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533 results on '"Porsteinsson, Anton P"'

1. Dynamic proportional loss of functional connectivity revealed change of left superior frontal gyrus in subjective cognitive decline: an explanatory study based on Chinese and Western cohorts

Author

Wang, Luyao, Hu, Wenjing, Dong, Fan, Sheng, Can, Wu, Jinglong, Han, Ying, Jiang, Jiehui, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jagust, William, Trojanowski, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Khachaturian, Zaven, Sorensen, Greg, Kuller, Lew, Raichle, Marcus, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, Marek M., Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Bernstein, Matthew, Thompson, Paul, Schuff, Norbert, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Taylor-Reinwald, Lisa, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M., Potkin, Steven G., Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Thal, Leon, Buckholtz, Neil, Albert, Marylyn, Frank, Richard, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, de Toledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T., Roberts, Peggy, Onyike, Chiadi, D’Agostino, Daniel, Kielb, Stephanie, Galvin, James E., Cerbone, Brittany, Michel, Christina A., Rusinek, Henry, de Leon, Mony J., Glodzik, Lidia, De Santi, Susan, Doraiswamy, PMurali, Petrella, Jeffrey R., Wong, Terence Z., Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, MSaleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, McAdams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H. S., Lu, Po H., Bartzokis, George, Graff-Radford, Neill R., Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Hsiung, Ging-Yuek Robin, Feldman, Howard, Mudge, Benita, Assaly, Michele, Bernick, Charles, Munic, Donna, Kertesz, Andrew, Rogers, John, Trost, Dick, Kerwin, Diana, Lipowski, Kristine, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Frey, Meghan, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N., Belden, Christine M., Jacobson, Sandra A., Sirrel, Sherye A., Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichae, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T.-Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Santulli, Robert B., Kitzmiller, Tamar J., Schwartz, Eben S., Sink, Kaycee M., Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Ponto, Laura L. Boles, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Neylan, Thomas, Grafman, Jordan, Davis, Melissa, Morrison, Rosemary, Hayes, Jacqueline, Finley, Shannon, Friedl, Karl, Fleischman, Debra, Arfanakis, Konstantinos, James, Olga, Massoglia, Dino, Fruehling, JJay, Harding, Sandra, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Yesavage, Jerome A., Taylor, Joy L., and Furst, Ansgar J.

Published
2025
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3. Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy

Author

Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Liu, Enchi, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Reinwald, Lisa Taylor, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M., Potkin, Steven, Shen, Li, Kelley, Faber, Kim, Sungeun, Nho, Kwangsik, Kachaturian, Zaven, Frank, Richard, Snyder, Peter J., Molchan, Susan, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Meyer, Javier Villanueva, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Morris, John C., Carroll, Maria, Leon, Sue, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geld-macher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, Leyla deToledo-Morrell, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T., Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, D’Agostino, Daniel, Kielb, Stephanie, Galvin, James E., Pogorelec, Dana M., Cerbone, Brittany, Michel, Christina A., Rusinek, Henry, de Leon, Mony J., Glodzik, Lidia, De Santi, Susan, Doraiswamy, P. Murali, Petrella, Jeffrey R., Wong, Terence Z., Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, Adams Ortiz, Catherine Mc, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Arrastia, Ramon Diaz, King, Richard, Weiner, Myron, Cook, Kristen Martin, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H.S., Lu, Po H., Bartzokis, George, Graff Radford, Neill R., Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R., Hake, AnnMarie, Matthews, Brandy R., Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Robin Hsiung, Ging-Yuek, Feldman, Howard, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek Marsel, Lipowski, Kristine, Wu, Chuang Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N., Belden, Christine M., Jacobson, Sandra A., Sirrel, Sherye A., Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O., Wolday, Saba, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T.Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Santulli, Robert B., Kitzmiller, Tamar J., Schwartz, Eben S., Sink, Kaycee M., Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Boles Ponto, Laura L., Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Barisano, Giuseppe, Iv, Michael, Choupan, Jeiran, and Hayden-Gephart, Melanie

Published
2025
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4. Neuropsychiatric Symptoms in AD: Clinical Trials Targeting Mild Behavioral Impairment: A Report from the International CTAD Task Force

Author

Soto, Maria, Rosenberg, P., Ballard, C., Vellas, B., Miller, D., Gauthier, S., Carrillo, M. C., Lyketsos, C., Ismail, Z., Abushakra, Susan, Afshar, Mohammad, Agus, Sam, Aiden, Paul, Alam, John, Algeciras-Schimnich, Alicia, Andrieu, Sandrine, Baruch, Amos, Bateman, Randall, Batrla, Richard, Baudler, Monika, Bell, Joanne, Bittner, Tobias, Bozeat, Sasha, Braunstein, Joel, Brooks, Dawn, Brooks, Tricia, Bullain, Szofia, Burmeister, Jan, Carrillo, Maria, Cho, Min, Collins, Emily, Cook, Gavin, Dague, Chris, De Santi, Susan, Doody, Rachelle, Dunn, Billy, Egan, Michael, Eriksson, Sven, Esquivel, Rianne, Fagan, Tom, Ferrell, Phyllis, Fillit, Howard, Gallagher, Michela, Grönblad, Anna-Kaija, Hains, Avis, Hampel, Harald, Hansson, Oskar, Hefting, Nanco, Hendrix, Suzanne, Ho, Carole, Hu, Helen, Jones, Daryl, Kinney, Gene, Kinnon, Paul, Kurzman, Ricky, Lannfelt, Lars, Lawson, John, LeBastard, Nathalie, Legrand, Valérie, Lewandowski, Nicole, Lim, Carine, Masterman, Donna, Masters, Colin, Lu, Ming, Mintun, Mark, Molinuevo, José Luis, Monteiro, Cecilia, Navia, Bradford, Odergren, Tomas, Osswald, Gunilla, Penny, Lewis, Pontecorvo, Michael, Porsteinsson, Anton, Rabe, Christine, Raman, Rema, Respondek, Gesine, Reyderman, Larisa, Rogers, Sharon, Rosenberg, Paul, Rosenzweig-Lipson, Sharon, Roskey, Mark, Carrie, Rubel, Saad, Ziad, Salloway, Stephen, Schindler, Rachel, Selkoe, Dennis, Shulman, Melanie, Sims, John, Sink, Kaycee, Sipe, Lisa, Skovronsky, Daniel, Somers, Elizabeth, Streffer, Johannes, Such, Pedro, Suhy, Joyce, Toloue, Masoud, Touchon, Jacques, Vandijck, Manu, Weiner, Michael, White, Anne, Wilson, David, Zago, Wagner, and Zhou, Jin

Published
2024
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5. Can We Use Blood Biomarkers as Entry Criteria and for Monitoring Drug Treatment Effects in Clinical Trials? A Report from the EU/US CTAD Task Force

Author

Angioni, D., Hansson, O., Bateman, R. J., Rabe, C., Toloue, M., Braunstein, J. B., Agus, S., Sims, J. R., Bittner, T., Carrillo, M. C., Fillit, H., Masters, C. L., Salloway, S., Aisen, P., Weiner, M., Vellas, B., Gauthier, S., Abushakra, Susan, Afshar, Mohammad, Alam, John, Algeciras-Schimnich, Alicia, Andrieu, Sandrine, Ballard, Clive, Baruch, Amos, Batrla, Richard, Baudler, Monika, Bell, Joanne, Bozeat, Sasha, Brooks, Dawn, Brooks, Tricia, Bullain, Szofia, Burmeister, Jan, Cho, Min, Collins, Emily, Cook, Gavin, Cummings, Jeffrey, Dague, Chris, De Santi, Susan, Doody, Rachelle, Dunn, Billy, Egan, Michael, Eriksson, Sven, Esquivel, Rianne, Fagan, Tom, Ferrell, Phyllis, Gallagher, Michela, Grönblad, Anna-Kaija, Hains, Avis, Hampel, Harald, Hefting, Nanco, Hendrix, Suzanne, Ho, Carole, Hu, Helen, Ismail, Zahinoor, Jones, Daryl, Kinney, Gene, Kinnon, Paul, Kurzman, Ricky, Lannfelt, Lars, Lawson, John, LeBastard, Nathalie, Legrand, Valérie, Lewandowski, Nicole, Lim, Carine, Lyketsos, Costantine, Masterman, Donna, Lu, Ming, Mintun, Mark, Molinuevo, José Luis, Monteiro, Cecilia, Navia, Bradford, Odergren, Tomas, Osswald, Gunilla, Penny, Lewis, Pontecorvo, Michael, Porsteinsson, Anton, Raman, Rema, Respondek, Gesine, Reyderman, Larisa, Rogers, Sharon, Rosenberg, Paul, Rosenzweig-Lipson, Sharon, Roskey, Mark, Carrie, Rubel, Saad, Ziad, Schindler, Rachel, Selkoe, Dennis, Shulman, Melanie, Sink, Kaycee, Sipe, Lisa, Skovronsky, Daniel, Somers, Elizabeth, Soto, Maria, Streffer, Johannes, Such, Pedro, Suhy, Joyce, Touchon, Jacques, Vandijck, Manu, White, Anne, Wilson, David, Zago, Wagner, and Zhou, Jin

Published
2023
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7. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew J., Nho, Kwangsik, Risacher, Shannon L., Kastenmüller, Gabi, Arnold, Matthias, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John C., Perrin, Richard J., Shaw, Leslie M., Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Sloan, Brittany, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C., Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I., Nir, Talia M., Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, Crawford, Karen, Yushkevich, Paul A., Das, Sandhitsu, Koeppe, Robert A., Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Franklin, Erin, Bernhardt, Haley, Taylor-Reinwald, Lisa, Korecka, Magdalena, Figurski, Michal, Neu, Scott, Apostolova, Liana G., Shen, Li, Foroud, Tatiana M., Nudelman, Kelly, Faber, Kelley, Wilmes, Kristi, Thal, Leon, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thomas, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Sheikh, Mohammed O., Singleton-Garvin, Jamika, Petrella, JeffreyR., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Raslau, Flavius D., Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H.S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van, Christopher H., Mecca, Adam P., Good, Susan P., MacAvoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunis, Susan, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris (Chinthaka), Robin Hsiung, Ging-Yuek, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M.-Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, MCCann, Kelly, Poe, Jessica, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristus, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Maillard, Pauline, Olichney, John, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T.-Y., Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., BolesPonto, Laura L., Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charles, Munic, Donna, O'Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Petersen, Ron, Neylan, Thomas, Grafman, Jordan, Danowski, Sarah, Nguyen-Barrera, Catherine, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Senjem, Matt, Foster, Norm, Kim, Sungeun, Sood, Ajay, Blanchard, Kimberly S., Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T., Petrella, Jeffrey R., Goldstein, Bonnie, Martin, Kimberly S., Reist, Christopher, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Rosen, Howard, Marshall, Gad, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Mackin, Scott, Jimenez-Maggiora, Gustavo, Drake, Erin, Donohue, Mike, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Faber, Kelley M., Nudelman, Kelly N., Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Meikle, Peter J., and Giles, Corey

Published
2023
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9. Measuring clinically relevant change in apathy symptoms in ADMET and ADMET 2.

