Identifying Novel Modifiable Risk Factors in Progressive Supranuclear Palsy (PSP): A Secondary Use Analysis of Clinical Trial Data

Abstract

Much of the current research efforts to treat neurological diseases have been focused on identifying novel disease biomarkers to aid in diagnosis, provide prognostic information, and monitor disease progression. Yet none have been found in Progressive Supranuclear Palsy (PSP). The goal of this work was to identify modifiable risk factors that predict disease progression and survival in PSP. This study performed a secondary analysis of de-identified data from several PSP clinical trials. A disease-specific rating scale, Progressive Supranuclear Palsy Rating Scale (PSPRS), and baseline variables (i.e., demographic variables, concomitant medications, baseline medical history, vital signs, etc.) were used to assess predictors of disease progression and survival. PSPRS metrics (individual items and domains) were examined and correlated with total PSPRS progression via Spearman’s correlations between individual questions and domains compared to the total PSPRS. To examine predictors of PSPRS progression using baseline variables, pooled linear regression model (PLM) analyses were performed. Baseline predictors were then compared to survival (time to death) by using multivariate Cox proportional-hazards models. Eye movements (oculomotor), gait, and postures were found to be good predictors of disease progression. Within the gait, posture, and oculomotor domains, disease progression of individual items clustered together, which indicate similar underlying mechanisms. Only benzodiazepine derivatives, along with a past medical history of immune system disorders, psychiatric disorders, and renal and urinary disorders were associated with faster disease progression in PSP. Survival analyses suggested that dysphagia, other bulbar items, and loss of oculomotor function were excellent predictors of survival in PSP patients. In summary, specific PSPRS items, PSPRS domains, concomitant medications, and baseline medical history were identified as potential risk factors that may predict progression and survival in PSP.