BackgroundThis study explored the relationship between symptoms of rapid eye movement sleep behaviour disorder, thermoregulation and sleep in Parkinson’s Disease.MethodsThe study group comprised 12 patients with Parkinson’s Disease and 11 healthy age-matched controls. We investigated markers of thermoregulation (core-body temperature profile), circadian rhythm (locomotor actigraphy) and sleep (polysomnography).ResultsThe mesor (the mean value around which the core temperature rhythm oscillates) of the core-body temperature in patients with Parkinson’s Disease was significantly lower than that of controls. In addition, the nocturnal fall in CBT (the difference between the mesor and the nadir temperature) was also significantly reduced in PD patients relative to controls. Furthermore, in patients the reduction in the amplitude of their core-body temperature profile was strongly correlated with the severity of self-reported rapid eye movement sleep behaviour disorder symptom, reduction in the percentage of REM sleep and prolonged sleep latency. By contrast, these disturbances of thermoregulation and sleep architecture were not found in controls and were not related to other markers of circadian rhythm or times of sleep onset and offset.ConclusionsThese findings suggest that the brainstem pathology associated with disruption of thermoregulation in Parkinson’s disease may also contribute to rapid eye movement sleep behavioural disorder. It is possible that detailed analysis of the core-body temperature profile in at risk populations such as those patients with idiopathic rapid eye movement sleep behaviour disorder might help identify those who are at high risk of transitioning to Parkinson’s Disease.

Quantum chemistry calculations have been used to study the metal-free hydrogenation reactions of a variety of simple aromatic, heteroaromatic, and related linear conjugated systems. We find that the barrier for uncatalyzed 1,4-hydrogenation is always substantially lower (by approximately 200 kJ mol-1) than that for 1,2-hydrogenation, despite similar reaction enthalpies. The presence of hydrogen fluoride as a catalyst is found to decrease the 1,2-hydrogenation barriers but, in most cases, to slightly increase the 1,4-hydrogenation barriers when a constrained geometric arrangement is employed. These qualitative observations are consistent with orbital symmetry considerations, which show that both the uncatalyzed 1,4-hydrogenation and the catalyzed 1,2-hydrogenation are formally symmetry-allowed processes. An extreme example of the catalyzed 1,2-hydrogenation of benzene is provided by the involvement of a second molecule of hydrogen, which leads to a substantial lowering of the barrier. The effect of catalysis was further investigated by applying a selection of additional catalysts to the 1,2- and 1,4-hydrogenation of benzene. A decreasing barrier with increasing catalyst acidity is generally observed for the catalytic 1,2-hydrogenation, but the situation is more complex for catalytic 1,4-hydrogenation. For the uncatalyzed 1,4-hydrogenation of aromatic systems containing one or more nitrogen heteroatoms, the barriers for [C,C], [C,N], and [N,N] hydrogenations are individually related to the reaction enthalpies by the Bell-Evans-Polanyi principle. In addition, for a given reaction enthalpy, the barriers for [C,C] hydrogenation are generally lower than those for [C,N] or [N,N] hydrogenation. Finally, we find that the distortion experienced by the reactants in forming the transition structure represents a secondary factor that influences the reaction barrier. The correlation between these quantities allows the 1,4-hydrogenation barriers to be predicted from a ground-state property.

Summary The vast majority of patients with idiopathic rapid eye movement sleep behaviour disorder will develop a neurodegenerative α‐synuclein‐related condition, such as Parkinson’s disease or dementia with Lewy bodies. The pathology underlying dream enactment overlaps anatomically with the brainstem regions that regulate circadian core body temperature. Previously, nocturnal core body temperature regulation has been shown to be impaired in Parkinson’s disease. However, no study to date has investigated nocturnal core body temperature changes in patients with idiopathic rapid eye movement sleep behaviour disorder, which may prove to be an early objective biomarker for α‐synucleinopathies. Ten healthy controls, 15 patients with idiopathic rapid eye movement sleep behaviour disorder, 31 patients with Parkinson’s disease and six patients with dementia with Lewy bodies underwent clinical assessment and nocturnal polysomnography with core body temperature monitoring. A validated cosinor method was utilised for core body temperature analysis. No differences in mesor, nadir or time of nadir were observed between groups. However, when compared with healthy controls, the amplitude of the nocturnal core body temperature (mesor minus nadir) was significantly reduced in patients with idiopathic rapid eye movement sleep behaviour disorder, Parkinson’s disease with concurrent rapid eye movement sleep behaviour disorder and dementia with Lewy bodies (p < 0.001, p = 0.043 and p = 0.017, respectively). Importantly, this relationship was not seen in those patients with Parkinson’s disease without rapid eye movement sleep behaviour disorder. In addition, there was a significant negative correlation between amplitude of the core body temperature and self‐reported rapid eye movement sleep behaviour disorder symptoms. Changes in thermoregulatory circadian rhythm may be specifically associated with the pathology underlying rapid eye movement sleep behaviour disorder rather than simply that of α‐synucleinopathy. These findings implicate thermoregulatory dysfunction as a potential early biomarker for development of rapid eye movement sleep behaviour disorder‐associated neurodegeneration, and suggest that subpopulations with differing pathological underpinnings might exist in Parkinson’s disease.

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