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2. Longevity factor klotho enhances cognition in aged nonhuman primates.

Author

Castner, Stacy, Gupta, Shweta, Wang, Dan, Moreno, Arturo, Chen, Chen, Poon, Yan, Groen, Aaron, Greenberg, Kenneth, David, Nathaniel, Boone, Tom, Baxter, Mark, Williams, Graham, Dubal, Dena, and Park, Cana

Subjects
Mice, Humans, Animals, Aged, Longevity, Glucuronidase, Aging, Cognition, Primates
Abstract

Cognitive dysfunction in aging is a major biomedical challenge. Whether treatment with klotho, a longevity factor, could enhance cognition in human-relevant models such as in nonhuman primates is unknown and represents a major knowledge gap in the path to therapeutics. We validated the rhesus form of the klotho protein in mice showing it increased synaptic plasticity and cognition. We then found that a single administration of low-dose, but not high-dose, klotho enhanced memory in aged nonhuman primates. Systemic low-dose klotho treatment may prove therapeutic in aging humans.

Published
2023

6. Dedicated anticoagulation management protocols in fragility femoral fracture care – a source of significant variance and limited effectiveness in improving time to surgery: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study

Author

Smith, Matthew, Yoong, Andrel, Lim, Jun Wei, Yousef, Omar, McDonald, Stephen, Chileshe, Chinga, Ramus, Camilla, Clements, Christopher, Barrett, Liam, Rockall, Oliver, Geetala, Rahul, Islam, Saif Ul, Nasar, Ahmad, Almond, Kieran, Hassan, Ladan Fatima Yusuf, Shah, Sohan, Brand, Robert Bruce, Yawar, Bakhat, Gilmore, Catherine, McAuley, Daryl, Khan, Waleed, Subramanian, Padmanabhan, Ahluwalia, Aashish, Ozbek, Leyla, Awasthi, Prashant, Sheikh, Hassaan, Barkley, Sarah, Ardolino, Toni, Denning, Alexander, Thiruchandran, Gaj, Fraig, Hossam, Salim, Omar, Iqbal, Rabia, Guy, Stephen, Hogg, Jack, Bagshaw, Oliver, Asmar, Samir, Mitchell, Stephen, Quek, Fang, Fletcher, James, French, Jonathan, Graham, Selina, Sloper, Philip, Sadique, Hammad, Matera, Valentina, Sohail, Zain, Leong, Justin Wei, Issa, Fares, Greasley, Lauren, Marsden, Samuel, Parry, Lucy, Mannan, Syed, Zaheen, Humayoon, Moriarty, Peter, Manning, William, Morris, Timothy, Brockbanks, Carole, Ward, Peter, Pearce, Kim, McMenemy, Louise, Mahmoud, Mohamed, Kieffer, Will, Lal, Aayush, Collis, Justin, Chandrasekaran, Karthik, Foxall-Smith, Michael, Raad, Marjan, Kempshall, Peter, Cheuk, Jocelyn, Leckey, Sam, Gupta, Rishav, Engelke, Daniel, Kemp, Mark, Venkatesan, Aakaash, Hussain, Adnan, Simons, Michiel, Raghavendra, Ram Mohan, Rohra, Satish, Deo, Sunny, Vasarhelyi, Ferenc, Thelwall, Claire, Cullen, Krista, Al-Obaidi, Bilal, Fell, Adam, Thaumeen, Ahmad, Dadabhoy, Maria, Ali, Mira, Ijaz, Sameer, Lin, David, Khan, Basharat, Alsonbaty, Mohamed, Lebe, Moritz, Millan, Ravi Kant, Imam, Sam, Theobald, Emma, Cormack, Jonathan, Sharoff, Lokesh, Eardley, Will, Jeyapalan, Rathan, Alcock, Liam, Clayton, Julia, Bates, Natalie, Mahmoud, Yousif, Osborne, Alex, Ralhan, Shvaita, Carpenter, Catriona, Ahmad, Mahmood, Ravi, Sanjeev Musuvathy, Konbaz, Tarek, Lloyd, Thomas, Sheikh, Nomaan, Swealem, Ahmed, Soroya, Emma, Rayan, Faizal, Ward, Thomas, Vasireddy, Aswinkumar, Clarke, Ellisiv, Sikdar, Oishi, Smart, Yat Wing, Windley, Joseph, Ilagan, Belen, Brophy, Edel, Joseph, Sarah, Lowery, Kathryn, Jamjoom, Ammer, Ismayl, Ghiath, Aujla, Randeep, Sambhwani, Sharan, Ramasamy, Arul, Khalaf, Ahmed, Ponugoti, Nikhil, Teng, Wai Huang, Masud, Saqib, Otoibhili, Eghe, Clarkson, Martin, Nafea, Mohamed, Sarhan, Mohamed, Hanna, Shady, Kelly, Andrew, Curtis, Alex, Gourbault, Lysander, Tarhini, Mariam, Platt, Nicholas, Fleming, Thomas, Pemmaraju, Gopalakrishna, Choudri, Mohammed