Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy. (July 2016)

• Record Type: Journal Article
• Authors: Tsai, Richard M.; Lobach, Iryna; Bang, Jee; Whitwell, Jennifer L.; Senjem, Matthew L.; Jack, Clifford R.; Rosen, Howard; Miller, Bruce; Boxer, Adam L.
• Is Part Of: Parkinsonism & related disorders. Volume 28(2016)
• Page Start: 29
• Page End: 35
• Publication Date: 2016-07
• Subjects: Progressive supranuclear palsy -- Clinical trials -- Biomarkers -- Imaging -- MRI; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2016.04.006
• Languages: English
• ISSNs: 1353-8020

Abstract

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. Highlights: vMRI outcomes are sensitive to PSP progression but not well correlated with clinical scale changes. vMRI outcomes may be useful to detect disease modifying effect in proof of concept studies. For clinically advanced PSP, progression may be better captured by vMRI than clinical measures. vMRI outcomes have excellent effect size and sample size estimate for future trials.