The contributing studies were funded by the Chief Scientist Office of the Scottish Executive (grant 217 NTU R37933), the Wellcome Trust (grants 075611 and WT088134/Z/09/A), and Row Fogo Charitable Trust. The imaging was performed at the Brain Research Imaging Centre Edinburgh, which is supported by the SINAPSE (Scottish Imaging Network, A Platform for Scientific Excellence) collaboration and the Chief Scientist Office of the Scottish Government (http://www.bric.ed.ac.uk/). This work was supported by European Union Horizon 2020 (EU H2020), PHC- 03 to 15, project No. 666881, SVDs@Target, and the Fondation Leducq Transatlantic Network of Excellence for Study of Perivascular Spaces in Small Vessel Disease, ref No. 16 CVD 05. Dr Loos was supported by the Dutch Alzheimer Foundation. ; Peer reviewed ; Publisher PDF
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Wellcome Trust (grant 088134/Z/09/A), the Scottish Funding Council and the Chief Scientist Office, Scotland, through the Scottish Imaging Network: A Platform for Scientific Excellence ('SINAPSE') and the European Union Horizon 2020 research and innovation programme SVDs@Target under grant agreement 666881. FD and TQ are funded by the Stroke Association/Garfield Weston Foundation and Stroke Association/Chief Scientist Office Senior Lectureships respectively. PMB is Stroke Association Professor of Stroke Medicine and is a NIHR Senior Investigator. The work was supported by the Fondation Leducq Transatlantic Network of Excellence in Small Vessel Disease ref no. 16 CVD 05, and the Horizon 2020 Programme PHC-03-15, project No 666881, 'SVDs @Target.' The work was conducted independently of the funders. ; Peer reviewed ; Publisher PDF
Grant support: Wellcome Trust (grant 088134/Z/09/A); Scottish Funding Council and the Chief Scientist Office of Scotland for funding the Scottish Imaging Network: A Platform for Scientific Excellence. F.D. holds an NHS Research Scotland and Stroke Association-Garfield Weston Foundation Senior Lectureship (grant TSA Lect 2015/04). J.S. was supported by the MUMC Academic Fund. J.M.W. receives support from the European Union Horizon 2020, PHC-03-15, project number 666881; "SVDs@Target," the Fondation Leducq Network for the Study of Perivascular Spaces in Small Vessel Disease, reference number 16 CVD 05; and the Row Fogo Charitable Trust, reference number AD.ROW4.35. BRO-D.FID3668413. The study was conducted independent of the funders. ; Peer reviewed ; Publisher PDF
This research has been conducted using the UK Biobank resource. The authors are grateful to UK Biobank participants. UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. ; Peer reviewed ; Publisher PDF
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding from the Stroke Association (DAD), Technology Strategy Board/ Innovate UK (46917-348146), Wellcome Trust (WT088134/Z/09/A), Row Fogo Charitable Trust, Lupus UK, National Institutes of Health (R01 EB004155-03), European Union Horizon 2020 PHC-03-15, project No 666881, SVDs@Target, and Fondation Leducq (Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, ref no. 16 CVD 05) is gratefully acknowledged. ; Peer reviewed ; Publisher PDF
Objectives: Transient ischaemic attack (TIA) is a medical emergency requiring rapid access to effective, organised, stroke prevention. There are about 90 000 TIAs per year in the UK. We assessed whether stroke-prevention services in the UK meet Government targets. Design: Cross-sectional survey. Setting: All UK clinical and imaging stroke-prevention services. Intervention: Electronic structured survey delivered over the web with automatic recording of responses into a database; reminders to non-respondents. The survey sought information on clinic frequency, staff, case-mix, details of brain and carotid artery imaging, medical and surgical treatments. Results: 114 stroke clinical and 146 imaging surveys were completed (both response rates 45%). Stroke-prevention services were available in most (97%) centres but only 31% operated 7 days/week. Half of the clinic referrals were TIA mimics, most patients (75%) were prescribed secondary prevention prior to clinic referral, and nurses performed the medical assessment in 28% of centres. CT was the most common and fastest first-line investigation; MR, used in 51% of centres, mostly after CT, was delayed up to 2 weeks in 26%; 51% of centres omitted blood-sensitive (GRE/T2*) MR sequences. Carotid imaging was with ultrasound in 95% of centres and 59% performed endarterectomy within 1 week of deciding to operate. Conclusions: Stroke-prevention services are widely available in the UK. Delays to MRI, its use in addition to CT while omitting key sequences to diagnose haemorrhage, limit the potential benefit of MRI in stroke prevention, but inflate costs. Assessing TIA mimics requires clinical neurology expertise yet nurses run 28% of clinics. Further improvements are still required for optimal stroke prevention.
