Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis

著者: Diana I. Bocancea, Anna L. Svenningsson, Anna C. van Loenhoud, Colin Groot, Frederik Barkhof, Olof Strandberg, Ruben Smith, for the Alzheimer’s Disease Neuroimaging Initiative, Michael W Weiner, Paul Aisen, Ronald Petersen, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W Toga, Laurel Beckett, Robert C Green, Andrew J Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, Zaven S. Khachaturian, Maria Carrillo, William Z. Potter, Lisa L. Barnes, Marie Bernard, Héctor Alfredo Baptista González, Carole Ho, John K Hsiao, Jonathan Jackson, Eliezer Masliah, Donna Masterman, Ozioma C. Okonkwo, Laurie Ryan, Nina Silverberg, Adam Fleisher, Michael W Weiner, Diana Truran Sacrey, Juliet Fockler, Cat Conti, Dallas P. Veitch, John Neuhaus, Chengshi Jin, Rachel L. Nosheny, Miriam T. Ashford, Derek Flenniken, Adrienne Kormo, Robert C Green, Tom Montine, Cat Conti, Ronald Petersen, Paul Aisen, Michael S. Rafii, Rema Raman, Gustavo Jiménez, Michael Donohue, Devon Gessert, Jennifer Salazar, Caileigh Zimmerman, Yuliana Cabrera, Sarah Walter, Garrett Miller, Godfrey Coker, Taylor Clanton, Lindsey Hergesheimer, Stephanie Smith, Olusegun Adegoke, Payam Mahboubi, Shelley Moore, Jeremy Pizzola, Elizabeth Shaffer, Laurel Beckett, Danielle Harvey, Michael Donohue, Clifford R. Jack, Arvin Forghanian-Arani, Bret Borowski, Chad Ward, Christopher G. Schwarz, David T. Jones, Jeff Gunter, Kejal Kantarci, Matthew L. Senjem, Prashanthi Vemuri, Robert I. Reid, Nick C. Fox, Ian B. Malone, Paul M. Thompson, Sophia I. Thomopoulos, Talia M. Nir, Neda Jahanshad, Charles DeCarli, Alexander Knaack, Evan Fletcher, Danielle Harvey, Duygu Tosun, Stephanie Rossi Chen, Mark Choe, Karen Crawfor, Paul A. Yushkevich, Sandhitsu R. Das, William J. Jagust, Robert A. Koeppe, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C Morris, Richard J. Perrin, Nigel J. Cairns, Haley Bernhardt, Leslie M. Shaw, Michal Figurski, Arthur W Toga, Karen Crawfor, Scott Neu, Andrew J Saykin, Kwangsik Nho, Shannon L. Risacher, Liana G. Apostolova, Li Shen, Tatiana Foroud, Kelly Nudelman, Kelley Faber, Michael W Weiner, John K Hsiao, Lisa C. Silbert, Jeffrey Kaye, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Karen Dagerman, Bryan M Spann, James Brewer, Helen Vanderswag, Jaimie Ziolkowski, Judith L. Heidebrink, Lisa Zbizek-Nulph, Joanne Lord, Lisa Zbizek-Nulph, Ronald Petersen, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, Javier Villanueva-Meyer, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass, Rachelle S. Doody, Munir Chowdhury, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Akiva Mintz, Beau M. Ances, John C Morris, David Winkfield, Maria Carroll, Angela Oliver, Stacy Schneider, David Geldmacher, Marissa Natelson Love, Randall Griffith, John Brockington, Hillel Grossman, Martin Goldstein, Jonathan Greenberg, Effie Mitsis, Raj C. Shah, Melissa Lamar, Patricia Samuel, Ranjan Duara, Maria T. Greig‐Custo, Rosemarie Rodriguez, Marilyn Albert, Chiadi Onyike, Leonie Farrington, Scott Rudow, Rottislav Brichko, Stephanie Kielb, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Martin Sadowski, Thomas Wısnıewskı, Melanie Shulman, Arline Faustin, Julia Rao, Karen M. Castro, Anaztasia