Cognitive decline heralds onset of symptomatic inherited prion disease

AbstractThe clinical effectiveness of any disease-modifying treatment for prion disease, as for other neurodegenerative disorders, will depend on early treatment before damage to neural tissue is irrevocable. Thus, there is a need to identify markers that predict disease onset in healthy at-risk individuals. Whilst imaging and neurophysiological biomarkers have shown limited use in this regard, we recently reported progressive neurophysiological changes in individuals with the inherited prion disease mutation P102L. We have also previously demonstrated a signature pattern of fronto-parietal dysfunction in mild prion disease. Here we address whether these cognitive features anticipate the onset of symptoms in a unique sample of patients with inherited prion disease. In the cross-sectional analysis, we analysed the performance of patients at three time points in the course of disease onset: prior to symptoms (n  = 27), onset of subjective symptoms without positive clinical findings (n  = 8) and symptomatic with positive clinical findings (n  = 24). In the longitudinal analysis, we analysed data from 24 patients who were presymptomatic at the time of recruitment and were followed up over a period of up to 17 years, of whom 16 remained healthy and eight converted to become symptomatic. In the cross-sectional analysis, the key finding was that, relative to a group of 25 healthy non-gene carrier controls, patients with subjective symptoms but without positive clinical f...

Source: Brain - April 9, 2021 Category: Neurology Source Type: research