Author

Tumati, Shankar, Herrmann, Nathan, Perin, Jaime, Rosenberg, Paul B., Lerner, Alan J., Mintzer, Jacobo, Padala, Prasad R., Brawman-Mintzer, Olga, van Dyck, Christopher H., Porsteinsson, Anton P., Craft, Suzanne, Levey, Allan, Shade, David, and Lanctôt, Krista L.

Abstract

Objectives: Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales. Design: Retrospective anchor- and distribution-based analyses of change in apathy symptom scores. Setting: Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively. Participants: Two hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer's disease. Measurements: The Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory – Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics. Results: Among the MCID was a decrease of four points (95% CI: −4.0 to −4.8) on the NPI-A, 0.56 points (95% CI: −0.47 to −0.65) on the DAIR, and three points on the AES-I (95% CI: −0.9 to −5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID. Conclusions: MCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Identify a shared neural circuit linking multiple neuropsychiatric symptoms with Alzheimer’s pathology

Author

Wang, Xixi, Ren, Ping, Mapstone, Mark, Conwell, Yeates, Porsteinsson, Anton P, Foxe, John J, Raizada, Rajeev DS, Lin, Feng, and and the Alzheimer’s Disease Neuroimaging Initiative

Subjects
Biological Psychology, Psychology, Brain Disorders, Mental Health, Aging, Neurodegenerative, Basic Behavioral and Social Science, Dementia, Acquired Cognitive Impairment, Behavioral and Social Science, Neurosciences, Clinical Research, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Brain, Brain Mapping, Cognitive Dysfunction, Female, Humans, Magnetic Resonance Imaging, Male, Mental Disorders, Multivariate Analysis, Neural Pathways, Peptide Fragments, Rest, tau Proteins, Alzheimer's disease, Functional magnetic resonance imaging, Mild cognitive impairment, Multivariate pattern analysis, Neuropsychiatric symptoms, and the Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology, Biomedical and clinical sciences, Health sciences
Abstract

Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD)-associated neurodegeneration. However, NPS lack a consistent relationship with AD pathology. It is unknown whether any common neural circuits can link these clinically disparate while mechanistically similar features with AD pathology. Here, we explored the neural circuits of NPS in AD-associated neurodegeneration using multivariate pattern analysis (MVPA) of resting-state functional MRI data. Data from 98 subjects (70 amnestic mild cognitive impairment and 28 AD subjects) were obtained. The top 10 regions differentiating symptom presence across NPS were identified, which were mostly the fronto-limbic regions (medial prefrontal cortex, caudate, etc.). These 10 regions' functional connectivity classified symptomatic subjects across individual NPS at 69.46-81.27%, and predicted multiple NPS (indexed by Neuropsychiatric Symptom Questionnaire-Inventory) and AD pathology (indexed by baseline and change of beta-amyloid/pTau ratio) all above 70%. Our findings suggest a fronto-limbic dominated neural circuit that links multiple NPS and AD pathology. With further examination of the structural and pathological changes within the circuit, the circuit may shed light on linking behavioral disturbances with AD-associated neurodegeneration.

Published
2019

11. Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial)

Author

Zeng, Lijuan, primary, Perin, Jamie, additional, Gross, Alden L., additional, Shade, David, additional, Lanctôt, Krista L., additional, Lerner, Alan J., additional, Mintzer, Jacobo E., additional, Brawman‐Mintzer, Olga, additional, Padala, Prasad R., additional, van Dyck, Christopher H., additional, Porsteinsson, Anton P., additional, Craft, Suzanne, additional, Levey, Allan, additional, Herrmann, Nathan, additional, and Rosenberg, Paul B., additional

Published
2024
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13. Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis

Author

Zhou, Xiaopu, Chen, Yu, Mok, Kin Y, Zhao, Qianhua, Chen, Keliang, Chen, Yuewen, Hardy, John, Li, Yun, Fu, Amy KY, Guo, Qihao, Ip, Nancy Y, Saykin, Andrew J, Toga, Arthur W, Borowski, Bret, Ward, Chad, DeCarli, Charles, Mathis, Chet, Jack, Clifford R, Harvey, Danielle, Holtzman, David, Jones, David, Gessert, Devon, Lilly, Eli, Reiman, Eric M, Franklin, Erin, Hefti, Franz, Sorensen, Greg, Jimenez, Gustavo, Fillit, Howard, Gunter, Jeff, Salazar, Jennifer, Hsiao, John, Morris, John, Trojanowki, John Q, Neu, Karen Crawford Scott, Kantarci, Kejal, Faber, Kelley, Harless, Kelly, Chen, Kewei, Nho, Kwangsik, Beckett, Laurel, Thal, Lean, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Shen, Li, Hergesheimer, Lindsey, Taylor-Reinwald, Lisa, Mesulam, M Marcel, Korecka, Magdalena, Raichle, Marc, Carrillo, Maria, Albert, Marilyn, Senjem, Matt, Bernstein, Matthew, Donohue, Michael, Weiner, Michael, Figurski, Michal, Buckholtz, Neil, Fox, Nick, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Aisen, Paul, Thompson, Paul, Davies, Peter, Snyder, Peter J, Snyder, Peter, Vemuri, Prashanthi, Frank, Richard, Koeppe, Robert A, Green, Robert C, Petersen, Ronald, Walter, Sarah, Paul, Steven, Potkin, Steven, Kim, Sungeun, Foroud, Tatiana M, Montine, Tom, Lee, Virginia, Jagust, William, Potter, William, Cabrera, Yuliana, Khachaturian, Zaven, Fleisher, Adam, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Norbash, Alexander, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Ulysse, Anaztasia, Budson, Andrew E, Kertesz, Andrew, Oliver, Angela, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, and Porsteinsson, Anton P

Subjects
Biological Sciences, Genetics, Alzheimer's Disease, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Neurosciences, Dementia, Acquired Cognitive Impairment, Brain Disorders, Prevention, Neurodegenerative, Aging, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Good Health and Well Being, Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Asian People, China, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Immune System, Male, Middle Aged, Potassium Channels, Inwardly Rectifying, Risk Factors, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, GWAS, immune, risk variant, whole-genome sequencing
Abstract

Alzheimer's disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10-14), two common variants, GCH1 (rs72713460, P = 4.36 × 10-5) and KCNJ15 (rs928771, P = 3.60 × 10-6), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype-phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE, GCH1, and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system.

Published
2018

14. Temporospatial components of brain ERPs as biomarkers for Alzheimer's disease

Author

Chapman, Robert M, Gardner, Margaret N, Klorman, Rafael, Mapstone, Mark, Porsteinsson, Anton P, Antonsdottir, Inga M, and Kamalyan, Lily

Subjects
Biological Psychology, Psychology, Alzheimer's Disease, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Acquired Cognitive Impairment, Neurosciences, Aging, Brain Disorders, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Alzheimer's disease, Brain event-related potentials, Brain spatial information, Diagnosis, Discriminant analysis, Electrophysiology, Posterior probabilities, Principal components analysis, Receiver-operating characteristic, Temporal ERP components, Temporospatial ERPs, Two-step PCA, Genetics, Biological psychology
Abstract

IntroductionDeveloping biomarkers that distinguish individuals with Alzheimer's disease (AD) from those with normal cognition remains a crucial goal for improving the health of older adults. We investigated adding brain spatial information to temporal event-related potentials (ERPs) to increase AD identification accuracy over temporal ERPs alone.MethodsWith two-step principal components analysis, we applied multivariate analyses that incorporated temporal and spatial ERP information from a cognitive task. Discriminant analysis used temporospatial ERP scores to classify participants as belonging to either the AD or healthy control group.ResultsTemporospatial ERPs produced a cross-validated area under the curve of 0.84. Adding spatial information through a formal procedure significantly improves classification accuracy.DiscussionA weighted combination of temporospatial ERP markers performs well in detecting AD. Because ERPs are noninvasive and inexpensive, they may be promising biomarkers for AD that can add functional information to other biomarker systems while providing the individual's probability of correct classification.

Published
2018

15. Temporospatial components of brain ERPs as biomarkers for Alzheimers disease.

Author

Chapman, Robert, Gardner, Margaret, Klorman, Rafael, Porsteinsson, Anton, Antonsdottir, Inga, Kamalyan, Lily, and Mapstone, Mark

Subjects
Aging, Alzheimers disease (AD), Brain event-related potentials (ERP), Brain spatial information, Diagnosis, Discriminant analysis, Electrophysiology, Posterior probabilities, Principal components analysis (PCA), Receiver-operating characteristic (ROC), Temporal ERP components, Temporospatial ERPs, Two-step PCA
Abstract

INTRODUCTION: Developing biomarkers that distinguish individuals with Alzheimers disease (AD) from those with normal cognition remains a crucial goal for improving the health of older adults. We investigated adding brain spatial information to temporal event-related potentials (ERPs) to increase AD identification accuracy over temporal ERPs alone. METHODS: With two-step principal components analysis, we applied multivariate analyses that incorporated temporal and spatial ERP information from a cognitive task. Discriminant analysis used temporospatial ERP scores to classify participants as belonging to either the AD or healthy control group. RESULTS: Temporospatial ERPs produced a cross-validated area under the curve of 0.84. Adding spatial information through a formal procedure significantly improves classification accuracy. DISCUSSION: A weighted combination of temporospatial ERP markers performs well in detecting AD. Because ERPs are noninvasive and inexpensive, they may be promising biomarkers for AD that can add functional information to other biomarker systems while providing the individuals probability of correct classification.

Published
2018

16. A phase 3 trial of IV immunoglobulin for Alzheimer disease

Author

Relkin, Norman R, Thomas, Ronald G, Rissman, Robert A, Brewer, James B, Rafii, Michael S, van Dyck, Christopher H, Jack, Clifford R, Sano, Mary, Knopman, David S, Raman, Rema, Szabo, Paul, Gelmont, David M, Fritsch, Sandor, Aisen, Paul S, Ahern, Geoffrey, Yaari, Roy, Sabbagh, Marwan, Mirza, Nadeem, Bernick, Charles, Bell, Karen, Turner, R Scott, Obisesan, Thomas, Chertkow, Howard, Zabar, Yuval, Knopman, David, Mintzer, Jacobo, Grossman, Hillel, Sadowski, Martin, Wu, Chuang-Kuo, Quinn, Joseph, Borrie, Michael, Petrie, William, Ott, Brian, Keegan, Andrew, Grossberg, George, Bari, Moammed, Cohen, Sharon, Richter, Ralph, Lerner, Alan, Mulnard, Ruth, Potkin, Steven, Rafii, Michael, Brockington, John, Hsiung, Robin, Schultz, Susan, Burns, Jeffrey, Jicha, Gregory, Burke, William, Arnold, Steven, Porsteinsson, Anton, Smith, Amanda, Schneider, Lon, Quiceno, Mary, Zamrini, Edward, Asthana, Sanjay, Burgat, FT, Duara, Ranjan, and van Dyck, Christopher

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Dementia, Clinical Research, Acquired Cognitive Impairment, Clinical Trials and Supportive Activities, Aging, Brain Disorders, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, 6.1 Pharmaceuticals, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Brain, Canada, Cognition, Double-Blind Method, Female, Humans, Immunoglobulins, Intravenous, Male, Middle Aged, Nootropic Agents, Peptide Fragments, Treatment Failure, United States, Alzheimer's Disease Cooperative Study, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia.MethodsIn a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants.ResultsNo beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo.ConclusionsParticipants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo.Clinicaltrialsgov identifierNCT00818662.Classification of evidenceThis study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD.

