TitleProgression of brain atrophy in PSP and CBS over 6 months and 1 year.
Publication TypeJournal Article
Year of Publication2016
AuthorsDutt S, Binney RJ, Heuer HW, Luong P, Attygalle S, Bhatt P, Marx GA, Elofson J, Tartaglia MC, Litvan I, McGinnis SM, Dickerson BC, Kornak J, Waltzman D, Voltarelli L, Schuff N, Rabinovici GD, Kramer JH, Jack CR, Miller BL, Rosen HJ, Boxer AL
Corporate AuthorsAL-108-231 investigators
JournalNeurology
Volume87
Issue19
Pagination2016-2025
Date Published2016 Nov 08
ISSN1526-632X
KeywordsAged, Atrophy, Basal Ganglia, Cerebral Cortex, Disease Progression, Female, Follow-Up Studies, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Statistics, Nonparametric, Supranuclear Palsy, Progressive
Abstract

OBJECTIVE: To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents.

METHODS: Six- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial.

RESULTS: Patients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale.

CONCLUSIONS: Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects.

DOI10.1212/WNL.0000000000003305
Alternate JournalNeurology
PubMed ID27742814
PubMed Central IDPMC5109951
Grant ListK24 AG045333 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
P01 AG017586 / AG / NIA NIH HHS / United States
R01 AG038791 / AG / NIA NIH HHS / United States
R01 AG032306 / AG / NIA NIH HHS / United States
U54 NS092089 / NS / NINDS NIH HHS / United States