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1. 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

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

Published
2021
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4. Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis

Author

Lo, Jessica W., Crawford, John D., Desmond, David W., Bae, Hee-Joon, Lim, Jae-Sung, Godefroy, Olivier, Roussel, Martine, Kang, Yeonwook, Jahng, Seungmin, Köhler, Sebastian, Staals, Julie, Verhey, Frans, Chen, Christopher, Xu, Xin, Chong, Eddie J., Kandiah, Nagaendran, Yatawara, Chathuri, Bordet, Régis, Dondaine, Thibaut, Mendyk, Anne-Marie, Brodaty, Henry, Traykov, Latchezar, Mehrabian, Shima, Petrova, Neli, Kim, Ki Woong, Bae, Jong Bin, Han, Ji Won, Lipnicki, Darren M., Lam, Ben, and Sachdev, Perminder S.

Published
2021
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6. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

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

Published
2019
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7. Association of Prediabetes and Type 2 Diabetes With Cognitive Function After Stroke: A STROKOG Collaboration Study

Author

Lo, Jessica W., Crawford, John D., Samaras, Katherine, Desmond, David W., Köhler, Sebastian, Staals, Julie, Verhey, Frans R.J., Bae, Hee-Joon, Lee, Keon-Joo, Kim, Beom Joon, Bordet, Régis, Cordonnier, Charlotte, Dondaine, Thibaut, Mendyk, Anne-Marie, Lee, Byung-Chul, Yu, Kyung-Ho, Lim, Jae-Sung, Kandiah, Nagaendran, Chander, Russell J., Yatawara, Chathuri, Lipnicki, Darren M., and Sachdev, Perminder S.

Published
2020
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10. Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis

Author

Lo, Jessica W, Lo, Jessica W, Crawford, John D, Desmond, David W, Bae, Hee-Joon, Lim, Jae-Sung, Godefroy, Olivier, Roussel, Martine, Kang, Yeonwook, Jahng, Seungmin, Köhler, Sebastian, Staals, Julie, Verhey, Frans, Chen, Christopher, Xu, Xin, Chong, Eddie J, Kandiah, Nagaendran, Yatawara, Chathuri, Bordet, Régis, Dondaine, Thibaut, Mendyk, Anne-Marie, Brodaty, Henry, Traykov, Latchezar, Mehrabian, Shima, Petrova, Neli, Kim, Ki Woong, Bae, Jong Bin, Han, Ji Won, Lipnicki, Darren M, Lam, Ben, Sachdev, Perminder S, Stroke Cognition STROKOG Collabora, Lo, Jessica W, Lo, Jessica W, Crawford, John D, Desmond, David W, Bae, Hee-Joon, Lim, Jae-Sung, Godefroy, Olivier, Roussel, Martine, Kang, Yeonwook, Jahng, Seungmin, Köhler, Sebastian, Staals, Julie, Verhey, Frans, Chen, Christopher, Xu, Xin, Chong, Eddie J, Kandiah, Nagaendran, Yatawara, Chathuri, Bordet, Régis, Dondaine, Thibaut, Mendyk, Anne-Marie, Brodaty, Henry, Traykov, Latchezar, Mehrabian, Shima, Petrova, Neli, Kim, Ki Woong, Bae, Jong Bin, Han, Ji Won, Lipnicki, Darren M, Lam, Ben, Sachdev, Perminder S, and Stroke Cognition STROKOG Collabora

Abstract

BACKGROUND AND PURPOSE: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium.METHODS: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects.RESULTS: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th-75th percentile: 1.21-4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (-0.053 SD/year [95% CI, -0.073 to -0.033]; P<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=-0.078 SD/year [95% CI, -0.11 to -0.045]; P<0.001 for global cognition in a subgroup analysis).CONCLUSIONS: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

Published
2022

13. The Efficacy of Transdermal Rivastigmine in Mild to Moderate Alzheimer’s Disease with Concomitant Small Vessel Cerebrovascular Disease: Findings from an Open-Label Study

Author

Yatawara,Chathuri, Zailan,Fatin Zahra, Chua,Esther Vanessa, Lim,Linda Lay Hoon, Silva,Eveline, Wang,Joanna Sihan, Ng,Adeline, Ng,Kok Pin, Kandiah,Nagaendran, Yatawara,Chathuri, Zailan,Fatin Zahra, Chua,Esther Vanessa, Lim,Linda Lay Hoon, Silva,Eveline, Wang,Joanna Sihan, Ng,Adeline, Ng,Kok Pin, and Kandiah,Nagaendran