Published
2017

19. The cingulate cortex of older adults with excellent memory capacity

Author

Lin, Feng, Ren, Ping, Mapstone, Mark, Meyers, Steven P, Porsteinsson, Anton, Baran, Timothy M, and Initiative, for the Alzheimer's Disease Neuroimaging

Subjects
Biological Psychology, Psychology, Aging, Mental Health, Alzheimer's Disease, Acquired Cognitive Impairment, Brain Disorders, Clinical Research, Dementia, Behavioral and Social Science, Neurodegenerative, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Aged, Aged, 80 and over, Amnesia, Cognition, Cognitive Dysfunction, Female, Gyrus Cinguli, Humans, Male, Memory, Nerve Net, Neuropsychological Tests, Supernormal, Cingulate cortex, Cerebral amyloid deposition, Functional connectivity, Alzheimer's Disease Neuroimaging Initiative, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Memory deterioration is the earliest and most devastating cognitive deficit in normal aging and Alzheimer's disease (AD). Some older adults, known as "Supernormals", maintain excellent memory. This study examined relationships between cerebral amyloid deposition and functional connectivity (FC) within the cingulate cortex (CC) and between CC and other regions involved in memory maintenance between Supernormals, healthy controls (HC), and those at risk for AD (amnestic mild cognitive impairment [MCI]). Supernormals had significantly stronger FC between anterior CC and R-hippocampus, middle CC (MCC) and L-superior temporal gyrus, and posterior CC (PCC) and R-precuneus, while weaker FC between MCC and R-middle frontal gyrus and MCC and R-thalamus than other groups. All of these FC were significantly related to memory and global cognition in all participants. Supernormals had less amyloid deposition than other groups. Relationships between global cognition and FC were stronger among amyloid positive participants. Relationships between memory and FC remained regardless of amyloid level. This revealed how CC-related neural function participates in cognitive maintenance in the presence of amyloid deposition, potentially explaining excellent cognitive function among Supernormals.

Published
2017

20. Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment

Author

Ren, Ping, Lo, Raymond Y, Chapman, Benjamin P, Mapstone, Mark, Porsteinsson, Anton, Lin, Feng, and Initiative, the Alzheimer’s Disease Neuroimaging

Subjects
Biological Psychology, Psychology, Clinical Research, Dementia, Aging, Brain Disorders, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, Acquired Cognitive Impairment, Neurological, Aged, Aged, 80 and over, Amyloid beta-Peptides, Brain Mapping, Cognitive Dysfunction, Corpus Striatum, Disease Progression, Female, Follow-Up Studies, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory, Peptide Fragments, Rest, tau Proteins, Amyloid-beta, low-frequency fluctuation, mild cognitive impairment, pTau, resting state fMRI, striatum, Alzheimer’s Disease Neuroimaging Initiative, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

The striatum is a critical functional hub in understanding neurological disorders. However, the Alzheimer's disease (AD)-associated striatal change is unclear, as is the relationship between striatal change and AD pathology. Three-year resting-state fMRI data from 15 healthy control (HC) and 20 mild cognitive impairment (MCI) participants were obtained. We analyzed the amplitude of low-frequency fluctuations (ALFF) (0.01-0.08 Hz) and two subdivided bands (slow-4:0.027-0.073 Hz; slow-5:0.01-0.027 Hz). We calculated Aβ/pTau ratio using baseline cerebrospinal fluid pTau and Aβ1-42 to represent AD pathology. Compared to HC, MCI participants showed greater decline in right putaminal ALFF, including the slow-4 band. Greater decline of ALFF in the right putamen was significantly related to the memory decline over time and lower baseline Aβ/pTau ratio regardless of age or group. The slow-4 band, relative to slow-5 band, showed a stronger correlation between Aβ/pTau ratio and decline of ALFF in the right putamen. The results suggest that the putaminal function declines early in the AD-associated neurodegeneration. The continuous decline in putaminal ALFF, especially slow-4 band, may be a sensitive marker of AD pathology such as Aβ/pTau ratio regardless of clinical diagnosis.

Published
2016

21. Cognitive and Neural Effects of Vision‐Based Speed‐of‐Processing Training in Older Adults with Amnestic Mild Cognitive Impairment: A Pilot Study

Author

Lin, Feng, Heffner, Kathi L, Ren, Ping, Tivarus, Madalina E, Brasch, Judith, Chen, Ding-Geng, Mapstone, Mark, Porsteinsson, Anton P, and Tadin, Duje

Subjects
Brain Disorders, Behavioral and Social Science, Neurosciences, Mental Health, Clinical Research, Rehabilitation, Aging, Mental health, Activities of Daily Living, Aged, Amnesia, Attention, Cognitive Dysfunction, Comprehension, Computer-Assisted Instruction, Female, Geriatric Assessment, Humans, Male, Neuropsychological Tests, Photic Stimulation, Pilot Projects, Single-Blind Method, Treatment Outcome, speed of processing, mild cognitive impairment, central executive network, default mode network, Medical and Health Sciences, Geriatrics
Abstract

ObjectivesTo examine the cognitive and neural effects of vision-based speed-of-processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects with an active control (mental leisure activities (MLA)).DesignRandomized single-blind controlled pilot trial.SettingAcademic medical center.ParticipantsIndividuals with aMCI (N = 21).InterventionSix-week computerized VSOP training.MeasurementsMultiple cognitive processing measures, instrumental activities of daily living (IADLs), and two resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN).ResultsVSOP training led to significantly greater improvements in trained (processing speed and attention: F1,19  = 6.61, partial η(2)  = 0.26, P = .02) and untrained (working memory: F1,19  = 7.33, partial η(2)  = 0.28, P = .01; IADLs: F1,19  = 5.16, partial η(2)  = 0.21, P = .03) cognitive domains than MLA and protective maintenance in DMN (F1, 9  = 14.63, partial η(2)  = 0.62, P = .004). VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z = -2.37, P = .02).ConclusionTarget and transfer effects of VSOP training were identified, and links between VSOP training and two neural networks associated with aMCI were found. These findings highlight the potential of VSOP training to slow cognitive decline in individuals with aMCI. Further delineation of mechanisms underlying VSOP-induced plasticity is necessary to understand in which populations and under what conditions such training may be most effective.

Published
2016

22. ERP C250 shows the elderly (cognitively normal, Alzheimer’s disease) store more stimuli in short-term memory than Young Adults do

Author

Chapman, Robert M, Gardner, Margaret N, Mapstone, Mark, Klorman, Rafael, Porsteinsson, Anton P, Dupree, Haley M, Antonsdottir, Inga M, and Kamalyan, Lily

Subjects
Biomedical and Clinical Sciences, Neurosciences, Brain Disorders, Clinical Research, Aging, Acquired Cognitive Impairment, Alzheimer's Disease, Dementia, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Aged, Alzheimer Disease, Evoked Potentials, Female, Humans, Male, Memory, Short-Term, Event-Related Potentials, Electrophysiology, Alzheimer's disease, Short-term memory, Principal Components Analysis, Short-latency ERP component C250, Alzheimer’s disease, Engineering, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory.MethodsWe used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus.ResultsIn Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1.ConclusionsBoth normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained.SignificanceC250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia.

Published
2016

23. Mental Fatigability and Heart Rate Variability in Mild Cognitive Impairment

Author

Lin, Feng, Ren, Ping, Cotton, Kelly, Porsteinsson, Anton, Mapstone, Mark, and Heffner, Kathi L

Subjects
Allied Health and Rehabilitation Science, Biomedical and Clinical Sciences, Health Sciences, Neurosciences, Aging, Brain Disorders, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Cardiovascular, Dementia, Clinical Research, Basic Behavioral and Social Science, Behavioral and Social Science, Mental Health, Alzheimer's Disease, Mental health, Good Health and Well Being, Aged, Cognitive Dysfunction, Female, Heart Rate, Humans, Magnetic Resonance Imaging, Male, Mental Fatigue, Neural Pathways, Neuroimaging, Prefrontal Cortex, Putamen, Stress, Psychological, mild cognitive impairment, mental fatigability, cardiovascular reactivity, frontobasal ganglia circuitry, physiological stress regulation, Clinical Sciences, Public Health and Health Services, Cognitive Sciences, Geriatrics, Clinical sciences, Health services and systems, Clinical and health psychology
Abstract

ObjectivesAdaptive physiological stress regulation is rarely studied in mild cognitive impairment (MCI). Here we targeted mental fatigability (MF) as a determinant of altered high frequency heart rate variability (HF-HRV) reactivity in individuals with MCI, and examined frontobasal ganglia circuitry as a neural basis supporting the link between MF and HF-HRV reactivity.MethodsWe measured mental fatigability and HF-HRV during a 60-minute cognitive stress protocol in 19 individuals with MCI. HF-HRV responses were modeled using a quadratic equation. Resting state functional connectivity of intra- and inter-network frontobasal ganglia circuitry was assessed using blood-oxygen-level-dependent magnetic resonance imaging among seven of the participants.ResultsLower MF was associated with faster and greater rebound in U-shape HF-HRV reactivity, which linked to a stronger connectivity between right middle frontal gyrus and left putamen.ConclusionsResults suggest that MF may contribute to abnormal physiological stress regulation in MCI, and fronto basal ganglia circuitry may support the link.

