How Time Rules: Diurnal Motor Patterns in de novo Parkinson’s Disease

Several small-scale studies have shown that motor performance in Parkinson's disease (PD) fluctuates throughout the day. Studies specifically focusing on de novo patients are, however, lacking.To evaluate the effect of clock time on motor performance in de novo drug-naïve patients with PD.We retrieved MDS-UPDRS III scores for 421 de novo PD patients from the PPMI cohort and stratified them into three groups based on time of assessment: group 1) 7:00-10:00; group 2) 10:00-13:00, and group 3) 13:00-18:00. Groups were compared using Kruskal-Wallis test and results corrected for multiple testing. In addition, we obtained 27 wearable sensor reports, objectively capturing bradykinesia scores in a home setting over a 6-day continuous period, in 12 drug-naïve patients from the Parkinson's Kinetigraph Registry held at King's College Hospital London. Time spent in severe bradykinesia scores were broken down into five daytime (06:00-21:00) three-hourly epochs and scores compared using the Friedman test.There were no group differences in demographic or other clinical variables for the cross-sectional analysis. MDS-UPDRS III total scores worsened significantly during the course of the day (median 18 (group 1); 20 (group 2); and 23 (group 3); p = 0.001). In the longitudinal wearable sensor cohort, diurnal variations were present in percentage of time spent in severe bradykinesia (p < 0.001) with the lowest percentage during the 09:00-12:00 epoch (69.56±16.68%), when most patients are awake and start daily activity, and the highest percentage during the 18:00-21:00 epoch (73.58±16.35%).This exploratory study shows the existence of a diurnal pattern of motor function in patients with de novo PD. The results obtained were corroborated by objective measurements in a small longitudinal cohort confirming a similar diurnal motor score variation.