Ulysse, Shannon Chen, Mohammed O. Sheikh, P. Murali Doraiswamy, Jeffrey R Petrella, Olga James, Salvador Borges‐Neto, Jason Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark, Steven E. Arnold, Charles D. Smith, Gregory A. Jicha, Riham El Khouli, Flavius D. Raslau, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Anton P Porsteinsson, Kim Martin, Nancy Kowalski, Melanie Keltz, Bonnie S. Goldstein, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Gaby Thai, Aimee Pierce, Beatriz Yáñez‐Rivera, Elizabeth Sosa, Megan Witbracht, Brendan Kelley, Trung Nguyen, Kyle Womack, Dana Mathews, Allan I. Levey, James J. Lah, Ihab Hajjar, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Daniel Silverman, Sarah Kremen, Liana G. Apostolova, Kathleen Tingus, Edmond Teng, Neill R. Graff‐Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Scott Herring, Christopher H. van Dyck, Adam P. Mecca, Susan P. Good, Martha G. MacAvoy, Richard E. Carson, Pradeep Varma, Howard Chertkow, Susan Vaitekunis, Chris Hosein, Sandra E. Black, Bojana Stefanovic, Chris Heyn, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternak, Irina Rachinsky, Andrew Kertesz, Dick Drost, Ian Grant, Brittanie Muse, Emily Rogalskı, Jordan Robso, M-Marsel Mesulam, Chuang‐Kuo Wu, Nancy E. Johnson, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Howard J. Rosen, Bruce L. Miller, David C. Perry, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Kelly McCann, Jessica Poe, Reisa A. Sperling, Keith A Johnson, Gad A. Marshall, Jerome A. Yesavage, Joy L. Taylor, Steven Chao, Jaila Coleman, Jessica D White, Barton Lane, Christine M. Belden, Alireza Atri, Bryan M. Spann, Kelly A Clar, Ronald Killiany, Robert A. Stern, Jesse Mez, Neil W. Kowall, Andrew E. Budson, Thomas O. Obisesan, Oyonumo Ntekim, Saba Wolday, Javed Khan, Evaristus Nwulia, Sheeba Nadarajah, Alan J. Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Vernice Bates, Michelle Rainka, Michael Borrie, C Lee, Dr Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M Carlsson, Allison Perrin, Anna Burke, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, Brendan Kelley, David Hart, Earl A. Zimmerman, Dzintra Celmins, Del D. Miller, Laura L. Boles Ponto, Karen Ekstam Smith, Hristina Koleva, Hyungsub Shim, Ki Won Nam, Susan K. Schultz, Jeff D. Williamson, Suzanne Craft, Jo Cleveland, Mia Yang, Kaycee M. Sink, Brian R. Ott, Jonathan Drake, Geoffrey Tremont, Lori A. Daiello, Jonathan Drake, Marwan Sabbagh, Aaron Ritter, Charles Bernick, Donna Munic, Akiva Mintz, Abigail O’Connelll, Jacobo Mintzer, Arthur Wiliams, Joseph C. Masdeu, Jiong Shi, Angelica Garcia, Marwan Sabbagh, Paul Newhouse, Steven Potkin, Stephen Salloway, Paul Malloy, Stephen Correia, Smita Kittur, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Norman Relkin, Gloria Chiang, Athena Lee, Michael Lin, Lisa Ravdin, Michael W Weiner, Paul Aisen, Michael W Weiner, Paul Aisen, Ronald Petersen, Robert C Green, Danielle Harvey, William Jagust, John C Morris, Andrew J Saykin, Leslie M. Shaw, Arthur W. Toga, John Q. Trojanowki, Thomas C. Neylan, Jordan Grafman, Robert C Green, Tom Montine, Michael W Weiner, Ronald Petersen, Paul Aisen, Gustavo Jiménez, Michael Donohue, Devon Gessert, Jennifer Salazar, Caileigh