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1. 5.1 The Role of Blood Pressure, Aortic Stiffness, and Haemodynamics in Brain Health in Older People with Type 2 Diabetes Mellitus

Author

Christopher Karayiannis, Chris Moran, Richard Beare, James Sharman, Thanh Phan, Amanda Thrift, Wei Wang, and Velandai Srikanth

Subjects
Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Aims: Type 2 diabetes (T2D) is associated with dementia, and abnormal blood pressure (BP), aortic stiffness, and haemodynamics. We aimed to study the contribution of such factors to brain structure and cognition, relative to the contribution of metabolic factors in T2D such as insulin resistance and adiposity, in older people with T2D. Methods: Cross-sectional sample with T2D in the Cognition and Diabetes in Older Tasmanians–Blood Pressure (CDOT-BP) study. Measurements included neuropsychological battery, brain MRI, and Mobil-o-Graph-derived (IEM, Germany) aortic BP and haemodynamics. We studied associations of exposure variables with outcomes using structural equation modelling for cognition, and simple linear regression for brain structure, using standardised coefficients to determine relative contribution of variables to the outcomes in combined regression models. Results: 202 participants (mean age 68.5 years, mean HbA1c = 6.42%). Augmentation index was associated with processing speed (p < 0.05). The contribution of augmentation index to processing speed (standardized β = −0.237) was greater than waist-hip ratio (β = −0.175) and use of oral glucose lowering medications and insulin (β = −0.126), but less than age (β = −0.431). Peripheral systolic BP, pulse wave velocity, and peripheral nocturnal systolic BP dipping were associated with measures of white matter integrity (fractional anisotropy and mean diffusivity, p < 0.05) but not with cortical thickness. Conclusion: BP, aortic stiffness and altered haemodynamics contribute to early cognitive change and loss of white matter integrity in T2D. The novel association between nocturnal BP dipping and white matter integrity deserves further investigation. Measuring white matter integrity may be useful to detect the effect of these vascular factors on the brain.

Published
2020
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2. Prevalence of brain MRI markers of haemorrhagic risk in patients with stroke and atrial fibrillation

Author

Christopher Karayiannis, Cathy Soufan, Ronil V Chandra, Thanh G Phan, Kitty Wong, Shaloo Singhal, Lee-Anne Slater, John Ly, Chris Moran, and Velandai Srikanth

Subjects
Atrial Fibrillation, Stroke, MRI, microhemorrhage, microbleeds, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background and Purpose: Cerebral microbleeds, cortical superficial siderosis, white matter lesions and cerebral atrophy may signify greater bleeding risk particularly in patients in whom anticoagulation is to be considered. We investigated their prevalence and associations with stroke type in patients with stroke and atrial fibrillation. Material and Methods: Cross-sectional sample, Monash Medical Centre (Melbourne, Australia) between 2010 and 2013, with brain MRI. MRI abnormalities were rated using standardized methods. Logistic regression was used to study associations adjusting for age and sex.Results: There were 170 patients, mean age 78 years (SD 9.8), 154 (90.6%) with ischemic stroke. Prevalence of MRI markers were: any microbleed 49%, multiple (≥2) microbleeds 30%, confluent white matter lesions 18.8%, siderosis 8.9%, severe cerebral atrophy 37.7%. Combinations of the severe manifestations of these markers were much less prevalent (2.9% to 12.4%). Compared with ischemic stroke, those with hemorrhagic stroke were more likely to have ≥10 microbleeds (OR 5.50 95% CI 1.46-20.77, p=0.012) and siderosis (OR 6.24, 95% CI 1.74-22.40, p=0.005). Siderosis was associated with multiple microbleeds (OR 8.14, 95% CI 2.38 - 27.86, p = 0.001). Patients admitted with hemorrhagic stroke and multiple microbleeds were more frequently anticoagulated prior to stroke (6/7, 85.7%) than in those with single (1/2, 50%) or no microbleeds (4/7, 57%). Conclusion: Multiple CMBs, severe WML, and severe cerebral atrophy were common individually in hospitalized patients with stroke and AF, but less so in combination. A higher burden of CMBs may be associated with ICH in stroke patients with AF.

