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1. C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype

Author

McCabe, John J., primary, Walsh, Cathal, additional, Gorey, Sarah, additional, Harris, Katie, additional, Hervella, Pablo, additional, Iglesias-Rey, Ramon, additional, Jern, Christina, additional, Li, Linxin, additional, Miyamoto, Nobukazu, additional, Montaner, Joan, additional, Pedersen, Annie, additional, Purroy, Francisco F., additional, Rothwell, Peter M., additional, Sudlow, Cathie L., additional, Ueno, Yuji, additional, Vicente-Pascual, Mikel, additional, Whiteley, Will N., additional, Woodward, Mark, additional, and Kelly, Peter J., additional

Published
2024
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3. Observer Agreement on Computed Tomography Perfusion Imaging in Acute Ischemic Stroke

Author

El-Tawil, Salwa, Mair, Grant, Huang, Xuya, Sakka, Eleni, Palmer, Jeb, Ford, Ian, Kalra, Lalit, Wardlaw, Joanna, Muir, Keith W., Adami, Alessandro, Cerase, Alfonso, Garcia, Ana, von Heijne, Anders, Peeters, Andre, von Heijne, Anders, Zini, Andrea, Carneiro, Angelo, Patterson, Chris, Roffe, Christine, Freedman, Daniel, Scoffings, Daniel, Krieger, Derk W, Mitra, Dipayan, Berge, Eivind, Cora, Elena Adela, O’Brien, Eoin, Bertholds, Eric, Murat, Ethem, Moreton, Fiona, Tan, Garryck, Potter, Gillian, Rinaldi, Giuseppe, Madigan, Jeremy, Leyon, Joe, Du Plessis, Johann, Hewitt, Jonathan, Alves, José Eduardo, Egido, Jose, Sztriha, Laszlo, Esbjoernsson, Magnus, Correia, Manuel, Griebe, Martin, Dharmasiri, Michelle, Kirmi, Olga, Geraghty, Olivia, García-Bermejo, Pablo, Sutton, Patrick, Bhogal, Pervinder, White, Philip, Ferdinand, Phillip, Anjum, Qazi, Sellar, Robin, von Kummer, Rüdiger, Andole, Sreeman, Vundavalli, Sriram, Webb, Thomas, Das, Tilak, Matys, Tomasz, Goddard, Tony, Gontu, Vamsi, Sawlani, Vijay, Puetz, Volker, and Whiteley, Will

Published
2019
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4. Confusion after a game of bridge

Author

Whiteley, Will and Dennis, Martin

Subjects
Adenocarcinoma -- Complications and side effects, Stroke (Disease) -- Risk factors, Stroke (Disease) -- Diagnosis, Stroke (Disease) -- Case studies, Vertigo -- Diagnosis, Health, Psychology and mental health
Published
2007

7. Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Author

Sandercock Peter, Lindley Richard, Wardlaw Joanna, Dennis Martin, Innes Karen, Cohen Geoff, Whiteley Will, Perry David, Soosay Vera, Buchanan David, Venables Graham, Czlonkowska Anna, Kobayashi Adam, Berge Eivind, Slot Karsten, Murray Veronica, Peeters Andre, Hankey Graeme J, Matz Karl, Brainin Michael, Ricci Stefano, Cantisani Teresa A, Gubitz Gordon, Phillips Stephen J, Antonio Arauz, Correia Manuel, Lyrer Phillippe, Kane Ingrid, and Lundstrom Erik

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. Design International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. Results The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. Conclusion The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. Trial registration ISRCTN25765518

Published
2011
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8. How to design a hypertension treatment trial that informs care of older people with frailty: a survey of clinicians in Ireland and the UK.

Author

Veenhuizen, Miriam, Todd, Oliver, Anand, Atul, and Whiteley, Will

Subjects
HYPERTENSION, ANTIHYPERTENSIVE agents, INTERNATIONAL relations, EVALUATION of human services programs, ATTITUDE (Psychology), SOCIAL networks, MEDICAL personnel, HUMAN services programs, MEDICAL protocols, SURVEYS, QUESTIONNAIRES, DECISION making in clinical medicine, ELDER care, MEDICAL societies, COMORBIDITY, OLD age
Abstract

