Early assessment, diagnosis and treatment of Parkinsonism and Related Syndromes study (ExPRESS): a protocol for an observational study on incident parkinsonism.

introductionExisting evidence from cohort studies of atypical parkinsonism has demonstrated that median time from symptom onset to diagnosis is 3.4 years for progressive supranuclear palsy (PSP) and 3.1 years for multiple system atrophy (MSA). This compares to only 1.0-1.2 years in Parkinson's disease (PD). Earlier diagnosis is essential to facilitate recruitment to disease-modifying treatment trials. In the Early Assessment, Diagnosis and Treatment of Parkinsonism and Related Syndromes study, we will prospectively assess patients across the UK with incident parkinsonism and determine the best predictors to improve early diagnosis of the 'Parkinson-plus' syndromes (PPS) and build a trial-ready cohort. METHODS AND ANALYSIS: In this longitudinal prospective clinical cohort study, we will recruit 500 people with incident parkinsonism or syndromes associated with later PPS. Participants must be within 12 months of their first secondary care appointment for either motor disturbance or other symptoms of prodromes to PPS. Participants will return a self-completed questionnaire about their symptoms and have a structured neurological assessment by a clinician capturing key clinical features, clinical diagnostic criteria and quantitative clinical scales. Blood for DNA and plasma will be collected at baseline. 120 participants recruited to a subset of study sites will be invited to undergo detailed biomarker assessments such as additional blood collection, lumbar puncture, skin biopsy, MRI, cognitive assessments and digital biomarker assessments.We will stratify participants according to their most likely clinical diagnosis at 4 years post-baseline as the gold standard clinical diagnosis. This will be supplemented by neuropathological examination where available. We will use multivariable logistic modelling to identify early predictors of atypical PPS versus PD. Lifetime follow-up will be carried out using medical records linkage with participant consent. ETHICS AND DISSEMINATION: Ethical approvals have been granted by the Queen Square Research Ethics Committee (Ref: 14/LO/1575), with approval from the Health Research Authority and each participating site. Findings from the study will be published in academic journals and presented at UK-wide and international conferences, as well as disseminated via patient advocacy groups and charities including the PSP Association, Cure PSP, Rare Dementia Support and the MSA Trust.