Published
2016
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3. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Henry Ma, Eleni Sakka, Hugues Chabriat, Duncan Wilson, Appu Suman, Peter J. Kelly, SL Ho, Charlotte Zerna, Eric Jouvent, Lawrence K.S. Wong, Anthea Parry, Frances Harrington, Jan Stam, Christopher Patterson, Rustam Al-Shahi Salman, Shigeru Inamura, Krishna A Dani, Henry Houlden, Sebastian Thilemann, Kotaro Iida, Chao Xu, Eunbin Ko, Daniel Guisado-Alonso, Urs Fischer, Caroline E. Lovelock, Man Yu Tse, Wing Chi Fong, Azlisham Mohd Nor, Clare Shakeshaft, Philippe Maeder, Henrik Gensicke, Stefan T. Engelter, James Okwera, Christopher Chen, Dulka Manawadu, John F. Corrigan, Efrat Kliper, Shelagh B. Coutts, Alexander P. Leff, Kam Tat Leung, Chathuri Yatawara, Leopold Hertzberger, M. Eline Kooi, Kazuhisa Yoshifuji, Hing Lung Ip, Keon-Joo Lee, Sanjeevikumar Meenakishundaram, Hiroyuki Irie, Marc Randall, Hatice Ozkan, Hideo Hara, Jill Abrigo, Raquel Delgado-Mederos, Shaloo Singhal, Enrico Flossmann, Beatriz Gómez-Ansón, Paul O'Mahony, Carmen Barbato, Ahamad Hassan, Francesca M Chappell, Harald Proschel, Vincent Mok, Masashi Nishihara, Lakshmanan Sekaran, Derya Selcuk Demirelli, Chu Peng Hoi, Hakan Ay, Joan Martí-Fàbregas, Rebeca Marín, Anne Cristine Guevarra, Martin Cooper, Einor Ben Assayag, Anne-Marie Mendyk, Christine Roffe, Myung Suk Jang, Maarten van Gemert, Hannah Cohen, Jae-Sung Lim, YK Wong, Bonnie Y.K. Lam, Janet Putterill, Wouter Schoonewille, Nick S. Ward, Nikola Sprigg, Kui Kai Lau, Bernard Esisi, Peter M. Rothwell, Henk Verbiest, Kirsty Harkness, Elisa Merino, Gareth Ambler, Arumug Nallasivam, Nigel Smyth, Paul A. Armitage, Heinrich Mattle, Pol Camps-Renom, Martin M. Brown, David Cohen, Min Lou, Pankaj Sharma, Sarah Gunkel, Elles Douven, Andreas Charidimou, Djamil Vahidassr, Cathy Soufan, Alexandros A Polymeris, Michael G. Hennerici, Chris Moran, Rachel Marsh, Mahmud Sajid, Kyohei Fujita, David J. Werring, Joanna M. Wardlaw, Derek Hayden, Joseph Kwan, Timothy J. England, Jaap van der Sande, Luis Prats-Sánchez, Paul Guyler, Ryan Hoi Kit Cheung, Koon-Ho Chan, Frank-Erik de Leeuw, Simone Browning, Jon Scott, Adrian Barry, Alejandro Martínez-Domeño, Luc Bracoub, Dinesh Chadha, Ijaz Anwar, Deborah Kelly, Moon-Ku Han, Anil M. Tuladhar, Thomas Gattringer, Fiona Carty, Abduelbaset Elmarim, Syed Mansoor, Enrico Flossman, Dilek Necioglu Orken, Jane Sword, Velandai Srikanth, Ping Wing Ng, Thomas W. Leung, Richard Shek-kwan Chang, Hans Rolf Jäger, Marwan El-Koussy, Jeroen Hendrikse, Khaled Darawil, Kazunori Toyoda, Mathuri Prabhakaran, Karim Mahawish, Ethem Murat Arsava, Jihoon Kang, Kwok Kui Wong, Michael Power, Felix Fluri, Enas Lawrence, Maam Mamun, Sissi Ispoglou, Mathew Burn, Siu Hung Li, Henry K.F. Mak, Kaori Miwa, Els De Schryver, Franz Fazekas, Jonathan G. Best, Louise Shaw, Hen Hallevi, Keith W. Muir, Ilse Burger, Adrian