title: Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Memory and Aging Center, University of California at San Francisco, San Francisco, CA, USA. Electronic address: Richard.Tsai@ucsf.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Tsai
authors.affiliation: Department of Epidemiology and Biostatistics, Division of Biostatistics, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Iryna
authors.initials: I
authors.lastname: Lobach
authors.affiliation: Memory and Aging Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Jee
authors.initials: J
authors.lastname: Bang
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Whitwell
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Memory and Aging Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Rosen
authors.affiliation: Memory and Aging Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.affiliation: Memory and Aging Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
mesh_terms: D001284:Atrophy / Q000473:pathology; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Clinical trials; Imaging; MRI; Progressive supranuclear palsy