Tossing and Turning in Bed: A Wearable Sensor Documents Abnormal Nocturnal Movements in Parkinson's Disease

Abstract

Background: Sleep interruptions and nocturnal hypokinesia are common in Parkinson's disease (PD). Pilot work using wearable technologies showed fewer nocturnal movements in patients with advanced PD compared to controls. However, the prevalence of these impairments in early stage of the disease and the influence of non-motor symptoms, and dopaminergic medication are unknown. Methods: This study evaluated wearable sensor data collected in 305 patients with PD at different Hohen and Yahr disease stages (HY HY H&Y3=77) and 205 healthy controls (HC). Subjects wore a tri-axial accelerometer continuously (24/7) on the lower back for at least 2 days. Percent upright-time and nighttime walking were defined based on the vertical axis of the acceleration signal and were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed during the night evaluated nocturnal movements. Findings: Nocturnal lying-time was similar between PD and controls (p=0.501), however, the number of turns and the turn velocity significantly decreased (p<0.001) with H&Y stage. Advanced patients (H&Y3) had more upright periods during the night while the number and velocity of their turns were reduced (p<=0.021). Recently diagnosed patients (<1 year from diagnosis) were similar to controls in number of nocturnal turns (p=0.148) but showed longer turning time (p=0.001) and reduced turn magnitude (p=0.002). Nocturnal movements were significantly correlated with non-motor symptoms, cognition, and dopaminergic medication. Interpretation: Reduced nocturnal movements are already detectable in recently diagnosed patients and are associated with increased PD motor severity and dysautonomia. Using wearable sensors for continuous monitoring at night may offer an unbiased, objective measure of disease severity that could enhance optimal nighttime dopaminergic treatment and utilization of turning strategies. Funding Statement: European Commission (FP7 project V-TIME-278169), The Michael J Fox Foundation for Parkinson's research, a grant from Biogen Inc and by the NIHR/Wellcome Trust Clinical Research Facility (CRF). Declaration of Interests: Anat Mirelman, Jeff Hausdorff and Nir Giladi report having submitted a patent for assessment of mobility using wearable sensors in Parkinson's disease. The intellectual property rights are held by the Tel Aviv Medical Center. Prof. Mirelman and Hausdorff also serve as consultants for the Michael J Fox Foundation, Biogen, Sanofi (JH) and Neuroderm (AM) in areas relating to the use of wearable sensors to assess mobility in PD. JMH and AM have received grant funding from the European Commission and MJFF. Lynn Rochester reports no conflict of interests pertaining to the manuscript. She receives grants from the Medical Research Council, European Commission, NIHR, Wellcome Trust, EPSRC, Parkinson's UK, and the Stroke Association. Alice Nieuwboer reports no conflict of interest pertaining to the manuscript. She has received grant funding from the European Commission. Bastiaan R Bloem currently serves on the editorial of Practical Neurology and Digital Biomarkers, has received honoraria from serving on the scientific advisory board for Abbvie, Biogen, UCB and Walk with Path, has received fees for speaking at conferences from AbbVie, Zambon, Roche, GE Healthcare and Bial, and has received research support from the Netherlands Organization for Scientific Research, the Michael J Fox Foundation, UCB, Abbvie, the Stichting Parkinson Fonds, the Hersenstichting Nederland, the Parkinson’s Foundation, Verily Life Sciences, Horizon 2020, the Topsector Life Sciences and Health, and the Parkinson Vereniging. Jesse Cederbaum and Mirek Brys are shareholders in Biogen, Inc. Nir Giladi reports reports counseling for: Neuroderm, Intec Pharma, Teva, Genzyme-Sanofi, Biogen, Lysosomal Therapeutics, Denali, Cellanis, GaitBetter, Vibrant and Sionara; that he holds shares or options in Lysosomal Therapeutics, Cellanis, GaitBetter and Vibrant; that he has received royalties from Lysosomal Therapeutics; that he received honorarium from UCB, Teva, Novartis, Abbvie, Genzyme-Sanofie, Neuroderm, Bial, Shire, MDS; that he has chaired the DSMBs for Teva and Pharma2B; that he is a PI on a Center Grant given by Biogen to TLVMC. Inbar Hillel, Silvia Sel Din, Laura Avanzino, Inbal Maidan, Talia Herman, Meir Kestenbaum, Avner Thaler, Tanya Gurevich and Avi Orr Urtreger report no disclosures pertaining to the manuscript. Ethics Approval Statement: The studies were approved by local ethical committees and were performed according to the principles of the Declaration of Helsinki. All participants gave their informed written consent prior to participation.