Wong, Nils Peters, Susana Muñoz-Maniega, Yusuke Yakushiji, David Calvet, Mark White, Michael McCormick, Vinodh Krishnamurthy, David Hargroves, Jan C. Purrucker, Tae Jin Song, Masayuki Shiozawa, Noortje A.M. Maaijwee, Prasanna Aghoram, Nicolas Christ, Lino Ramos, Yannie Soo, Thanh G. Phan, Parashkev Nachev, David J. Seiffge, Kim Wiegertjes, Leo H. Bonati, Chahin Pachai, Oi Ling Chan, Yvo B.W.E.M. Roos, Santiago Medrano-Martorell, Natan M. Bornstein, Elizabeth A. Warburton, Richard Li, Prabel Datta, Pascal P. Gratz, Edmund Ka Ming Wong, Hedley C. A. Emsley, Marie-Yvonne Douste-Blazy, Gunaratam Gunathilagan, Nagaendran Kandiah, Masatoshi Koga, Roland Veltkamp, Lee-Anne Slater, Suk Fung Tsang, Beom Joon Kim, Simon Jung, Zeynep Tanriverdi, Sarah Caine, Peter J. Koudstaal, Laurence Legrand, Kari Saastamoinen, Ale Algra, Jean-Louis Mas, Christine Delmaire, Fidel Nuñez, Robert J. van Oostenbrugge, Sebastian Eppinger, Lillian Choy, Robert Luder, Vincent I.H. Kwa, Aad van der Lugt, Marie Dominique Fratacci, Stephen Makin, Layan Akijian, Régis Bordet, Mi Hwa Yang, Ying Zhou, Elio Giallombardo, Adrian R Parry-Jones, John S. Thornton, Amos D. Korczyn, Narayanaswamy Venketasubramanian, David J. Williams, Aravindakshan Manoj, Julie Staals, Solveig Horstmann, Dianne H.K. van Dam-Nolen, Claire Cullen, Benjamin Wagner, Jun Tanaka, Martin Dennis, Stef Bakker, Gregory Y.H. Lip, L. Jaap Kappelle, Robin Lemmens, Achim Gass, David Mangion, Matthew Smith, Toshio Imaizumi, Wenyan Liu, Jeremy Molad, Christopher Price, Paul J. Nederkoorn, P. J. A. M. Brouwers, Vincent Thijs, Sze Ho Ma, Mark Schembri, Peter Wilkinson, Janice E. O’Connell, Karen Ma, John Ly, Leonidas Panos, Chung Yan Chan, Toshihiro Ide, Christopher Traenka, Joost Jöbsis, Gargi Banerjee, Paul Berntsen, Michael J. Thrippleton, Raymond T.F. Cheung, Christopher Karayiannis, Werner H. Mess, Robert Simister, Jayesh Modi Medanta, Syuhei Ikeda, John Mitchell, Linxin Li, Mauro S.B. Silva, Eric Vicaut, John Coyle, Shoichiro Sato, Michelle Davis, Jonathan Birns, Richard J. Perry, Sean M. Murphy, KC Teo, Maria del C. Valdés Hernández, Bibek Gyanwali, Tarek A. Yousry, Kath Pasco, Sebastian Köhler, Joachim Fladt, Edward S. Hui, Philippe Lyrer, Young Dae Kim, Anna K. Heye, Eric E. Smith, Saima Hilal, Ender Uysal, Ji Hoe Heo, Ysoline Beigneux, Cisca Linn, Hee-Joon Bae, Simon Leach, Winnie C.W. Chu, Ronil V. Chandra, Neurology, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, MUMC+: HZC Med Staf Spec Klinische Neurofys (9), RS: Carim - B06 Imaging, MUMC+: HZC Klinische Neurofysiologie (5), Klinische Neurowetenschappen, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Neurologie (3), RS: Carim - B05 Cerebral small vessel disease, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Med Staf Spec Neurologie (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Beeldvorming, and MUMC+: DA BV Klinisch Fysicus (9)

