UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease

Wilson, Heather; Pagano, Gennaro; Niccolini, Flavia; Muhlert, Nils; Mehta, Mitul A; Searle, Graham; Gunn, Roger N; ... Politis, Marios; + view all (2020) The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease. Parkinsonism & Related Disorders , 77 pp. 163-169. 10.1016/j.parkreldis.2019.02.027. Green open access

[thumbnail of Wilson_Politis_PDE4_SleepPD_RevisedText_Clean.pdf]
Preview
Text
Wilson_Politis_PDE4_SleepPD_RevisedText_Clean.pdf - Accepted Version

Download (216kB) | Preview

Abstract

INTRODUCTION: Preclinical studies suggest a link between cAMP/PKA signalling, phosphodiesterase 4 (PDE4) expression and excessive daytime sleepiness (EDS). Here, we investigated in vivo the association between PDE4 expression and EDS in Parkinson's disease (PD) patients using [11C]rolipram PET and MR imaging. METHODS: Eighteen participants, 12 PD and 6 healthy controls, underwent one [11C]rolipram PET and a multi-modal MRI scan. Probabilistic tractography was performed on subjects' diffusion data to functionally parcellate the striatum according with projections to limbic cortical areas. The severity of EDS was assessed using the Epworth Sleepiness Scale (ESS). To assess PDE4 expression in PD patients with EDS, the PD cohort was divided according to the presence (n = 5) or absence (n = 7) of EDS, defined using validated cut-off of score ≥10 on the ESS as score ≥10 on the ESS. RESULTS: PD patients with EDS showed significantly increased [11C]rolipram volume of distribution (VT) in the caudate (P = 0.029), hypothalamus (P = 0.013), hippocampus (P = 0.036) and limbic striatum (P = 0.030) compared to patients without EDS. Furthermore, higher ESS scores correlated with increased [11C]rolipram VT in the caudate (r = 0.77; P = 0.003), hypothalamus (r = 0.84; P = 0.001), hippocampus (r = 0.81; P = 0.001) and limbic subdivisions of the striatum (r = 0.80; P = 0.003). CONCLUSION: Our findings translate into humans preclinical data indicating that EDS is associated with elevated PDE4 in regions regulating sleep. The severity of EDS in PD was associated with elevated PDE4 expression; thus, suggesting a role of PDE4 in the pathophysiology of EDS in PD.

Type: Article
Title: The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.parkreldis.2019.02.027
Publisher version: https://doi.org/10.1016/j.parkreldis.2019.02.027
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Diffusion tensor imaging, Excessive daytime sleepiness, Parkinson's disease, Phosphodiesterase 4, Positron emission tomography, Rolipram
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10069921
Downloads since deposit
64Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item