Published
2016

24. Trajectories of Neuropsychiatric Symptoms and Cognitive Decline in Mild Cognitive Impairment

Author

David, Nicholas D, Lin, Feng, Porsteinsson, Anton P, and Initiative, Alzheimer's Disease Neuroimaging

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Dementia, Neurodegenerative, Clinical Research, Acquired Cognitive Impairment, Rehabilitation, Alzheimer's Disease, Behavioral and Social Science, Neurosciences, Mental Health, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Aging, 2.1 Biological and endogenous factors, Neurological, Mental health, Aged, Aged, 80 and over, Atrophy, Brain, Cognition, Cognitive Dysfunction, Databases, Factual, Disease Progression, Female, Humans, Male, Neuropsychological Tests, Proportional Hazards Models, Prospective Studies, Psychiatric Status Rating Scales, Risk Factors, Neuropsychiatric symptoms, mild cognitive impairment, latent class analysis, Alzheimer's Disease Neuroimaging Initiative, Clinical Sciences, Public Health and Health Services, Cognitive Sciences, Geriatrics, Clinical sciences, Health services and systems, Clinical and health psychology
Abstract

ObjectiveTo characterize the course of neuropsychiatric symptoms (NPS) in adults with mild cognitive impairment (MCI), and to examine baseline individual-level predictors and associated cognitive and functional outcomes.DesignA 2-year prospective cohort study.SettingMulticenter clinical settings.ParticipantsFive hundred sixty individuals with MCI at baseline.MeasurementsNPS severity (measured using Neuropsychiatric Inventory Questionnaire) and cognitive and functional outcomes were assessed at baseline and every 6 months thereafter. Potential individual-level predictors were collected at baseline.ResultsThree latent classes of NPS courses were identified using growth mixture modeling: a stable class in which a low NPS burden remained relatively unchanged over time (N = 503, 89.8%); a worsened class in which an initially moderate NPS burden increased (N = 39, 7.0%); and an improved class in which an initially high NPS burden decreased (N = 18, 3.2%). There were no associations between class membership and baseline individual characteristics. Members of the worsened class were 1.74 times more likely to be diagnosed with incident Alzheimer disease (AD) than members of the stable class (95% confidence interval: 1.07-2.84). The worsened class also showed significantly more rapid declines in cognitive and functional outcomes than the stable class. Class membership did not predict rate of brain atrophy.ConclusionsPatients with MCI may experience different trajectories of NPS over time. Patients with worsening NPS may be at greater risk of developing AD and severe cognitive and functional impairment.

Published
2016

26. Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial

Author

Lyketsos, Constantine G., Porsteinsson, Anton P., Avramopoulos, Dimitri, Munro, Cynthia, Lee, Hochang, Bienko, Nicholas, Shade, Dave, Ehrhardt, Stephan, Jones, Jennifer, Casper, Anne Shanklin, Frangakis, Constantine, Lears, Andy, Baksh, Sheriza, Perin, Jamie, Ryan, Laurie, McKelvy, Alvin D., Rosenberg, Paul, Nowrangi, Milap, Lawrence, Sarah, Schultz, Meghan, Jamil, Nimra, Devanand, D.P., Simon-Pearson, Laura, Pelton Jacobo Mintzer, Gregory, Brawman-Mintzer, Olga, Williams, Arthur, Awkar, Anthony, Keltz, Melanie, Kowalski, Nancy, Lane, Kaitlyn, Martin, Kim, Salem-Spencer, Susan, Widman, Asa, Pollock, Bruce G., Kumar, Sanjeev, Lourenco, Lillian, Mulsant, Benoit H., Lago, Kyle, Rajji, Tarek K., Schneider, Lon S., Becerra, Maurcio, Dagerman, Karen, Pawluczyk, Sonia, Teodoro, Liberty, Munro, Cynthia A., Rosenberg, Paul B., Devanand, Davangere P., Mintzer, Jacobo, Ismail, Zahinoor, Baksh, Sheriza N., Drye, Lea T., and Shade, David M.

Published
2019
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27. Longitudinal Effects of Metabolic Syndrome on Alzheimer and Vascular Related Brain Pathology

Author

Lin, Feng, Lo, Raymond Y, Cole, Daniel, Ducharme, Simon, Chen, Ding-Geng, Mapstone, Mark, and Porsteinsson, Anton

Subjects
Biological Psychology, Health Sciences, Psychology, Clinical Research, Nutrition, Dementia, Alzheimer's Disease, Brain Disorders, Cerebrovascular, Aging, Acquired Cognitive Impairment, Biomedical Imaging, Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Vascular Cognitive Impairment/Dementia, Alzheimer's Disease Related Dementias (ADRD), Neurosciences, Neurodegenerative, 2.1 Biological and endogenous factors, Neurological, Mental health, Metabolic syndrome, Alzheimer pathology, Mild cognitive impairment, Vascular pathology, Alzheimer's Disease Neuroimaging Initiative
Abstract

Background/aimsThis study examines the longitudinal effect of metabolic syndrome (MetS) on brain-aging indices among cognitively normal (CN) and amnestic mild cognitive impairment (aMCI) groups [single-domain aMCI (saMCI) and multiple-domain aMCI (maMCI)].MethodsThe study population included 739 participants (CN = 226, saMCI = 275, and maMCI = 238) from the Alzheimer's Disease Neuroimaging Initiative, a clinic-based, multi-center prospective cohort. Confirmatory factor analysis was employed to determine a MetS latent composite score using baseline data of vascular risk factors. We examined the changes of two Alzheimer's disease (AD) biomarkers, namely [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) regions of interest and medial temporal lobe volume over 5 years. A cerebrovascular aging index, cerebral white matter (cWM) volume, was examined as a comparison.ResultsThe vascular risk was similar in all groups. Applying generalized estimating equation modeling, all brain-aging indices declined significantly over time. Higher MetS scores were associated with a faster decline of cWM in the CN and maMCI groups but with a slower decrement of regional glucose metabolism in FDG-PET in the saMCI and maMCI groups.ConclusionAt the very early stage of cognitive decline, the vascular burden such as MetS may be in parallel with or independent of AD pathology in contributing to cognitive impairment in terms of accelerating the disclosure of AD pathology.

Published
2014

28. APOLLOE4 Phase 3 study of oral ALZ‐801/valiltramiprosate in APOE ε4/ε4 homozygotes with early Alzheimer's disease: Trial design and baseline characteristics.

Author

Abushakra, Susan, Porsteinsson, Anton P., Sabbagh, Marwan, Watson, David, Power, Aidan, Liang, Earvin, MacSweeney, Emer, Boada, Merce, Flint, Susan, McLaine, Rosalind, Kesslak, J. Patrick, Hey, John A., and Tolar, Martin

Subjects
ALZHEIMER'S disease, APOLIPOPROTEIN E, CLINICAL trials, MILD cognitive impairment, MAGNETIC resonance imaging
Abstract

INTRODUCTION: The approved amyloid antibodies for early Alzheimer's disease (AD) carry a boxed warning about the risk of amyloid‐related imaging abnormalities (ARIAs) that are highest in apolipoprotein E (APOE) ε4/ε4 homozygotes. ALZ‐801/valiltramiprosate, an oral brain‐penetrant amyloid beta oligomer inhibitor is being evaluated in APOE ε4/ε4 homozygotes with early AD. METHODS: This Phase 3 randomized, double‐blind, placebo‐controlled, 78‐week study of ALZ‐801 administered as 265 mg twice per day tablets, enrolled 50‐ to 80‐year‐old homozygotes with Mini‐Mental State Examination (MMSE) ≥ 22 and Clinical Dementia Rating–Global Score 0.5 or 1.0. The study is powered to detect a 2.0 to 2.5 drug–placebo difference on the Alzheimer's Disease Assessment Scale 13‐item Cognitive subscale primary outcome with 150 subjects/arm. The key secondary outcomes are Clinical Dementia Rating–Sum of Boxes and Instrumental Activities of Daily Living; volumetric magnetic resonance imaging and fluid biomarkers are additional outcomes. RESULTS: The APOLLOE4 Phase 3 trial enrolled 325 subjects with a mean age of 69 years, 51% female, MMSE 25.6, and 65% mild cognitive impairment. Topline results are expected in 2024. DISCUSSION: APOLLOE4 is the first disease‐modification AD trial focused on APOE ε4/ε4 homozygotes. Oral ALZ‐801 has the potential to be the first effective and safe anti‐amyloid treatment for the high‐risk APOE ε4/ε4 population. Highlights: The APOLLOE4 Phase 3, placebo‐controlled, 78‐week study is designed to evaluate the efficacy and safety of ALZ‐801 265 mg twice per day in early Alzheimer's disease (AD) subjects with the apolipoprotein E (APOE) ε4/ε4 genotype.The enrolled early AD population (N = 325) has 51% females, a mean age = 69 years, and a mean Mini‐Mental State Examination = 25.6, with the majority being mild cognitive impairment subjects, a similar disease stage to the lecanemab Phase 3 AD trial (Clarity AD).The primary outcome is the cognitive Alzheimer's Disease Assessment Scale 13‐item Cognitive subscale, with two functional measures as key secondary outcomes (Clinical Dementia Rating–Sum of Boxes, Amsterdam‐Instrumental Activities of Daily Living), and with hippocampal volume and fluid biomarkers as additional outcomes.The study is unique in allowing a large number of microhemorrhages or siderosis at baseline magnetic resonance imaging, lesions that indicate concomitant cerebral amyloid angiopathy (CAA).At baseline, 32% of the enrolled population had at least 1 microhemorrhage, 24% had 1 to 4, and 8% had > 4 microhemorrhages; 10% had at least 1 siderosis lesion; with more males than females having microhemorrhages (63% vs. 37%) and siderosis (68% vs. 32%).Study results will become available in the second half of 2024 and, if positive, ALZ‐801 may become the first oral drug to demonstrate a favorable benefit/risk profile in APOE ε4/ε4 AD subjects. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Mapping of validated apathy scales onto the apathy diagnostic criteria for neurocognitive disorders

Author

Bawa, Kritleen Kaur, primary, Sankhe, Krushnaa, additional, Md, Daniel Bateman, additional, Cummings, Jeffrey L., additional, Ereshefsky, Larry, additional, Husain, Masud, additional, Ismail, Zahinoor, additional, Manera, Valeria, additional, Mintzer, Jacobo, additional, Moebius, Hans J., additional, Mortby, Moyra E, additional, Porsteinsson, Anton P., additional, Robert, Philippe, additional, Miller, David S., additional, and Lanctôt, Krista L., additional

Published
2023
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30. Blood‐based biomarkers for predicting treatment response in the Apathy in Dementia Methylphenidate Trial 2 randomized clinical trial

Author

Tumati, Shankar, primary, Vieira, Danielle, additional, Bawa, Kritleen Kaur, additional, Andreazza, Ana C., additional, Mintzer, Jacobo, additional, Scherer, Roberta, additional, Rosenberg, Paul B., additional, van Dyck, Christopher H, additional, Padala, Prasad R, additional, Brawman‐Mintzer, Olga, additional, Porsteinsson, Anton P., additional, Lerner, Alan J., additional, Craft, Suzanne, additional, Levey, Allan I., additional, Burke, William J, additional, Perin, Jamie, additional, Shade, David, additional, Herrmann, Nathan, additional, and Lanctôt, Krista L., additional

Published
2023
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31. Prevalence of Cerebral Microhemorrhages and Cortical Superficial Siderosis in APOE4/4 Homozygotes with Early Alzheimer’s disease: Baseline Findings from Phase 3 Trial of Oral ALZ‐801 in APOE4/4 Homozygotes (APOLLOE4)

Author

Abushakra, Susan, primary, McLaine, Rosalind, additional, Barakos, Jerome, additional, Porsteinsson, Anton P., additional, Watson, David, additional, MacSweeney, Emer, additional, Liang, Earvin, additional, Kesslak, Patrick, additional, Suhy, Joyce, additional, Power, Aidan, additional, Hey, John A., additional, and Tolar, Martin, additional

Published
2023
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33. Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease

