Neurological Insights into Sleep Disorders in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition and physical functioning. Sleep deprivation negatively impacts human physical, mental, and behavioral functions. Sleep disturbances include problems falling asleep, disturbances occurring during sleep, abnormal movements during sleep, insufficient sleep, and excessive sleep. The most recognizable and known sleep disorders, such as rapid-eye-movement behavior disorder (RBD), insomnia, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), sleep-related breathing disorders (SRBDs), and circadian-rhythm-related sleep–wake disorders (CRSWDs), have been associated with PD. RBD and associated emotional disorders are common non-motor symptoms of PD. In individuals, sleep disorders and cognitive impairment are important prognostic factors for predicting progressing neurodegeneration and developing dementia conditions in PD. Studies have focused on RBD and its associated neurological changes and functional deficits in PD patients. Other risks, such as cognitive decline, anxiety, and depression, are related to RBD. Sleep-disorder diagnosis is challenging, especially in identifying the essential factors that disturb the sleep–wake cycle and the co-existence of other concomitant sleep issues, motor symptoms, and breathing disorders. Focusing on sleep patterns and their disturbances, including genetic and other neurochemical changes, helps us to better understand the central causes of sleep alterations and cognitive functions in PD patients. Relations between α-synuclein aggregation in the brain and gender differences in sleep disorders have been reported. The existing correlation between sleep disorders and levels of α-synuclein in the cerebrospinal fluid indicates the risk of progression of synucleinopathies. Multidirectional approaches are required to correlate sleep disorders and neuropsychiatric symptoms and diagnose sensitive biomarkers for neurodegeneration. The evaluation of sleep pattern disturbances and cognitive impairment may aid in the development of novel and effective treatments for PD.

The Genetic Landscape of Sleep Disorders in Parkinson’s Disease

“…RBD is a sleep disorder characterized by abnormal motor behavior associated with dream mentation and loss of atonia during REM sleep [ 3 ]. Scientific attention over RBD has increased due to its association with α-synucleinopathies.…”

“…A recent meta-analysis study showed that PD patients with heterozygous GBA variants are at high risk of developing RBD. PD patients with GBA variants, like N370S and L444P, are at an even higher RBD risk than PD patients without these variants [ 3 , 12 ]. Moreover, in a recent study Perez-Lloret et al found that GBA _N370S_rs76763715 was associated with more frequent pRBD among PD patients.…”

“…The prevalence rate of RLS is 5–15% in the general population. Most studies have shown a higher rate of RLS among PD patients compared to a control population [ 3 ]. The exact pathogenesis of RLS is not well understood, but the beneficial effects of dopaminergic drugs and the results of several functional imaging studies support the hypothesis of a dopaminergic nigrostriatal pathway involvement.…”

“…GBA mutations carriers-OR = 3.13 for pRBD sGBA and GD-PD had higher frequencies of RBD A recent meta-analysis PD heterozygous GBA patients-high risk RBD GBA variants, like N370S and L444P-higher RBD risk in PD patients GBA_N370S_rs76763715-more frequent pRBD among PD patients GBA variants, like rs2230288/E326K, rs75548401/T369M, and rs369068553/V460L-RBD [3,7,[11][12][13]…”

“…Sleep disorders, such as REM sleep behavior disorder (RBD), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), insomnia, obstructive sleep apnea and circadian rhythm disturbances are common in idiopathic PD (iPD). In particular, individuals suffering from RBD carry a risk of >85% to manifest PD after 15–20 years, and the associated neurodegenerative process is α-synucleinopathy in 95% of cases [ 3 ]. The contribution of common genetic variants to the clinical variability in sporadic PD is a hot topic of scientific research.…”