Zimmerman, Sarah Walter, Olusegun Adegoke, Payam Mahboubi, Sarah Danowski, Godfrey Coker, Taylor Clanton, Jeremy Pizzola, Elizabeth Shaffer, Thomas C. Neylan, Jacqueline Hayes, Shannon Finley, Danielle Harvey, Michael Donohue, Matt A. Bernstein, Bret Borowski, Jeff Gunter, Matthew L. Senjem, Kejal Kantarci, Chad Ward, Duygu Tosun, Stephanie Rossi Chen, Susan Landau, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, John C Morris, Richard J. Perrin, Erin Franklin, Leslie M. Shaw, John Q. Trojanowki, Magdalena Korecka, Arthur W. Toga, Karen Crawfor, Andrew J Saykin, Tatiana M Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Kristi Wilmes, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Karen Dagerman, Bryan M Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Yaakov Stern, Lawrence S. Honig, Akiva Mintz, Raj C. Shah, Ajay Sood, Kimberly S. Blanchard, Debra Fleischman, Konstantinos Arfanakis, Dr Ranjan Duara, Daniel Varón, P. Murali Doraiswamy, Jeffrey R Petrella, Olga James, Salvador Borges‐Neto, Terence Z. Wong, Anton P Porsteinsson, Bonnie S. Goldstein, Kimberly S. Martin, Gaby Thai, Aimee Pierce, Christopher Reist, Beatriz Yáñez‐Rivera, Elizabeth Sosa, Megan Witbracht, Carl Sadowsky, Walter Martínez, Teresa Villena, Howard J. Rosen, David Perr, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Kelly McCann, Jessica Poe, Reisa A. Sperling, Keith A Johnson, Christine M. Belden, Alireza Atri, Bryan M Spann, Kelly A Clar, Edward Zamrini, Marwan Sabbagh, Thomas O. Obisesan, Oyonumo Ntekim, Saba Wolday, Evaristus Nwulia, Sheeba Nadarajah, Sterling Johnson, Sanjay Asthana, Cynthia M Carlsson, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Joy L. Taylor, Steven Chao, Jaila Coleman, Jessica D White, Barton Lane, Allyson Rosen, Jared Tinklenberg, Michael Lin, Gloria Chiang, Lisa Ravdin, Norman Relkin, Abigail O’Connelll, Jacobo Mintzer, Arthur Wiliams, R. Scott Mackin, Paul Aisen, Rema Raman, Michael Donohue, Devon Gessert, Jennifer Salazar, Caileigh Zimmerman, Sarah Walter, Olusegun Adegoke, Payam Mahboubi, Scott Mackin, Michael W Weiner, Paul Aisen, Rema Raman, Susan Landau, Andrew J Saykin, Arthur W. Toga, Charles DeCarli, Robert A Koeppe, Robert C Green, Erin Drake, Michael W Weiner, Paul Aisen, Rema Raman, Mike Donohue, Scott Mackin, Craig Nelson, David Bickford, Meryl A. Butters, Michelle Zmuda, Matt A. Bernstein, Bret Borowski, Jeff Gunter, Matthew L. Senjem, Kejal Kantarci, Chad Ward, Denise Reyes, Robert A Koeppe, Susan Landau, Arthur W Toga, Karen Crawfor, Scott Neu, Andrew J Saykin, Tatiana M Foroud, Kelley Faber, Kwangsik Nho, Kelly Nudelman, Scott Mackin, Howard J. Rosen, Craig Nelson, David Bickford, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, Dariella Fernandez, Meryl A. Butters, Michelle Zmuda, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Renaud La Joie, Howard J. Rosen, Michael J. Pontecorvo, Gil D. Rabinovici, Wiesje M. van der Flier, Oskar Hansson, Rik Ossenkoppele - Brain 2023 被引用: 49

Mechanisms of resilience against tau pathology in individuals across the Alzheimer's disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer's disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer's disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.