Introduction: Rapid Eye Movement (REM) sleep Behavior disorder (RBD) is a REM sleep parasomnia characterized by dream enacting behaviors allowed by the loss of physiological atonia during REM sleep. This disorder is recognized as a prodromal stage of neurodegenerative disease, in particular Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). Therefore, a timely identification of biomarkers able to predict an early conversion into neurodegeneration is of utmost importance. Areas covered: In this review, the authors provide updated evidence regarding the presence of neuropsychological, electrophysiological and neuroimaging markers in isolated RBD (iRBD) patients when the neurodegeneration is yet to come. Expert opinion: Cognitive profile of iRBD patients is characterized by the presence of impairment in visuospatial abilities and executive function that is observed in α-synucleinopathies. However, longitudinal studies showed that impaired executive functions, rather than visuospatial abilities, augmented conversion risk. Cortical slowdown during wake and REM sleep suggest the presence of an ongoing neurodegenerative process paralleled by cognitive decline. Neuroimaging findings showed that impairment nigrostriatal dopaminergic system might be a good marker to identify those patients at higher risk of short-term conversion. In spite of a growing body of evidence the identification of biomarkers still represents a critical issue in iRBD.

Insomnia is one of the most common mental disorders and the most frequent sleep disorder encountered in clinical practice, with a prevalence of about 7% in the European population. Insomnia Disorder (ID) is defined as a disturbance of sleep initiation or maintenance, followed by a feeling of non-restorative sleep and several diurnal consequences ranging from occupational and social difficulties to cognitive impairment. Cognitive-Behavioral Therapy for Insomnia (CBT-I) is considered the first-choice therapy for this disorder because its effectiveness has been proven to be greater in the long term with fewer side effects in comparison to pharmacotherapy. Although its effectiveness has been well established, it has been reported that nearly 40% of patients do not achieve remission after treatment. This finding could be the consequence of heterogeneity of ID between patients. It has been proposed that this heterogeneity might be ascribable to indices that are not related to sleep quality and quantity, such as comorbidities, life events, and personality traits. However, several works focused on the role of sleep markers, in particular objective total sleep time, for the phenotypization of ID and treatment response. The aim of this work is to summarize the available scientific literature regarding the impact of ID subtype on CBT-I response.

Sleep State Misperception (SSM) is described as the tendency of Insomnia Disorder (ID) patients to overestimate Sleep Latency (SL) and underestimate Total Sleep Time (TST). Literature exploring topographical components in ID with SSM is scarce and does not allow us to fully understand the potential mechanisms underlying this phenomenon. This study aims to evaluate the existence of sleep EEG topography alterations in ID patients associated with SSM compared to Healthy Controls (HC), focusing on two distinct periods: the Sleep Onset (SO) and the whole night. Twenty ID patients (mean age: 43.5±12.7; 7M/13F) and 18 HCs (mean age: 41.6±11.9; 8M/10F) underwent a night of Polysomnography (PSG) and completed sleep diaries the following morning upon awakening. Two SSM indices, referring to the misperception of SL (SLm) and TST (TSTm), were calculated by comparing objective and subjective sleep indices extracted by PSG and sleep diary. According to these indices, the entire sample was split into 4 sub-groups: ID +SLm vs HC -SLm; ID +TSTm vs HC -TSTm. Considering the SO, the two-way mixed-design ANOVA showed a significant main effect of Groups pointing to a decreased delta/beta ratio in the whole scalp topography. Moreover, we found a significant interaction effect for the sigma and beta bands. Post Hoc tests showed higher sigma and beta power in anterior and temporo-parietal sites during the SO period in IDs +SLm compared to HC -SLm. Considering the whole night, the unpaired t-test revealed in IDs +TSTm significantly lower delta power during NREM, and lower delta/beta ratio index during NREM and REM sleep compared to HCs -TSTm. Finally, we found diffuse significant negative correlations between SSM indices and the delta/beta ratio during SO, NREM, and REM sleep. The main finding of the present study suggests that higher SL overestimation and TST underestimation are both phenomena related to diffuse cortical hyperarousal interpreted as a sleep state-independent electrophysiological correlate of the SSM, both during the SO and the whole night.

Summary: Diagnostic manuals describe insomnia disorder (ID) characterised by fatigue and sleepiness as diurnal consequences of nocturnal symptoms. However, patients with ID do not frequently report sleepiness in the clinical setting. The present study aimed to investigate subjective sleepiness in ID measured through the Epworth Sleepiness Scale (ESS) and its independence towards daytime functioning and fatigue, and to evaluate cognitive behavioural therapy for insomnia (CBT‐I) improvement in daytime consequences and their relationship to sleepiness and fatigue. We retrospectively collected the ESS evaluation in a large sample of 105 healthy controls (HCs), 671 patients with ID, and 602 patients with sleep disorders characterised by excessive daytime sleepiness (EDS). Moreover, we conducted a pre–post evaluation of the ESS in a sub‐sample of patients with ID who underwent CBT‐I. Component 2 of the Insomnia Severity Index and Profile of Mood States–Fatigue Inertia Scale was used to evaluate daytime functioning and fatigue. Patients with ID reported ESS levels comparable to that observed in HCs and significantly lower than the EDS group. No significant correlation arose between ESS and the diurnal impact of the disorder, suggesting the independence between daytime functioning and sleepiness in ID. Contrarily, insomnia severity and diurnal impact significantly correlated with fatigue. Data showed a statistically significant increase in sleepiness after CBT‐I, despite significantly improving daytime consequences and fatigue. Although diagnostic manuals report sleepiness and fatigue as daytime consequences of sleep symptoms in patients with ID, these retrospective data indicate a dissociation between these entities. This evidence aligns with the core feature of ID: the hyperarousal status that pervades patients also during wakefulness.