Progression of prodromal motor and non‐motor symptoms in the premotor phase study – 2‐year follow‐up data

Background and purpose The neuropathological process starts years before the diagnosis of Parkinson's disease ( PD ). Assessment of prodromal features in healthy individuals may help to define those with high risk for future PD . Our aim was to evaluate the presence and progression of prodromal markers in individuals with low risk [healthy controls ( HC ), n = 14] and high risk for PD ( HR ‐ PD , n = 34) and early PD ( n = 14) patients. Methods Several risk or prodromal markers were combined to define HR ‐ PD . Other prodromal markers were followed in 6‐month intervals for 2 years. As recommended by the Movement Disorder Society Task Force, likelihood ratios ( LR s) of markers, motor scores and PD probability scores were calculated and compared. Results The baseline LR for non‐motor prodromal markers was significantly higher in PD and HR ‐ PD compared to HC . Within 2 years, changes in these LR s did not significantly differ between the groups. Motor worsening was significant only in the PD group (50% of the patients) against HR ‐ PD (15%) and HC (7%). Change in the non‐motor prodromal LR did not significantly correlate with motor worsening, but higher baseline non‐motor LR s were associated with Unified Parkinson's Disease Rating Scale III values at 2 years of follow‐up. Conclusions Our study shows that the frequency of non‐motor prodromal markers is higher in the HR ‐ PD group but does not increase within 2 years. The progression of motor and non‐motor markers seems to be independent, but higher baseline non‐motor burden is associated with the motor status after 2 years. Moreover, our data argue for a high impact of motor markers in the risk estimation for future PD .