Exploring the heterogeneity of cognitive profile in patients with Progressive Supranuclear Palsy (PSP) enrolled in the ABBV-8E12 trial and the relationship to brain volumes

Progressive supranuclear palsy (PSP), is a rare neurodegenerative disorder involving deterioration of certain areas of the brain that result in it frequently being confused with Parkinson's disease. PSP can have a wide range of clinical presentations that include not only motor but also behavioural and cognitive impairments. Its most classical clinical presentation is called PSP-Richardson’s syndrome (PSP-RS) and is characterized by vertical supranuclear gaze palsy (i.e. inability to look in a vertical direction as a result of brain damage), postural instability, and unexplained falls (Höglinger, Respondek, & Stamelou, 2017). The prevalence of PSP was recently estimated at 10.84/100,000. PSP can often present with several other symptoms, including speech and language disorders and progressive deterioration of social comportment and cognition (e.g. executive dysfunction) but is only detected at later stages when the motor component begins. A better characterization of PSP patients according to the different cognitive and brain Magnetic Resonance Imaging (MRI) profiles could provide increased precision for understanding differences in presentation and progression of disease. Our project proposes a multimodal (multiple modalities including MRI clinical parameters) and longitudinal (over time) approach that would lead to a better characterization of PSP phenotypes (observable characteristics) so as to ultimately identify markers that would help in the design of more efficient clinical trials. This in the hope that early correct identification of PSP patients would lead to novel avenues for targeted treatments.