Introduction At all ages, randomised trials demonstrate lower mortality and cardiovascular disease incidence with blood pressure (BP) lowering. However, this may not generalise to older people with frailty. We aimed to determine the acceptability to clinicians of key aspects of trial designs using different BP targets and strategies to better manage hypertension in the context of frailty. Methods We conducted a multinational survey of clinicians managing hypertension in older people, distributed using an online survey link amongst professional societies and social networks. Questions described case histories of patients who were frail with different systolic blood pressures (SBP), treatment target, strategy and target trial population. Results In total, 114 responses were received (48 primary care, 66 secondary care). A majority would consider recruiting patients to a trial of relaxing treatment in those whose SBP < 130 mm Hg; a majority would consider recruiting to a trial intensifying treatment in patients with SBP > 150 mm Hg. Respondents elected to intensify treatment by: choosing the next step by NICE guidelines, adding a new treatment agent at full dose, or adding two agents at half dose. Conclusion A majority of clinicians surveyed would recruit older people to a trial intensifying treatment where SBP is more than 150 mm Hg and where patients have high cardiovascular risk or to a trial relaxing treatment where the SBP is below 130 mm Hg and where the patient has frailty. [ABSTRACT FROM AUTHOR]

Published
2021
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9. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research

Author

METACOHORTS Consortium, Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carole, Chabriat, Hughes, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, and Yang, Yuan-Han

Subjects
R1
Published
2016

10. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration : An initiative of the Joint Programme for Neurodegenerative Disease Research

Author

Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, Leeuw, Frank-Erik De, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, Oostenbrugge, Robert van, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip MW., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Salman, Rustam Al-Shahi, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, Boxtel, Martin van, Grond, Jeroen van der, Lugt, Aad van der, Yang, Yuan-Han, Metacohorts Consortium, [GIN] Grenoble Institut des Neurosciences (GIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Epidemiology, [SCCO.NEUR]Cognitive science/Neuroscience, Health Policy, Clinical Neurology, Neurodegeneration, Cohorts, Survey, Small vessel disease, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Developmental Neuroscience, Journal Article, Dementia, Neurodegeneration, Geriatrics and Gerontology, Survey, Cerebrovascular disease, Cohorts
Abstract

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

Published
2016

11. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research

Author

ZL Algemene Neurologie Medisch, Circulatory Health, Brain, Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H. C., Davis, S., Hankey, G., Lees, K. R., Ovbiagele, B., Weir, C., Bae, Hee Joon, Bath, Philip MW, Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, San Yun, Lim, Jae Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, Yang, Yuan Han, ZL Algemene Neurologie Medisch, Circulatory Health, Brain, Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H. C., Davis, S., Hankey, G., Lees, K. R., Ovbiagele, B., Weir, C., Bae, Hee Joon, Bath, Philip MW, Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, San Yun, Lim, Jae Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, and Yang, Yuan Han

Published
2016

12. Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute ischaemic stroke in the third International Stroke Trial (IST-3) : secondary analysis of a randomised controlled trial.

Author

Wardlaw, Joanna M, Sandercock, Peter, Cohen, Geoff, Farrall, Andrew, Lindley, Richard, von Kummer Dresden, Rudiger, von Heijne, Anders, Bradey, Nick, Peeters, Andre, Cala, Lesley, Adami, Alessandro, Morris, Zoe, Potter, Gillian, Murray, Gordon, Whiteley, Will, Perry, David, Sakka, Eleni, Lundström, Erik, Wardlaw, Joanna M, Sandercock, Peter, Cohen, Geoff, Farrall, Andrew, Lindley, Richard, von Kummer Dresden, Rudiger, von Heijne, Anders, Bradey, Nick, Peeters, Andre, Cala, Lesley, Adami, Alessandro, Morris, Zoe, Potter, Gillian, Murray, Gordon, Whiteley, Will, Perry, David, Sakka, Eleni, and Lundström, Erik