Subjects
Adult, Male, Risk, EXTERNAL VALIDATION, medicine.medical_specialty, Neurology, MODELS, Clinical Neurology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Recurrence, Internal medicine, Antithrombotic, Humans, Medicine, Prospective cohort study, 610 Medicine & health, Stroke, METAANALYSIS, Aged, Ischemic Stroke, Science & Technology, medicine.diagnostic_test, business.industry, Proportional hazards model, Magnetic resonance imaging, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, Magnetic Resonance Imaging, Ischemic Attack, Transient, ATRIAL-FIBRILLATION, Cardiology, Female, Neurology (clinical), Neurosciences & Neurology, business, Intracranial Hemorrhages, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Fibrinolytic agent, Cohort study
Abstract

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Published
2021

4. Endovascular Management of Ischemic Stroke

Author

Anish Kapadia, Adam A. Dmytriw, Simon Rupe Khangure, Hubert Lee, Christopher Karayiannis, Carmen Parra-Farinas, Fateme Salehi, Fabio Settecase, Ronil V. Chandra, Sarah Power, Peter Howard, Anderson Chun On Tsang, Farah K. Aleisa, Vitor Mendes Pereira, Waleed Brinjikji, Alejandro M. Spiotta, Karl-Olof Lövblad, Aleksandra Pikula, Lee-Anne Slater, Vincent M. Tutino, Robert A. Willinsky, Velandai Srikanth, Leonardo Renieri, Thabele (Bay) M. Leslie-Mazwi, Cathy Soufan, David Turkel-Parrella, Emanuele Orrù, Stefano Maria Priola, Victor X. D. Yang, Achelle Cortel-LeBlanc, John Thornton, Tadeu A. Fantaneanu, M. Imran Chaudry, Shivaprakash B. Hiremath, Joanna D. Schaafsma, Hamed Asadi, Jameel Khalid Rasheedi, David Volders, Nicola Limbucci, Christoph Wipplinger, Amey R. Savardekar, Christopher Hilditch, Aquilla S. Turk, Ghouth Waggass, Jose Danilo Bengzon Diestro, Charles Handley, Jonathan Coutinho, Albert Ho Yuen Chiu, Kevin Phan, Christopher R. Pasarikovski, Manraj Kanwal Singh Heran, Timo Krings, Aditya Bharatha, Maria Isabel Vargas, Thien J. Huynh, Jenny P. Tsai, Ana Filipa Geraldo, Christoph J. Griessenauer, Hugo Cuellar, William Guest, Raymond Turner, Robert W. Regenhardt, Nimer Adeeb, and Aman B. Patel

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Ischemic stroke, Cardiology, Medicine, business
Published
2021

5. Blood Pressure, Aortic Stiffness, Hemodynamics, and Cognition in Twin Pairs Discordant for Type 2 Diabetes

Author

Christopher Karayiannis, Velandai Srikanth, James E. Sharman, Stephen Quinn, Wei Chun Wang, Thanh G. Phan, Amanda G. Thrift, Amanda G. Wood, Richard Beare, and Chris Moran

Subjects
0301 basic medicine, Male, medicine.medical_specialty, endocrine system diseases, Hemodynamics, Blood Pressure, Type 2 diabetes, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Cognition, Vascular Stiffness, Internal medicine, medicine, Dementia, Humans, Cerebral perfusion pressure, Aorta, Aged, business.industry, General Neuroscience, Australia, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, Brain, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Blood pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Cerebrovascular Circulation, Cardiology, Aortic stiffness, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract

BACKGROUND Type 2 diabetes (T2D) is associated with an increased risk of cognitive impairment and dementia with poorly understood underlying mechanisms. OBJECTIVE We examined the role of blood pressure (BP), aortic stiffness, and hemodynamics in this association. METHODS Cross-sectional sample of late middle-aged twins discordant for T2D from the Australian Twin Registry. Measurements included neuropsychological battery and brain MRI including arterial spin labelling (ASL) to measure cerebral perfusion. Mobil-o-Graph devices were used to non-invasively obtain 24-hour BP, aortic stiffness, and hemodynamic measures. Using mixed modelling, we studied associations of T2D with cognition, MRI measures, BP, aortic stiffness, and hemodynamics. RESULTS There were 23 twin pairs with mean age 63.7 (SD = 6.1) years. T2D (β=-0.45, p