This work was funded by the Row Fogo Charitable Trust (MH, VG-C) grant no. BRO-D.FID3668413 and the Wellcome Trust (patient recruitment, scanning, primary study Ref No. WT088134/Z/09/A). The study was conducted independently of the funders who do not hold the data and did not participate in the study design or analyses the EU H2020 and Fondation Leducq Network grants as specified. Funds from European Union Horizon 2020, PHC-03-15, project No 666881, 'SVDs@Target' and Fondation Leducq Network for the Study of Perivascular Spaces in Small Vessel Disease, ref no. 16 CVD 05 are gratefully acknowledged. ; Peer reviewed ; Publisher PDF
Acknowledgements: We thank the LBC1936 members and project staff. Study Funding: The LBC1936 and this research are supported by Age UK (Disconnected Mind project), the UK Medical Research Council [MRC; G0701120, G1001245, MR/M013111/1, MR/R024065/1], and the University of Edinburgh. SRC, MEB, and IJD were also supported by a National Institutes of Health (NIH) research grant R01AG054628. JMW, IJD are also supported by a Wellcome Trust Strategic Award (Ref 104036/Z/14/Z). MCVH is funded by the Row Fogo Charitable Trust (grant No. BROD.FID3668413). SRC was also supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 221890/Z/20/Z). Imaging and image analysis was performed at the Brain Research Imaging Centre (http://www.sbirc.ed.ac.uk/), Edinburgh, supported by the Scottish Funding Council SINAPSE Collaboration. LCAC acknowledges 4 Luciano funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division. MVH is funded by the Row Fogo Charitable Trust Centre for Research into Ageing and the Brain (Ref No: AD.ROW4.35. BRO-D.FID3668413). JMW received funding from the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. ; Peer reviewed ; Publisher PDF
Acknowledgements This work is supported by the MRC Doctoral Training Programme in Precision Medicine (JB); the Wellcome Trust (patient recruitment, scanning, and primary study - Reference No. WT088134/Z/09/A); the UK Dementia Research Institute, which receives its funding from DRI Ltd, funded by the UK MRC, Alzheimer's Society, and Alzheimer's Research UK; the Fondation Leducq Network for the Study of Perivascular Spaces in Small Vessel Disease (16 CVD 05); The Row Fogo Charitable Trust Centre for Research into ageing and the Brain (MVH) (BRO-D.FID3668413); a British Heart Foundation Chair award (RMT) (CH/12/4/29762); and NHS Lothian Research and Development Office (MJT); European Union Horizon 2020, PHC-03-15, project No666881. We thank the participants, their families, radiographers at Edinburgh Imaging, and the Stroke Research Network at the University of Edinburgh. ; Peer reviewed ; Publisher PDF
Funding Information: The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Wellcome Trust [grant number WT088134/Z/09/A ; SDJM, FC]; Row Fogo Charitable Trust (MCVH, FC, AKH, PAA); Scottish Funding Council Scottish Imaging Network A Platform for Scientific Excellence collaboration (JMW); NHS Lothian R + D Department (MJT); the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK MRC, Alzheimer's Research UK and the Alzheimer's Society (MS, FC, ES, JMW); the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease [reference number 16 CVD 05] (MS); and European Union Horizon 2020 [project number 666881, SVDs@Target] (MS, FC). We acknowledge the participants, their relatives, and carers for their participation in this study, and the staff of NHS Lothian Stroke Services and Brain Research Imaging Centre Edinburgh for their assistance in recruiting and assessing the patients. ; Peer reviewed ; Publisher PDF
The project was funded by the Wellcome Trust (WT088134/Z/09/A; S.D.J.M, project costs), the Row Fogo Charitable Trust (M.d.C.V.H., A.K.H.), AgeUK (S.M.-M.), the European Union Horizon 2020 project 666881, SVDs@Target (F.M.C.). The Brain Imaging Centre is supported by the Scottish Funding Council SINAPSE Initiative (www.sinapse.ac.uk); funding from the Fondation Leducq (16-CVD-05) is gratefully acknowledged. J.S. was supported by Maastricht University Medical Centre Academic Fund. The study was conducted independently of the funders. The Article Processing Charge was funded by the Wellcome Trust via the University of Edinburgh. ; Peer reviewed ; Publisher PDF
