Are Sleep Disturbances Preclinical Markers of Parkinson’s Disease?

Abstract

Parkinson's disease (PD) is a neurobehavioral disorder characterized by motor symptoms and signs, and non-motor abnormalities such as olfactory dysfunction, pain, sleep disorders and cognitive impairment. Amongst these alterations, sleep disturbances play an important role in the pathology, but presence of disturbed sleep is not currently considered in diagnosis. However, sleeping problems may precede by many years the classic motor abnormalities of PD and should be clinically evaluated as a potential marker before disease onset. The first disturbance reported with this potential was the disorder REM sleep behaviour and currently several other disturbances have gained importance as potential markers, such as excessive daytime sleepiness, restless legs syndrome and new evidence also points to changes in circadian rhythms. Here we present a brief review of the major evidence indicating that sleep disturbances precede the motor symptoms in PD and neurodegeneration occurs in regions that could underlie these phenomena in order to provide support for the conclusion that disturbances of sleep should be considered as valuable preclinical markers for PD.

Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson's disease phenotypes

“…This is especially true of sleep disturbances such as RBD: the majority of RBD sufferers will go on to develop PD or a related disorder (Schenck et al, 2013). Therefore, it is increasingly thought that sleep disorders such as RBD may represent a prodromal phase of PD that precedes clinical onset of the disease by on average 14  years (dos Santos et al, 2015, Iranzo et al, 2013). Thus non-motor disorders of PD may offer a presymptomatic window for study and treatment, allowing earlier intervention as well as the development of drugs that could actually target the causes of the disease as opposed to merely treating the symptoms when irreversible brain damage has already taken place.…”

Neuropsychiatric symptoms in untreated Parkinson’s disease

“…As causative factors, besides the neurodegenerative processes within sleep regulatory brain circuitries, DRT and concomitant medications (eg, antidepressants) as well as comorbidities or other NMS (such as depression) are proposed 144. Sleep-related problems are also reported to increase the risk of development of PD in the later life similarly to anxiety disorders and depression146,150,151 or RLS,152 and because they usually precede the classic motor abnormalities of PD by many years, they should be clinically evaluated as a potential marker for PD before its onset 153,154. Similarly, sleep dysfunctions occur in untreated PD as well 155,156.…”

Sleep stability and transitions in patients with idiopathic REM sleep behavior disorder and patients with Parkinson’s disease

“…RBD is closely associated with PD (Munhoz and Teive, 2014), and patients suffering from idiopathic RBD (iRBD) are at great risk of subsequently developing Parkinsonism or dementia (Schenck et al, 2013(Schenck et al, , 2003(Schenck et al, , 1996. Several studies have focused on analysis of sleep data in the search for PD biomarkers (Dos Santos et al, 2014). These have examined measures of sleep spindle densities, RSWA, slow wave characteristics (Christensen et al, 2014b;Kempfner et al, 2014a,b;Latreille et al, 2014Latreille et al, , 2011Postuma et al, 2010) and other measures of abnormalities of brain stem function, including autonomic functions such as heart-rate variability (Sorensen et al, 2013a(Sorensen et al, , 2012 and other non-motor symptoms (Garcia-Ruiz et al, 2014;Sakakibara et al, 2014).…”