Abstract

Chathuri Yatawara,1 Fatin Zahra Zailan,1 Esther Vanessa Chua,1 Linda Lay Hoon Lim,1 Eveline Silva,1 Joanna Sihan Wang,1 Adeline Ng,1 Kok Pin Ng,1 Nagaendran Kandiah1– 3 1Department of Neurology, National Neuroscience Institute, Singapore, Singapore; 2Duke-NUS Medical School, Singapore, Singapore; 3Lee Kong Chian School of Medicine-Imperial College London, Nanyang Technological University, Singapore, SingaporeCorrespondence: Nagaendran KandiahNational Neuroscience Institute, Level 3, Clinical Staff Office, 11 Jalan Tan Tock Seng, Singapore, 308433, SingaporeTel +65 6357 7171Fax +65 6357 7137Email Nagaendran.Kandiah@singhealth.com.sgBackground: Rivastigmine is used to treat cognitive impairment in Alzheimer’s disease (AD); however, the efficacy of Rivastigmine in patients with AD and concomitant small vessel cerebrovascular disease (svCVD) remains unclear. We investigated the effectiveness of Rivastigmine Patch in patients with AD and svCVD.Methods: In this open-label study, 100 patients with AD and MRI confirmed svCVD received 9.5mg/24 hours Rivastigmine transdermal treatment for 24 weeks. The primary outcome was global cognition indexed using the ADAS-Cog. Secondary outcomes included clinical-rated impression of change (indexed using (ADCS‐CGIC), activities of daily living (indexed using ADCS-ADL) and side effects.Results: Overall, performance on the ADAS-Cog after 24 weeks deteriorated by 1.78 (SD = 5.29) points. Fifty-two percent of the sample demonstrated improvement or remained stable, while 48% demonstrated worsening of ADAS-Cog scores. Of the 52%, significant improvement (2 or more-point decline) on the ADAS-Cog was observed in 25% of the sample, with a mean change of − 5.08 (SD = 3.11). A decline on the ADAS-Cog was observed in 48% of the sample, with a mean change of 6 (SD = 2.98) points. Cognitive outcome did not interact with severity of svCVD. ADCS-ADL scores remained stable from baseline to week 24 and ADCS‐CGIC reports

Published
2021

14. 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

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

Published
2021
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15. The Efficacy of Transdermal Rivastigmine in Mild to Moderate Alzheimer’s Disease with Concomitant Small Vessel Cerebrovascular Disease: Findings from an Open-Label Study

Author

Yatawara, Chathuri, primary, Zailan, Fatin Zahra, additional, Chua, Esther Vanessa, additional, Lim, Linda Lay Hoon, additional, Silva, Eveline, additional, Wang, Joanna Sihan, additional, Ng, Adeline, additional, Ng, Kok Pin, additional, and Kandiah, Nagaendran, additional

Published
2021
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22. Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals.

Author

Wong, Fennie Choy Chin, Saffari, Seyed Ehsan, Yatawara, Chathuri, Ng, Kok Pin, Kandiah, Nagaendran, and Alzheimer’s Disease Neuroimaging Initiative

Subjects
WHITE matter (Nerve tissue), EXECUTIVE function, ALZHEIMER'S disease
Abstract

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated.Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined.Methods: This study included 72 subjects from the Alzheimer's Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function.Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003).Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Published
2021
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23. Baseline Neurodegeneration Influences the Longitudinal Effects of Tau on Cognition.

Author

Ng, Kok Pin, Cheng, Grand H.-L., Yatawara, Chathuri, Rosa-Neto, Pedro, Gauthier, Serge, Kandiah, Nagaendran, Kandiahfor the Alzheimer’s Disease Neuroimaging Initiative Nagaendran, and Alzheimer’s Disease Neuroimaging Initiative

Subjects
TAU proteins, EXECUTIVE function, NEURODEGENERATION, COGNITION, NEUROPSYCHOLOGICAL tests, MILD cognitive impairment
Abstract

