|Title||Progression of brain atrophy in PSP and CBS over 6 months and 1 year.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Dutt 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 Authors||AL-108-231 investigators|
|Date Published||2016 Nov 08|
|Keywords||Aged, 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|
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.
|PubMed Central ID||PMC5109951|
|Grant List||K24 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