Is motor reserve associated with a rapid progression of Parkinson disease?

BackgroundThe motor reserve estimates (MRes) derived from a residual approach correlate with motor severity in Parkinson's disease (PD), leaving the independent effect of motor reserve on clinical outcomes unclear.ObjectiveInvestigate the independent influence of motor reserve on the long-term outcome.MethodsUsing the Parkinson's Progression Markers Initiative (PPMI) and Pusan National University Hospital (PNUH) datasets, we investigated the association of MRes with progression of motor severity as well as risk of phenoconversion to Hoehn & Yahr (H&Y) stage 3. Two MRes types were calculated: (1) original MRes, negative conversion of standardized residuals from a generalized linear model (GLM) between putaminal dopamine transporter (DAT) levels and motor severity, and (2) modified MRes, standardized residuals from the GLM between original MRes and motor scores.ResultsOriginal MRes correlated with baseline motor scores, while modified MRes did not. Modified MRes in both cohorts were associated with a rapid increase in motor severity (linear mixed effect model, interaction between MRes and disease duration; PPMI, Movement Disorder Society sponsored Unified Parkinson Disease Rating Scale part III [MDS-UPDRS III], estimate 2.248 × 10^-3, p < 0.001; PNUH, UPDRS III, estimate 0.027, p = 0.014) In both cohorts, Kaplan-Meier plots showed high modified MRes indicated higher risk of progression to H&Y stage 3. Mediation models using original MRes agreed that high MRes were associated with an accelerated increase in motor scores.ConclusionsIndependent of baseline motor severity, MRes were associated with rapid motor deterioration and high risk of progression to H&Y stage 3.