Author

Salloway, Stephen, Sperling, Reisa, Fox, Nick C, Blennow, Kaj, Klunk, William, Raskind, Murray, Sabbagh, Marwan, Honig, Lawrence S, Porsteinsson, Anton P, Ferris, Steven, Reichert, Marcel, Ketter, Nzeera, Nejadnik, Bijan, Guenzler, Volkmar, Miloslavsky, Maja, Wang, Daniel, Lu, Yuan, Lull, Julia, Tudor, Iulia Cristina, Liu, Enchi, Grundman, Michael, Yuen, Eric, Black, Ronald, and Brashear, H Robert

Subjects
Acquired Cognitive Impairment, Neurosciences, Clinical Research, Aging, Alzheimer's Disease, Dementia, Neurodegenerative, Biomedical Imaging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Antibodies, Monoclonal, Humanized, Apolipoproteins E, Biomarkers, Brain, Cognition, Double-Blind Method, Edema, Female, Humans, Intention to Treat Analysis, Male, Middle Aged, Neuropsychological Tests, Phosphorylation, Positron-Emission Tomography, Severity of Illness Index, Treatment Failure, tau Proteins, Bapineuzumab 301 and 302 Clinical Trial Investigators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundBapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease.MethodsWe conducted two double-blind, randomized, placebo-controlled, phase 3 trials involving patients with mild-to-moderate Alzheimer's disease--one involving 1121 carriers of the apolipoprotein E (APOE) ε4 allele and the other involving 1331 noncarriers. Bapineuzumab or placebo, with doses varying by study, was administered by intravenous infusion every 13 weeks for 78 weeks. The primary outcome measures were scores on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment) and the Disability Assessment for Dementia (DAD, with scores ranging from 0 to 100 and higher scores indicating less impairment). A total of 1090 carriers and 1114 noncarriers were included in the efficacy analysis. Secondary outcome measures included findings on positron-emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB-PET) and cerebrospinal fluid phosphorylated tau (phospho-tau) concentrations.ResultsThere were no significant between-group differences in the primary outcomes. At week 78, the between-group differences in the change from baseline in the ADAS-cog11 and DAD scores (bapineuzumab group minus placebo group) were -0.2 (P=0.80) and -1.2 (P=0.34), respectively, in the carrier study; the corresponding differences in the noncarrier study were -0.3 (P=0.64) and 2.8 (P=0.07) with the 0.5-mg-per-kilogram dose of bapineuzumab and 0.4 (P=0.62) and 0.9 (P=0.55) with the 1.0-mg-per-kilogram dose. The major safety finding was amyloid-related imaging abnormalities with edema among patients receiving bapineuzumab, which increased with bapineuzumab dose and APOE ε4 allele number and which led to discontinuation of the 2.0-mg-per-kilogram dose. Between-group differences were observed with respect to PIB-PET and cerebrospinal fluid phospho-tau concentrations in APOE ε4 allele carriers but not in noncarriers.ConclusionsBapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE ε4 carriers. (Funded by Janssen Alzheimer Immunotherapy and Pfizer; Bapineuzumab 301 and 302 ClinicalTrials.gov numbers, NCT00575055 and NCT00574132, and EudraCT number, 2009-012748-17.).

Published
2014

34. The impact of AD drug treatments on event-related potentials as markers of disease conversion.

Author

Chapman, Robert M, Porsteinsson, Anton P, Gardner, Margaret N, Mapstone, Mark, McCrary, John W, Sandoval, Tiffany C, Guillily, Maria D, Reilly, Lindsey A, and DeGrush, Elizabeth

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Alzheimer's Disease, Neurodegenerative, Acquired Cognitive Impairment, Clinical Research, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Brain Disorders, 2.1 Biological and endogenous factors, Detection, screening and diagnosis, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Cholinesterase Inhibitors, Cognitive Dysfunction, Disease Progression, Electroencephalography, Evoked Potentials, Female, Follow-Up Studies, Humans, Male, Nootropic Agents, Treatment Outcome, Alzheimer's disease, AD drug treatments, biomarker, discriminant analysis, EEG, event-related potentials, mild cognitive impairment, neurophysiology, prediction, principal components analysis, Neurology & Neurosurgery, Clinical sciences
Abstract

This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer's disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting.

Published
2013

35. Neuropsychiatric symptoms in Alzheimer's disease: past progress and anticipation of the future.

Author

Geda, Yonas E, Schneider, Lon S, Gitlin, Laura N, Miller, David S, Smith, Gwenn S, Bell, Joanne, Evans, Jovier, Lee, Michael, Porsteinsson, Anton, Lanctôt, Krista L, Rosenberg, Paul B, Sultzer, David L, Francis, Paul T, Brodaty, Henry, Padala, Prasad P, Onyike, Chiadikaobi U, Ortiz, Luis Agüera, Ancoli-Israel, Sonia, Bliwise, Donald L, Martin, Jennifer L, Vitiello, Michael V, Yaffe, Kristine, Zee, Phyllis C, Herrmann, Nathan, Sweet, Robert A, Ballard, Clive, Khin, Ni A, Alfaro, Cara, Murray, Patrick S, Schultz, Susan, Lyketsos, Constantine G, and Neuropsychiatric Syndromes Professional Interest Area of ISTAART

Subjects
Neuropsychiatric Syndromes Professional Interest Area of ISTAART, Humans, Alzheimer Disease, Mental Disorders, Agitation/aggression, Alzheimer's disease, Apathy, Behavioral and psychological symptoms of dementia, Delusions, Dementia, Depression, Hallucinations, Mild behavioral impairment, Mild cognitive impairment, Neuropsychiatric symptoms, Psychosis, Sleep disorders, Behavioral and Social Science, Mental Health, Alzheimer's Disease, Acquired Cognitive Impairment, Aging, Neurosciences, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Neurological, Clinical Sciences, Geriatrics
Abstract

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS-PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome-specific synthetic reviews and recommendations prepared by NPS-PIA workgroups on depression, apathy, sleep, agitation, and psychosis.

