Imperial College London
Alternate

ProfessorRogerGunn

Faculty of Medicine, Department of Brain Sciences

Emeritus Professor of Molecular Neuroimaging
 
 
 
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r.gunn

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wilson:2019:10.1016/j.parkreldis.2019.02.027,
author = {Wilson, H and Pagano, G and Niccolini, F and Muhlert, N and Mehta, MA and Searle, G and Gunn, RN and Rabiner, EA and Foltynie, T and Politis, M},
doi = {10.1016/j.parkreldis.2019.02.027},
journal = {Parkinsonism and Related Disorders},
pages = {163--169},
title = {The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease},
url = {http://dx.doi.org/10.1016/j.parkreldis.2019.02.027},
volume = {77},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Wilson,H
AU  - Pagano,G
AU  - Niccolini,F
AU  - Muhlert,N
AU  - Mehta,MA
AU  - Searle,G
AU  - Gunn,RN
AU  - Rabiner,EA
AU  - Foltynie,T
AU  - Politis,M
DO  - 10.1016/j.parkreldis.2019.02.027
EP  - 169
PY  - 2019///
SN  - 1353-8020
SP  - 163
TI  - The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease
T2  - Parkinsonism and Related Disorders
UR  - http://dx.doi.org/10.1016/j.parkreldis.2019.02.027
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30824285
UR  - http://hdl.handle.net/10044/1/68972
VL  - 77
ER  -
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