Longitudinal Cognitive Function in Progressive Supranuclear Palsy-A Review of the Evidence for Progression

Progressive supranuclear palsy is a rare and rapidly progressive neurodegenerative syndrome. Clinical manifestations are heterogeneous and include Parkinsonism, postural instability, oculomotor dysfunction and cognitive impairment, with 80% of patients progressing to dementia within 3 years. Cognitive impairment is consistently associated with poorer outcomes independent of motor function, including increased mortality, morbidity, caregiver burden and healthcare utilization. The prototypic cognitive phenotype of PSP demonstrates marked deficits in executive functions and slowed processing speed accompanied by neuropsychiatric symptoms. Cross-sectionally, these deficits are readily detected across a range of cognitive screening tools and more comprehensive neuropsychological batteries. Brief bedside assessments, such as the Frontal Assessment Battery, are highly effective at differentiating PSP from idiopathic Parkinson's disease soon after motor symptom onset. However, as the field increasingly moves toward disease-modifying trials that include cognitive outcome measures the purpose of cognitive assessment shifts; from supporting a clinical diagnosis, to measuring progression thereafter. The sensitivity to change of commonly used cognitive outcome measures is therefore a priority. In this narrative review we evaluate longitudinal cognitive assessment in PSP. We specifically focus on the unique challenges of cognitive assessment in this patient group and propose measurement priorities for future development.