Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI
Susan M Landau, Andy Horng, Allison Fero, William J Jagust, Alzheimer's Disease Neuroimaging Initiative, Michael Weiner, Paul Aisen, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R Jack Jr, William Jagust, J Q Trojanowki, Arthur W Toga, Laurel Beckett, Robert C Green, Anthony Gamst, Andrew J Saykin, John Morris, William Z Potter, Robert C Green, Tom Montine, Ronald Petersen, Paul Aisen, Anthony Gamst, Ronald G Thomas, Michael Donohue, Sarah Walter, Clifford R Jack Jr, Anders Dale, Matthew Bernstein, Joel Felmlee, Nick Fox, Paul Thompson, Norbert Schuff, Gene Alexander, Charles DeCarli, William Jagust, Dan Bandy, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Chet Mathis, John Morris, Nigel J Cairns, Lisa Taylor-Reinwald, J Q Trojanowki, Les Shaw, Virginia M-Y Lee, Magdalena Korecka, Arthur W Toga, Karen Crawford, Scott Neu, Laurel Beckett, Danielle Harvey, Anthony Gamst, John Kornak, Andrew J Saykin, Tatiana M Foroud, Steven Potkin, Li Shen, Zaven Kachaturian, Richard Frank, Peter J Snyder, Susan Molchan, Jeffrey Kaye, Sara Dolen, Joseph Quinn, Lon Schneider, Sonia Pawluczyk, Bryan M Spann, James Brewer, Helen Vanderswag, Judith L Heidebrink, Joanne L Lord, Ronald Petersen, Kris Johnson, Rachelle S Doody, Javier Villanueva-Meyer, Munir Chowdhury, Yaakov Stern, Lawrence S Honig, Karen L Bell, John C Morris, Mark A Mintun, Stacy Schneider, Daniel Marson, Randall Griffith, David Clark, Hillel Grossman, Cheuk Tang, George Marzloff, Leyla deToledo-Morrell, Raj C Shah, Ranjan Duara, Daniel Varon, Peggy Roberts, Marilyn S Albert, Nicholas Kozauer, Maria Zerrate, Henry Rusinek, Mony J de Leon, Susan M De Santi, P Murali Doraiswamy, Jeffrey R Petrella, Marilyn Aiello, Steve Arnold, Jason H Karlawish, David Wolk, Charles D Smith, Curtis A Given 2nd, Peter Hardy, Oscar L Lopez, MaryAnn Oakley, Donna M Simpson, M Saleem Ismail, Connie Brand, Jennifer Richard, Ruth A Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Ramon Diaz-Arrastia, Kristen Martin-Cook, Michael DeVous, Allan I Levey, James J Lah, Janet S Cellar, Jeffrey M Burns, Heather S Anderson, Mary M Laubinger, Liana Apostolova, Daniel H S Silverman, Po H Lu, Neill R Graff-Radford, Francine Parfitt, Heather Johnson, Martin Farlow, Scott Herring, Ann M Hake, Christopher H van Dyck, Martha G MacAvoy, Amanda L Benincasa, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Michele Assaly, Andrew Kertesz, John Rogers, Dick Trost, Charles Bernick, Donna Munic, Chuang-Kuo Wu, Nancy Johnson, Marsel Mesulam, Carl Sadowsky, Walter Martinez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A Sperling, Dorene M Rentz, Keith A Johnson, Allyson Rosen, Jared Tinklenberg, Wes Ashford, Marwan Sabbagh, Donald Connor, Sandra Jacobson, Ronald Killiany, Alexander Norbash, Anil Nair, Thomas O Obisesan, Annapurni Jayam-Trouth, Paul Wang, Alan Lerner, Leon Hudson, Paula Ogrocki, Charles DeCarli, Evan Fletcher, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Dr Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M Carlsson, Steven G Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Barry A Hendin, Douglas W Scharre, Maria Kataki, Earl A Zimmerman, Dzintra Celmins, Alice D Brown, Godfrey Pearlson, Karen Blank, Karen Anderson, Andrew J Saykin, Robert B Santulli, Jessica Englert, Jeff D Williamson, Kaycee M Sink, Franklin Watkins, Brian R Ott, Edward Stopa, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J Rosen, Bruce L Miller, Jacobo Mintzer, Crystal Flynn Longmire, Kenneth Spicer, Susan M Landau, Andy Horng, Allison Fero, William J Jagust, Alzheimer's Disease Neuroimaging Initiative, Michael Weiner, Paul Aisen, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R Jack Jr, William Jagust, J Q Trojanowki, Arthur W Toga, Laurel Beckett, Robert C Green, Anthony Gamst, Andrew J Saykin, John Morris, William Z Potter, Robert C Green, Tom Montine, Ronald Petersen, Paul Aisen, Anthony Gamst, Ronald