Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy

AL-108-231 Investigators

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Progressive Supranuclear Palsy
Atrophy
Brain
Mesencephalon
Color
Clinical Trials
Activities of Daily Living
Geriatrics
England
Disease Progression
Linear Models
Outcome Assessment (Health Care)

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. / AL-108-231 Investigators.

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

Research output: Contribution to journalArticle

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title = "Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy",
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.",
keywords = "Biomarkers, Clinical trials, Imaging, MRI, Progressive supranuclear palsy",
author = "{AL-108-231 Investigators} and Tsai, {Richard M.} and Iryna Lobach and Jee Bang and Whitwell, {Jennifer L.} and Senjem, {Matthew L.} and Jack, {Clifford R.} and Howard Rosen and Bruce Miller and Boxer, {Adam L.} and David Williams and Lafontaine, {Anne Louise} and Connie Marras and Mandar Jog and Michael Panisset and Anthony Lang and Lesley Parker and Stewart, {Alistair J.} and Corvol, {Jean Christophe} and Azulay, {Jean Philippe} and Philippe Couratier and Brit Mollenhauer and Stefan Lorenzl and Albert Ludolph and Reiner Benecke and Gunter Hoglinger and Axel Lipp and Heinz Reichmann and Dirk Woitalla and Dennis Chan and Adam Zermansky and David Burn and Andrew Lees and Illana Gozes and Adam Boxer and Miller, {Bruce L.} and Lobach, {Iryna V.} and Erik Roberson and Lawrence Honig and Edward Zamrini and Rajesh Pahwa and Yvette Bordelon and Erika Driver-Dunkley and Stephanie Lessig and Mark Lew and Kyle Womack and Brad Boeve and Joseph Ferrara and Argyle Hillis and Daniel Kaufer and Rajeev Kumar",
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day = "1",
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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 - Boxer, Adam

AU - Miller, Bruce L.

AU - Lobach, Iryna V.

AU - Roberson, Erik

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

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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