Abstract

BACKGROUND: Brain scans are essential to exclude haemorrhage in patients with suspected acute ischaemic stroke before treatment with alteplase. However, patients with early ischaemic signs could be at increased risk of haemorrhage after alteplase treatment, and little information is available about whether pre-existing structural signs, which are common in older patients, affect response to alteplase. We aimed to investigate the association between imaging signs on brain CT and outcomes after alteplase. METHODS: IST-3 was a multicentre, randomised controlled trial of intravenous alteplase (0·9 mg/kg) versus control within 6 h of acute ischaemic stroke. The primary outcome was independence at 6 months (defined as an Oxford Handicap Scale [OHS] score of 0-2). 3035 patients were enrolled to IST-3 and underwent prerandomisation brain CT. Experts who were unaware of the random allocation assessed scans for early signs of ischaemia (tissue hypoattenuation, infarct extent, swelling, and hyperattenuated artery) and pre-existing signs (old infarct, leukoaraiosis, and atrophy). In this prespecified analysis, we assessed interactions between these imaging signs, symptomatic intracranial haemorrhage (a secondary outcome in IST-3) and independence at 6 months, and alteplase, adjusting for age, National Institutes of Health Stroke Scale (NIHSS) score, and time to randomisation. This trial is registered at ISRCTN.com, number ISRCTN25765518. FINDINGS: 3017 patients were assessed in this analysis, of whom 1507 were allocated alteplase and 1510 were assigned control. A reduction in independence was predicted by tissue hypoattenuation (odds ratio 0·66, 95% CI 0·55-0·81), large lesion (0·51, 0·38-0·68), swelling (0·59, 0·46-0·75), hyperattenuated artery (0·59, 0·47-0·75), atrophy (0·74, 0·59-0·94), and leukoaraiosis (0·72, 0·59-0·87). Symptomatic intracranial haemorrhage was predicted by old infarct (odds ratio 1·72, 95% CI 1·18-2·51), tissue hypoattenuation (1·54, 1·04-2·27), and hype, I was part of the The IST-3 Collaborative Group, hence part as group author.

Published
2015
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13. Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute ischaemic stroke in the third international stroke trial (IST-3): Secondary analysis of a randomised controlled trial

Author

UCL - (SLuc) Service de neurologie, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Wardlaw, Joanna M., Sandercock, Peter, Cohen, Geoff, Farrall, Andrew, Lindley, Richard I., von Kummer, Rudiger, von Heijne, Anders, Bradey, Nick, Peeters, André, Cala, Lesley, Adami, Alessandro, Morris, Zoe, Potter, Gillian, Murray, Gordon, Whiteley, Will, Perry, David, Sakka, Eleni, UCL - (SLuc) Service de neurologie, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Wardlaw, Joanna M., Sandercock, Peter, Cohen, Geoff, Farrall, Andrew, Lindley, Richard I., von Kummer, Rudiger, von Heijne, Anders, Bradey, Nick, Peeters, André, Cala, Lesley, Adami, Alessandro, Morris, Zoe, Potter, Gillian, Murray, Gordon, Whiteley, Will, Perry, David, and Sakka, Eleni

Abstract

Background: Brain scans are essential to exclude haemorrhage in patients with suspected acute ischaemic stroke before treatment with alteplase. However, patients with early ischaemic signs could be at increased risk of haemorrhage after alteplase treatment, and little information is available about whether pre-existing structural signs, which are common in older patients, affect response to alteplase. We aimed to investigate the association between imaging signs on brain CT and outcomes after alteplase. Methods: IST-3 was a multicentre, randomised controlled trial of intravenous alteplase (0·9 mg/kg) versus control within 6 h of acute ischaemic stroke. The primary outcome was independence at 6 months (defined as an Oxford Handicap Scale [OHS] score of 0-2). 3035 patients were enrolled to IST-3 and underwent prerandomisation brain CT. Experts who were unaware of the random allocation assessed scans for early signs of ischaemia (tissue hypoattenuation, infarct extent, swelling, and hyperattenuated artery) and pre-existing signs (old infarct, leukoaraiosis, and atrophy). In this prespecified analysis, we assessed interactions between these imaging signs, symptomatic intracranial haemorrhage (a secondary outcome in IST-3) and independence at 6 months, and alteplase, adjusting for age, National Institutes of Health Stroke Scale (NIHSS) score, and time to randomisation. This trial is registered at ISRCTN.com, number ISRCTN25765518. Findings: 3017 patients were assessed in this analysis, of whom 1507 were allocated alteplase and 1510 were assigned control. A reduction in independence was predicted by tissue hypoattenuation (odds ratio 0·66, 95% CI 0·55-0·81), large lesion (0·51, 0·38-0·68), swelling (0·59, 0·46-0·75), hyperattenuated artery (0·59, 0·47-0·75), atrophy (0·74, 0·59-0·94), and leukoaraiosis (0·72, 0·59-0·87). Symptomatic intracranial haemorrhage was predicted by old infarct (odds ratio 1·72, 95% CI 1·18-2·51), tissue hypoattenuation (1·54, 1·04-2·27), and hype

Published
2015

15. Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]) : 18-month follow-up of a randomised controlled trial.

