TY - JOUR
T1 - Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy
AU - AL-108-231 Investigators
AU - Tsai, Richard M.
AU - Lobach, Iryna
AU - Bang, Jee
AU - Whitwell, Jennifer L.
AU - Senjem, Matthew L.
AU - Jack, Clifford R.
AU - Rosen, Howard
AU - Miller, Bruce
AU - Boxer, Adam L.
AU - Williams, David
AU - Lafontaine, Anne Louise
AU - Marras, Connie
AU - Jog, Mandar
AU - Panisset, Michael
AU - Lang, Anthony
AU - Parker, Lesley
AU - Stewart, Alistair J.
AU - Corvol, Jean Christophe
AU - Azulay, Jean Philippe
AU - Couratier, Philippe
AU - Mollenhauer, Brit
AU - Lorenzl, Stefan
AU - Ludolph, Albert
AU - Benecke, Reiner
AU - Hoglinger, Gunter
AU - Lipp, Axel
AU - Reichmann, Heinz
AU - Woitalla, Dirk
AU - Chan, Dennis
AU - Zermansky, Adam
AU - Burn, David
AU - Lees, Andrew
AU - Gozes, Illana
AU - Lobach, Iryna V.
AU - Roberson, Erik D.
AU - Honig, Lawrence
AU - Zamrini, Edward
AU - Pahwa, Rajesh
AU - Bordelon, Yvette
AU - Driver-Dunkley, Erika
AU - Lessig, Stephanie
AU - Lew, Mark
AU - Womack, Kyle
AU - Boeve, Brad
AU - Ferrara, Joseph
AU - Hillis, Argyle
AU - Kaufer, Daniel
AU - Kumar, Rajeev
AU - Xie, Tao
AU - Knopman, David S.
N1 - Publisher Copyright:
© 2016.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Clinical trials
KW - Imaging
KW - MRI
KW - Progressive supranuclear palsy
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U2 - 10.1016/j.parkreldis.2016.04.006
DO - 10.1016/j.parkreldis.2016.04.006
M3 - Article
C2 - 27132501
AN - SCOPUS:84964669924
SN - 1353-8020
VL - 28
SP - 29
EP - 35
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -