Orexin and Sleep Disturbances in Alpha-Synucleinopathies: a Systematic Review.

PURPOSE OF REVIEW: Sleep disturbances are amongst most frequent non-motor symptoms of Parkinson's Disease (PD), and they are similarly frequently reported in other alpha-syncleinopathies, such as Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). More recently, the orexin system has been implicated in control of arousal based on salient environmental set points, and its dysregulation in sleep issues in alpha-synucleinopathies suggested by the findings from the translational animal models. However, its role in the patients with alpha-synucleinopathies remains unclear. We thus set to systematically review, and to critically assess, contemporary evidence on the association of the orexinergic system and sleep disturbances in alpha-synucleinopathies. In this systematic review, studies investigating orexin and sleep in alpha-synucleinopathies (Rapid Eye Movement (REM) Behaviour Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) were identified using electronic database searches of PubMed, Web of Science and PsychINFO using MeSH terms, keywords, and title words such as "Alpha-synucleinopathies" AND "Orexin" AND "Sleep Disturbances". RECENT FINDINGS: 17 studies were included in this systemic review, of which 2 studies on RBD, 10 on PD, 4 on DLB, and 1 on MSA patients. Taken together, RBD and PD studies suggest a potential adaptive increase in orexin levels in early stages of the neurodegenerative process, with reduced levels more often reported for later, more advanced stages of illness. To date, no differences in orexin levels were demonstrated between MSA patients and healthy controls. There is a dearth of studies on the role of orexin levels in alpha-synucleinopathies. Moreover, significant methodologic limitations in the current body of work, including use of non-standardised research protocols and lack of prospective, multi-centre studies, disallow for any finite conclusion in regards to underlying pathomechanisms. Nonetheless, a picture of a complex, multifaceted relationship between the dysregulation of the orexinergic pathway and sleep disturbances in alpha-synucleinopathies is emerging. Hence, future studies disentangling orexinergic pathomechanisms of alpha-syncleinopathies are urgently needed to obtain a more comprehensive account of the role of orexinergic pathway in alpha-synucleinopathies. Pharmacological manipulations of orexins may have multiple therapeutic applications in treatment strategies, disease diagnosis, and might be effective for treating both motor and non-motor symptoms.

How can sleep disorders affect our reaction towards external stressors: a lesson from the COVID-19 outbreak.

BACKGROUND: The COVID-19 outbreak produced extensive psychological consequences, especially among vulnerable populations. Sleep was identified as one of the most common "indirect targets" of the pandemia, with up to 74.8% of patients surviving from COVID-19 complaining of new-onset sleep disorders. However, so far, the clinic-psychological impact of the outbreak in patients affected by pre-existing sleep disorders has not been examined in details. MATERIALS AND METHODS: In the present study, we aim to assess the effect of the COVID-19 outbreak in a cohort of 190 adult patients affected by sleep disorders, compared to 265 age and sex-matched healthy sleepers. The assessment was implemented throughout the use of ad hoc anamnestic questions, exploration of dream content, and validated questionnaires, aiming to capture the broad range of the neuropsychological nuances of the COVID-19 impact. RESULTS: Subjects with pre-existent sleep disorders faced a more severe impact in terms of sleep quality and amount compared to healthy sleepers, presenting longer sleep latency, reduced sleep efficacy, and greater use of hypnotics and medications. On the other hand, healthy sleepers experienced deeper variation in sleeping habits, sleep duration, and greater impact on dream activity in terms of content, emotionality, and presence of recurrent dreams. Finally, in our sample, being female represents an important aggravating factor in the pandemic experience, both in terms of sleep deterioration and with respect to physical and mental health. For instance, females indeed presented the highest scores of Pittsburgh Sleep Quality Index (PSQI) both in cases and control groups (respectively 10 ± 3.8 vs 7.3 ± 3.9 in cases and 6.6 ± 3.6 vs 6.0 ± 3.4 in controls, p-value < 0.001). CONCLUSION: Pre-existent sleep disorders and the female sex might represent risk factors increasing the clinic-psychological burden in dramatic scenarios, such as the COVID-19 pandemia, requiring dedicated attention from clinicians.

The Contribution of Sleep Texture in the Characterization of Sleep Apnea.

Obstructive sleep apnea (OSA) is multi-faceted world-wide-distributed disorder exerting deep effects on the sleeping brain. In the latest years, strong efforts have been dedicated to finding novel measures assessing the real impact and severity of the pathology, traditionally trivialized by the simplistic apnea/hypopnea index. Due to the unavoidable connection between OSA and sleep, we reviewed the key aspects linking the breathing disorder with sleep pathophysiology, focusing on the role of cyclic alternating pattern (CAP). Sleep structure, reflecting the degree of apnea-induced sleep instability, may provide topical information to stratify OSA severity and foresee some of its dangerous consequences such as excessive daytime sleepiness and cognitive deterioration. Machine learning approaches may reinforce our understanding of this complex multi-level pathology, supporting patients' phenotypization and easing in a more tailored approach for sleep apnea.