Article Text
Abstract
My ABN fellowship focusses on the syndromes caused by frontotemporal lobar degeneration. Despite distinctive pathological causes, these highly heterogeneous syndromes overlap in clinical manifesta- tions and pathophysiology. This is both a challenge and an opportunity for future trials aimed at slowing the diseases or treating their symptoms. By modelling phenotypic data and long-term outcomes, I will determine the features of blood, brain and behaviour that predict survival. The “PIck’s disease and Pro- gressive supranuclear palsy Prevalence and INcidence” study (PiPPIN), has 440 participants from previous recruitment phases, of whom 318 have died. I have recruited 91 from an expected 220-250 patients in this 3rd phase. My initial analysis of existing samples will test the hypothesis that metabolic signatures dif- ferentiate disorders (PSP, FTD, controls). Preliminary results from N=269 samples confirm multiple metabolic differences between patients and controls, focussing within the lipid pathways. This will be analysed in relation to clinical severity, phenotype, and survival outcomes. Subsequent analysis will integrate cognitive/behavioural profiles, magnetic resonance imaging and spectroscopy, and blood biomarkers (including metabolites) in multivariate models of survival. Prediction of survival does not indicate causation but will generate hypotheses of promising targets for intervention and tools for risk-based stratification.