Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies.

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = -0.69), memory (RE model = -0.64), and executive function (RE model = -0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

Sleeping with time in mind? A literature review and a proposal for a screening questionnaire on self-awakening.

Some people report being able to spontaneously "time" the end of their sleep. This ability to self-awaken challenges the idea of sleep as a passive cognitive state. Yet, current evidence on this phenomenon is limited, partly because of the varied definitions of self-awakening and experimental approaches used to study it. Here, we provide a review of the literature on self-awakening. Our aim is to i) contextualise the phenomenon, ii) propose an operating definition, and iii) summarise the scientific approaches used so far. The literature review identified 17 studies on self-awakening. Most of them adopted an objective sleep evaluation (76%), targeted nocturnal sleep (76%), and used a single criterion to define the success of awakening (82%); for most studies, this corresponded to awakening occurring in a time window of 30 minutes around the expected awakening time. Out of 715 total participants, 125 (17%) reported to be self-awakeners, with an average age of 23.24 years and a slight predominance of males compared to females. These results reveal self-awakening as a relatively rare phenomenon. To facilitate the study of self-awakening, and based on the results of the literature review, we propose a quick paper-and-pencil screening questionnaire for self-awakeners and provide an initial validation for it. Taken together, the combined results of the literature review and the proposed questionnaire help in characterising a theoretical framework for self-awakenings, while providing a useful tool and empirical suggestions for future experimental studies, which should ideally employ objective measurements.

Cognitive Reserve in Isolated Rapid Eye-Movement Sleep Behavior Disorder.

Isolated rapid-eye-movement sleep behaviour disorder (RBD) is considered the prodromal stage of α-synucleinopathies (e.g., Parkinson's disease and dementia with Lewy bodies); however, iRBD patients show a wide variety in the progression timing (5-15 years). The model of cognitive reserve (CR) might contribute to explaining this phenomenon. Our exploratory study aimed to evaluate, for the first time, the impact of CR level on cognitive performance in polysomnography-confirmed iRBD patients. Fifty-five iRBD patients (mean age ± SD: 66.38 ± 7.51; M/F 44/11) underwent clinical and neuropsychological evaluations at the time of diagnosis. The CR Index questionnaire was part of the clinical assessment. We found that iRBD patients with high levels of CR showed: (i) the lowest percentage of mild cognitive impairment (10%), and (ii) the best performance in visuo-constructive and verbal memory functions (i.e., the recall of the Rey-Osterrieth complex figure test). Our results suggest that CR might help iRBD patients better cope with the cognitive decline related to the neurodegenerative process, providing the first preliminary findings supporting CR as a possible protective factor in this condition. This might pave the way for future longitudinal studies to evaluate the role of CR as a modulating factor in the timing of iRBD conversion and cognitive deterioration development.

A data-driven approach to neuropsychological features in isolated REM behaviour disorder: A latent class analysis.

Recent evidence demonstrated that neuropsychological assessment may be considered a valid marker of neurodegeneration in idiopathic REM sleep behaviour disorder (iRBD). However, little is known about the possible neuropsychological heterogeneity within the iRBD population. This retrospective study aimed to identify and describe different neuropsychological phenotypes in iRBD patients by means of a data-driven approach using latent class analysis. A total of 289 iRBD patients underwent a neuropsychological assessment evaluating cognitive domains: global cognition, language, short- and long-term memory, executive functions and visuospatial abilities. The presence of mild cognitive impairment (MCI) was also assessed. Latent class analysis was carried out to identify iRBD subtypes according to neuropsychological scores. The most parsimonious model identified three latent classes. Groups were labelled as follows: Class 2 "severely impaired" (n = 83/289): mean pathological scores in different tests, a high percentage of MCI multiple-domain and impairment in all neuropsychological domains. Class 1 "moderately impaired" (n = 44/289): mean neuropsychological score within the normal value, a high percentage of MCI (high risk to phenoconversion) and great impairment in the visuospatial domain. Class 3 "slightly impaired" (n = 162/289): no deficit worthy of attention except for short- and long-term memory. Our results suggest three different clinical phenotypes within the iRBD population. These findings may be relevant in the future for predicting the clinical trajectories of phenoconversion in iRBD.

"Thinking About Thinking" in Insomnia Disorder: The Effect of Cognitive-Behavioral Therapy for Insomnia on Sleep-Related Metacognition.

Metacognition is defined as the ability to reflect on one's mental state and to govern thoughts and beliefs. Metacognitive dysfunctions are typical of several psychopathologic conditions, and also a feature of insomnia disorder, possibly playing a crucial role in its genesis and maintenance. In the context of insomnia, metacognition describes how individuals react to their own sleep-related thoughts and beliefs, boosting the hyperarousal state experienced by these patients. Up to now, no studies evaluated the effect of cognitive behavioral therapy for insomnia (CBT-I) on metacognitive functioning. Therefore, the aim of our study was to evaluate the effect of CBT-I administered in group format in patients with insomnia disorder. As expected, all patients showed significant improvements in both insomnia and sleep diary parameters after treatment. Furthermore, an improvement was observed also in dysfunctional metacognitive levels, assessed by means of the Metacognitions Questionnaire-Insomnia (MCQ-I). However, 63% of patients still showed a MCQ-I score above the clinical cutoff after treatment. Dividing the sample on the basis of MCQ-I questionnaire scores after CBT-I, we found that patients, who still presented metacognitive impairment, received significant beneficial effects from CBT-I both on insomnia symptoms and on dysfunctional beliefs, but not on dysfunctional metacognitive functioning. These findings suggest that metacognition should be carefully evaluated in insomnia patients and further studies are needed to evaluate long-term implications of this remaining dysfunction.

The reliability of objective total sleep time in predicting the effectiveness of cognitive-behavioral therapy for insomnia.

BACKGROUND: Despite insomnia diagnosis is based only on subjective sleep assessment, recent literature suggested the usefulness of objective sleep duration for the identification of two insomnia phenotypes based on objective total sleep time (oTST). In particular, insomnia with short sleep duration (SS) (oTST<6 h) seems to receive less benefit from Cognitive-Behavioral Therapy for Insomnia (CBT-I) compared to patients with normal sleep duration (NS) (oTST≥6 h). The aim of this study is to evaluate CBT-I response of patients previously divided into SS and NS and to assess the agreement between oTST measured by polysomnography (PSG) and by actigraphy in identifying the two subgroups. METHODS: Fifty-three insomnia patients (50.9% females; mean age 56.53 ± 11.43) underwent a baseline PSG and an actigraphic evaluation to identify SS and NS subjects. Insomnia Severity Index (ISI) and sleep diaries data (wakefulness after sleep onset) were considered primary outcomes. All the other sleep diaries variables were used as secondary outcomes. RESULTS: Throughout PSG we identified 22 NS (41.5%) and 31 SS (58.5%) patients, whereas actigraphic evaluation identified 38 NS (71.7%) and 15 SS (28.3%) patients. All subjects showed significant improvement after treatment, however, no effect of group membership was found to influence CBT-I response. Strikingly, actigraphy and PSG differed in identifying the two subgroups. Specifically, only 27 out 53 (51%) were consistently classified as SS [K = 0.086, 95% confidence interval: -0.132 to 0.305, p = 0.448]. CONCLUSIONS: Our results challenge the reliability and usefulness of oTST in predicting CBT-I effectiveness. Future studies might focus on night-to-night variability experienced by insomnia patients for the prediction of CBT-I outcomes.