Modeling Trajectories of Brain Damage in Progressive Supranuclear Palsy: A Longitudinal Multimodal MRI Study (S5.002)

Objective: To study longitudinally clinical, cognitive, and neuroimaging changes in patients with progressive supranuclear palsy syndrome (PSPs). Background: There is great interest in the identification of reliable biomarkers of PSPs progression. Methods: We enrolled 21 patients with Richardson’s syndrome (PSP-RS) and 10 with PSP-parkinsonism (PSP-P). Patients underwent clinical and neuropsychological evaluation and MRI scan at baseline and after a mean follow-up (FU) of 1.4 years. At baseline, MRI was obtained from 35 healthy controls. Diffusion tensor (DT) metrics of white matter (WM) tracts were assessed in both PSPs groups. Cortical thickness changes were investigated in PSP-RS patients. Results: Both PSPs groups showed significant motor impairment and cognitive decline, that appeared more severe in PSP-RS than in PSP-P patients. Apathy worsened in both groups, while depression and behavioral changes in PSP-RS only. At study entry, PSP-RS patients presented focal thinning of fronto-temporal and cingulate cortical areas bilaterally, compared to controls. Over time, cortical thinning progressed in cingulate cortex bilaterally, left fronto-temporal and insular cortices. At baseline, PSP-RS patients showed a widespread WM damage in midbrain, superior cerebellar peduncles, corpus callosum and the main long-range tracts. During FU, WM damage progressed in these patients in the corpus callosum, frontotemporal/-parietal connections, but not in infratentorial WM. In PSP-RS, WM damage progression correlated with the worsening of disability and behavioral dysfunction. DT MRI analysis showed that, at baseline, PSP-P patients had WM damage in the anterior corpus callosum, external capsule, corona radiate, and superior longitudinal fasciculus bilaterally, compared to controls; these same regions showed a subtle progression of damage during FU. Conclusions: In PSPs patients, the progression of WM microstructural damage is prominent compared to cortical damage and it is related to the worsening of clinical symptoms. MRI differences between clinical phenotypes might reflect the different extent and distribution of the underlying tau pathology.