Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy

Richard M. Tsai, Iryna V Lobach, Jee Bang, Jennifer L. Whitwell, Matthew L. Senjem, Clifford R Jack Jr, Howard Rosen, Bruce L Miller, Adam L Boxer, AL-108-231 Investigators

Research output: Contribution to journalArticleResearchpeer-review

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
Pages (from-to)29-35
Number of pages7
JournalParkinsonism and Related Disorders
Volume28
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

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

Cite this

Tsai, R. M., Lobach, I. V., Bang, J., Whitwell, J. L., Senjem, M. L., Jack Jr, C. R., ... AL-108-231 Investigators (2016). Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy. Parkinsonism and Related Disorders, 28, 29-35. https://doi.org/10.1016/j.parkreldis.2016.04.006
Tsai, Richard M. ; Lobach, Iryna V ; Bang, Jee ; Whitwell, Jennifer L. ; Senjem, Matthew L. ; Jack Jr, Clifford R ; Rosen, Howard ; Miller, Bruce L ; Boxer, Adam L ; AL-108-231 Investigators. / Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy. In: Parkinsonism and Related Disorders. 2016 ; Vol. 28. pp. 29-35.
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Tsai, RM, Lobach, IV, Bang, J, Whitwell, JL, Senjem, ML, Jack Jr, CR, Rosen, H, Miller, BL, Boxer, AL & AL-108-231 Investigators 2016, 'Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy' Parkinsonism and Related Disorders, vol. 28, pp. 29-35. https://doi.org/10.1016/j.parkreldis.2016.04.006

Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy. / Tsai, Richard M.; Lobach, Iryna V; Bang, Jee; Whitwell, Jennifer L.; Senjem, Matthew L.; Jack Jr, Clifford R; Rosen, Howard; Miller, Bruce L; Boxer, Adam L; AL-108-231 Investigators.

In: Parkinsonism and Related Disorders, Vol. 28, 01.07.2016, p. 29-35.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy

AU - Tsai, Richard M.

AU - Lobach, Iryna V

AU - Bang, Jee

AU - Whitwell, Jennifer L.

AU - Senjem, Matthew L.

AU - Jack Jr, Clifford R

AU - Rosen, Howard

AU - Miller, Bruce L

AU - Boxer, Adam L

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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.

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