Junaid, Burahee, Abdus, Hassan, Labiba, Hamid, Laveeza, Loveday, David, Edres, Kareem, Schankat, Kerstin, Granger, Luke, Goodbun, Matthew, Parikh, Sunny, Johnson-Lynn, Sarah, Griffiths, Alexandra, Rai, Avinash, Chandler, Henry, Guiot, Luke, Appleyard, Thomas, Robinson, Karen, Fong, Angus, Watts, Anna, Stedman, Tobias, Walton, Victoria, Inman, Dominic, Liaw, Frank, Hadfield, James, McGovern, Julia, Baldock, Thomas, White, Jonathan, Seah, Matthew, Jacob, Neville, Ali, Zaid Haj, Goff, Thomas, Sanalla, Ahmed, Gomati, Ayoub, Nordin, Louise, Hassan, Eslam, Ramadan, Omar, Teoh, Kar Hao, Baskaran, Dinnish, Ngwayi, James, Abbakr, Lina, Blackmore, Noah, Mansukhani, Sameer, Guryel, Enis, Harper, Adam, Cashman, Emily, Brooker, Joanne, Pack, Louise, Regan, Nora, Wagner, Wilhelm, Selim, Amr, Archer, Debbie, McConaghie, Gregory, Patel, Ravi, Gibson, William, Pasapula, Chandra S, Youssef, Hesham, Aziz, Md Abdul, Subhash, Sadhin, Banaszkiewicz, Paul, Elzawahry, Ahmed, Neo, Chryssa, Wei, Nicholas, Bhaskaran, Arun, Sharma, Abhishek, Factor, Danielle, Shahin, Fatma, Shields, David, Ferreira, Catarina Dores Fernandes, Jeyakumar, Gowsikan, Liao, Quintin, Sinnerton, Robert, Ashwood, Neil, Sarhan, Islam, Ker, Andrew, Phelan, Sean, Paxton, James, McAuley, Joseph, Moulton, Lawrence, Mohamed, Ahmed, Dias, Ana, Ho, Beatrice, Francis, Daniel, Miller, Sarah, Phillips, Jon, Jones, Robin, Arthur, Calum, Oag, Erlend, Thutoetsile, Kamogelo, Bell, Katrina, Milne, Kirsty, Whitefield, Reiss, Patel, Kuntal, Singh, Abhimanyu, Morris, Geraint, Parkinson, Dawn, Patil, Amogh, Hamid, Hassan, Syam, Kevin, Singh, Rohit, Menon, Deepak, Crooks, Sophie, Borland, Steven, Rohman, Adam, Nicholson, Alys, Smith, Ben, Hafiz, Nauman, Kolhe, Shivam, Waites, Matthew, Piper, Dani, Westacott, David, Grimshaw, Jessica, Bott, Alasdair, Berry, Alexander, Battle, Joseph, Flannery, Oliver, Iyengar, Karthikeyan P, Thakur, Abdul Wadood, Yousef, Mina, Bansod, Vaibhav, El-nahas, Walaa, Dawe, Edward, Oladeji, Emmanuel, Federer, Simon, Trompeter, Alex, Pritchard, Anna, Shurovi, Badrun, Jordan, Chris, Little, Max, Sivaloganathan, Sivanshankar, Shaunak, Shalin, Watters, Hazel, Luck, Joshua, Zbaeda, Mohamed, Frasquet-Garcia, Antonio, Warner, Christian, Telford, Jeremy, Rooney, Joanna, Attwood, Joseph, Wilson, Faye, Panagiotopoulos, Andreas, Keane, Conal, Scott, Helen, Mazel, Rebecca, Maggs, Joanna, Skinner, Edward, McMunn, Finlay, Lau, Joshua, Ravikumar, Kasetti, Thakker, Dev, Gill, Moneet, McCarthy, Phillip, Fossey, Gavin, Shah, Sohaib, McAlinden, Gavan, McGoldrick, Peter, O'Brien, Scarlett, Patil, Sunit, Millington, Antonia, Umar, Hamza, Sehdev, Simran, Dyer-Hill, Thomas, Yu Kwan, Tsun, Tanagho, Andy, Hagnasir, Ahmed, White, Thomas, Bano, Christopher, Kissin, Eleanor, Ghani, Rafia, Thomas, Philip S W, McMullan, Mark, Walmsley, Matthew, Elgendy, Mohamed, Winstanley, Robert, Round, Joanne, Baxter, Mark, Thompson, Emett, Hogan, Kathryn, Youssef, Khaled, Fetouh, Sherif, Hopper, Graeme P, Simpson, Cameron, Warren, Craig, Waugh, Dominic, Nair, Gopikrishnan, Ballantyne, Andy, Blacklock, Calum, O'Connell, Ciara, Toland, Gemma, McIntyre, Joshua, Ross, Lauren, Badge, Ravindra, Loganathan, Deeraj, Turner, Ian, Ball, Matthew, Maqsood, Saad, Deierl, Krisztian, Beer, Alexander, Tan, Arthur Chen Wun, Mackinnon, Thomas, Gade, Venkat, Gill, James, Yu San, Kay, Archunan, Maheswaran Warren, Shaikh, Mariyam, Ugbah, Onyinye, Uwaoma, Sade, Pillai, Anand, Nath, Upamanyu, Rohan, Farhan-Alanie, M. M., Dixon, J., Irvine, S., Walker, R., and Eardley, W. G. P.