This project was funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215). L.S is funded by the Virtual Brain Cloud from European comission (grant no. H2020-SC1-DTH-2018-1). C.R.B is funded by National Institutes of Health (NIH) research grant R01AG054628. S.R.C is funded by National Institutes of Health (NIH) research grant (R01AG054628), Medical Research Council (MR/R024065/1), Age UK and Economic and Social Research Council. R.E.M. was supported by Alzheimer's Research UK major project grant ARUKPG2017B-10. C.H was supported by an MRC Human Genetics Unit programme grant "Quantitative traits in health and disease" (U.MC_UU_00007/10). H.C.W received funding from Wellcome Trust. J.W is funded by TauRx pharmaceuticals Ltd and received Educational grant from Biogen paid to Alzheimer Scotland/Brain Health Scotland. G.W received GRAMPIAN UNIVERSITY HOSPITALS NHS TRUST, Scottish Government—Chief Scientist Office, ROLAND SUTTON ACADEMIC TRUST, Medical Research Scotland, Sutton Academic Trust and ROLAND SUTTON ACADEMIC TRUST. J.M.W received Wellcome Trust Strategic Award, MRC UK Dementia Research Institute and MRC project grants, Fondation Leducq, Stroke Association, British Heart Foundation, Alzheimer Society, and the European Union H2020 PHC-03-15 SVDs@Target grant (666881). D.S received MRC (MR/S010351/1), MRC (MR/W002388/1) and MRC (MR/W002566/1). A.M is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 847776. In addition, A.M has received grant support from The Sackler Trust, outside of the work presented. N.B received grant to institution from GSK as part of GSK/Oxford FxG initiative. A.N.H received John Black Charitable Fund-Rosetrees, H2020 funding from European Comission-Project Virtual Brain Cloud, AI for the Discovery of new therapies in Parkinson's (A2926), Rising Start Initiative—stage 2, Brain-Gut Microbiome (Call: PAR-18-296; Award ID: 1U19AG063744-01), Gut-liver-brain biochemical axis in Alzheimer's disease (5RF1AG057452-01), Virtual Brain Cloud (Call: H2020-SC1-DTH- 2018-1; Grant agreement ID: 826421). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006) and is currently supported by the Wellcome Trust (216767/Z/19/Z). Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" [STRADL] Reference 104036/Z/14/Z). We are grateful to all the families who took part; the general practitioners and the Scottish School of Primary Care for their help in recruiting them; and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants, and nurses. ; Peer reviewed ; Publisher PDF
ACKNOWLEDGEMENTS We would like to thank all of the Generation Scotland participants for their contribution to this study. We also thank the research assistants, clinicians and technicians for their help in collecting the data. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. This study was also supported and funded by the Wellcome Trust Strategic Award 'Stratifying Resilience and Depression Longitudinally' (STRADL) (Reference 104036/Z/14/Z). We acknowledge the support of the British Heart Foundation (RE/18/5/34216). CG is supported by the Medical Research Council and the University of Edinburgh through the Precision Medicine Doctoral Training Programme. MCB is supported by a Guarantors of Brain Non-Clinical Post-Doctoral Fellowship. JMW is funded by the UK Dementia Research Institute which is funded by the UK Medical Research Council, Alzheimer's Research UK and Alzheimer's Society ; Peer reviewed ; Publisher PDF
In: Twin research and human genetics: the official journal of the International Society for Twin Studies (ISTS) and the Human Genetics Society of Australasia, Band 18, Heft 6, S. 738-745
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 polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115–8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.
Funding Information: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) Reference 104036/Z/14/Z). CG is supported by The Medical Research Council and The University of Edinburgh through the Precision Medicine Doctoral Training program. SRC is supported by the UK Medical Research Council [MR/R024065/1] and a National Institutes of Health (NIH) research grant R01AG054628. Acknowledgements The authors thank all of the STRADL and Generation Scotland participants for their time and effort taking part in this study. We would also like to thank all of the research assistants, clinicians and technicians for their help in the collecting this data. ; Peer reviewed ; Publisher PDF
