Abstract Details

Title Longitudinal Rates of Brain Atrophy Differ Across Progressive Supranuclear Palsy Clinical Variants

Topic Movement Disorders

Presentation(s) P1 - Poster Session 1 (11:45 AM-12:45 PM)

Poster/Presentation
Number 5-025

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.

Authors/Disclosures
Mahesh Kumar, MBBS PRESENTER	Dr. Kumar has nothing to disclose.
Nirubol Tosakulwong	Nirubol Tosakulwong has nothing to disclose.
Stephen Weigand	Stephen Weigand has nothing to disclose.
Farwa Ali, MD (Mayo Clinic)	Dr. Ali has nothing to disclose.
Yehkyoung C. Stephens, PA	Mrs. Stephens has nothing to disclose.
Mary M. Machulda, PhD (Mayo Clinic)	The institution of Dr. Machulda has received research support from NIH.
Christopher Schwarz	The institution of Christopher Schwarz has received research support from NIH.
Matthew Senjem (Mayo Clinic)	Matthew Senjem has received stock or an ownership interest from Align Technology, Inc.. Matthew Senjem has received stock or an ownership interest from Inovio Biomedical Corp.. Matthew Senjem has received stock or an ownership interest from Johnson & Johnson. Matthew Senjem has received stock or an ownership interest from Mesa Laboratories, Inc.. Matthew Senjem has received stock or an ownership interest from Nvidia Inc.. Matthew Senjem has received stock or an ownership interest from LHC Group, Inc.. Matthew Senjem has received stock or an ownership interest from Natus Medical Incorporated. Matthew Senjem has received stock or an ownership interest from Varex Imaging Corporation. Matthew Senjem has received personal compensation in the range of $100,000-$499,999 for serving as a IT Technical Specialist II with Mayo Clinic.
Clifford R. Jack, Jr., MD (Mayo Clinic)	The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
Keith A. Josephs, Jr., MD, FAAN (Mayo Clinic)	Dr. Josephs has nothing to disclose.
Jennifer Whitwell, PhD (Mayo Clinic)	The institution of Dr. Whitwell has received research support from NIH.

��ɫ��

��ɫ��