Published
2024
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8. The impact of anticoagulant medications on fragility femur fracture care: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study

Author

Smith, Matthew, Yoong, Andrel, Lim, Jun Wei, Yousef, Omar, McDonald, Stephen, Chileshe, Chinga, Ramus, Camilla, Clements, Christopher, Barrett, Liam, Rockall, Oliver, Geetala, Rahul, Islam, Saif Ul, Nasar, Ahmad, Almond, Kieran, Hassan, Ladan Fatima Yusuf, Shah, Sohan, Brand, Robert Bruce, Yawar, Bakhat, Gilmore, Catherine, McAuley, Daryl, Khan, Waleed, Subramanian, Padmanabhan, Ahluwalia, Aashish, Ozbek, Leyla, Awasthi, Prashant, Sheikh, Hassaan, Barkley, Sarah, Ardolino, Toni, Denning, Alexander, Thiruchandran, Gaj, Fraig, Hossam, Salim, Omar, Iqbal, Rabia, Guy, Stephen, Hogg, Jack, Bagshaw, Oliver, Asmar, Samir, Mitchell, Stephen, Quek, Fang, Fletcher, James, French, Jonathan, Graham, Selina, Sloper, Philip, Sadique, Hammad, Matera, Valentina, Sohail, Zain, Leong, Justin Wei, Issa, Fares, Greasley, Lauren, Marsden, Samuel, Parry, Lucy, Mannan, Syed, Zaheen, Humayoon, Moriarty, Peter, Manning, William, Morris, Timothy, Brockbanks, Carole, Ward, Peter, Pearce, Kim, McMenemy, Louise, Mahmoud, Mohamed, Kieffer, Will, Lal, Aayush, Collis, Justin, Chandrasekaran, Karthik, Foxall-Smith, Michael, Raad, Marjan, Kempshall, Peter, Cheuk, Jocelyn, Leckey, Sam, Gupta, Rishav, Engelke, Daniel, Kemp, Mark, Venkatesan, Aakaash, Hussain, Adnan, Simons, Michiel, Raghavendra, Ram Mohan, Rohra, Satish, Deo, Sunny, Vasarhelyi, Ferenc, Thelwall, Claire, Cullen, Krista, Al-Obaidi, Bilal, Fell, Adam, Thaumeen, Ahmad, Dadabhoy, Maria, Ali, Mira, Ijaz, Sameer, Lin, David, Khan, Basharat, Alsonbaty, Mohamed, Lebe, Moritz, Millan, Ravi Kant, Imam, Sam, Theobald, Emma, Cormack, Jonathan, Sharoff, Lokesh, Eаrdley, Will, Jeyapalan, Rathan, Alcock, Liam, Clayton, Julia, Bates, Natalie, Mahmoud, Yousif, Osborne, Alex, Ralhan, Shvaita, Carpenter, Catriona, Ahmad, Mahmood, Ravi, Sanjeev Musuvathy, Konbaz, Tarek, Lloyd, Thomas, Sheikh, Nomaan, Swealem, Ahmed, Soroya, Emma, Rayan, Faizal, Ward, Thomas, Vasireddy, Aswinkumar, Clarke, Ellisiv, Sikdar, Oishi, Smart, Yat Wing, Windley, Joseph, Ilagan, Belen, Brophy, Edel, Joseph, Sarah, Lowery, Kathryn, Jamjoom, Ammer, Ismayl, Ghiath, Aujla, Randeep, Sambhwani, Sharan, Ramasamy, Arul, Khalaf, Ahmed, Ponugoti, Nikhil, Teng, Wai Huang, Masud, Saqib, Otoibhili, Eghe, Clarkson, Martin, Nafea, Mohamed, Sarhan, Mohamed, Hanna, Shady, Kelly, Andrew, Curtis, Alex, Gourbault, Lysander, Tarhini, Mariam, Platt, Nicholas, Fleming, Thomas, Pemmaraju, Gopalakrishna, Choudri, Mohammed Junaid, Burahee, Abdus, Hassan, Labiba, Hamid, Laveeza, Loveday, David, Edres, Kareem, Schankat, Kerstin, Granger, Luke, Goodbun, Matthew, Parikh, Sunny, Johnson-Lynn, Sarah, Griffiths, Alexandra, Rai, Avinash, Chandler, Henry, Guiot, Luke, Appleyard, Thomas, Robinson, Karen, Fong, Angus, Watts, Anna, Stedman, Tobias, Walton, Victoria, Inman, Dominic, Liaw, Frank, Hadfield, James, McGovern, Julia, Baldock, Thomas, White, Jonathan, Seah, Matthew, Jacob, Neville, Ali, Zaid