Published
2019

6. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Christopher Price, P. J. A. M. Brouwers, Vincent Thijs, Sze Ho Ma, Mark Schembri, Raymond T.F. Cheung, Christopher Karayiannis, Werner H. Mess, Robert Simister, Peter Wilkinson, Jayesh Modi Medanta, Janice E. O’Connell, Karen Ma, Martin Dennis, Sean C. Murphy, John Ly, Velandai Srikanth, Hing Lung Ip, Mathew Burn, Saima Hilal, Ijaz Anwar, Richard Shek-kwan Chang, Christopher Chen, Carmen Barbato, Hatice Ozkan, Achim Gass, Louise Shaw, Hen Hallevi, Aravindakshan Manoj, Julie Staals, Frances Harrington, Henry Houlden, Hideo Hara, Kam Tat Leung, Christopher Traenka, Jeroen Hendrikse, Keon-Joo Lee, Elio Giallombardo, Ender Uysal, Edmund Ka Ming Wong, Joost Jöbsis, Gargi Banerjee, Dulka Manawadu, Rebeca Marín, John S. Thornton, Nick S. Ward, Vinodh Krishnamurthy, Thomas W. Leung, Ji Hoe Heo, Philippe Maeder, Masatoshi Koga, Michael Power, Marc Randall, Amos D. Korczyn, Narayanaswamy Venketasubramanian, Derya Selcuk Demirelli, Richard Li, Prabel Datta, Christine Guevarra, YK Wong, Ysoline Beigneux, Cisca Linn, Solveig Horstmann, Henk Verbiest, Kirsty Harkness, Eric Vicaut, John Coyle, Shoichiro Sato, Anne Marie Mendyk, Chathuri Yatawara, Alexandros A Polymeris, Lisa Hert, Joan Martí-Fàbregas, Felix Fluri, Cathy Soufan, Djamil Vahidassr, Lakshmanan Sekaran, Chu Peng Hoi, Maarten van Gemert, Andreas Charidimou, Robert Luder, Lillian Choy, Jaap van der Sande, Hannah Cohen, Jae-Sung Lim, Maam Mamun, Vincent I.H. Kwa, Kyohei Fujita, Joseph Kwan, Syuhei Ikeda, John Mitchell, Paul Berntsen, Michael J. Thrippleton, Shelagh B. Coutts, Simone Browning, Paul Guyler, Heinrich Mattle, Elles Douven, Jonathan Birns, M. Eline Kooi, Jan Stam, Hedley C. A. Emsley, David Mangion, David Calvet, Min Lou, Yannie Soo, Santiago Medrano-Martorell, Michael G. Hennerici, Chris Moran, Thomas Gattringer, Bernard Esisi, Kazuhisa Yoshifuji, Hakan Ay, Rustam Al-Shahi Salman, Joanna M. Wardlaw, Derek Hayden, Richard J. Perry, Gunaratam Gunathilagan, Hans Rolf Jäger, Frank-Erik de Leeuw, Luis Prats-Sánchez, Pankaj Sharma, Mi Hwa Yang, Marie Yvonne Douste-Blazy, Enas Lawrence, Nils Peters, Elisa Merino, KC Teo, Ethem Murat Arsava, Luc Bracoub, Dinesh Chadha, Linxin Li, Nikola Sprigg, Adrian R Parry-Jones, Pascal P. Gratz, Siu Hung Li, Stephen Makin, Arumug Nallasivam, Jane Sword, Mauro S.B. Silva, Ping Wing Ng, Layan Akijian, Krishna A Dani, Sebastian Thilemann, Marie Dominique Fratacci, Gareth Ambler, Nagaendran Kandiah, Lee-Anne Slater, Ilse Burger, Kath Pasco, Paul J. Nederkoorn, Suk Fung Tsang, Tae Jin Song, Henry Ma, Kaori Miwa, Keith W. Muir, Susana Muñoz-Maniega, Jihoon Kang, Nicolas Christ, Beom Joon Kim, Noortje A.M. Maaijwee, Kwok Kui Wong, Jon