Prodromal Progressive Supranuclear Palsy: insights from the UK Biobank


Background Prodromal Parkinson’s Disease is well described but prodromal Progressive Supranuclear Palsy (PSP) is much less understood. The diagnosis of PSP is typically delayed by an average of three years after symptom onset. Understanding the changes that occur in the prodromal and pre-diagnostic period will aid earlier diagnosis, clarify the natural history, and aid the design of early disease-modifying therapy trials. Objectives To determine motor and cognitive markers of prodromal PSP, with Parkinson’s disease as a comparator condition, in a large prospective cohort. Methods Baseline UK Biobank data from 502,504 individuals were collected between 2006 and 2010. Subsequent PSP and Parkinson’s disease cases were identified from primary and secondary care electronic health records’ diagnostic coding data and death registry, with 5,404 matched controls. Results 176 PSP cases (time to diagnosis 7.8±2.8 years) and 2,526 Parkinson’s disease cases (time to diagnosis 7.8±2.9 years) were identified. At baseline, those later diagnosed with PSP had slower reaction times, weaker hand grip, lower fluid intelligence, poorer prospective memory, worse self-rated health score and lower digit recall than controls. They had higher mortality than both Parkinson’s disease and control groups. Conclusions Motor slowing, cognitive dysfunction, and postural instability are clinical diagnostic features of PSP and are typically symptomatic three years before diagnosis. However, objective markers of these features are evident over seven years before diagnosis. This suggests a long prodromal course in PSP with subtle changes in motor and cognitive function.