Haj, Goff, Thomas, Sanalla, Ahmed, Gomati, Ayoub, Nordin, Louise, Hassan, Eslam, Ramadan, Omar, Teoh, Kar Hao, Baskaran, Dinnish, Ngwayi, James, Abbakr, Lina, Blackmore, Noah, Mansukhani, Sameer, Guryel, Enis, Harper, Adam, Cashman, Emily, Brooker, Joanne, Pack, Louise, Regan, Nora, Wagner, Wilhelm, Selim, Amr, Archer, Debbie, McConaghie, Gregory, Patel, Ravi, Gibson, William, Pasapula, Chandra S, Youssef, Hesham, Aziz, Md Abdul, Subhash, Sadhin, Banaszkiewicz, Paul, Elzawahry, Ahmed, Neo, Chryssa, Wei, Nicholas, Bhaskaran, Arun, Sharma, Abhishek, Factor, Danielle, Shahin, Fatma, Shields, David, Ferreira, Catarina Dores Fernandes, Jeyakumar, Gowsikan, Liao, Quintin, Sinnerton, Robert, Ashwood, Neil, Sarhan, Islam, Ker, Andrew, Phelan, Sean, Paxton, James, McAuley, Joseph, Moulton, Lawrence, Mohamed, Ahmed, Dias, Ana, Ho, Beatrice, Francis, Daniel, Miller, Sarah, Phillips, Jon, Jones, Robin, Arthur, Calum, Oag, Erlend, Thutoetsile, Kamogelo, Bell, Katrina, Milne, Kirsty, Whitefield, Reiss, Patel, Kuntal, Singh, Abhimanyu, Morris, Geraint, Parkinson, Dawn, Patil, Amogh, Hamid, Hassan, Syam, Kevin, Singh, Rohit, Menon, Deepak, Crooks, Sophie, Borland, Steven, Rohman, Adam, Nicholson, Alys, Smith, Ben, Hafiz, Nauman, Kolhe, Shivam, Waites, Matthew, Piper, Dani, Westacott, David, Grimshaw, Jessica, Bott, Alasdair, Berry, Alexander, Battle, Joseph, Flannery, Oliver, Iyengar, Karthikeyan P, Thakur, Abdul Wadood, Yousef, Mina, Bansod, Vaibhav, El-nahas, Walaa, Dawe, Edward, Oladeji, Emmanuel, Federer, Simon, Trompeter, Alex, Pritchard, Anna, Shurovi, Badrun, Jordan, Chris, Little, Max, Sivaloganathan, Sivanshankar, Shaunak, Shalin, Watters, Hazel, Luck, Joshua, Zbaeda, Mohamed, Frasquet-Garcia, Antonio, Warner, Christian, Telford, Jeremy, Rooney, Joanna, Attwood, Joseph, Wilson, Faye, Panagiotopoulos, Andreas, Keane, Conal, Scott, Helen, Mazel, Rebecca, Maggs, Joanna, Skinner, Edward, McMunn, Finlay, Lau, Joshua, Ravikumar, Kasetti, Thakker, Dev, Gill, Moneet, McCarthy, Phillip, Fossey, Gavin, Shah, Sohaib, McAlinden, Gavan, McGoldrick, Peter, O'Brien, Scarlett, Patil, Sunit, Millington, Antonia, Umar, Hamza, Sehdev, Simran, Dyer-Hill, Thomas, Yu Kwan, Tsun, Tanagho, Andy, Hagnasir, Ahmed, White, Thomas, Bano, Christopher, Kissin, Eleanor, Ghani, Rafia, Thomas, Philip S W, McMullan, Mark, Walmsley, Matthew, Elgendy, Mohamed, Winstanley, Robert, Round, Joanne, Baxter, Mark, Thompson, Emett, Hogan, Kathryn, Youssef, Khaled, Fetouh, Sherif, Hopper, Graeme P, Simpson, Cameron, Warren, Craig, Waugh, Dominic, Nair, Gopikrishnan, Ballantyne, Andy, Blacklock, Calum, O'Connell, Ciara, Toland, Gemma, McIntyre, Joshua, Ross, Lauren, Badge, Ravindra, Loganathan, Deeraj, Turner, Ian, Ball, Matthew, Maqsood, Saad, Deierl, Krisztian, Beer, Alexander, Tan, Arthur Chen Wun, Mackinnon, Thomas, Gade, Venkat, Gill, James, Yu San, Kay, Archunan, Maheswaran Warren, Shaikh, Mariyam, Ugbah, Onyinye, Uwaoma, Sade, Pillai, Anand, Nath, Upamanyu, Rohan, Farhan-Alanie, M.M., Chinweze, R., Walker, R., and Eardley, W.G.P.