Background: Cerebrospinal fluid t-tau (CSF t-tau) is a measure of neurodegeneration in Alzheimer's disease (AD) and has been increasingly demonstrated to be a non-specific biomarker within the AD continuum.Objective: We sought to test whether t-tau influences the longitudinal effects of amyloid-β (Aβ) and phospho-tau (p-tau) on memory and executive function (EF) in mild cognitive impairment (MCI).Methods: 319 MCI individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with baseline and 2-year CSF Aβ, p-tau, t-tau, and neuropsychological assessments were studied. Mediation and moderation analyses evaluated the role of t-tau in the effects of Aβ and p-tau on memory and EF over 2 years.Results: We found that high baseline p-tau but not Aβ was associated with higher t-tau and lower memory scores at 2 years follow-up. The association between p-tau and memory impairment was partially mediated by t-tau, whereby higher p-tau was indirectly associated with lower memory via higher t-tau. t-tau also moderated the association between p-tau and memory. When t-tau level was relatively lower, higher p-tau was associated with lower memory scores at 2 years. When t-tau level was higher, the memory scores were low regardless of the p-tau level.Conclusion: Tau-induced neurodegeneration is one key pathway by which AD pathology (p-tau) affects memory impairment. Furthermore, in individuals with lower levels of tau-induced neurodegeneration, higher levels of p-tau were required for memory impairment. Our findings suggest that t-tau plays a significant role in how early AD pathology affects cognitive outcomes. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

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

Published
2019
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28. Small Vessel Disease and Associations with Cerebrospinal Fluid Amyloid, Tau, and Neurodegeneration (ATN) Biomarkers and Cognition in Young Onset Dementia.

Author

Yatawara, Chathuri, Ng, Kok Pin, Cristine Guevarra, Anne, Wong, Benjamin, Yong, TingTing, Kandiah, Nagaendran, and O'Caoimh, Ronan

Subjects
*CEREBRAL small vessel diseases, *CEREBROSPINAL fluid, *COGNITION disorders, *AMYLOID, *COGNITION, *NEURODEGENERATION, *MILD cognitive impairment, *RESEARCH, *BLOOD vessels, *NERVE tissue proteins, *RESEARCH methodology, *MEDICAL cooperation, *EVALUATION research, *COMPARATIVE studies, *DEMENTIA, *AGE factors in disease, *PEPTIDES
Abstract

Background: Small vessel disease (SVD) and Alzheimer's disease (AD) frequently coexist; however, it remains unclear how they collectively affect cognition.Objective: We investigated associations between SVD and AD biomarkers, namely amyloid, tau, and neurodegeneration (ATN) in young onset dementia (YOD) and explored how SVD and ATN interact to affect cognition.Methods: 80 YOD individuals were recruited from a memory clinic. SVD burden (SVD+) was operationalized as a score >1 on the Staals scale and ATN was measured using cerebrospinal fluid (CSF).Results: SVD+ was associated with lower CSF Aβ1-42 (B = -0.20, 95% CI: -0.32 to -0.08) and greater neurodegeneration, indexed as hippocampal atrophy (B = -0.24, 95% CI: -0.40 to -0.04). SVD+ was not associated with tau. Cognitive impairment was associated with CSF Aβ1-42 (B = -0.35, 95% CI: -0.55 to -0.18) but not SVD. Rather, SVD was indirectly associated with cognition via reduced CSF Aβ1-42, specifically with global cognition (B = -0.03, 95% CI: -0.09 to -0.01) and memory (B = 0.08, 95% CI: -.01 to .21). SVD was indirectly associated with cognition via increased neurodegeneration in grey matter (Global cognition: B = -0.06, 95% CI: -0.17 to -0.03; Memory: B = 0.05, 95% CI: 0.01 to 0.18) and the hippocampus (Global cognition: B = -0.05, 95% CI: -0.11 to -0.01; Memory: B = 0.06, 95% CI: 0.01 to 0.17).Conclusion: In YOD, SVD burden was associated with AD pathology, namely CSF Aβ1-42. SVD indirectly contributed to cognitive impairment via reducing CSF Aβ1-42 and increasing neurodegeneration. [ABSTRACT FROM AUTHOR]

Published
2020
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29. Suicidal ideation is common in autosomal dominant Alzheimer's disease at-risk persons.

Author

Ng, Kok Pin, Richard‐Devantoy, Stéphane, Bertrand, Josie‐Anne, Jiang, Lai, Pascoal, Tharick A., Mathotaarachchi, Sulantha, Therriault, Joseph, Yatawara, Chathuri, Kandiah, Nagaendran, Greenwood, Celia M.T., Rosa‐Neto, Pedro, Gauthier, Serge, Richard-Devantoy, Stéphane, Bertrand, Josie-Anne, Rosa-Neto, Pedro, and Dominantly Inherited Alzheimer Network

Subjects
SUICIDAL ideation, ALZHEIMER'S disease, GERIATRIC Depression Scale, RANDOM effects model, APOLIPOPROTEIN E4, CEREBROSPINAL fluid
Abstract

