eprintid: 10055847
rev_number: 26
eprint_status: archive
userid: 608
dir: disk0/10/05/58/47
datestamp: 2018-09-13 15:41:48
lastmod: 2021-10-15 22:32:11
status_changed: 2018-09-13 15:41:48
type: article
metadata_visibility: show
creators_name: Tsai, RM
creators_name: Lobach, I
creators_name: Bang, J
creators_name: Whitwell, JL
creators_name: Senjem, ML
creators_name: Jack, CR
creators_name: Rosen, H
creators_name: Miller, B
creators_name: Boxer, AL
creators_name: AL-108-231 Investigators, 
title: Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F84
keywords: Biomarkers, Clinical trials, Imaging, MRI, Progressive supranuclear palsy, Atrophy, Biomarkers, Brain, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Supranuclear Palsy, Progressive
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions
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.
date: 2016-04-24
date_type: published
official_url: https://doi.org/10.1016/j.parkreldis.2016.04.006
oa_status: green
full_text_type: other
pmcid: PMC4914401
language: eng
primo: open
primo_central: open_green
article_type_text: Clinical Trial, Phase II
verified: verified_manual
elements_id: 1574637
doi: 10.1016/j.parkreldis.2016.04.006
pii: S1353-8020(16)30084-0
lyricists_name: Lees, Andrew
lyricists_id: AJLEE60
actors_name: Bracey, Alan
actors_id: ABBRA90
actors_role: owner
full_text_status: public
publication: Parkinsonism & Related Disorders
volume: 28
pagerange: 29-35
event_location: England
issn: 1873-5126
citation:        Tsai, RM;    Lobach, I;    Bang, J;    Whitwell, JL;    Senjem, ML;    Jack, CR;    Rosen, H;             ... AL-108-231 Investigators; + view all <#>        Tsai, RM;  Lobach, I;  Bang, J;  Whitwell, JL;  Senjem, ML;  Jack, CR;  Rosen, H;  Miller, B;  Boxer, AL;  AL-108-231 Investigators;   - view fewer <#>    (2016)    Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy.                   Parkinsonism & Related Disorders , 28    pp. 29-35.    10.1016/j.parkreldis.2016.04.006 <https://doi.org/10.1016/j.parkreldis.2016.04.006>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10055847/1/nihms-785506.pdf