Assessment of Nonmotor Fluctuations Using a Diary in Advanced Parkinson's Disease

Background: Since previous studies aimed to study nonmotor symptom (NMS) fluctuations in direct conjunction with motor oscillations, there are no data available on the temporal context of NMS fluctuations and motor oscillations in advanced Parkinson's disease (PD). Objective: To evaluate circadian patterns and temporal connections of NMS and motor fluctuations in PD. Methods: 15 controls, 17 non-fluctuating and 15 fluctuating PD patients completed two diaries by rating 4 key psychiatric (anxiety, depressive mood, inner restlessness, concentration/attention deficits), fatigue and 4 autonomic NMS (excessive sweating, sialorrhea, bladder urgency, dizziness) absent or present and motor function (Off, On with/without dyskinesia, and asleep) for every hour for 5 consecutive days. Results: NMS Off state hours (hours with NMS rated as present) were less frequent compared to motor Off state hours and NMS On-Off-switches were less prevalent compared to those of the motor state. Off time and number of On-Off-switches of psychiatric NMS were moderately correlated with motor Off time and number of motor On-Off switches on the individual patient level. Changes in NMS state occurred largely independent of changes in motor states with concordance rates of only 26-43% of all NMS changes for psychiatric and 7-17% for autonomic NMS. In controls and non-fluctuating PD patients, there were no NMS state switches in concordance to motor state switches. Conclusion: We provide first data on the temporal context of NMS fluctuations showing similar frequencies of psychiatric NMS Off, fatigue Off and motor Off times as well as their On-Off-fluctuations, but low concordance rates of NMS with motor On-Off-state switches. We found no evidence for NMS fluctuations in non-fluctuating PD patients. Our data implicate similar fluctuation patterns of mood NMS and motor function without close timing and/or different kinetics.