Sleep problems and hypothalamic dopamine D3 receptor availability in Parkinson disease.
OBJECTIVE
To investigate the relationship between hypothalamic D3 dopamine receptor availability and severity of sleep problems in Parkinson disease (PD).


METHODS
Twelve patients were assessed with PET and the high-affinity dopamine D3 receptor radioligand [11C]-propyl-hexahydro-naphtho-oxazin ([11C]-PHNO). Severity of sleep problems was rated with appropriate subitems of the Unified Parkinson's Disease Rating Scale part I (patient questionnaire) and the Epworth Sleepiness Scale.


RESULTS
We found that lower dopamine D3 receptor availability measured with [11C]-PHNO PET was associated with greater severity of excessive daytime sleepiness but not with problems of falling asleep or insomnia.


CONCLUSIONS
In our cohort of patients with PD, the occurrence of excessive daytime sleepiness was linked to reductions in hypothalamic dopamine D3 receptor availability. If these preliminary findings are confirmed in larger cohorts of patients with polysomnographic characterization, selective pharmacologic modulation of the dopaminergic D3 system could be used to increase daytime alertness in patients with PD.
From the Division of Brain Sciences (G.P., P.G.B., D.J.B., N.P.), Imperial College London; Imperial College NHS Trust (S.M.); Imanova Ltd (E.A.R.); National Parkinson Foundation International Centre of Excellence (E.A.R.), King's College London and National Institute for Health Research Biomedical Research Centre and King's College London; Institute of Neuroscience (D.J.B., N.P.), Newcastle University, UK; and Institute of Clinical Medicine (D.J.B., N.P.), University of Aarhus, Denmark.
Gennaro
G
Pagano
From the Division of Brain Sciences (G.P., P.G.B., D.J.B., N.P.), Imperial College London; Imperial College NHS Trust (S.M.); Imanova Ltd (E.A.R.); National Parkinson Foundation International Centre of Excellence (E.A.R.), King's College London and National Institute for Health Research Biomedical Research Centre and King's College London; Institute of Neuroscience (D.J.B., N.P.), Newcastle University, UK; and Institute of Clinical Medicine (D.J.B., N.P.), University of Aarhus, Denmark.
Sophie
S
Molloy
From the Division of Brain Sciences (G.P., P.G.B., D.J.B., N.P.), Imperial College London; Imperial College NHS Trust (S.M.); Imanova Ltd (E.A.R.); National Parkinson Foundation International Centre of Excellence (E.A.R.), King's College London and National Institute for Health Research Biomedical Research Centre and King's College London; Institute of Neuroscience (D.J.B., N.P.), Newcastle University, UK; and Institute of Clinical Medicine (D.J.B., N.P.), University of Aarhus, Denmark.
Peter G
PG
Bain
From the Division of Brain Sciences (G.P., P.G.B., D.J.B., N.P.), Imperial College London; Imperial College NHS Trust (S.M.); Imanova Ltd (E.A.R.); National Parkinson Foundation International Centre of Excellence (E.A.R.), King's College London and National Institute for Health Research Biomedical Research Centre and King's College London; Institute of Neuroscience (D.J.B., N.P.), Newcastle University, UK; and Institute of Clinical Medicine (D.J.B., N.P.), University of Aarhus, Denmark.
Eugenii A
EA
Rabiner
From the Division of Brain Sciences (G.P., P.G.B., D.J.B., N.P.), Imperial College London; Imperial College NHS Trust (S.M.); Imanova Ltd (E.A.R.); National Parkinson Foundation International Centre of Excellence (E.A.R.), King's College London and National Institute for Health Research Biomedical Research Centre and King's College London; Institute of Neuroscience (D.J.B., N.P.), Newcastle University, UK; and Institute of Clinical Medicine (D.J.B., N.P.), University of Aarhus, Denmark.
K Ray
KR
Chaudhuri
From the Division of Brain Sciences (G.P., P.G.B., D.J.B., N.P.), Imperial College London; Imperial College NHS Trust (S.M.); Imanova Ltd (E.A.R.); National Parkinson Foundation International Centre of Excellence (E.A.R.), King's College London and National Institute for Health Research Biomedical Research Centre and King's College London; Institute of Neuroscience (D.J.B., N.P.), Newcastle University, UK; and Institute of Clinical Medicine (D.J.B., N.P.), University of Aarhus, Denmark.
David J
DJ
Brooks
From the Division of Brain Sciences (G.P., P.G.B., D.J.B., N.P.), Imperial College London; Imperial College NHS Trust (S.M.); Imanova Ltd (E.A.R.); National Parkinson Foundation International Centre of Excellence (E.A.R.), King's College London and National Institute for Health Research Biomedical Research Centre and King's College London; Institute of Neuroscience (D.J.B., N.P.), Newcastle University, UK; and Institute of Clinical Medicine (D.J.B., N.P.), University of Aarhus, Denmark. nicola.pavese@imperial.ac.uk.
Nicola
N
Pavese
D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D015331:Cohort Studies; D015259:Dopamine Agents; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism*; D011795:Surveys and Questionnaires
C493593:DRD3 protein, human; D015259:Dopamine Agents; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3