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AimsIncreased gamma-aminobutyric acid type A (GABAA) receptor activity has been identified in hypersomnolence syndromes, but its role and regional cerebral topography of receptor occupancy in excessive daytime sleepiness (EDS) in Parkinson's disease (PD) is unknown. Dopaminergic functions or medications may contribute to EDS. Neuroimaging shows evidence of increased brain GABAergic activity in PD. We investigated the relationship between EDS, GABAA receptor binding, striatal dopamine and dopaminergic medication use in PD.MethodsSix PD patients underwent [11C]flumazenil GABAA receptor and [11C]dihydrotetrabenazine (DTBZ) dopaminergic positron emission tomography (PET), clinical and Epworth Sleepiness Scale (ESS) assessments.ResultsMean ESS score was 12.7 ± 4.5. Mean levodopa equivalent dose (LED) was 1,170 ± 616 mg. There was no significant correlation between nigrostriatal [11C]DTBZ PET (R = 0.138, p = 0.792) or disease duration (R = 0.209, p = 0.902) and ESS scores. In contrast, there was a significant inverse relationship between striatal GABAA receptor activity and ESS scores (β = -0.942, p = 0.024), more prominent in the caudate head (β = -0.949, p = 0.011). Therefore, frontal cortex binding was explored. A significant inverse relationship between frontal cortical GABAA receptor activity and ESS (R = -0.884, p = 0.042) was found. A trend toward positive association between LED and ESS (R = 0.773, p = 0.053), was weakened (β = -0.128, p = 0.738) by the addition of caudate head GABAA receptor activity into the model (β = -1.066, p = 0.055), suggesting that the association between LED and ESS may be mediated by GABAergic changes in the striatum.ConclusionIncreased striatal and frontal cortical GABAergic activity is a more significant determinant of daytime somnolence than dopaminergic functions in PD. Findings may augur novel inverse GABAA receptor agonist drug therapy for EDS in PD.
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