Scott, Leonidas Panos, Oi Ling Chan, Shigeru Inamura, Prasanna Aghoram, David Hargroves, Lino Ramos, Ying Zhou, Chung Yan Chan, Masayuki Shiozawa, Eleni Sakka, Michelle Davis, Matthew Smith, Leo H. Bonati, Dilek Necioglu Orken, Toshihiro Ide, Jaap Kappelle, Ale Algra, Charlotte Zerna, Laurence Legrand, Eric Jouvent, Roland Veltkamp, Simon Jung, Zeynep Tanriverdi, Shahoo Singhal, Sarah Caine, Natan M. Bornstein, Régis Bordet, Anil M. Tuladhar, Maarten Schrooten, John F. Corrigan, Alexander P. Leff, Kazunori Toyoda, Mathuri Prabhakaran, Kim Wiegertjes, Eunbin Ko, Wouter Schoonewille, Sebastian Köhler, Yvo B.W.E.M. Roos, Wing Chi Fong, Jun Tanaka, Abduelbaset Elmarim, Syed Mansoor, Peter J. Koudstaal, Kari Saastamoinen, Eric E. Smith, Paul O'Mahony, Hugues Chabriat, Duncan Wilson, Appu Suman, Dianne H.K. van Dam-Nolen, Parashkev Nachev, Ahamad Hassan, Maria del C. Valdés Hernández, Clare Shakeshaft, Stefan T. Engelter, James Okwera, Aad van der Lugt, Els De Schryver, Stef Bakker, Azlisham Mohd Nor, Yusuke Yakushiji, Robert J. van Oostenbrugge, Claire Cullen, Man Yu Tse, Sebastian Eppinger, Gregory Y.H. Lip, Kotaro Iida, Efrat Kliper, Bibek Gyanwali, Elizabeth A. Warburton, Hee-Joon Bae, Thanh G. Phan, Tarek A. Yousry, Henrik Gensicke, Christine Delmaire, Jean-Louis Mas, Jill Abrigo, Fiona Carty, Jan C. Purrucker, Masashi Nishihara, Leopold Hertzberger, Joachim Fladt, Einor Ben Assayag, Simon Leach, Winnie C.W. Chu, Edward S. Hui, Bonnie Y.K. Lam, Moon Ku Han, Francesca M Chappell, David Williams, Robin Lemmens, Philippe Lyrer, Hiroyuki Irie, Raquel Delgado-Mederos, Ronil V. Chandra, Nigel Smyth, Henry K.F. Mak, Young Dae Kim, Ryan Hoi Kit Cheung, Beatriz Gómez-Ansón, Fidel Nuñez, Anna K. Heye, Adrian Barry, Janet Putterill, Mark White, Alejandro Martínez-Domeño, Vincent Mok, Rachel Marsh, Mahmud Sajid, Timothy J. England, SL Ho, Christopher Patterson, Daniel Guisado-Alonso, Peter J. Kelly, Lawrence K.S. Wong, Anthea Parry, Enrico Flossman, Chao Xu, Marwan El-Koussy, Karim Mahawish, Sissi Ispoglou, Franz Fazekas, Toshio Imaizumi, David J. Seiffge, Wenyan Liu, Chahin Pachai, Adrian Wong, Khaled Darawil, Jeremy Molad, Sanjeevikumar Meenakishundaram, Enrico Flossmann, Harald Proschel, Caroline E. Lovelock, Christine Roffe, Kui Kai Lau, Michael McCormick, Peter M. Rothwell, Paul A. Armitage, Sarah Gunkel, Myung Suk Jang, Martin Cooper, Pol Camps-Renom, Martin M. Brown, David Cohen, David J. Werring, Koon-Ho Chan, Deborah Kelly, Neurology, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, Division 2, Radiology & Nuclear Medicine, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Klinisch Fysicus (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, and MUMC+: MA Med Staf Spec Neurologie (9)

