Neuropsychological characterization of typical and atypical progressive supranuclear palsy and comparison with Parkinson's disease

Abstract

This thesis examined the cognitive aspects of patients with progressive supranuclear palsy defined according to the recently proposed phenotypic distinctions (PSP+). 14 patients with PSP-Richardson’s syndrome (PSP-RS), 3 with PSP-Parkinsonism (PSP-P), 4 with PSP-Pure akinesia with gait freezing (PSP-PAGF) and 19 patients with idiopathic Parkinson’s disease (PD) were examined using a comprehensive battery of neuropsychological tests encompassing a wide range of cognitive domains. The results from the current thesis provide clear evidence that the PSP clinical phenotypes can be differentiated by a characteristic pattern and progression of cognitive deficits at a group (PSP+) and at a phenotypic level (PSP-RS, PSP-P, PSP-PAGF). Specifically, the pattern of cognitive deficits most useful in distinguishing between PSP+ and PD were psychomotor slowing and prominent ‘frontal’ executive dysfunction. In addition, longitudinal analyses revealed a differential decline of executive function in patients with PSP+ in comparison to PD. At the phenotypic level, patients with the classic variant of PSP (PSP-RS) could be distinguished from those with the ‘atypical’ phenotypes (PSP-P and PSP-PAGF) by a more severe and extensive pattern of cognitive impairments and longitudinal decline in executive function. These findings were broadly consistent with the reported pathological differences in PSP-RS, PSP-P, and PSP-PAGF. Results from this research confirm the existence of three distinct clinical phenotypes of PSP, which can be differentiated on pathological, clinical and cognitive grounds. In addition, this thesis indicates that neuropsychological assessment may be able to contribute to the in vivo differentiation of the PSP clinical phenotypes in clinical practice.