Published
2013

36. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Jo, Taeho, primary, Kim, Junpyo, additional, Bice, Paula, additional, Huynh, Kevin, additional, Wang, Tingting, additional, Arnold, Matthias, additional, Meikle, Peter J., additional, Giles, Corey, additional, Kaddurah-Daouk, Rima, additional, Saykin, Andrew J., additional, Nho, Kwangsik, additional, Kueider-Paisley, Alexandra, additional, Doraiswamy, P. Murali, additional, Blach, Colette, additional, Moseley, Arthur, additional, Thompson, Will, additional, St John-Williams, Lisa, additional, Mahmoudiandehkhordi, Siamak, additional, Tenenbaum, Jessica, additional, Welsh-Balmer, Kathleen, additional, Plassman, Brenda, additional, Risacher, Shannon L., additional, Kastenmüller, Gabi, additional, Han, Xianlin, additional, Baillie, Rebecca, additional, Knight, Rob, additional, Dorrestein, Pieter, additional, Brewer, James, additional, Mayer, Emeran, additional, Labus, Jennifer, additional, Baldi, Pierre, additional, Gupta, Arpana, additional, Fiehn, Oliver, additional, Barupal, Dinesh, additional, Meikle, Peter, additional, Mazmanian, Sarkis, additional, Rader, Dan, additional, Kling, Mitchel, additional, Shaw, Leslie, additional, Trojanowski, John, additional, van Duijin, Cornelia, additional, Nevado-Holgado, Alejo, additional, Bennett, David, additional, Krishnan, Ranga, additional, Keshavarzian, Ali, additional, Vogt, Robin, additional, Ikram, Arfan, additional, Hankemeier, Thomas, additional, Thiele, Ines, additional, Price, Nathan, additional, Funk, Cory, additional, Baloni, Priyanka, additional, Jia, Wei, additional, Wishart, David, additional, Brinton, Roberta, additional, Chang, Rui, additional, Farrer, Lindsay, additional, Au, Rhoda, additional, Qiu, Wendy, additional, Würtz, Peter, additional, Koal, Therese, additional, Mangravite, Lara, additional, Krumsiek, Jan, additional, Suhre, Karsten, additional, Newman, John, additional, Moreno, Herman, additional, Foroud, Tatania, additional, Sacks, Frank, additional, Jansson, Janet, additional, Weiner, Michael W., additional, Aisen, Paul, additional, Petersen, Ronald, additional, Jack, Clifford R., additional, Jagust, William, additional, Trojanowki, John Q., additional, Toga, Arthur W., additional, Beckett, Laurel, additional, Green, Robert C., additional, Morris, John C., additional, Perrin, Richard J., additional, Shaw, Leslie M., additional, Khachaturian, Zaven, additional, Carrillo, Maria, additional, Potter, William, additional, Barnes, Lisa, additional, Bernard, Marie, additional, Gonzalez, Hector, additional, Ho, Carole, additional, Hsiao, John K., additional, Jackson, Jonathan, additional, Masliah, Eliezer, additional, Masterman, Donna, additional, Okonkwo, Ozioma, additional, Perrin, Richard, additional, Ryan, Laurie, additional, Silverberg, Nina, additional, Fleisher, Adam, additional, Sacrey, Diana Truran, additional, Fockler, Juliet, additional, Conti, Cat, additional, Veitch, Dallas, additional, Neuhaus, John, additional, Jin, Chengshi, additional, Nosheny, Rachel, additional, Ashford, Miriam, additional, Flenniken, Derek, additional, Kormos, Adrienne, additional, Montine, Tom, additional, Rafii, Michael, additional, Raman, Rema, additional, Jimenez, Gustavo, additional, Donohue, Michael, additional, Gessert, Devon, additional, Salazar, Jennifer, additional, Zimmerman, Caileigh, additional, Cabrera, Yuliana, additional, Walter, Sarah, additional, Miller, Garrett, additional, Coker, Godfrey, additional, Clanton, Taylor, additional, Hergesheimer, Lindsey, additional, Smith, Stephanie, additional, Adegoke, Olusegun, additional, Mahboubi, Payam, additional, Moore, Shelley, additional, Pizzola, Jeremy, additional, Shaffer, Elizabeth, additional, Sloan, Brittany, additional, Harvey, Danielle, additional, Forghanian-Arani, Arvin, additional, Borowski, Bret, additional, Ward, Chad, additional, Schwarz, Christopher, additional, Jones, David, additional, Gunter, Jeff, additional, Kantarci, Kejal, additional, Senjem, Matthew, additional, Vemuri, Prashanthi, additional, Reid, Robert, additional, Fox, Nick C., additional, Malone, Ian, additional, Thompson, Paul, additional, Thomopoulos, Sophia I., additional, Nir, Talia M., additional, Jahanshad, Neda, additional, DeCarli, Charles, additional, Knaack, Alexander, additional, Fletcher, Evan, additional, Tosun-Turgut, Duygu, additional, Chen, Stephanie Rossi, additional, Choe, Mark, additional, Crawford, Karen, additional, Yushkevich, Paul A., additional, Das, Sandhitsu, additional, Koeppe, Robert A., additional, Reiman, Eric M., additional, Chen, Kewei, additional, Mathis, Chet, additional, Landau, Susan, additional, Cairns, Nigel J., additional, Householder, Erin, additional, Franklin, Erin, additional, Bernhardt, Haley, additional, Taylor-Reinwald, Lisa, additional, Korecka, Magdalena, additional, Figurski, Michal, additional, Neu, Scott, additional, Apostolova, Liana G., additional, Shen, Li, additional, Foroud, Tatiana M., additional, Nudelman, Kelly, additional, Faber, Kelley, additional, Wilmes, Kristi, additional, Thal, Leon, additional, Silbert, Lisa C., additional, Lind, Betty, additional, Crissey, Rachel, additional, Kaye, Jeffrey A., additional, Carter, Raina, additional, Dolen, Sara, additional, Quinn, Joseph, additional, Schneider, Lon S., additional, Pawluczyk, Sonia, additional, Becerra, Mauricio, additional, Teodoro, Liberty, additional, Dagerman, Karen, additional, Spann, Bryan M., additional, Vanderswag, Helen, additional, Ziolkowski, Jaimie, additional, Heidebrink, Judith L., additional, Zbizek-Nulph, Lisa, additional, Lord, Joanne L., additional, Mason, Sara S., additional, Albers, Colleen S., additional, Knopman, David, additional, Johnson, Kris, additional, Villanueva-Meyer, Javier, additional, Pavlik, Valory, additional, Pacini, Nathaniel, additional, Lamb, Ashley, additional, Kass, Joseph S., additional, Doody, Rachelle S., additional, Shibley, Victoria, additional, Chowdhury, Munir, additional, Rountree, Susan, additional, Dang, Mimi, additional, Stern, Yaakov, additional, Honig, Lawrence S., additional, Mintz, Akiva, additional, Ances, Beau, additional, Winkfield, David, additional, Carroll, Maria, additional, Stobbs-Cucchi, Georgia, additional, Oliver, Angela, additional, Creech, Mary L., additional, Mintun, Mark A., additional, Schneider, Stacy, additional, Geldmacher, David, additional, Love, Marissa Natelson, additional, Griffith, Randall, additional, Clark, David, additional, Brockington, John, additional, Marson, Daniel, additional, Grossman, Hillel, additional, Goldstein, Martin A., additional, Greenberg, Jonathan, additional, Mitsis, Effie, additional, Shah, Raj C., additional, Lamar, Melissa, additional, Samuels, Patricia, additional, Duara, Ranjan, additional, Greig-Custo, Maria T., additional, Rodriguez, Rosemarie, additional, Albert, Marilyn, additional, Onyike, Chiadi, additional, Farrington, Leonie, additional, Rudow, Scott, additional, Brichko, Rottislav, additional, Kielb, Stephanie, additional, Smith, Amanda, additional, Raj, Balebail Ashok, additional, Fargher, Kristin, additional, Sadowski, Martin, additional, Wisniewski, Thomas, additional, Shulman, Melanie, additional, Faustin, Arline, additional, Rao, Julia, additional, Castro, Karen M., additional, Ulysse, Anaztasia, additional, Chen, Shannon, additional, Sheikh, Mohammed O., additional, Singleton-Garvin, Jamika, additional, Petrella, JeffreyR., additional, James, Olga, additional, Wong, Terence Z., additional, Borges-Neto, Salvador, additional, Karlawish, Jason H., additional, Wolk, David A., additional, Vaishnavi, Sanjeev, additional, Clark, Christopher M., additional, Arnold, Steven E., additional, Smith, Charles D., additional, Jicha, Gregory A., additional, Raslau, Flavius D., additional, Lopez, Oscar L., additional, Oakley, MaryAnn, additional, Simpson, Donna M., additional, Porsteinsson, Anton P., additional, Martin, Kim, additional, Kowalski, Nancy, additional, Keltz, Melanie, additional, Goldstein, Bonnie S., additional, Makino, Kelly M., additional, Ismail, M. Saleem, additional, Brand, Connie, additional, Thai, Gaby, additional, Pierce, Aimee, additional, Yanez, Beatriz, additional, Sosa, Elizabeth, additional, Witbracht, Megan, additional, Kelley, Brendan, additional, Nguyen, Trung, additional, Womack, Kyle, additional, Mathews, Dana, additional, Quiceno, Mary, additional, Levey, Allan I., additional, Lah, James J., additional, Hajjar, Ihab, additional, Cellar, Janet S., additional, Burns, Jeffrey M., additional, Swerdlow, Russell H., additional, Brooks, William M., additional, Silverman, Daniel H.S., additional, Kremen, Sarah, additional, Apostolova, Liana, additional, Tingus, Kathleen, additional, Lu, Po H., additional, Bartzokis, George, additional, Woo, Ellen, additional, Teng, Edmond, additional, Graff-Radford, Neill R., additional, Parfitt, Francine, additional, Poki-Walker, Kim, additional, Farlow, Martin R., additional, Hake, Ann Marie, additional, Matthews, Brandy R., additional, Brosch, Jared R., additional, Herring, Scott, additional, van, Christopher H., additional, Mecca, Adam P., additional, Good, Susan P., additional, MacAvoy, Martha G., additional, Carson, Richard E., additional, Varma, Pradeep, additional, Chertkow, Howard, additional, Vaitekunis, Susan, additional, Hosein, Chris, additional, Black, Sandra, additional, Stefanovic, Bojana, additional, Heyn, Chris (Chinthaka), additional, Robin Hsiung, Ging-Yuek, additional, Kim, Ellen, additional, Mudge, Benita, additional, Sossi, Vesna, additional, Feldman, Howard, additional, Assaly, Michele, additional, Finger, Elizabeth, additional, Pasternak, Stephen, additional, Rachinsky, Irina, additional, Kertesz, Andrew, additional, Drost, Dick, additional, Rogers, John, additional, Grant, Ian, additional, Muse, Brittanie, additional, Rogalski, Emily, additional, Robson, Jordan, additional, Mesulam, M.-Marsel, additional, Kerwin, Diana, additional, Wu, Chuang-Kuo, additional, Johnson, Nancy, additional, Lipowski, Kristine, additional, Weintraub, Sandra, additional, Bonakdarpour, Borna, additional, Pomara, Nunzio, additional, Hernando, Raymundo, additional, Sarrael, Antero, additional, Rosen, Howard J., additional, Miller, Bruce L., additional, Perry, David, additional, Turner, Raymond Scott, additional, Johnson, Kathleen, additional, Reynolds, Brigid, additional, MCCann, Kelly, additional, Poe, Jessica, additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Marshall, Gad A., additional, Yesavage, Jerome, additional, Taylor, Joy L., additional, Chao, Steven, additional, Coleman, Jaila, additional, White, Jessica D., additional, Lane, Barton, additional, Rosen, Allyson, additional, Tinklenberg, Jared, additional, Belden, Christine M., additional, Atri, Alireza, additional, Clark, Kelly A., additional, Zamrini, Edward, additional, Sabbagh, Marwan, additional, Killiany, Ronald, additional, Stern, Robert, additional, Mez, Jesse, additional, Kowall, Neil, additional, Budson, Andrew E., additional, Obisesan, Thomas O., additional, Ntekim, Oyonumo E., additional, Wolday, Saba, additional, Khan, Javed I., additional, Nwulia, Evaristus, additional, Nadarajah, Sheeba, additional, Lerner, Alan, additional, Ogrocki, Paula, additional, Tatsuoka, Curtis, additional, Fatica, Parianne, additional, Maillard, Pauline, additional, Olichney, John, additional, Carmichael, Owen, additional, Bates, Vernice, additional, Capote, Horacio, additional, Rainka, Michelle, additional, Borrie, Michael, additional, Lee, T.-Y., additional, Bartha, Dr Rob, additional, Johnson, Sterling, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M., additional, Perrin, Allison, additional, Burke, Anna, additional, Scharre, Douglas W., additional, Kataki, Maria, additional, Tarawneh, Rawan, additional, Hart, David, additional, Zimmerman, Earl A., additional, Celmins, Dzintra, additional, Miller, Delwyn D., additional, BolesPonto, Laura L., additional, Smith, Karen Ekstam, additional, Koleva, Hristina, additional, Shim, Hyungsub, additional, Nam, Ki Won, additional, Schultz, Susan K., additional, Williamson, Jeff D., additional, Craft, Suzanne, additional, Cleveland, Jo, additional, Yang, Mia, additional, Sink, Kaycee M., additional, Ott, Brian R., additional, Drake, Jonathan, additional, Tremont, Geoffrey, additional, Daiello, Lori A., additional, Drake, Jonathan D., additional, Ritter, Aaron, additional, Bernick, Charles, additional, Munic, Donna, additional, O'Connelll, Abigail, additional, Mintzer, Jacobo, additional, Wiliams, Arthur, additional, Masdeu, Joseph, additional, Shi, Jiong, additional, Garcia, Angelica, additional, Newhouse, Paul, additional, Potkin, Steven, additional, Salloway, Stephen, additional, Malloy, Paul, additional, Correia, Stephen, additional, Kittur, Smita, additional, Pearlson, Godfrey D., additional, Blank, Karen, additional, Anderson, Karen, additional, Flashman, Laura A., additional, Seltzer, Marc, additional, Hynes, Mary L., additional, Santulli, Robert B., additional, Relkin, Norman, additional, Chiang, Gloria, additional, Lee, Athena, additional, Lin, Michael, additional, Ravdin, Lisa, additional, Petersen, Ron, additional, Neylan, Thomas, additional, Grafman, Jordan, additional, Danowski, Sarah, additional, Nguyen-Barrera, Catherine, additional, Hayes, Jacqueline, additional, Finley, Shannon, additional, Bernstein, Matthew, additional, Senjem, Matt, additional, Foster, Norm, additional, Kim, Sungeun, additional, Sood, Ajay, additional, Blanchard, Kimberly S., additional, Fleischman, Debra, additional, Arfanakis, Konstantinos, additional, Varon, Daniel, additional, Greig, Maria T., additional, Petrella, Jeffrey R., additional, Goldstein, Bonnie, additional, Martin, Kimberly S., additional, Reist, Christopher, additional, Sadowsky, Carl, additional, Martinez, Walter, additional, Villena, Teresa, additional, Rosen, Howard, additional, Marshall, Gad, additional, Peskind, Elaine R., additional, Petrie, Eric C., additional, Li, Gail, additional, Mackin, Scott, additional, Jimenez-Maggiora, Gustavo, additional, Drake, Erin, additional, Donohue, Mike, additional, Nelson, Craig, additional, Bickford, David, additional, Butters, Meryl, additional, Zmuda, Michelle, additional, Reyes, Denise, additional, Faber, Kelley M., additional, Nudelman, Kelly N., additional, Au, Yiu Ho, additional, Scherer, Kelly, additional, Catalinotto, Daniel, additional, Stark, Samuel, additional, Ong, Elise, additional, and Fernandez, Dariella, additional

Published
2023
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38. Review of valiltramiprosate (ALZ-801) for the treatment of Alzheimer's disease: a novel small molecule with disease modifying potential.

