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 language | English (US) |
|---|---|
| Journal | Parkinsonism and Related Disorders |
| DOIs | |
| State | Accepted/In press - Dec 29 2015 |
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Keywords
- Biomarkers
- Clinical trials
- Imaging
- MRI
- Progressive supranuclear palsy
ASJC Scopus subject areas
- Geriatrics and Gerontology
- Clinical Neurology
- Neurology
Cite this
Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy. / Tsai, Richard M.; Lobach, Iryna; Bang, Jee; Whitwell, Jennifer Lynn; Senjem, Matthew L.; Jack, Clifford R Jr.; Rosen, Howard; Miller, Bruce; Knopman, David S.
In: Parkinsonism and Related Disorders, 29.12.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy
AU - Tsai, Richard M.
AU - Lobach, Iryna
AU - Bang, Jee
AU - Whitwell, Jennifer Lynn
AU - Senjem, Matthew L.
AU - Jack, Clifford R Jr.
AU - Rosen, Howard
AU - Miller, Bruce
AU - Knopman, David S
PY - 2015/12/29
Y1 - 2015/12/29
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
UR - http://www.scopus.com/inward/record.url?scp=84964669924&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964669924&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2016.04.006
DO - 10.1016/j.parkreldis.2016.04.006
M3 - Article
C2 - 27132501
AN - SCOPUS:84964669924
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -