دانلود رایگان مقاله انگلیسی اختلالات خواب و بیماری پارکینسون - الزویر 2018

Summary

Parkinson disease is a common, age-related neurodegenerative disorder, projected to afflict millions of individuals in the near future. Understanding its etiology and identifying clinical, genetic or biological markers for Parkinson disease onset and progression is therefore of major importance. Various sleep-related disorders are the most common group of non-motor symptoms in advanced Parkinson disease, but they can also occur during its prodromal phase. However, with the exception of REM sleep behavior disorder, it is unclear whether they are part of the early pathological process of Parkinson disease, or if they develop as Parkinson disease advances because of treatments and neurodegeneration progression. The advancements in genetic studies in the past two decades have generated a wealth of information, and recent genetic studies offer new insight on the association of sleep-related disorders with Parkinson disease. More specifically, comparing genetic data between Parkinson disease and sleep-related disorders can clarify their association, which may assist in determining whether they can serve as clinical markers for Parkinson disease risk or progression. In this review, we discuss the current knowledge on the genetics of sleep-related disorders in Parkinson disease context, and the potential implications on research, diagnosis, counseling and treatment.

Conclusions

Generally, the genetic study of sleep related disorders still lags behind other medical fields, although in recent years some progress has been made. Only a few GWASs have been performed in sleep disorders, and while basic genetic twin and familial studies had been performed in the past, there are very few studies that applied next generation sequencing technologies on families with sleep-related disorders. So far, there is no evidence for overlap in genetic predisposition for PD and either insomnia, EDS, OSA or circadian sleep-wake cycle disruption. In addition, there is no known overlap between RLS/PLMS genetic markers and PD, although this should be further studied.

In contrast, there is convincing evidence that the genetic basis of PD and RBD overlap, at least partially. Since we now know that the vast majority of cases of RBD have in fact a synucleinopathy in progress, this is not surprising. Of note, although not surprising, these observations linking some PD genetic markers and RBD may have importance for future studies and clinical trials. For instance, when asymptomatic carriers of GBA mutations are being followed up, screening for RBD should be considered for early detection of conversion to a synucleinopathy. Such population of GBA mutation carriers with RBD could be ideal for future clinical trials, since they are highly likely to convert to PD or another synucleinopathy. More genetic studies on RBD are required to identify additional genetic factors that are either shared with PD or unique to RBD, which will allow better characterization of this population.