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Progression of brain atrophy in PSP and CBS over 6 months and 1 year

2016; Lippincott Williams & Wilkins; Volume: 87; Issue: 19 Linguagem: Inglês

10.1212/wnl.0000000000003305

1526-632X

Shubir Dutt, Richard J. Binney, Hilary W. Heuer, Phi Luong, Suneth Attygalle, Priyanka Bhatt, Gabe Marx, Jonathan Elofson, Maria Carmela Tartaglia, Irene Litvan, Scott M. McGinnis, Bradford C. Dickerson, John Kornak, Dana Waltzman, Lisa Voltarelli, Norbert Schuff, Gil D. Rabinovici, Joel H. Kramer, Clifford R. Jack, Bruce L. Miller, Howard J. Rosen, Adam L. Boxer, David R. Williams, Anne Lafontaine, Connie Marras, Mandar Jog, Michael Panisset, Anthony E. Lang, Lesley H. Parker, Alistair Stewart, Jean‐Christophe Corvol, Jean‐Philippe Azulay, Philippe Couratier, Brit Mollenhauer, Stefan Lorenzl, Albert Ludolph, R. Benecke, Günter U. Höglinger, Axel Lipp, Heinz Reichmann, Dirk Woitalla, Dennis Chan, Adam Zermansky, David J. Burn, Andrew J. Lees, Illana Gozes, Adam L. Boxer, Bruce L. Miller, Iryna Lobach, Erik D. Roberson, Lawrence S. Honig, Edward Zamrini, Rajesh Pahwa, Yvette Bordelon, Erika Driver-Dunkley, Stephanie Lessig, Mark Lew, Kyle Womack, Bradley F. Boeve, Joseph M. Ferrara, Argyle Hillis, Daniel Kaufer, Rajeev Kumar, Tao Xie, Steven A. Gunzler, Theresa Zesiewicz, Praveen Dayalu, Lawrence I. Golbe, Murray Grossman, Joseph Jankovic, Scott McGinnis, A. Parra Santiago, Paul Tuite, Stuart Isaacson, Julie Leegwater‐Kim, Irene Litvan, David S. Knopman, Lon S. Schneider, Rachelle S. Doody, Mary Koestler, Clifford R. Jack, Viviana Van Deerlin, Christopher Randolph, Steve Whitaker, Joe Hirman, Michael Gold, Bruce H. Morimoto,

Alzheimer's disease research and treatments

Objective: To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents. Methods: Six- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial. Results: Patients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale. Conclusions: Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects.