Timing and Kinetics of Nonmotor Fluctuations in Advanced Parkinson's Disease

Nonmotor symptoms (NMS) are known to fluctuate together with motor oscillations in advanced PD, but their timing and kinetics remains enigmatic.

To evaluate timing and kinetics of NMS fluctuations.

Analysis of diary data from 17 fluctuating PD patients. Diaries were completed by rating NMS as absent (defined herein as NMS On state) or present (NMS Off state) and motor function for every hour for 5 consecutive days. Timing and kinetics were analyzed by synchronizing motor Off periods and subsequent cross-classification of NMS Off periods for each motor Off hour into 2×2 contingency tables.

We found clear temporal connections of NMS Off periods with motor Off periods only for anxiety/depression, concentration/attention deficiency and bladder urgency. Psychiatric NMS Off periods had a longer duration (median: 3-4 hours) compared to motor Off periods (2 hours; P < 0.05, Mann-Whitney U-test).

Our data on timing and kinetics of NMS fluctuations show close temporal connection with motor Off periods only for mood and cognitive symptoms. Variances in both timing and/or kinetics of NMS fluctuations might explain both the weak/absent correlations of NMS and motor symptom severity in fluctuating patients and the rather low rates of simultaneous switches between On and Off states for NMS and motor function.