Longitudinal Rates of Brain Atrophy Differ Across Progressive Supranuclear Palsy Clinical Variants
Mahesh Kumar1, Nirubol Tosakulwong2, Stephen Weigand2, Farwa Ali1, Yehkyoung Stephens1, Mary Machulda3, Christopher Schwarz4, Matthew Senjem4, Clifford Jack4, Keith Josephs1, Jennifer Whitwell4
1Department of Neurology, 2Department of Health Sciences Research, 3Department of Psychiatry and Psychology, 4Department of Radiology, Mayo Clinic
Objective:
To determine whether longitudinal regional rates of brain atrophy differ across the different clinical variants of progressive supranuclear palsy (PSP).
Background:
Progressive supranuclear palsy is a neurodegenerative disorder characterized by progressive atrophy of brainstem, subcortical and frontal brain regions. It is unknown whether patterns of longitudinal brain atrophy differ between classic PSP-Richardson’s syndrome (PSP-RS) and the cortical and subcortical clinical variants of PSP.
Design/Methods:
88 PSP participants (50 PSP-RS, 18 PSP-Cortical, 20 PSP-Subcortical) and 32 controls underwent two serial 3T MRI with a 12-month interval. Grey matter or tissue volumes were calculated for 10 regions-of-interest, and mixed-effects regression analysis was performed to compare annualized rates of atrophy across groups, accounting for age, scan interval, sex and total intracranial volume. Sample sizes required to power placebo-controlled treatment trials to detect a 20% treatment effect with 80% power were calculated for rates of atrophy and change in the PSP Rating Scale.
Results:
Rates of midbrain and cerebellar dentate atrophy were greater in all PSP variants compared to controls, with similar trends for subthalamic nucleus. PSP-RS showed greater midbrain atrophy rates compared to the other variants. PSP-cortical showed greater rates of pallidum, putamen and caudate atrophy compared to controls and PSP-RS. Both PSP-RS and PSP-cortical showed greater rates of superior frontal and precentral atrophy compared to controls, with no differences between variants. Midbrain provided the smallest sample size estimates of all brain regions for PSP-RS (170 participants per arm), comparable to the PSP Rating Scale (159 participants). The smallest samples size estimates for PSP-cortical (113 participants) and PSP-subcortical (538 participants) were obtained with the PSP Rating Scale.
Conclusions:
Regional patterns of brain atrophy differ across PSP clinical variants, although sample size estimates suggest that the PSP Rating scale is the optimum outcome measure for clinical treatment trials recruiting different PSP clinical variants.
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