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Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease

2015; Lippincott Williams & Wilkins; Volume: 85; Issue: 14 Linguagem: Inglês

10.1212/wnl.0000000000001991

1526-632X

Sebastian Palmqvist, Henrik Zetterberg, Niklas Mattsson, Per Johansson, Lennart Minthon, Kaj Blennow, Mattias Olsson, Oskar Hansson, Oskar Hansson, Lennart Minthon, Håkan Toresson, Katarina Nägga, Sebastian Palmqvist, Erik Stomrud, Per Johansson, Christer Nilsson, Maria H Nilsson, Niklas Mattsson, Daniel Lindqvist, Susanna Vestberg, Shorena Janelidze, Henrik Zetterberg, Kaj Blennow, Ulf Andréasson, Danielle van Westen, Jimmy Lätt, Peter Mannfolk, Markus Nilsson, Olof Strandberg, Pia C. Sundgren, Freddy Ståhlberg, Olof Lindberg, Eric Westman, Lars‐Olof Wahlund, Per Wollmer, Ruben Smith, Tomas Olsson, Michael D. Weiner, Paul Aisen, Michael D. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Anthony Gamst, Andrew J. Saykin, John C. 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, Anders M. Dale, Matt A. Bernstein, Joel P. Felmlee, Nick C. Fox, Paul M. Thompson, Norbert Schuff, Gene E. Alexander, Charles DeCarli, William J. Jagust, Dan Bandy, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chester A. Mathis, John C. Morris, Nigel J. Cairns, Lisa Taylor‐Reinwald, John 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 Foroud, Steven G. Potkin, Li Shen, Zaven Kachaturian, Richard Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Sara Dolen, Joseph Quinn, Lon S. Schneider, Sonia Pawluczyk, Bryan M. Spann, James M. Brewer, Helen Vanderswag, Judith L. Heidebrink, Joanne 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 A. Clark, Hillel Grossman, Cheuk Y. Tang, George Marzloff, Leyla deToledo‐Morrell, Raj C. Shah, Ranjan Duara, Daniel Varón, Peggy Roberts CAN, 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, S. R. Arnold, Jason H. Karlawish, David A. Wolk, Charles D. Smith, Curtis A. Given, 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 D. Devous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Heather S. Anderson, Mary M. Laubinger, Liana Apostolova, Daniel Silverman, Po H. Lu, Neill R. Graff‐Radford, Francine Parfitt, Heather Johnson, Martin R. Farlow, Scott Herring, Ann Marie Hake, Christopher H. van Dyck, Martha G. MacAvoy, Amanda L. Benincasa, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra E. 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 Martínez, 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 J. Connor, Sandra A. Jacobson, Ronald Killiany, Alexander Norbash, Anil K. Nair, Thomas O. Obisesan, Annapurni Jayam‐Trouth, Paul Wang, Alan J. Lerner, Leon Hudson, Paula Ogrocki, Charles DeCarli, E. Fletcher, Owen Carmichael, Smita Kittur, Michael Borrie, T‐Y Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana Nguyen, Pierre N. Tariot, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Barry Hendin, Douglas W. Scharre, Maria Kataki, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. 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 G. Stopa, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Jacobo Mintzer, Crystal Flynn Longmire, Kenneth Spicer,

Functional Brain Connectivity Studies

Objective: To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). Methods: From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined with [ 18 F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer9s Disease Neuroimaging Initiative study. Results: The best CSF measures for identifying MCI-AD were Aβ42/total tau (t-tau) and Aβ42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93–0.94). The best PET measures performed similarly (AUC 0.92–0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03–0.12, p < 0.05). Using nonoptimized cutoffs, CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately. Conclusions: Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy. Classification of evidence: This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.