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Subregional neuroanatomical change as a biomarker for Alzheimer's disease

2009; National Academy of Sciences; Volume: 106; Issue: 49 Linguagem: Inglês

10.1073/pnas.0906053106

1091-6490

Dominic Holland, James Brewer, Donald J. Hagler, Christine Fennema‐Notestine, Anders M. Dale, Michael D. Weiner, Leon J. Thal, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Anthony Gamst, William Z. Potter, Tom Montine, Dale Anders, Matt A. Bernstein, Joel P. Felmlee, Nick C. Fox, Paul M. Thompson, Norbert Schuff, Gene E. Alexander, Dan Bandy, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Les Shaw, Virginia M.‐Y. Lee, Magdalena Korecka, Karen Crawford, Scott Neu, Danielle Harvey, John Kornak, Zaven Kachaturian, Richard Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Remi Vorobik, Joseph F. Quinn, Lon S. Schneider, Sonia Pawluczyk, Bryan Spann, Adam Fleisher, Helen Vanderswag, Judith L. Heidebrink, Joanne Lord, 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, Beverly Badger, Hillel Grossman, Cheuk Y. Tang, Jessica Stern, Leyla deToledo‐Morrell, Raj C. Shah, Julie Bach, Ranjan Duara, Richard Isaacson, Silvia Strauman, Marilyn Albert, Julia Pedroso, Jaimie Toroney, Henry Rusinek, Mony J. de Leon, Susan M De Santi, P. Murali Doraiswamy, Jeffrey R. Petrella, Marilyn Aiello, Christopher M. Clark, Cassie Pham, Jessica Nuñez, Charles D. Smith, Curtis A. Given, Peter Hardy, Steven T. DeKosky, MaryAnn Oakley, Donna M. Simpson, M. Saleem Ismail, Anton P. Porsteinsson, Colleen McCallum, Steven C. Cramer, Ruth A. Mulnard, 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, George Bartzokis, Daniel Silverman, Po H. Lu, Rita Fletcher, Francine Parfitt, Heather Johnson, Martin R. Farlow, Scott Herring, Ann Marie Hake, Christopher H. van Dyck, Martha G. MacAvoy, Laurel A. Bifano, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra E. Black, Simon J. Graham, Curtis Caldwell, Howard Feldman, Michele Assaly, Ging‐Yuek Robin Hsiung, Andrew Kertesz, John Rogers, Dick Trost, Charles Bernick, Darren R. Gitelman, Nancy Johnson, Marsel Mesulam, Carl Sadowsky, Teresa Villena, Scott Mesner, Paul Aisen, Kathleen Johnson, Kelly E. Behan, Reisa A. Sperling, Dorene M. Rentz, Keith A. Johnson, Allyson Rosen, Jared Tinklenberg, Wes Ashford, Marwan N. Sabbagh, Donald J. Connor, Sanja Obradov, Ronald Killiany, Alexander Norbash, Thomas O. Obisesan, Annapurni Jayam‐Trouth, Paul P. Wang, Alexander P. Auchus, Juebin Huang, Robert P. Friedland, Charles DeCarli, Evan Fletcher, Owen Carmichael, Smita Kittur, Seema Mirje, Sterling C. Johnson, Michael Borrie, T.-Y. Lee, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Diane Highum, Adrian Preda, Dana Nguyen, Pierre N. Tariot, Barry Hendin, Douglas W. Scharre, Maria Kataki, David Q. Beversdorf, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Sam Gandy, Marjorie E. Marenberg, Barry W. Rovner, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Andrew J. Saykin, Robert B. Santulli, Nadia Paré, Jeff D. Williamson, Kaycee M. Sink, Huntington Potter, Balebail Ashok Raj, Amy T. Giordano, Brian R. Ott, Chuang‐Kuo Wu, Ronald A. Cohen, Kerri Wilks, Beth Safirstein,

Dementia and Cognitive Impairment Research

Regions of the temporal and parietal lobes are particularly damaged in Alzheimer's disease (AD), and this leads to a predictable pattern of brain atrophy. In vivo quantification of subregional atrophy, such as changes in cortical thickness or structure volume, could lead to improved diagnosis and better assessment of the neuroprotective effects of a therapy. Toward this end, we have developed a fast and robust method for accurately quantifying cerebral structural changes in several cortical and subcortical regions using serial MRI scans. In 169 healthy controls, 299 subjects with mild cognitive impairment (MCI), and 129 subjects with AD, we measured rates of subregional cerebral volume change for each cohort and performed power calculations to identify regions that would provide the most sensitive outcome measures in clinical trials of disease-modifying agents. Consistent with regional specificity of AD, temporal-lobe cortical regions showed the greatest disease-related changes and significantly outperformed any of the clinical or cognitive measures examined for both AD and MCI. Global measures of change in brain structure, including whole-brain and ventricular volumes, were also elevated in AD and MCI, but were less salient when compared to changes in normal subjects. Therefore, these biomarkers are less powerful for quantifying disease-modifying effects of compounds that target AD pathology. The findings indicate that regional temporal lobe cortical changes would have great utility as outcome measures in clinical trials and may also have utility in clinical practice for aiding early diagnosis of neurodegenerative disease.