G Thomas, Michael Donohue, Sarah Walter, Clifford R Jack Jr, Anders Dale, Matthew Bernstein, Joel Felmlee, Nick Fox, Paul Thompson, Norbert Schuff, Gene Alexander, Charles DeCarli, William Jagust, Dan Bandy, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Chet Mathis, John Morris, Nigel J Cairns, Lisa Taylor-Reinwald, J Q Trojanowki, Les Shaw, Virginia M-Y Lee, Magdalena Korecka, Arthur W Toga, Karen Crawford, Scott Neu, Laurel Beckett, Danielle Harvey, Anthony Gamst, John Kornak, Andrew J Saykin, Tatiana M Foroud, Steven Potkin, Li Shen, Zaven Kachaturian, Richard Frank, Peter J Snyder, Susan Molchan, Jeffrey Kaye, Sara Dolen, Joseph Quinn, Lon Schneider, Sonia Pawluczyk, Bryan M Spann, James Brewer, Helen Vanderswag, Judith L Heidebrink, Joanne L Lord, Ronald Petersen, Kris Johnson, Rachelle S Doody, Javier Villanueva-Meyer, Munir Chowdhury, Yaakov Stern, Lawrence S Honig, Karen L Bell, John C Morris, Mark A Mintun, Stacy Schneider, Daniel Marson, Randall Griffith, David Clark, Hillel Grossman, Cheuk Tang, George Marzloff, Leyla deToledo-Morrell, Raj C Shah, Ranjan Duara, Daniel Varon, Peggy Roberts, Marilyn S Albert, Nicholas Kozauer, Maria Zerrate, Henry Rusinek, Mony J de Leon, Susan M De Santi, P Murali Doraiswamy, Jeffrey R Petrella, Marilyn Aiello, Steve Arnold, Jason H Karlawish, David Wolk, Charles D Smith, Curtis A Given 2nd, Peter Hardy, Oscar L Lopez, MaryAnn Oakley, Donna M Simpson, M Saleem Ismail, Connie Brand, Jennifer Richard, Ruth A Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Ramon Diaz-Arrastia, Kristen Martin-Cook, Michael DeVous, Allan I Levey, James J Lah, Janet S Cellar, Jeffrey M Burns, Heather S Anderson, Mary M Laubinger, Liana Apostolova, Daniel H S Silverman, Po H Lu, Neill R Graff-Radford, Francine Parfitt, Heather Johnson, Martin Farlow, Scott Herring, Ann M Hake, Christopher H van Dyck, Martha G MacAvoy, Amanda L Benincasa, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Michele Assaly, Andrew Kertesz, John Rogers, Dick Trost, Charles Bernick, Donna Munic, Chuang-Kuo Wu, Nancy Johnson, Marsel Mesulam, Carl Sadowsky, Walter Martinez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A Sperling, Dorene M Rentz, Keith A Johnson, Allyson Rosen, Jared Tinklenberg, Wes Ashford, Marwan Sabbagh, Donald Connor, Sandra Jacobson, Ronald Killiany, Alexander Norbash, Anil Nair, Thomas O Obisesan, Annapurni Jayam-Trouth, Paul Wang, Alan Lerner, Leon Hudson, Paula Ogrocki, Charles DeCarli, Evan Fletcher, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Dr Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M Carlsson, Steven G Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Barry A Hendin, Douglas W Scharre, Maria Kataki, Earl A Zimmerman, Dzintra Celmins, Alice D Brown, Godfrey Pearlson, Karen Blank, Karen Anderson, Andrew J Saykin, Robert B Santulli, Jessica Englert, Jeff D Williamson, Kaycee M Sink, Franklin Watkins, Brian R Ott, Edward Stopa, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J Rosen, Bruce L Miller, Jacobo Mintzer, Crystal Flynn Longmire, Kenneth Spicer
Abstract
Objective: To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective cohort study.
Methods: We first investigated the reliability of florbetapir- PET in patients with AD and patients with MCI using CSF-Aβ1-42 as a comparison amyloid measurement. We then compared florbetapir- vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data.
Results: Florbetapir and CSF-Aβ1-42 +/- status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir- scans were a reliable representation of amyloid status. Florbetapir- AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir- patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir- participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants.
Conclusions: Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir- ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype.
© 2016 American Academy of Neurology.
Figures
Source: PubMed