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Circadian dysfunction and fluctuations in gait initiation impairment in Parkinson’s disease

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Abstract

In people with Parkinson’s disease (PD), anticipatory postural adjustments may be prolonged, reduced in amplitude, or absent, contributing to impaired gait initiation. In addition to motor symptoms, disturbance of the circadian rhythm (CR) is one of the common non-motor symptoms of PD. The purpose of this study was to investigate whether time of day modulates the magnitude of gait initiation impairment, and furthermore, if there is any relationship between CR dysfunction and impaired postural control in PD. Seven consecutive 24-h periods of wrist actigraphy (as a measure of CR), and then gait initiation studies (at two different times, 9:00 a.m. and 2:30 p.m., of the same day) were conducted in two cohorts of ten subjects each: people with PD, and age-matched control subjects. We found that in the PD group, the amplitude of medial/lateral center of pressure (CoP) excursions were significantly reduced in the afternoon as compared with the morning session across all trials (p < 0.05). Actigraphy results showed that CR amplitude was significantly decreased (p < 0.05) in the PD group, which suggests that the PD group suffered from CR disruption. More importantly, changes in medial/lateral CoP displacement were correlated with abnormal CR amplitude in the PD group. These findings provide novel evidence that diurnal fluctuations in treatment-resistant motor symptoms of PD, such as postural and gait initiation deficits, are associated with CR dysfunction. This study supports the idea that therapeutic correction of circadian misalignment should be considered in combination with pharmaceutical and rehabilitation treatments of motor symptoms in PD.

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Acknowledgements

We would like to thank Farzana Boman for her invaluable contribution in recruiting subjects, data collection and analysis; Siddhi Tavildar and Thomas Ruopp for their significant help in creating and developing the data analysis programs, the study participants for their time, and the Parkinson’s Association of San Diego for their support in recruiting volunteers with PD.

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Correspondence to Laila Alibiglou.

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Dr. Liu and Dr. Ancoli-Israel received grant support from the NIH (UL1RR031980) and NIA (AG08415).

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The authors have no conflicts of interest to disclose.

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Stewart, J., Bachman, G., Cooper, C. et al. Circadian dysfunction and fluctuations in gait initiation impairment in Parkinson’s disease. Exp Brain Res 236, 655–664 (2018). https://doi.org/10.1007/s00221-017-5163-5

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