Author

Sandercock, Peter, Joanna, Wardlaw, Dennis, Martin, Cohen, Geoff, Murray, Gordon, Innes, Karen, Whiteley, Will, Lindley, Richard, Venables, Graham, Czlonkowska, Anna, Kobayashi, Adam, Ricci, Stefano, Myrray, Verronica, Berge, Eivind, Slot, Karsten, Hankey, Graeme J, Correia, Manuel, Peeters, Andre, Matz, Mats, Lyrer, Phillippe, Gubitz, Gord, Phillips, Stephen J, Arauz, Antonio, Lundström, E, Sandercock, Peter, Joanna, Wardlaw, Dennis, Martin, Cohen, Geoff, Murray, Gordon, Innes, Karen, Whiteley, Will, Lindley, Richard, Venables, Graham, Czlonkowska, Anna, Kobayashi, Adam, Ricci, Stefano, Myrray, Verronica, Berge, Eivind, Slot, Karsten, Hankey, Graeme J, Correia, Manuel, Peeters, Andre, Matz, Mats, Lyrer, Phillippe, Gubitz, Gord, Phillips, Stephen J, Arauz, Antonio, and Lundström, E

Abstract

BACKGROUND: Few data are available from randomised trials about the effect of thrombolysis with alteplase on long-term functional outcome in patients who have had acute ischaemic stroke and no trial has reported effects on health-related quality of life. A secondary objective of the third International Stroke Trial (IST-3) was to assess the effect of thrombolysis on such outcomes at 18 months. METHODS: In this open-label, international, multicentre, randomised, controlled trial, 3035 patients with ischaemic stroke from 12 countries were randomly allocated within 6 h of onset via a secure central system to either intravenous alteplase (0·9 mg/kg; n=1515) plus standard care or standard care alone (control; n=1520). 2348 patients were scheduled for 18-month follow-up. For our main analysis, survivors were assessed at 18 months with the Oxford handicap scale (OHS; the primary outcome was the adjusted odds of OHS score 0-2). We also used the EuroQoL (EQ) instrument and asked questions about overall functioning and living circumstances. We analysed the OHS and the five EQ domains by ordinal logistic regression and calculated the mean difference between treatment groups in EQ utility index and visual analogue scale score. Analyses were adjusted for key baseline prognostic factors. This study is registered with controlled-trials.com, number ISRCTN25765518. FINDINGS: At 18 months, 408 (34·9%) of 1169 patients in the alteplase group versus 414 (35·1%) of 1179 in the control group had died (p=0·85). 391 (35·0%) of 1117 patients versus 352 (31·4%) of 1122 had an OHS score of 0-2 (adjusted odds ratio [OR] 1·28, 95% CI 1·03-1·57; p=0·024). Treatment was associated with a favourable shift in the distribution of OHS grades (adjusted common OR 1·30, 95% CI 1·10-1·55; p=0·002). Alteplase treatment was associated with significantly higher overall self-reported health (adjusted mean difference in EQ utility index 0·060; p=0·019). The differences between the groups in visual analogue sc, I was part of the The IST-3 Collaborative Group, hence part as group author.

Published
2013
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16. Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Author

Sandercock, Peter, Lindley, Richard, Wardlaw, Joanna, Dennis, Martin, Innes, Karen, Cohen, Geoff, Whiteley, Will, Perry, David, Soosay, Vera, Buchanan, David, Venables, Graham, Czlonkowska, Anna, Kobayashi, Adam, Berge, Eivind, Slot, Karsten Bruins, Murray, Veronica, Peeters, Andre, Hankey, Graeme J, Matz, Karl, Brainin, Michael, Ricci, Stefano, Cantisani, Teresa A, Gubitz, Gordon, Phillips, Stephen J, Antonio, Arauz, Correia, Manuel, Lyrer, Phillippe, Kane, Ingrid, Lundstrom, Erik, Emsley, Hedley, IST-3 collaborative group, Sandercock, Peter, Lindley, Richard, Wardlaw, Joanna, Dennis, Martin, Innes, Karen, Cohen, Geoff, Whiteley, Will, Perry, David, Soosay, Vera, Buchanan, David, Venables, Graham, Czlonkowska, Anna, Kobayashi, Adam, Berge, Eivind, Slot, Karsten Bruins, Murray, Veronica, Peeters, Andre, Hankey, Graeme J, Matz, Karl, Brainin, Michael, Ricci, Stefano, Cantisani, Teresa A, Gubitz, Gordon, Phillips, Stephen J, Antonio, Arauz, Correia, Manuel, Lyrer, Phillippe, Kane, Ingrid, Lundstrom, Erik, Emsley, Hedley, and IST-3 collaborative group