Published
2024
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18. Oligomeric Aβ in the monkey brain impacts synaptic integrity and induces accelerated cortical aging

Author

Beckman, Danielle, Ott, Sean, Donis-Cox, Kristine, Janssen, William G, Bliss-Moreau, Eliza, Rudebeck, Peter H, Baxter, Mark G, and Morrison, John H

Subjects
Biological Psychology, Biochemistry and Cell Biology, Biological Sciences, Psychology, Brain Disorders, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Neurosciences, Dementia, Neurological, Alzheimer's disease, rhesus monkey, microglia, A beta Os, synapse, Alzheimer’s disease, AβOs
Abstract

As the average age of the population continues to rise, the number of individuals affected with age-related cognitive decline and Alzheimer's disease (AD) has increased and is projected to cost more than $290 billion in the United States in 2019. Despite significant investment in research over the last decades, there is no effective treatment to prevent or delay AD progression. There is a translational gap in AD research, with promising drugs based on work in rodent models failing in clinical trials. Aging is the leading risk factor for developing AD and understanding neurobiological changes that affect synaptic integrity with aging will help clarify why the aged brain is vulnerable to AD. We describe here the development of a rhesus monkey model of AD using soluble oligomers of the amyloid beta (Aβ) peptide (AβOs). AβOs infused into the monkey brain target a specific population of spines in the prefrontal cortex, induce neuroinflammation, and increase AD biomarkers in the cerebrospinal fluid to similar levels observed in patients with AD. Importantly, AβOs lead to similar dendritic spine loss to that observed in normal aging in monkeys, but so far without detection of amyloid plaques or tau pathology. Understanding the basis of synaptic impairment is the most effective route to early intervention and prevention or postponement of age-related cognitive decline and transition to AD. These initial findings support the use of monkeys as a platform to understand age-related vulnerabilities of the primate brain and may help develop effective disease-modifying therapies for treatment of AD and related dementias.

Published
2019

19. A United Kingdom prospective, multicentre, observational cohort study investigating tolerance of anti-cancer systemic therapy in the elderly: The TOASTIE study.

Author

Dearden, Helen Clare, primary, Rowe, Michael, additional, Peters, Adam, additional, Rohan, Maria, additional, Marsh, Alexandra, additional, Gee, Abigail Louise, additional, Zucker, Kieran, additional, Quesne, Gemma, additional, Heseltine, Jonathan, additional, Prichard, Rachel, additional, Scott, Deborah, additional, ONeill, Conor, additional, Brunner, Clair, additional, Howells, Joni, additional, Conteh, Veronica, additional, Aujayeb, Avinash, additional, Yan, Xiangfei, additional, Rodgers, Lisa Jane, additional, Martin, Sally, additional, and Baxter, Mark, additional

Published
2024
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20. UKIOG Cancer Update 2023

Author

Booth, Mary E., primary, Clements, Hollie A., additional, Helbrow, Jonathan, additional, Baxter, Mark A., additional, Bleaney, Christopher W., additional, Hawkins, Maria A., additional, Markar, Sheraz R., additional, Peters, Christopher J., additional, Smyth, Elizabeth C., additional, and Crosby, Tom D.L., additional

Published
2024
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22. Interest in non-social novel stimuli as a function of age in rhesus monkeys

Author

Bliss-Moreau, Eliza and Baxter, Mark G

Subjects
Biological Psychology, Psychology, Prevention, Behavioral and Social Science, Aging, Basic Behavioral and Social Science, ageing, macaque, novelty
Abstract

Human cognitive and affective life changes with healthy ageing; cognitive capacity declines while emotional life becomes more positive and social relationships are prioritized. This may reflect an awareness of limited lifetime unique to humans, leading to a greater interest in maintaining social relationships at the expense of the non-social world in the face of limited cognitive and physical resources. Alternately, fundamental biological processes common to other primate species may direct preferential interest in social stimuli with increasing age. Inspired by a recent study that described a sustained interest in social stimuli but diminished interest in non-social stimuli in aged Barbary macaques, we carried out a conceptual replication to test whether old rhesus monkeys lost interest in non-social stimuli. Male and female macaques (Macaca mulatta; N = 243) 4-30 years old were tested with a food puzzle outfitted with an activity monitor to evaluate their propensity to manipulate the puzzle in order to free a food reward. We found no indication that aged monkeys were less interested in the puzzle than young monkeys, nor were they less able to solve it.

Published
2019

23. Selective Loss of Thin Spines in Area 7a of the Primate Intraparietal Sulcus Predicts Age-Related Working Memory Impairment

Author

Motley, Sarah E, Grossman, Yael S, Janssen, William GM, Baxter, Mark G, Rapp, Peter R, Dumitriu, Dani, and Morrison, John H