Subjects
INTRACEREBRAL HEMORRHAGE, 030204 cardiovascular system & hematology, AMYLOID ANGIOPATHY, PREDICT, Brain Ischemia, 0302 clinical medicine, SMALL VESSEL DISEASE, Medicine, CHINESE PATIENTS, 10. No inequality, Stroke, medicine.diagnostic_test, DEMENTIA, Hazard ratio, Absolute risk reduction, Brain, Atrial fibrillation, ASSOCIATION, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Magnetic Resonance Imaging, 3. Good health, Ischemic Attack, Transient, Cardiology, Life Sciences & Biomedicine, Intracranial Hemorrhages, medicine.drug, Cohort study, medicine.medical_specialty, RECURRENT STROKE, Clinical Neurology, 610 Medicine & health, Neuroimaging, Article, WARFARIN, 03 medical and health sciences, Internal medicine, Journal Article, Humans, Intracerebral hemorrhage, Science & Technology, business.industry, Warfarin, Magnetic resonance imaging, T2-ASTERISK-WEIGHTED MR-IMAGES, medicine.disease, ATRIAL-FIBRILLATION, Neurosciences & Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 208975.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2.45 (1.82-3.29) for intracranial haemorrhage and 1.23 (1.08-1.40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4.55 [95% CI 3.08-6.72] for intracranial haemorrhage vs 1.47 [1.19-1.80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5.52 [3.36-9.05] vs 1.43 [1.07-1.91]; and for >/=20 cerebral microbleeds, aHR 8.61 [4.69-15.81] vs 1.86 [1.23-1.82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for >/=20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

Published
2019

7. 5.1 The Role of Blood Pressure, Aortic Stiffness, and Haemodynamics in Brain Health in Older People with Type 2 Diabetes Mellitus

Author

Amanda G. Thrift, Thanh G. Phan, Christopher Karayiannis, James E. Sharman, Richard Beare, Velandai Srikanth, Wei Wang, and Chris Moran

Subjects
lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, lcsh:Specialties of internal medicine, business.industry, Hemodynamics, Type 2 Diabetes Mellitus, General Medicine, Blood pressure, lcsh:RC581-951, lcsh:RC666-701, Internal medicine, medicine, Cardiology, Aortic stiffness, Older people, business
Abstract

Aims: Type 2 diabetes (T2D) is associated with dementia, and abnormal blood pressure (BP), aortic stiffness, and haemodynamics. We aimed to study the contribution of such factors to brain structure and cognition, relative to the contribution of metabolic factors in T2D such as insulin resistance and adiposity, in older people with T2D. Methods: Cross-sectional sample with T2D in the Cognition and Diabetes in Older Tasmanians–Blood Pressure (CDOT-BP) study. Measurements included neuropsychological battery, brain MRI, and Mobil-o-Graph-derived (IEM, Germany) aortic BP and haemodynamics. We studied associations of exposure variables with outcomes using structural equation modelling for cognition, and simple linear regression for brain structure, using standardised coefficients to determine relative contribution of variables to the outcomes in combined regression models. Results: 202 participants (mean age 68.5 years, mean HbA1c = 6.42%). Augmentation index was associated with processing speed (p < 0.05). The contribution of augmentation index to processing speed (standardized β = −0.237) was greater than waist-hip ratio (β = −0.175) and use of oral glucose lowering medications and insulin (β = −0.126), but less than age (β = −0.431). Peripheral systolic BP, pulse wave velocity, and peripheral nocturnal systolic BP dipping were associated with measures of white matter integrity (fractional anisotropy and mean diffusivity, p < 0.05) but not with cortical thickness. Conclusion: BP, aortic stiffness and altered haemodynamics contribute to early cognitive change and loss of white matter integrity in T2D. The novel association between nocturnal BP dipping and white matter integrity deserves further investigation. Measuring white matter integrity may be useful to detect the effect of these vascular factors on the brain.

