Clinical correlations of microstructural changes in progressive supranuclear palsy

In patients with progressive supranuclear palsy (PSP), previous reports have shown a severe white matter (WM) damage involving supra and infratentorial regions including cerebellum. In the present study, we investigated potential correlations between WM integrity loss and clinical-cognitive features of patients with PSP. By using magnetic resonance imaging and diffusion tensor imaging with tract based spatial statistic analysis, we analyzed WM volume in 18 patients with PSP and 18 healthy controls (HCs). All patients and HCs underwent a detailed clinical and neuropsychological evaluation. Relative to HCs, patients with PSP showed WM changes encompassing supra and infratentorial areas such as corpus callosum, fornix, midbrain, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior cerebellar peduncle, superior longitudinal fasciculus, uncinate fasciculus, cingulate gyrus, and cortico-spinal tract bilaterally. Among different correlations between motor-cognitive features and WM structural abnormalities, we detected a significant association between fronto-cerebellar WM loss and executive cognitive impairment in patients with PSP. Our findings, therefore, corroborate the hypothesis that cognitive impairment in PSP may result from both “intrinsic” and “extrinsic” frontal lobe dysfunction, likely related to cerebellar disconnection.