Disease stage dependency of motor and non-motor fluctuations in Parkinson's disease

Recent data suggested a decrease in non-motor fluctuations in late-stage Parkinson's disease (PD), but systematic data on non-motor fluctuations over the whole disease course are mainly lacking. We performed a meta-analysis of two studies with very similar cross-sectional cohort designs, namely the German multicenter Non Motor Fluctuation in PD study and the Swedish part of the European multicenter study Care for Late Stage Parkinsonism. We included only patients with documented motor fluctuations in the analyses. Disease stage was estimated using the Hoehn and Yahr score, motor symptoms using the Unified PD Rating Scale part III motor score and non-motor symptom (NMS) fluctuations using the modified version of the NMS scale assessing a broad range of NMS in motor On and Off state. We included 101 patients (55% men; median age: 71 (interquartile range, IQR 65-78) years with Hoehn and Yahr stages ranging from 1 to 5 [median (IQR) 3.0 (2.0-4.0); distribution of patients in Hoehn and Yahr stages was n = 42 (42%) in stages 2/3 and n = 48 (48%) in stages 4/5]. We found a clear dependency of non-motor burden on Hoehn and Yahr stage with increasing symptom severity, but decreasing fluctuation amplitudes for motor and NMS (difference of symptom severity between On and Off state) with disease stage progression. Indeed, in Hoehn and Yahr stage 5, we did not detect significant NMS fluctuations. Multivariate regression with major demographic and clinical covariates confirmed these results. In conclusion, NMS fluctuations showed a similar disease stage dependency as observed for motor fluctuations with decreasing fluctuation amplitude with disease progression.