Predictors of functional decline in early Parkinson's Disease: NET-PD LS1 Cohort

Background: Data on predictors of decline in PD are largely based on de-novo populations and limited to the use of motor outcomes that fail to capture the full scope of disease. Objective: Determine the clinical predictors of decline in early treated PD using a novel multi-domain measure. Methods: Data from NINDS Exploratory Trials in PD Long-Term Study 1 (NET-PD LS1), a multicenter Phase 3 study of creatine in early treated PD, were analyzed. Functional decline was defined by a global outcome metric (GO) that consisted of: Schwab and England ADL scale, PD 39-item Questionnaire, Unified PD Rating Scale, Ambulatory Capacity Score, Symbol Digit Modalities Test, and Modified Rankin Scale. Univariate and multivariate models were used to test the association of predictors of interest with a standardized rank-sum of the GO. Results: 765 of 1741 participants completed five-year assessments and were included. Older age at disease onset (p > 0.0001), higher baseline levodopa equivalent dose (p = 0.01), and worse Scales for Outcomes of Parkinsons Disease Cognition score (p = 0.001) at baseline were the strongest predictors of functional decline in multivariate analysis. PD symptom subtype was not a significant predictor of outcome (p = 0.42). The full model was only a modest predictor of change in GO (R2 = 0.186). Conclusions: This is the largest study to systematically assess predictors of functional decline in early treated PD over several years, and the first to use a multi-domain outcome measure of decline. Older age at disease onset and worse cognition, and not PD subtype, were predictors of decline.