Objectives: To study the frequency of suicidal ideation and its association with clinical and neurobiological correlates among cognitively intact autosomal dominant Alzheimer's disease (ADAD) at-risk individuals.Methods/design: In a cross-sectional study of 183 ADAD at-risk individuals (91 mutation carriers and 92 noncarriers), we compared the frequency of suicidal ideation among carriers and noncarriers. Linear mixed-effects models with family-level random effects evaluated the relationships between geriatric depression scale (GDS), neuropsychiatric inventory-questionnaire (NPI-Q), and suicidal ideation scores among all ADAD at-risk individuals. An interaction term was added to the regression models to evaluate the interactions of suicidal ideation and mutation status on neuropsychiatric symptoms.Results: Twenty-six (14.20%) ADAD at-risk individuals (13 [14.28%] carriers and 13 [14.13%] noncarriers) had suicidal ideation. The frequency of suicidal ideation did not differ between carriers and noncarriers. Suicidal ideation was associated with higher GDS among all ADAD at-risk individuals. When stratified into mutation carrier status, noncarriers with suicidal ideation had higher GDS than carriers. There was no statistically significant association between suicidal ideation and NPI-Q among ADAD at-risk individuals. Awareness of mutation status, neuropsychological performances, and cerebrospinal fluid AD biomarkers were not associated with suicidal ideation among carriers and noncarriers.Conclusions: Suicidal ideation is common among cognitively intact ADAD at-risk individuals. While ADAD at-risk individuals with suicidal ideation have greater depressive symptoms, noncarriers with suicidal ideation have higher GDS scores than carriers. Interestingly, awareness of the mutation status was not associated with suicidal ideation in our study. Early identification of suicidal thoughts can facilitate timely interventions to prevent suicidal behaviours. Keywords autosomal dominant Alzheimer's diseasedominantly inherited Alzheimer's networkneuropsychiatric symptomssuicidal ideation. [ABSTRACT FROM AUTHOR]

Published
2020
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36. APOE4 and confluent WMH have a synergistic effect on episodic memory impairment in prodromal dementia.

Author

Kumar, Dilip, Yatawara, Chathuri, Wang, Brian Zhiyang, Wong, Benjamin, Tan, Yi Jayne, Zailan, Fatin Zahra, Ng, Kok Pin, and Kandiah, Nagaendran

Abstract

Background: White matter hyperintensities (WMH) are a known risk factor for cognitive decline (C.Puzo el. al. 2019). While the ε4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline in concomitance with WMH (D.Tsuang et. al. 2013), it remains unclear how APOE4 affects the relationship between WMH and cognitive decline, specifically in the prodromal stage of dementia. Our objective was thus to determine how APOE4 moderates the relationship between WMH and cognition in prodromal dementia. Method: 216 participants with prodromal dementia underwent magnetic resonance imaging (MRI), neuropsychological testing (global and domain‐specific), cardiovascular risk factor assessments and APOE genotyping. Visual ratings for WMH as well as total and lobar WMH volumes were quantified. Moderation analysis was performed to determine the influence of APOE4 on the relationship between WMH and performance on global and domain‐specific cognitive measures (executive function, episodic memory, attention, language) in moderation analysis (Figure 1). The role of confluent and non‐confluent WMH subtype on cognition was additionally studied using moderation analysis and logistic regression (Figure 1). Result: APOE4 carriers (n = 49) had poorer memory and higher global WMH (p = 0.04), temporal WMH (p = 0.01) and occipital WMH (p = 0.02) compared to APOE4 non‐carriers (n = 167). APOE4 strengthened the relationship between higher total WMH burden and worse episodic memory performance (Fig.2a). At the lobar WMH level, APOE4 strengthened associations between frontal, temporal, parietal and occipital WMH and episodic memory performance (Fig.2b, Fig.2c, Fig.2d, and Fig.2e) with large sized effects (β). APOE4 did not interact with either total or lobar WMH to predict worse cognition in other cognitive domains. Moreover, APOE4 strengthened the relationship between frontal WMH with episodic memory in the confluent WMH subgroup (Fig.2f). Logistic regression model showed memory impairment was 4.81 times more likely to develop in patients carrying APOE4 and with confluent WMH compared to APOE4 non‐carriers and those with non‐confluent WMH (OR 4.81, β 1.57, p<0.01). Conclusion: The impact of WMH on memory may be strongest in APOE4 carriers at the prodromal dementia stage. Clinicians targeting WMH would need to consider the APOE4 allele and WMH severity status to strategize cognitive interventions. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Behavioral and Biological Mechanisms of Social Functioning in Children with Autism Spectrum Disorder: A Randomized Clinical Trial for a Novel Intervention