Author

Lee, Daniel, Antonsdottir, Inga M., Clark, Emily D., and Porsteinsson, Anton P.

Subjects
ALZHEIMER'S disease treatment, THERAPEUTIC use of immunoglobulins, NEUROBEHAVIORAL disorders, COGNITIVE ability, PHARMACOKINETICS
Abstract

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, functional impairments, and neuropsychiatric symptoms. Valiltramiprosate is a tramiprosate prodrug being investigated as a novel treatment for AD. The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'ALZ-801' or 'valiltramiprosate.' Alzheon press releases were reviewed for emerging clinical information. Valiltramiprosate is an oral, well-tolerated synthetic valine-conjugate prodrug of tramiprosate. Valiltramiprosate's active metabolite include tramiprosate and 3-sulfopropanoic acid. Proposed mechanism of action is multiligand binding to Aβ42 which stabilizes amyloid monomers to prevent peptide aggregation and oligomerization. Pharmacokinetic studies show 52% oral bioavailability, rapid absorption, approximately 40% brain-drug exposure, and near complete renal clearance. Compared to tramiprosate, valiltramiprosate extends plasma tramiprosate half-life and improves interindividual pharmacokinetic variability. Interim analyses from valiltramiprosate's phase II biomarker trial show: (1) significant reductions in plasma p-tau181 and related AD fluid biomarkers; (2) brain structure preservation and reduced hippocampal atrophy by MRI; and (3) improvements on cognitive assessments at multiple timepoints. Its phase III clinical trial in ApoE ε4 homozygotes is near completion. Valiltramiprosate's clinical trial data show early indications of efficacy with potential disease modifying effect in AD. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Principal components analysis of agitation outcomes in Alzheimer's disease

Author

Yesavage, Jerome A., Taylor, Joy L., Friedman, Leah, Rosenberg, Paul B., Lazzeroni, Laura C., Leoutsakos, Jeannie-Marie S., Kinoshita, Lisa M., Perlow, Mark J., Munro, Cynthia A., Devanand, D.P., Drye, Lea T., Mintzer, Jacobo E., Pollock, Bruce G., Porsteinsson, Anton P., Schneider, Lon S., Shade, David M., Weintraub, Daniel, Lyketsos, Constantine G., and Noda, Art

Published
2016
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41. 18F-florbetapir Positron Emission Tomography–determined Cerebral β-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery

Author

Klinger, Rebecca Y., James, Olga G., Borges-Neto, Salvador, Bisanar, Tiffany, Li, Yi-Ju, Qi, Wenjing, Berger, Miles, Terrando, Niccolò, Newman, Mark F., Doraiswamy, P. Murali, Mathew, Joseph P., Weiner, Michael W., Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, M. Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Green, Robert C., Montine, Tom, Petersen, Ronald, Aisen, Paul, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Balasubramanian, Archana B., Mason, Jennifer, Sim, Iris, Beckett, Laurel, Harvey, Danielle, Donohue, Michael, Jack, Clifford R., Jr., Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCArli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Jagust, William, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Morris, John C., Cairns, Louis Nigel J., Franklin, Erin, Taylor-Reinwald, Lisa, Shaw, Leslie M., Trojanowki, John Q., Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Weiner, Michael W., Thal, Lean, Khachaturian, Zaven, Thal, Leon, Buckholtz, Neil, Weiner, Michael W., Snyder, Peter J., Potter, William, Paul, Steven, Albert, Marilyn, Frank, Richard, Khachaturian, Zaven, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Silbert, Lisa, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Petersen, Ronald, Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Pavlik, Valory, Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Morris, John C., Carroll, Maria, Creech, Mary L., Franklin, Erin, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, Shah, Raj C., deToledo-Morrell, Leyla, Duara, Ranjan, Greig-Custo, Maria T., Barker, Warren, Albert, Marilyn, Onyike, Chiadi, D’Agostino, Daniel, II, Kielb, Stephanie, Sadowski, Martin, Sheikh, Mohammed O., Ulysse, Anaztasia, Gaikwad, Mrunalini, Petrella, Jeffrey R., Wong, Terence Z., Coleman, Edward, Arnold, Steven E., Karlawish, Jason H., Wolk, David A., Clark, Christopher M., Smith, Charles D., Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H.S., Lu, Po H., Bartzokis, George, Graff-Radford, Neill R, Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Varma, Pradeep, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Ging-Yuek, Hsiung, Robin, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternack, Stephen, Rachisky, Irina, Trost, Dick, Kertesz, Andrew, Bernick, Charles, Munic, Donna, Mesulam, Marek-Marsel, Rogalski, Emily, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Yesavage, Jerome, Taylor, Joy L., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N., Belden, Christine M., Jacobson, Sandra A., Sirrel, Sherye A., Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O., Wolday, Saba, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, DeCarli, Charles, Carmichael, Owen, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Burke, Anna, Milliken, Ann Marie, Trncic, Nadira, Fleisher, Adam, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Kelley, Brendan, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Sink, Kaycee M., Gordineer, Leslie, Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Tremont, Geoffrey, Daiello, Lori A., Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Perry, David, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Rogers, John, Kertesz, Andrew, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Smith, Karen Ekstam, Koleva, Hristina, Nam, Ki Won, Shim, Hyungsub, Relkin, Norman, Chiang, Gloria, Lin, Michael, Ravdin, Lisa, Smith, Amanda, Ashok Raj, Balebail, Fargher, Kristin, Weiner, Michael W., Aisen, Paul, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Green, Robert C., Harvey, Danielle, Jack, Clifford R., Jr., Jagust, William, Morris, John C., Saykin, Andrew J., Shaw, Leslie M., Toga, Arthur W., Trojanowki, John Q., Neylan, Thomas, Grafman, Jordan, Grafman, Jordan, Green, Robert C., Montine, Tom, Weiner, Michael, Petersen, Ronald, Aisen, Paul, Thomas, Ronald G., Donohue, Michael, Gessert, Devon, Sather, Tamie, Davis, Melissa, Morrison, Rosemary, Jiminez, Gus, Neylan, Thomas, Hayes, Jacqueline, Finely, Shannon, Harvey, Danielle, Donohue, Michael, Jack, Clifford R., Jr., Bernstein, Matthew, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kantarci, Kejal, Ward, Chad, Jagust, William, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Landau, Susan, Morris, John C., Cairns, Nigel J., Householder, Erin, Shaw, Leslie M., Trojanowki, John Q., Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Toga, Arthur W., Crawford, Karen, Neu, Scott, Saykin, Andrew J., Foroud, Tatiana M., Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Weiner, Michael W., Friedl, Karl, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Brewer, James, Vanderswag, Helen, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Fleischman, Debra, Arfanakis, Konstantinos, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T, Petrella, Jeffrey R., Porsteinsson, Anton P., Goldstein, Bonnie, Martin, Kimberly S., Potkin, Steven G., Preda, Adrian, Nguyen, Dana, Mintzer, Jacobo, Massoglia, Dino, Brawman-Mintzer, Olga, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Jagust, William, Landau, Susan, Rosen, Howard, Perry, David, Turner, Raymond Scott, Behan, Kelly, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Sabbagh, Marwan N., Jacobson, Sandra A., Sirrel, Sherye A., Obisesan, Thomas O., Wolday, Saba, Allard, Joanne, Johnson, Sterling C., Fruehling, J. Jay, Harding, Sandra, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Yesavage, Jerome A., Taylor, Joy L., Furst, Ansgar J., Chao, Steven, Relkin, Norman, Chiang, Gloria, Ravdin, Lisa, Blumenthal, James A., Karhausen, Jorn A., Kertai, Miklos D., Podgoreanu, Mihai V., Stafford-Smith, Mark, Swaminathan, Madhav, Warner, David S., Funk, Bonita L., Balajonda, Narai, Brassard, Rachele, Cooter, Mary, Toulgoat-Dubois, Yanne, Waweru, Peter, Babyak, Michael A., Blumenthal, James A., Browndyke, Jeffrey N., Welsh-Bohmer, Kathleen A., Sketch, Michael H., Jr., Bennett, Ellen R., Graffagnino, Carmelo, Laskowitz, Daniel T., Strittmatter, Warren J., Collins, Kevin, Smigla, Greg, Shearer, Ian, D’Amico, Thomas A., Daneshmand, Mani A., Gaca, R. Jeffrey G., Glower, Donald D., Haney, Jack, Harpole, R. David, Hartwig, Mathew G., Hughes, G. Chad, Klapper, Jacob A., Lin, Shu S., Lodge, Andrew J., Milano, Carmelo A., Plichta, Ryan P., Schroeder, Jacob N., Smith, Peter K., and Tong, Betty C.

Published
2018
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42. Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment

Author

Tuena, Cosimo, Maestri, Sara, Serino, Silvia, Pedroli, Elisa, Stramba-Badiale, Marco, Riva, Giuseppe, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Brewer, Jame, Fleisher, Adam, Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Albers, Colleen S., Petersen, Ronald, Mason, Sara S., Knopman, David, Johnson, Kri, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Morris, John C., Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thoma, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Doraiswamy, P. Murali, Petrella, Jeffrey R., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Khouli, Riham El, Raslau, Flavius D., Lopez, Oscar L., Oakley, Maryann, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H. S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van Dyck, Christopher H., Mecca, Adam P., Good, Susan P., Macavoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunas, Susan, Hosein, Chri, Black, Sandra, Stefanovic, Bojana, Heyn, Chri, Hsiung, Ging-Yuek Robin, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M. -Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Weiner, Micheal W., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Mccann, Kelly, Poe, Jessica, Marshall, Gad A., Sperling, Reisa A., Johnson, Keith A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristu, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curti, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, Decarli, Charle, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T. -Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., Ponto, Laura L. Bole, Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charle, Munic, Donna, O’Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Null, Null, Serino, Silvia (ORCID:0000-0002-8422-1358), Riva, Giuseppe (ORCID:0000-0003-3657-106X), Tuena, Cosimo, Maestri, Sara, Serino, Silvia, Pedroli, Elisa, Stramba-Badiale, Marco, Riva, Giuseppe, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Brewer, Jame, Fleisher, Adam, Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Albers, Colleen S., Petersen, Ronald, Mason, Sara S., Knopman, David, Johnson, Kri, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Morris, John C., Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thoma, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Doraiswamy, P. Murali, Petrella, Jeffrey R., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Khouli, Riham El, Raslau, Flavius D., Lopez, Oscar L., Oakley, Maryann, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H. S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van Dyck, Christopher H., Mecca, Adam P., Good, Susan P., Macavoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunas, Susan, Hosein, Chri, Black, Sandra, Stefanovic, Bojana, Heyn, Chri, Hsiung, Ging-Yuek Robin, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M. -Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Weiner, Micheal W., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Mccann, Kelly, Poe, Jessica, Marshall, Gad A., Sperling, Reisa A., Johnson, Keith A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristu, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curti, Fatica, Parianne, Fletcher, Evan, Maillard, Pauline, Olichney, John, Decarli, Charle, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T. -Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., Ponto, Laura L. Bole, Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charle, Munic, Donna, O’Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Null, Null, Serino, Silvia (ORCID:0000-0002-8422-1358), and Riva, Giuseppe (ORCID:0000-0003-3657-106X)

Abstract

BackgroundIncreasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up.MethodsFour hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests.ResultsWhile controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gai

Published
2023

43. Prognostic value of plasma biomarkers in a clinical trial of mild‐to‐moderate Alzheimer's Disease.

Author

Qiu, Yuqi, Messer, Karen, Jacobs, Diane M., Salmon, David P., Kaplita, Stephen, Wellington, Cheryl L, Stukas, Sophie K, Askew, Brianna, Brewer, James B., Brody, Mark, Donahue, Lia, Drake, Jonathan D, Grossman, Katheryn, Hendrix, Suzanne B., Jicha, Gregory A, Leger, Gabriel C., Porsteinsson, Anton P., Shadyab, Aladdin H., Taylor, Curtis, and Thomas, Ronald G.

