Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy

Richard M. Tsai, Iryna Lobach, Jee Bang, Jennifer L. Whitwell, Matthew L. Senjem, Clifford R. Jack, Howard Rosen, Bruce Miller, Adam L. Boxer, David Williams, Anne Louise Lafontaine, Connie Marras, Mandar Jog, Michael Panisset, Anthony Lang, Lesley Parker, Alistair J. Stewart, Jean Christophe Corvol, Jean Philippe Azulay, Philippe CouratierBrit Mollenhauer, Stefan Lorenzl, Albert Ludolph, Reiner Benecke, Gunter Hoglinger, Axel Lipp, Heinz Reichmann, Dirk Woitalla, Dennis Chan, Adam Zermansky, David Burn, Andrew Lees, Illana Gozes, Adam Boxer, Bruce L. Miller, Iryna V. Lobach, Erik Roberson, Lawrence Honig, Edward Zamrini, Rajesh Pahwa, Yvette Bordelon, Erika Driver-Dunkley, Stephanie Lessig, Mark Lew, Kyle Womack, Brad Boeve, Joseph Ferrara, Argyle Hillis, Daniel Kaufer, Rajeev Kumar, Tao Xie, Steven Gunzler, Theresa Zesiewicz, Praveen Dayalu, Lawrence Golbe, Joseph Jankovic, Scott McGinnis, Anthony Santiago, Paul Tuite, Stuart Isaacson, Julie Leegwater-Kim, Irene Litvan, Murray Grossman, David S. Knopman, Lon S. Schneider, Rachelle S. Doody, Lawrence I. Golbe, Erik D. Roberson, Mary Koestler, Viviana Van Deerlin, Christopher Randolph, Steve Whitaker, Joe Hirman, Michael Gold, Bruce H. Morimoto

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Introduction: There are no effective treatments for progressive supranuclear palsy (PSP). Volumetric MRI (vMRI) may be a useful surrogate outcome measure in PSP clinical trials. The goal of the study was to evaluate the potential of vMRI to correlate with clinical outcomes from an international clinical trial population. Methods: PSP patients (n = 198) from the AL-108-231 trial who had high quality vMRI and Progressive Supranuclear Palsy Rating Scale (PSPRS), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Schwab and England Activities of Daily Living (SEADL), Color Trails Test, Geriatric Depression Screen (GDS) and one year Clinician Global Impression of Change (CGIC) data from the baseline and 52 week visits were included. Linear regression was used to relate baseline values and annual clinical rating scale changes to annual regional vMRI changes (whole brain, ventricular, midbrain and superior cerebellar peduncle volumes). Results: Effect sizes (Cohen's d) measuring disease progression over one year were largest for vMRI (midbrain [1.27] and ventricular volume [1.31]) but similar to PSPRS (1.26). After multiple comparison adjustment, annual changes in PSPRS, RBANS, SEADL, Color Trails Test, GDS and one year CGIC were modestly correlated with annual vMRI changes (p < 0.05). Baseline neuropsychological status on RBANS (p = 0.019) and Color Trails (p < 0.01) predicted annual midbrain atrophy rates. Conclusion: Standard vMRI measurements are sensitive to disease progression in large, multicenter PSP clinical trials, but are not well correlated with clinical changes. vMRI changes may be useful as supportive endpoints in PSP trials.

Original languageEnglish (US)
Pages (from-to)29-35
Number of pages7
JournalParkinsonism and Related Disorders
Volume28
DOIs
StatePublished - Jul 1 2016

Bibliographical note

Funding Information:
This work was supported by the National Institute of Health/National Institute of Aging (grant numbers K24 AG045333-01 , R01 AG032306 ). We would like to thank The AL-108-231 Study Group: Australia: David Williams; Canada: Anne Louise Lafontaine, Connie Marras, Mandar Jog, Michael Panisset, Anthony Lang, Lesley Parker, Alistair J. Stewart; France: Jean-Christophe Corvol, Jean-Philippe Azulay, Philippe Couratier; Germany: Brit Mollenhauer, Stefan Lorenzl, Albert Ludolph, Reiner Benecke, Gunter Hoglinger, Axel Lipp, Heinz Reichmann, Dirk Woitalla; United Kingdom: Dennis Chan, Adam Zermansky, David Burn, Andrew Lees; Israel: Illana Gozes, United States: Adam Boxer, Bruce L. Miller, Iryna V. Lobach, Erik Roberson, Lawrence Honig, Edward Zamrini, Rajesh Pahwa, Yvette Bordelon, Erika Driver-Dunkley, Stephanie Lessig, Mark Lew, Kyle Womack, Brad Boeve, Joseph Ferrara, Argyle Hillis, Daniel Kaufer, Rajeev Kumar, Tao Xie, Steven Gunzler, Theresa Zesiewicz, Praveen Dayalu, Lawrence Golbe, Murray Grossman, Joseph Jankovic, Scott McGinnis, Anthony Santiago, Paul Tuite, Stuart Isaacson, Julie Leegwater-Kim, Irene Litvan, Murray Grossman, David S. Knopman, Bruce L. Miller, Lon S. Schneider, Rachelle S. Doody, Lawrence I. Golbe, Erik D. Roberson, Mary Koestler, Clifford R. Jack, Jr., Viviana Van Deerlin, Christopher Randolph, Steve Whitaker, Joe Hirman, Michael Gold, Bruce H. Morimoto.

Keywords

  • Biomarkers
  • Clinical trials
  • Imaging
  • MRI
  • Progressive supranuclear palsy

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