Author

Yatawara, Chathuri Jeevanthi

Abstract

A child diagnosed with Autism Spectrum Disorder (ASD) shows significant difficulty with social interaction and social communication, which has profound consequences on their mental health, employment opportunities and quality of life. Various theories provide discussion for the etiology of these social and communication impairments, however further research is required to focus our understanding towards the most empirically supported theories. Therefore, the first aim of this dissertation was to evaluate which theories are supported by current empirical literature to explain the etiology of poor social functioning in children with ASD. The second aim of this dissertation was to investigate a promising new treatment to improve social functioning in young children with ASD. The first study in this dissertation investigated empirical support for nonverbal social skills widely believed to be important for healthy social functioning, namely, the capacity to identify faces and facial expressions, engage in joint attention, fixate on the eye region of faces and understand/use gestures during social interactions. A meta-analysis with fifteen studies in Chapter 2 demonstrated that these nonverbal social skills play a significant role in predicting healthy social functioning in children with ASD, an effect associated with a medium effect size. This relationship was independent of the type of nonverbal social skill and the participants’ age and gender, suggesting that the proposed nonverbal social skills play a significant role in social functioning throughout childhood and across both genders. A critical review of current behavioral and biological evidence in Chapter 3 identified that these nonverbal social skills may become impaired in children with ASD as a result of hyper-arousal and anxiety experienced during social situations. Additionally, the experience of anxiety was argued to have cascading effects on the development of secondary mechanisms that may impede social skills, such as perceptual difficulties with perceiving facial features as a whole and cognitive difficulties understanding the meaning of faces. Interestingly, Chapter 4 suggested that young children with ASD, who experience anxiety, as reported by parents, continue to attend to faces more than objects, as measured by eye tracking technology. Additionally, greater attention to faces compared to objects was not associated with social functioning in these children. These findings extend our understanding of social impairments in children with ASD by suggesting that the experience of anxiety may not reduce attention to faces. Intervention for these social impairments remains limited in young children with ASD, and therefore, a second aim of this dissertation was to explore a novel treatment. A critical review in Chapter 5 describes how the neuropeptide oxytocin regulates the capacity for social skills and the experience of hyper-arousal and anxiety. We argued that the greatest benefits of oxytocin treatment may occur during the younger years of life when neural systems are plastic and children are most sensitive to experience dependent growth. The safety and efficacy of oxytocin treatment in young children with ASD was investigated using a randomized placebo-controlled trial, presented in Chapter 6. Here, a five week course of oxytocin treatment was found to significantly improve parent rated social functioning in 31 children with ASD aged between 3 and 8 years. These findings were further supported by experimenter rated global improvements and parent observation ratings of improved eye contact. In summary, this dissertation contributes to the literature by refining current perspectives on the etiology of social impairments in ASD and demonstrating the therapeutic potential of oxytocin as a novel treatment for these impairments in young children with ASD.

Published
2014

50. Neuropsychiatric symptoms in South-East Asian patients with mild cognitive impairment and dementia: prevalence, subtypes, and risk factors.

Author

Yatawara, Chathuri, Hiu, Shaun, Tan, Laura, and Kandiah, Nagaendran

Subjects
*NEUROBEHAVIORAL disorders, *DEMENTIA, *MILD cognitive impairment, *COGNITION disorders, *COGNITIVE ability, *GERIATRIC psychiatry, *MEMORY Assessment Scales
Abstract

Background: The subtypes and risk factors of neuropsychiatric symptoms remain largely unexplored in South-East Asian populations.Objective: We investigated the prevalence, subtypes, and risk factors, namely, demographic, medical morbidity, and cognitive impairment associated with neuropsychiatric symptoms in a South-East Asian cohort of patients with mild cognitive impairment (MCI) and dementia.Methods: A clinical cohort of 38 MCI and 198 mild-moderate dementia patients were assessed using the Neuropsychiatric Inventory-Questionnaire.Results: Neuropsychiatric symptoms were equally prevalent among patients with MCI (74%) and mild-moderate dementia (85%). Three subtypes of symptoms were identified for each diagnostic group; for MCI, they included mood disturbances, anxiety/sleep problems, and psychosis, while for dementia, the subtypes included behavioral disturbances, psychosis/mood, and hyperactive behaviors. The largest risk for neuropsychiatric symptoms for both MCI and dementia patients was male gender. Among patients with MCI, burden of cerebrovascular disease and global cognitive impairment were small risks for neuropsychiatric symptoms, while for patients with dementia, an older age (>65 years) was a small risk and lower educational attainment was a moderate risk.Discussion: These findings contribute to the worldwide epidemiology of neuropsychiatric symptoms in MCI and dementia and highlight that the profile of symptoms, subtypes, and risks is fairly homogenous across Western and Asian cultures. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2018
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