Subjects
Biomedical and Clinical Sciences, Neurosciences, Behavioral and Social Science, Acquired Cognitive Impairment, Basic Behavioral and Social Science, Aging, Neurodegenerative, Brain Disorders, Underpinning research, 1.2 Psychological and socioeconomic processes, Neurological, Mental health, Animals, Cell Death, Dendritic Spines, Female, Forecasting, Macaca mulatta, Male, Memory Disorders, Memory, Short-Term, Parietal Lobe, Random Allocation, aging, area 7a, dendritic spines, primate, thin spines, working memory, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Brodmann area 7a of the parietal cortex is active during working memory tasks in humans and nonhuman primates, but the composition and density of dendritic spines in area 7a and their relevance both to working memory and cognitive aging remain unexplored. Aged monkeys have impaired working memory, and we have previously shown that this age-induced cognitive impairment is partially mediated by a loss of thin spines in prefrontal cortex area 46, a critical area for working memory. Because area 46 is reciprocally connected with area 7a of the parietal cortex and 7a mediates visual attention integration, we hypothesized that thin spine density in area 7a would correlate with working memory performance as well. To investigate the synaptic profile of area 7a and its relevance to working memory and cognitive aging, we investigated differences in spine type and density in layer III pyramidal cells of area 7a in young and aged, male and female rhesus macaques (Macaca mulatta) that were cognitively assessed using the delayed response test of working memory. Area 7a shows age-related loss of thin spines, and thin spine density positively correlates with delayed response performance in aged monkeys. In contrast, these cells show no age-related changes in dendritic length or branching. These changes mirror age-related changes in area 46 but are distinct from other neocortical regions, such as V1. These findings support our hypothesis that cognitive aging is driven primarily by synaptic changes, and more specifically by changes in thin spines, in key association areas.SIGNIFICANCE STATEMENT This study advances our understanding of cognitive aging by demonstrating the relevance of area 7a thin spines to working memory performance. This study is the first to look at cognitive aging in the intraparietal sulcus, and also the first to report spine or dendritic measures for area 7a in either young adult or aged nonhuman primates. These results contribute to the hypothesis that thin spines support working memory performance and confirm our prior observation that cognitive aging is driven by synaptic changes rather than changes in dendritic morphology or neuron death. Importantly, these data show that age-related working memory changes are not limited to disruptions of the prefrontal cortex but also include an association region heavily interconnected with prefrontal cortex.

Published
2018

24. An Open Resource for Non-human Primate Imaging

Author

Milham, Michael P, Ai, Lei, Koo, Bonhwang, Xu, Ting, Amiez, Céline, Balezeau, Fabien, Baxter, Mark G, Blezer, Erwin LA, Brochier, Thomas, Chen, Aihua, Croxson, Paula L, Damatac, Christienne G, Dehaene, Stanislas, Everling, Stefan, Fair, Damian A, Fleysher, Lazar, Freiwald, Winrich, Froudist-Walsh, Sean, Griffiths, Timothy D, Guedj, Carole, Hadj-Bouziane, Fadila, Hamed, Suliann Ben, Harel, Noam, Hiba, Bassem, Jarraya, Bechir, Jung, Benjamin, Kastner, Sabine, Klink, P Christiaan, Kwok, Sze Chai, Laland, Kevin N, Leopold, David A, Lindenfors, Patrik, Mars, Rogier B, Menon, Ravi S, Messinger, Adam, Meunier, Martine, Mok, Kelvin, Morrison, John H, Nacef, Jennifer, Nagy, Jamie, Rios, Michael Ortiz, Petkov, Christopher I, Pinsk, Mark, Poirier, Colline, Procyk, Emmanuel, Rajimehr, Reza, Reader, Simon M, Roelfsema, Pieter R, Rudko, David A, Rushworth, Matthew FS, Russ, Brian E, Sallet, Jerome, Schmid, Michael Christoph, Schwiedrzik, Caspar M, Seidlitz, Jakob, Sein, Julien, Shmuel, Amir, Sullivan, Elinor L, Ungerleider, Leslie, Thiele, Alexander, Todorov, Orlin S, Tsao, Doris, Wang, Zheng, Wilson, Charles RE, Yacoub, Essa, Ye, Frank Q, Zarco, Wilbert, Zhou, Yong-di, Margulies, Daniel S, and Schroeder, Charles E

Subjects
Biological Psychology, Psychology, Neurosciences, Biomedical Imaging, Animals, Brain, Connectome, Datasets as Topic, Information Dissemination, Magnetic Resonance Imaging, Neuroimaging, Primates, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

Published
2018

30. Timing of cyclic estradiol treatment differentially affects cognition in aged female rhesus monkeys.

Author

Baxter, Mark G, Santistevan, Anthony C, Bliss-Moreau, Eliza, and Morrison, John H

Subjects
Prefrontal Cortex, Animals, Macaca mulatta, Estradiol, Estrogens, Ovariectomy, Models, Animal, Cognition, Memory, Short-Term, Reaction Time, Age Factors, Female, Aging, Estrogen, Contraception/Reproduction, Neurosciences, Behavioral and Social Science, Basic Behavioral and Social Science, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, estrogen, macaque, aging, prefrontal, working memory, Psychology, Cognitive Sciences, Behavioral Science & Comparative Psychology
Abstract

