.
Outputs will include reliable data on cognition long-term after stroke, stratified by prior cognition, stroke and patient-related variables, improved risk prediction and understanding the influence of neuroimaging, vascular, inflammatory and genetic markers. Participants will be in follow-up and consented for re-contact, facilitating future clinical trials.Summary of Results
Post-stroke cognitive impairment (PSCI) is very common and decline in memory and thinking ability is a major concern for stroke survivors. Currently there are no effective preventions or therapies. Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is a Priority Programme in Vascular Dementia funded by the Stroke Association, British Heart Foundation and Alzheimer’s Society. We set out to recruit 2000 participants and aimed to assess the rates of PSCI and dementia occurring up to two years after stroke. We not only looked at thinking and memory, but also their health, education and lifestyle factors to help us to build a picture of how their memory may have changed and how this relates to their stroke. We also collected brain scans, blood pressure and blood samples to look for any changes that might be related. All recruitment and follow up for the study is now complete.
Participants were recruited from 50 hospitals in the UK within six weeks of stroke. We recruited 2437 participants with a stroke or transient ischaemic attack (TIA) that met our study inclusion and exclusion criteria. These participants had an average age of 68 years and 40.3% were female. The majority (80%) of participants had a mild stroke or TIA, 18.5% had a severe stroke.
Just over half (51.6%) of participants at their first study appointment had normal cognitive function. Minor neurocognitive disorder was present in 34.9% of participants, major cognitive disorder in 13.5% (ranging from mild to severe). These baseline data and our statistical analysis plan is now available online and this initial analysis shows significant cognitive burden at this early timepoint despite the relatively mild stroke population. Initial results of the study were presented at the European Stroke Organisation Conference 2024 in Basel. Analysis of follow up data is being completed, we will use these data to make significant progress with determining the rates of PSCI up to at least two years after stroke.We performed a substudy in 250 participants to validate our central data collection and definition of cognitive impairment against a gold standard clinical diagnosis of cognitive impairment or dementia. This provides confidence in the central method of determining cognitive status for use in future trials and demonstrates the added value of the R4VaD study.
We have now received information on recurrent stroke/vascular events, prescribed medicines and death (cause and date) for this population beyond the end of the study via data linkage to hospital records, allowing analysis of long-term outcomes for this cohort.
Blood samples were collected for genome-wide association study (GWAS) analysis from 1159 patients from 31 participating sites. Further blood samples were collected for assessment of inflammatory biomarkers from 407 participants at 14 participating sites. Advanced brain magnetic resonance imaging (MRI) was performed in 202 patients at four centres (Aberdeen, Cambridge, Edinburgh, London UCL); this was done as close as possible to the R4VaD early follow up time point. Results of both of these studies are being analysed and prepared for preparation.
The study was paused in March 2020 at the start of the COVID-19 pandemic. We were able to re-commence recruitment shortly afterwards to obtain objective data on COVID-19 and stroke. We have obtained data on the prevalence of COVID-19 in patients with stroke, examined the relationship between the two illnesses and to evaluate the clinical and neuropsychological impact of COVID-19 on these patients. A paper is in preparation.
A substudy led by University College London found that over 40% of 338 participants reported sexual dysfunction 6 to 12 weeks after stroke. This is a neglected area and R4VaD is the largest study of this topic to date. We hope the study will inform clinical guidelines and management. The results were presented at UK Stroke Forum 2024 and the presenter, Dr Hatice Capar, was awarded the Warlow prize for best abstract and another prize for best early career researcher. A paper will shortly be submitted.
Several other papers are close to completion with a view to publish this year including results of the neuroimaging substudy and validation of the 4 and 7 level ordinal scales for classifying degree of PSCI which shows that this may provide a standardised method for use in future clinical trials.
To assist with the study, we had a Patient & Public Involvement advisory group. This involved 7 members, made up of stroke survivors, carers and family members who were selected via applications to a scheme run by the Stroke Association. We asked for their feedback on various aspects of the study, and kept in touch through emails and newsletters, to update on our progress. We also regularly received enquiries from members of the public who were keen to be involved in the study, either as participants or as stroke survivors or family members who are keen to help out with research in some way, showing the wide-reaching interest in this research. Members of this panel have also advised on other selected studies demonstrating the added value of the R4VaD study.
Information on the rates of memory and thinking problems after stroke is limited. This means that understanding how and why cognition is affected is difficult. We aim to provide further information on this, which will help build a better picture of how it is affected, what the risk factors are and how to better advise patients on their outlook for recovery. Our outputs will include long term cognition after stroke, relationship to prior cognition and other variables such as medical and socioeconomic factors. We will also aid mechanistic understanding by investigating the relationship between cognition and vascular factors such as blood pressure, brain imaging markers such as white matter lesions, and inflammatory and genetic markers from blood samples. Furthermore, participants were able to consent to be contacted with information about additional studies and clinical trials, not only giving patients access to potential future therapies, but also providing researchers with access to a pool of well characterised individuals which will facilitate these studies.
Overall, we will improve awareness and understanding of post stroke cognitive impairment, improve patient care, advice and be able to improve patient services.REC name
Scotland A: Adults with Incapacity only
REC reference
18/SS/0055
Date of REC Opinion
9 Jul 2018
REC opinion
Further Information Favourable Opinion