Published
2020

8. O3‐11‐06: TYPE 2 DIABETES AND BRAIN GLUCOSE METABOLISM: A DISCORDANT TWIN STUDY

Author

Christopher Karayiannis, Richard Beare, Wei Wang, Thanh G. Phan, Chris Moran, and Velandai Srikanth

Subjects
medicine.medical_specialty, Discordant Twin, Epidemiology, business.industry, Health Policy, Type 2 diabetes, Carbohydrate metabolism, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2018

9. P1‐444: A TWIN STUDY OF TYPE 2 DIABETES, BRAIN STRUCTURE, AND FUNCTION

Author

Thanh G. Phan, Amanda G. Wood, Christopher Karayiannis, James E. Sharman, Amanda G. Thrift, Chris Moran, Wei Wang, Richard Beare, Stephen Quinn, and Velandai Srikanth

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Brain Structure and Function, Type 2 diabetes, medicine.disease, Twin study, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Endocrinology, Developmental Neuroscience, Internal medicine, medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published
2018

10. P4-343: THE ROLE OF BLOOD PRESSURE, AORTIC STIFFNESS, AND HAEMODYNAMICS IN BRAIN HEALTH IN OLDER PEOPLE WITH TYPE 2 DIABETES MELLITUS

Author

Christopher Karayiannis, Velandai Srikanth, James E. Sharman, Amanda G. Thrift, Thanh G. Phan, Wei Wang, Richard Beare, and Chris Moran

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Hemodynamics, Type 2 Diabetes Mellitus, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Blood pressure, Developmental Neuroscience, Internal medicine, medicine, Cardiology, Aortic stiffness, Neurology (clinical), Geriatrics and Gerontology, Older people, business
Published
2019

11. [O4–01–06]: A TWIN STUDY OF TYPE 2 DIABETES AND COGNITION: THE ROLE OF CENTRAL AORTIC HEMODYNAMICS AND CEREBRAL PERFUSION

Author

James E. Sharman, Velandai Srikanth, Chris Moran, Christopher Karayiannis, Richard Beare, Thanh G. Phan, Stephen Quinn, and Amanda G. Thrift

Subjects
medicine.medical_specialty, Aortic hemodynamics, Epidemiology, business.industry, Health Policy, Cognition, Type 2 diabetes, medicine.disease, Twin study, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Anesthesia, Internal medicine, medicine, Cardiology, Neurology (clinical), Geriatrics and Gerontology, Cerebral perfusion pressure, business
Published
2017

12. Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF

Author

Vincent Thijs, Naoyuki Hasebe, Kelly D. Flemming, Christopher Karayiannis, Roland Veltkamp, Nobuyuki Sato, Kam Tat Leung, Cathy Soufan, Yannie Soo, Yuichiro Kawamura, Lee-Anne Slater, Thanh G. Phan, Solveig Horstmann, Ji Hoe Heo, Su Mei Goh, Lawrence K.S. Wong, Shamir Haji, Ronil V. Chandra, Robin Lemmens, Vincent Mok, Tae Jin Song, Tsukasa Saito, Jinkwon Kim, Velandai Srikanth, Andreas Charidimou, Dilek Necioglu Orken, and Toshio Imaizumi

Subjects
medicine.medical_specialty, 030204 cardiovascular system & hematology, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, Internal medicine, Atrial Fibrillation, Medicine, Humans, Stroke, Cerebral Hemorrhage, business.industry, Incidence (epidemiology), Anticoagulants, Atrial fibrillation, Odds ratio, medicine.disease, Confidence interval, Meta-analysis, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract

Objectives:To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants.Methods:This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models.Results:We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19–6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07–14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04–0.55) among CMB-negative patients to 0.81% (95% CI 0.17–1.45) in CMB-positive patients (p = 0.01) and 2.48% (95% CI 1.2–6.2) in patients with ≥5 CMBs (p = 0.001). There was no association between CMBs and recurrent ischemic stroke.Conclusions:The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.

Published
2016

13. Intensive vs Standard Blood Pressure Control for Older Adults

Author

Thanh G. Phan, Velandai Srikanth, and Christopher Karayiannis

Subjects
Blood pressure control, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, Text mining, Blood pressure, business.industry, Emergency medicine, medicine, 030212 general & internal medicine, General Medicine, 030204 cardiovascular system & hematology, business
Published
2016

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