Abstract

Background: Informative, readily accessible plasma biomarkers of pathology, neuroinflammation, and neurodegeneration in Alzheimer's disease (AD) could enhance targeted approaches to AD trial design and treatment. In post‐hoc analyses, we examined whether plasma biomarkers (Aβ1‐40, Aβ1‐42, total tau, p‐tau‐181, NfL, and GFAP) predicted 48‐week change in cognitive (ADAS‐Cog11), global function (CDR‐SB), and volumetric MRI (6 cortical regions and 2 whole brain measures) outcomes in T2 Protect AD, a phase‐2 placebo‐controlled RCT of troriluzole in mild‐to‐moderate AD (NCT03605667). Method: At least one baseline biomarker measurement was available for 319 of 350 trial participants, forming the analytic sample. No significant treatment effects were found in T2 Protect AD (Feldman 2021, JPAD 8(4):s46); thus, treatment arms were pooled for this analysis. Baseline levels of, and 48‐week changes in, plasma biomarkers were assessed for association with 48‐week change in outcomes using linear regression adjusted for relevant covariates. Combinations of baseline plasma biomarkers that best predicted 48‐week decline on the ADAS‐Cog11 and CDR‐SB were identified using LASSO regression. Statistical significance level was 5%; p‐values were Bonferroni corrected for multiple comparisons. Result: Participant characteristics are presented in Table 1. Higher baseline plasma NfL predicted greater 48‐week decline on ADAS‐Cog11 (p = 0.026) and CDR‐SB (p = 0.048; Fig. 1A). LASSO revealed that the combination of baseline plasma NfL, total tau, and Aβ42/40 ratio best predicted 48‐week decline on ADAS‐Cog11, whereas baseline NfL alone best predicted 48‐week decline on CDR‐SB. Regarding MRI outcomes, baseline NfL predicted increase in ventricular volume (p = 0.018; Fig 1A). Baseline NfL, GFAP, and p‐tau‐181 each predicted 48‐week decline in mid‐temporal cortical volume (all p<0.02; Fig.1B); LASSO results were similar. The only significant association between 48‐week biomarker change and clinical outcomes was between increased plasma NfL and worsening CDR‐SB. Conclusion: Elevated baseline plasma NfL predicted greater 48‐week decline on cognitive, global function, and MRI measures in a clinical trial of mild‐to‐moderate AD. Furthermore, greater increase in plasma NfL over time was associated with greater clinical decline. Plasma NfL is an easily accessible biomarker that may enhance AD clinical trial design and treatment strategies. Acknowledgement: Trial funding by Biohaven Pharmaceuticals; data and trial coordination by the Alzheimer's Disease Cooperative Study (ADCS). [ABSTRACT FROM AUTHOR]

Published
2023
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44. Prevalence of Amyloid-Related Imaging Abnormalities in APOE4/4 Homozygotes with Early Alzheimer’s Disease: Baseline Findings from Ongoing Clinical Trials of Oral Anti-Amyloid Agent ALZ-801 (Valiltramiprosate) (P5-6.003)

Author

Abushakra, Susan, primary, Mandelbaum, Rosalind, additional, Barakos, Jerome, additional, Scheltens, Philip, additional, Porsteinsson, Anton P., additional, Watson, David, additional, MacSweeney, Emer, additional, Sabbagh, Marwan, additional, Liang, Earvin, additional, Kesslak, Patrick, additional, Suhy, Joyce, additional, Power, Aidan, additional, Hey, John, additional, and Tolar, Martin, additional

Published
2023
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45. Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2)

Author

Lanctôt, Krista L., primary, Chen, Clara, additional, Mah, Ethan, additional, Kiss, Alex, additional, Li, Abby, additional, Shade, Dave, additional, Scherer, Roberta W., additional, Vieira, Danielle, additional, Coulibaly, Hamadou, additional, Rosenberg, Paul B., additional, Lerner, Alan J., additional, Padala, Prasad R., additional, Brawman-Mintzer, Olga, additional, van Dyck, Christopher H., additional, Porsteinsson, Anton P., additional, Craft, Suzanne, additional, Levey, Allan, additional, Burke, William J., additional, Mintzer, Jacobo, additional, and Herrmann, Nathan, additional

Published
2023
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47. Correlation between changes in apathy and global cognition in apathetic associated with Alzheimer's disease: analysis of the Apathy Dementia Methylphenidate 2 (ADMET 2) clinical trial

Author

Lanctôt, Krista, primary, Sankhe, Krushnaa, additional, Perin, Jamie, additional, Herrmann, Nathan, additional, Brawman-Mintzer, Olga, additional, Lerner, Alan J., additional, Mintzer, Jacobo, additional, Padala, Prasad R., additional, Rosenberg, Paul B., additional, Shade, David M., additional, van Dyck, Christopher H., additional, and Porsteinsson, Anton P., additional

Published
2023
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48. Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease

Author

Weintraub, Daniel, Drye, Lea T., Porsteinsson, Anton P., Rosenberg, Paul B., Pollock, Bruce G., Devanand, Devangere P., Frangakis, Constantine, Ismail, Zahinoor, Marano, Christopher, Meinert, Curtis L., Mintzer, Jacobo E., Munro, Cynthia A., Pelton, Gregory, Rabins, Peter V., Schneider, Lon S., Shade, David M., Yesavage, Jerome, and Lyketsos, Constantine G.

Published
2015
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49. Attributable Cost of Dementia: Demonstrating Pitfalls of Ignoring Multiple Health Care System Utilization

Author

Lei, Lianlian, Cooley, Susan G., Phibbs, Ciaran S., Kinosian, Bruce, Allman, Richard M., Porsteinsson, Anton P., and Intrator, Orna

Subjects
United States. Veterans Health Administration -- Services, Economic aspects, Services, Health care industry, Dementia -- Economic aspects, Health care industry -- Services
Abstract

Dementia has been reported to carry a significant cost burden to governments and to individuals (Hurd et al. 2013; Kelley et al. 2015). For the United States' Veterans Health Administration [...], Objectives. To determine dementia prevalence and costs attributable to dementia using Veterans Health Administration (VHA) data with and without Medicare data. Data Sources. VHA inpatient, outpatient, purchased care and other data and Medicare enrollment, claims, and assessments in fiscal year (FY) 2013.Study Design. Analyses were conducted with VHA data alone and with combined VHA and Medicare data. Dementia was identified from a VHA sanctioned list of ICD-9 diagnoses. Attributable cost of dementia was estimated using recycled predictions. Data Collection. Veterans age 65 and older who used VHA and were enrolled in Traditional Medicare in FY 2013 (1.9 million).Principal Findings. VHA records indicated the prevalence of dementia in FY 2013 was 4.8 percent while combined VHA and Medicare data indicated the prevalence was 7.4 percent. Attributable cost of dementia to VHA was, on average, $ 10,950 per veteran per year (pvpy) using VHA alone and $6,662 pvpy using combined VHA and Medicare data. Combined VHA and Medicare attributable cost of dementia was $11,285 pvpy. Utilization attributed to dementia using VHA data alone was lower for long-term institutionalization and higher for supportive care services than indicated in combined VHA and Medicare data.Conclusions. Better planning for clinical and cost-efficient care requires VHA and Medicare to share data for veterans with dementia and likely more generally.Key Words. Health care costs, medicare, medicaid, VA Health Care System

Published
2018
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50. Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

Author

Sankhe, Krushnaa, Tumati, Shankar, Perin, Jamie, Rivet, Luc, Vieira, Danielle, Rosenberg, Paul B., Herrmann, Nathan, Shade, David, Lerner, Alan J., Padala, Prasad R, Brawman‐Mintzer, Olga, van Dyck, Christopher H., Porsteinsson, Anton P., Craft, Suzanne, Levey, Allan I., Mintzer, Jacobo, and Lanctôt, Krista L.

Abstract

Background: Apathy in Alzheimer's disease (AD) is associated with cognitive impairment, particularly executive functions such as selective attention, making it unclear whether apathy should be a separate treatment target. Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is the largest and most recent trial assessing apathy and cognition. This analysis assessed whether changes in apathy correlated to changes in various cognitive domains in ADMET 2. Method: In this multicentre, randomized, placebo‐controlled trial, 200 participants with mild to moderate AD received 20 mg methylphenidate (MPH) or placebo (PLB) for 6 months. The Neuropsychiatric Inventory apathy (NPI‐A) subscale measured apathy. Cognitive tests included Mini‐Mental State Exam (MMSE), Hopkins Verbal Learning‐immediate (HVLT‐I) and delayed (HVLT‐D), Digit Span forward (DF) and backward (DB), Trail Making (TMT A and B), Action Verbal Fluency (AV), Category Fluency (CF), and Boston Naming Test (BNT). Linear mixed models were conducted with cognitive change scores as the dependent variable and time and change in NPI‐A as the independent variable, overall and in each treatment group. All models were adjusted for baseline cognitive test score and NPI‐apathy, age, sex, diabetes, and treatment group. Result: 199 ADMET 2 participants (131 (66%) male) were included. For all participants, worsening apathy was associated with worsening MMSE (B (SE) = ‐0.10 (0.03), p = 0.003), CF (B (SE) = ‐0.13 (0.04), p = 0.0009), and HVLT‐I (B (SE) = ‐0.13 (0.05), p = 0.005). In the MPH group (n = 98), worsening apathy was associated only with worsening CF (B (SE) = ‐0.21 (0.06), p = 0.0008). In the PLB group (n = 101), worsening apathy was associated with worsening MMSE (B (SE) = ‐0.13 (0.05), p = 0.006), HVLT‐I (B (SE) = ‐0.30 (0.06), p = 0.000002), and HVLT‐D (B (SE) = ‐0.06 (0.02), p = 0.002). Changes in apathy were not associated with performance on the remaining cognitive tests. Conclusion: Changes in apathy are associated with changes in cognition as part of the natural history of AD. However, this association is disrupted by MPH treatment and suggests that improvements in apathy in AD with MPH were not driven by cognitive changes. These results are consistent with the view that apathy as a syndrome is related to, but distinct from cognition. [ABSTRACT FROM AUTHOR]

Published
2024
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