Abstract

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. DESIGN: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. RESULTS: The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. CONCLUSION: The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large

Published
2011

20. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Author

Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, and Yang, Yuan-Han

Subjects
Dementia, Cerebrovascular disease, Neurodegeneration, Cohorts, Survey, Small vessel disease
Abstract

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

21. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Author

Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, Yang, Yuan-Han, Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, and Yang, Yuan-Han

Abstract

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

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22. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Author

Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, Yang, Yuan-Han, Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, and Yang, Yuan-Han

Abstract

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

Full Text
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23. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Author

Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, Yang, Yuan-Han, Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, and Yang, Yuan-Han

Abstract

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

Full Text
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24. METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Author

Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, Yang, Yuan-Han, Dichgans, Martin, Wardlaw, Joanna, Smith, Eric, Zietemann, Vera, Seshadri, Sudha, Sachdev, Perminder, Biessels, Geert Jan, Fazekas, Franz, Benavente, Oscar, Pantoni, Leonardo, De Leeuw, Frank-Erik, Norrving, Bo, Matthews, Paul, Chen, Christopher, Mok, Vincent, Düring, Marco, Whiteley, Will, Shuler, Kirsten, Alonso, Alvaro, Black, Sandra E., Brayne, Carol, Chabriat, Hugues, Cordonnier, Charlotte, Doubal, Fergus, Duzel, Emrah, Ewers, Michael, Frayne, Richard, Hachinski, Vladimir, Ikram, Mohammad Arfan, Jessen, Frank, Jouvent, Eric, Linn, Jennifer, O'Brien, John, van Oostenbrugge, Robert, Malik, Rainer, Mazoyer, Bernard, Schmidt, Reinhold, Sposato, Luciano A., Stephan, Blossom, Swartz, Richard H., Vernooij, Meike, Viswanathan, Anand, Werring, David, Abe, Koji, Allan, Louise, Arba, Francesco, Diener, H.-C., Davis, S., Hankey, G., Lees, K.R., Ovbiagele, B., Weir, C., Bae, Hee-Joon, Bath, Philip M.W., Bordet, Regis, Breteler, Monique, Choi, Seong, Deary, Ian, DeCarli, Charles, Ebmeier, Klaus, Feng, Lei, Greenberg, Steven M., Ihara, Masafumi, Kalaria, Rajesh, Kim, SanYun, Lim, Jae-Sung, Lindley, Richard I., Mead, Gillian, Murray, Alison, Quinn, Terry, Ritchie, Craig, Sacco, Ralph, Al-Shahi Salman, Rustam, Sprigg, Nikola, Sudlow, Cathie, Thomas, Alan, van Boxtel, Martin, van der Grond, Jeroen, van der Lugt, Aad, and Yang, Yuan-Han

Abstract

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

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25. Questions about authorisation of alteplase for ischaemic stroke.

Author

Sandercock, Peter, Lindley, Richard, Wardlaw, Joanna M., Murray, Gordon, Whiteley, Will, and Cohen, Geoff

Subjects
*STROKE treatment, *TISSUE plasminogen activator, *CLINICAL drug trials, *DRUG efficacy, *PLACEBOS, *THERAPEUTICS
Abstract

The authors respond to a correspondence published within the issue in which the sender raised concerns about the use of alteplase to treat acute ischaemic stroke. Topics covered include the consistency of the results delivered by a 2004 review of the National Institute of Neurological Disorders and Stroke's trial on the benefit of alteplase, and the reason behind drug company Boehringer Ingelheim's discontinuation of the supply of drug and placebo for the third International Stroke Trial.

Published
2014
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26. Confusion after a game of bridge.

Author

Whiteley W and Dennis M

Subjects
Brain pathology, Confusion pathology, Female, Humans, Magnetic Resonance Imaging methods, Middle Aged, Spinal Cord pathology, Stroke complications, Stroke etiology, Tomography, X-Ray Computed methods, Brain Neoplasms complications, Confusion etiology, Play and Playthings
Published
2007
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