Some evidence suggests that there may be a limited "window of opportunity" for beneficial effects of hormone therapy after menopause in women. We tested whether the timing of cyclic estradiol (E2) treatment impacted its effect on cognitive function in aged, surgically menopausal (ovariectomized) rhesus monkeys. Monkeys were assigned to one of four treatment conditions after ovariectomy: either vehicle or E2 treatment for the duration of the protocol, vehicle for the first 2 years of the protocol followed by E2 for the remainder (delayed treatment), or E2 for the first 11 months of the protocol followed by vehicle for the remainder (withdrawn treatment). Delayed treatment addressed the hypothesis that E2 treatment initiated more than 2 years postovariectomy would have a reduced effect on cognitive function. Withdrawn treatment mirrored current clinical advice to women to use hormone therapy in the initial postmenopausal period then discontinue it. Two periods of cognitive testing assessed treatment effects on cognition over time. E2 treatment predominantly affected a prefrontal cortex-dependent test of spatiotemporal working memory (delayed response). Monkeys with delayed E2 treatment modestly improved in delayed response performance over time, whereas vehicle-treated monkeys declined. Monkeys with withdrawn E2 treatment maintained their performance across assessments, as did monkeys treated with E2 across the entire protocol. These findings suggest that a "window of opportunity" for hormone treatment after cessation of ovarian function, if present in nonhuman primates, lasts longer than 2 years. They also support the notion that beneficial effects of hormone therapy may persist after discontinuation of treatment. (PsycINFO Database Record

Published
2018

31. Estradiol Treatment in a Nonhuman Primate Model of Menopause Preserves Affective Reactivity

Author

Bliss-Moreau, Eliza and Baxter, Mark G

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Applied and Developmental Psychology, Contraception/Reproduction, Aging, Basic Behavioral and Social Science, Estrogen, Behavioral and Social Science, Prevention, Affect, Animals, Behavior, Animal, Estradiol, Estrogens, Female, Macaca mulatta, Male, Menopause, Models, Animal, Ovariectomy, Reaction Time, hormone, rhesus monkey, emotion, macaque, affect, Neurosciences, Cognitive Sciences, Behavioral Science & Comparative Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Human affective life changes with age, becoming more positive and less negative in later life. This change occurs even as aging leads to declines in health and cognitive outcomes. Despite these well-documented effects in humans, the extent to which affective processes change as a result of aging in nonhuman animals, particularly nonhuman primates, is unclear. As a first step toward developing an animal model for human affective aging, we tested aged, surgically menopausal aged and middle-aged gonadally intact female rhesus monkeys (Macaca mulatta) on a classic index of affective reactivity in monkeys, the Human Intruder Task. The Human Intruder Task evaluates behavioral responses to varying levels of threat. Aged, surgically menopausal monkeys received hormone replacement therapy consisting of a cyclic estradiol regimen or vehicle injections as a control. Average responsivity to threat did not vary by condition, but middle-aged monkeys and aged monkeys on estradiol were more reactive to the most potent level of threat than to a moderate level of threat, replicating previously published results in other age groups and male monkeys. In contrast, aged monkeys who were not on estradiol did not show such calibration to threat level. These findings suggest that estrogen may be important for maintaining more youthful affective responding. They also illustrate the utility of behavioral assays of affective reactivity in nonhuman primate models of cognitive and reproductive aging in humans. (PsycINFO Database Record

Published
2018

32. Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors

Author

Stavraka, Chara, Pouptsis, Athanasios, Synowiec, Alicja, Angelis, Vasileios, Satterthwaite, Liyana, Khan, Sam, Chauhan, Meera, Holden, Chloe, Young, Sally, Karampera, Christina, Martinou, Maria, Mills-Baldock, Tina, Baxter, Mark, Barry, Ainsley, Eccles, Bryony, Iveson, Timothy, Shiu, Kai-Keen, Hill, Mark, Abdel-Raouf, Sherif, Graham, Janet Shirley, Thomas, Anne, and Ross, Paul J.

Published
2021
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38. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

