Prediagnostic Progressive Supranuclear Palsy - Insights from the UK Biobank.

INTRODUCTION: Prediagnostic features of Parkinson's Disease are well described but prediagnostic Progressive Supranuclear Palsy (PSP) is less understood. The diagnosis of PSP is delayed by an average of three years after symptom onset. Understanding the changes that occur in the prediagnostic period will aid earlier diagnosis, clarify the natural history, and may aid the design of early disease-modifying therapy trials. We set out to identify motor and cognitive markers of prediagnostic 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 5404 matched controls. RESULTS: 176 PSP cases (time to diagnosis 7.8 ± 2.8 years) and 2526 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, prospective memory, self-rated health scores and digit recall than controls. Reaction times were correlated with time to diagnosis. The PSP group 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 that are typically symptomatic three years before diagnosis. Objective markers of these features were evident on average 7.8 years before diagnosis. Our findings suggest the existence of a long prediagnostic phase in PSP, with subtle changes in motor and cognitive function.Acknowledgement: This research has been conducted using data from the UK Biobank, a major biomedical database. The UK Biobank is generously supported by its founding funders the Wellcome Trust and UK Medical Research Council, as well as the Department of Health, Scottish Government, the Northwest Regional Development Agency, British Heart Foundation and Cancer Research UK. Funding: This study was co-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge (BRC-1215-20014) and the Cambridge Brain Bank; the Holt Fellowship (RG86564); the Medical Research Council (MR/P01271X/1;SUAG051/G101400 and SUAG004/051/RG91365); and the Cambridge Centre for Parkinson-plus (RG95450). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care