Abstract
Clinical and biochemical diversity of Parkinson's disease (PD) presents a major challenge for accurate diagnosis and prediction of its progression. We propose, develop and optimize PD clinical scores as efficient integrated progression biomarkers for prediction of the likely rate of cognitive decline in PD patients. We considered 269 drug-naïve participants from the Parkinson's Progression Marker Initiative database, diagnosed with idiopathic PD and observed between 4 and 6 years. Nineteen baseline clinical and pathological measures were systematically considered. Relative variable importance and logistic regressions were used to optimize combinations of significant baseline measures as integrated biomarkers. Parkinson's disease cognitive decline scores were designed as new clinical biomarkers using optimally categorized baseline measures. Specificities and sensitivities of the biomarkers reached ~93% for prediction of severe rate of cognitive decline (with more than 5 points decline in 4 years on the Montreal Cognitive Assessment scale), and up to ~73% for mild-to-moderate decline (between 1 and 5 points decline). The developed biomarkers and clinical scores could resolve the long-standing clinical problem about reliable prediction of PD progression into cognitive deterioration. The outcomes also provide insights into the contributions of individual clinical and pathological measures to PD progression, and will assist with better-targeted treatment regiments, stratification of clinical trial and their evaluation.