Author

Gault, Abigail, Agnieszka, Michael, Bedair, Ahmed, Ghaus, Aisha, Akingboye, Akinfemi, Maynard, Alec, Pawsey, Alexander, Suwaidan, Ali Abdulnabi, Okines, Alicia, Massey, Alison, Kwan, Amy, Ferreira, Ana, Angelakas, Angelos, Wu, Anjui, Tivey, Ann, Armstrong, Anne, Madhan, Annet, Pillai, Annet, Poon-King, Ashley, Kurec, Bartlomiej, Usborne, Caroline, Dobeson, Caroline, Thirlwell, Christina, Mitchell, Christian, Sng, Christopher, Scrase, Christopher, Jingree, Christopher, Brunner, Clair, Fuller, Claire, Griffin, Clare, Barrington, Craig, Muller, Daniel, Ottaviani, Diego, Gilbert, Duncan, Tacconi, Eliana, Copson, Ellen, Renninson, Emily, Cattell, Emma, Burke, Emma, Smith, Fiona, Holt, Francesca, Soosaipillai, Gehan, Boyce, Hayley, Shaw, Heather, Hollis, Helen, Bowyer, Helen, Anil, Iris, Illingworth, Jack, Gibson, Jack, Bhosle, Jaishree, Best, James, Barrett, Jane, Noble, Jillian, Sacco, Joseph, Chacko, Joseph, Chackathayil, Julia, Banfill, Kathryn, Feeney, Laura, Horsley, Laura, Cammaert, Lauren, Mukherjee, Leena, Eastlake, Leonie, Devereaux, Louise, Melcher, Lucinda, Cook, Lucy, Teng, Mabel, Hewish, Madeleine, Bhattacharyya, Madhumita, Choudhury, Mahbuba, Baxter, Mark, Scott-Brown, Martin, Fittall, Matthew, Tilby, Michael, Rowe, Michael, Alihilali, Mohammed, Galazi, Myria, Yousaf, Nadia, Chopra, Neha, Cox, Nicola, Chan, Olivia, Sheikh, Omar, Ramage, Paul, Greaves, Paul, Leonard, Pauline, Hall, Peter S, Naksukpaiboon, Piangfan, Corrie, Pippa, Peck, Rahul, Sharkey, Rachel, Bolton, Rachel, Sargent, Rebecca, Jyothirmayi, Rema, Goldstein, Robert, Oakes, Roderick, Shotton, Rohan, Kanani, Ruhi, Board, Ruth, Pettengell, Ruth, Claydon, Ryan, Moody, Sam, Massalha, Samah, Kathirgamakarthigeyan, Sangary, Dolly, Saoirse, Derby, Sarah, Lowndes, Sarah, Benafif, Sarah, Eeckelaers, Sarah, Kingdon, Sarah, Ayers, Sarah, Brown, Sean, Ellis, Shawn, Parikh, Shefali, Pugh, Sian, Shamas, Simon, Wyatt, Simon, Grumett, Simon, Lau, Sin, Wong, Yien Ning Sophia, McGrath, Sophie, Cornthwaite, Stephanie, Hibbs, Stephen, Tillet, Tania, Rabbi, Taslima, Robinson, Tim, Roques, Tom, Angelis, Vasileios, Woodcock, Victoria, Brown, Victoria, Peng, YingYing, Drew, Yvette, Hudson, Zoe, Lee, Lennard Y W, Cazier, Jean-Baptiste, Starkey, Thomas, Briggs, Sarah E W, Arnold, Roland, Bisht, Vartika, Booth, Stephen, Campton, Naomi A, Cheng, Vinton W T, Collins, Graham, Curley, Helen M, Earwaker, Philip, Fittall, Matthew W, Gennatas, Spyridon, Goel, Anshita, Hartley, Simon, Hughes, Daniel J, Kerr, David, Lee, Alvin J X, Lee, Rebecca J, Lee, Siow Ming, Mckenzie, Hayley, Middleton, Chris P, Murugaesu, Nirupa, Newsom-Davis, Tom, Olsson-Brown, Anna C, Palles, Claire, Powles, Thomas, Protheroe, Emily A, Purshouse, Karin, Sharma-Oates, Archana, Sivakumar, Shivan, Smith, Ashley J, Topping, Oliver, Turnbull, Chris D, Várnai, Csilla, Briggs, Adam D M, Middleton, Gary, and Kerr, Rachel

Published
2020
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47. Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital

Author

Lee, Rebecca J., Wysocki, Oskar, Zhou, Cong, Shotton, Rohan, Tivey, Ann, Lever, Louise, Woodcock, Joshua, Albiges, Laurence, Angelakas, Angelos, Arnold, Dirk, Aung, Theingi, Banfill, Kathryn, Baxter, Mark, Barlesi, Fabrice, Bayle, Arnaud, Besse, Benjamin, Bhogal, Talvinder, Boyce, Hayley, Britton, Fiona, Calles, Antonio, Castelo-Branco, Luis, Copson, Ellen, Croitoru, Adina E., Dani, Sourbha S., Dickens, Elena, Eastlake, Leonie, Fitzpatrick, Paul, Foulon, Stephanie, Frederiksen, Henrik, Frost, Hannah, Ganatra, Sarju, Gennatas, Spyridon, Glenthøj, Andreas, Gomes, Fabio, Graham, Donna M., Hague, Christina, Harrington, Kevin, Harrison, Michelle, Horsley, Laura, Hoskins, Richard, Huddar, Prerana, Hudson, Zoe, Jakobsen, Lasse H., Joharatnam-Hogan, Nalinie, Khan, Sam, Khan, Umair T., Khan, Khurum, Massard, Christophe, Maynard, Alec, McKenzie, Hayley, Michielin, Olivier, Mosenthal, Anne C., Obispo, Berta, Patel, Rushin, Pentheroudakis, George, Peters, Solange, Rieger-Christ, Kimberly, Robinson, Timothy, Rogado, Jacobo, Romano, Emanuela, Rowe, Michael, Sekacheva, Marina, Sheehan, Roseleen, Stevenson, Julie, Stockdale, Alexander, Thomas, Anne, Turtle, Lance, Viñal, David, Weaver, Jamie, Williams, Sophie, Wilson, Caroline, Palmieri, Carlo, Landers, Donal, Cooksley, Timothy, Dive, Caroline, Freitas, André, and Armstrong, Anne C.

Published
2022
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