Rates, risks and routes to reduce vascular dementia (R4VaD), a UK-wide multicentre prospective observational cohort study of cognition after stroke: baseline data and statistical analysis plan (ISRCTN18274006)

Background: Stroke is often followed by vascular cognitive impairment and vascular dementia; these are the most feared complication of stroke. However, there is limited understanding of post-stroke cognitive impairment. Methods: Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. Patients with haemorrhagic or ischaemic stroke, or transient ischaemic attack, were recruited within six weeks of stroke from hospitals across the UK. Consent was obtained from patients with capacity or from relatives/friends in those without capacity. The primary outcome is cognition and its severity assessed using a 7-level ordinal outcome. Final cognition will be compared in those with mild stroke/TIA (worst NIHSS <=7) versus severe stroke (NIHSS >7). Secondary outcomes will include function, mood and quality of life. Results: We recruited 2441 patients from 50 hospitals. Of these, 2437 (99.8%) had a qualifying event of stroke or TIA. The mean age was 68.2 years (standard deviation 13.5), females 981 (40.3%), onset to recruitment 6 days [interquartile range 3-13] and diagnosis ICH 193 (7.9%), ischaemic stroke 2101 (86.2%), TIA 143 (5.9%). The distribution of cognition at baseline was: normal 1256 (51.6%), minor neurocognitive disorder-single domain 530 (21.8%), minor neurocognitive disorder-multi domain 320 (13.1%), major neurocognitive disorder-mild 237 (9.7%), major neurocognitive disorder-moderate 90 (3.7%) and major neurocognitive disorder-severe 3 (0.1%). We provide the statistical analysis plan in the appendix. Conclusion: We provide baseline data and the SAP. Final follow-up will be completed in quarter 2 2024. The data highlight the substantial under-appreciated cognitive burden of stroke, even in the first few days and weeks. ### Competing Interest Statement PB is Stroke Association Professor of Stroke Medicine and an emeritus NIHR Senior Investigator. He has received honoraria from CoMind, DiaMedica, Phagenesis and Roche and has share options with CoMind and DiaMedica. LJW was funded by the British Heart Foundation (SAVANNAS, PG/19/69/34636). FD is funded by a Stroke Association-Garfield Weston Foundation Senior Clinical Lectureship (TSA LECT 2015/04) and an NHS Research Scotland Research Fellowship. TQ is funded by a Stroke Association/Chief Scientist Office Scotland Senior Clinical Lectureship for studies in post-stroke cognitive decline. He has received investigator initiated funding from BMS and Pfizer for projects on cardiovascular disease and cognition. HSM is supported by infrastructure support from the Cambridge University Hospitals NIHR Comprehensive Biomedical Research Centre. RM has received BP monitor- ing equipment for research from Omron and is working with them to develop a telemonitoring system. All fees for this work are paid to his institution. TGR is a NIHR Senior Investigator. DW has received Honoraria (speaking) from Bayer 2016, 2017, 2018 (talks or debates on ICH, atrial fibrillation, dementia); Honoraria (chairing) from Portola and Bayer (2019); Consultancy fees from Bayer (2017; embolic stroke of undetermined source), Alnylam (2019; CAA), Portola (2019, 2020; andexanet alpha). APJ is funded by a Stroke Association Margaret Giffen Reader Award (SA L-RC 19\100000). RT is funded through a British Heart Foundation Chair Award (CH/12/4/29762). HE is funded by Lancashire Teaching Hospitals NHS Foundation Trust and Lancaster University. JMW chaired the European Stroke Organisation Guideline Method Working Group on Small vessel Diseases Part 1 Covert SVD and Part 2 Lacunar Ischemic Stroke and the European Stroke Organisation Conference 2021 and 2022 The other authors have no declarations. ### Clinical Protocols ### Funding Statement R4VaD is funded by the UK Stroke Association, British Heart Foundation and Alzheimers Society Priority Programme Award in Vascular Dementia (16 VAD 07) and the UK MRC Dementia Platform UK. The work is also supported by the UK MRC Dementia Research Institute. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: R4VaD was approved by Ethics Committees in Scotland (A Research Ethics Committee; Ref 18/SS/055), England (Health Research Authority), Wales (Health and Care Research) and Northern Ireland (all Northeast Newcastle and North Tyneside 1; 18/NE/0150). NHS Research and Innovation Office approval was given in each participating site. R4VaD is registered ([ISRCTN18274006][1]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The CI, with approval from the TSC as necessary, will consider all reasonable requests to share individual participant data on provision of a protocol detailing aims, hypotheses, analyses, tables, figures and publication plan. Where possible, we will perform the analyses; alternatively, de-identified data and a data dictionary will be provided for remote analyses, subject to signed data access agreement. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN18274006