Cholinergic Markers and Cytokines in OSA Patients.

The role of inflammation and dysfunction of the cholinergic system in obstructive sleep apnea (OSA) has not exhaustively clarified. Thus, in this study, we explore the non-neuronal cholinergic system and the balance of T helper (Th) 17- and T regulatory (Treg)-related cytokines in OSA patients. The study includes 33 subjects with obstructive sleep apnea and 10 healthy controls (HC). The expression levels of cholinergic system component, RAR-related orphan receptor (RORc), transcription factor forkhead box protein 3 (Foxp3) and cytokines were evaluated. Th17- and Treg-related cytokines, choline levels and acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activity were quantified in OSA and control subjects. AChE and nicotinic receptor α 7 subunit (α7nAChR) gene expression and serum levels of choline, AChE and BuChE were lower in OSA patients than in the HC group. Compared with the HC group, OSA patients exhibited an increased expression, secretion and serum levels of pro-inflammatory cytokines, a reduced expression, secretion and serum levels of transforming growth factor (TGF)ß and reduced Foxp3 mRNA levels. The Th17/Treg-related cytokine ratio was higher in the OSA group. Our results confirm and reinforce the hypothesis that OSA may be considered a systemic inflammatory disease, and that an imbalance of non-neuronal cholinergic and pro/anti-inflammatory cytokines may contribute to development and progression of comorbidities in OSA subjects. The evaluation of Th17/Treg-related cytokine may provide an additional explanation for OSA pathogenesis and clinical features, opening new directions for the OSA management.

Sleep disturbances and cognitive decline: recommendations on clinical assessment and the management.

In 2004, in Genoa (Italy), the Italian Dementia Research Association (SINDem) was born. The first congress of this new scientific society took place in Rome in 2006. SINDem soon recognized the importance to investigate sleep problems in cognitive decline and created a national "sleep study group "composed by neurologists and sleep specialists. In 2012, The SINDem study group, in close relationship with the Italian Association of sleep medicine (AIMS), published the study "Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients ", confirming the high prevalence of sleep disturbances in a wide Italian population of persons with cognitive decline. The study was supported by a grant from the Italian Minister of Health and was conducted with the fundamental contribution of the Italian National Research Center (CNR). In 2014, the same group published the paper "Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review". The recommendations are wide and directed to professionals (neurologists but not exclusively) to try to establish uniform levels of care, promote collaborative studies into areas of uncertainty, and define the qualitative characteristics of Dementia Reference Centers about sleep disturbances.

Sleep disorders in menopause: results from an Italian Multicentric Study.

Menopause in the female life cycle is a special period due to important hormonal, physical and psychological changes. Sleep disruption represents a common complaint for midlife and menopausal women, related to primary sleep disorders, including insomnia, sleep disordered breathing, restless legs syndrome (RLS), mood and anxiety disorder, other medical illness, hormonal-related vasomotor symptoms, and aging per se. Aims of our study were to evaluate the prevalence of sleep disorders in a sample of pre and post menopausal women, and to investigate the relationship between sleep and other medical disorders, and life habits. Among workers in the six participant centers, we enrolled 334 women, aged between 40 and 60 years, that completed a questionnaire that included screening on menarche, menstrual cycle, fertility, parity, menopause, life habits, personal medical and sleep history and related treatment, and self-administered scales for sleep quality (PSQI), excessive daytime sleepiness [Epworth Sleepiness Scale (ESS)], mood disorder [Beck Depression Inventory (BDI)], Berlin Questionnaire for sleep disordered breathing (SDB), IRLS diagnostic interview and Rating Scale. Menopausal and perimenopausal women showed an increased prevalence of poor sleep, high risk of SDB, and mood disorder; menopausal women also reported increased RLS severity. Mood disorder had a significant impact on night sleep measures and excessive daytime sleepiness, as well as on RLS severity, and had a greater prevalence in hypertensive women. Sleep disturbances are frequent in menopausal women. Their aetiology is unclear, but probably multifactorial, and many factors contribute to the sleep disruption. Our data suggest the importance of correctly investigate and address sleep problems associated with menopause, through sleep history, and a sleep study could be obtained if clinically warranted. Pharmacological and behavioural treatment strategies should then be aimed at improving sleep and life quality in perimenopausal and menopausal women.

Multicenter Study on Sleep and Circadian Alterations as Objective Markers of Mild Cognitive Impairment and Alzheimer's Disease Reveals Sex Differences.

BACKGROUND: Circadian and sleep disturbances are associated with increased risk of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Wearable activity trackers could provide a new approach in diagnosis and prevention. OBJECTIVE: To evaluate sleep and circadian rhythm parameters, through wearable activity trackers, in MCI and AD patients as compared to controls, focusing on sex dissimilarities. METHODS: Based on minute level data from consumer wearable devices, we analyzed actigraphic sleep parameters by applying an electromedical type I registered algorithm, and the corresponding circadian variables in 158 subjects: 86 females and 72 males (42 AD, 28 MCI, and 88 controls). Moreover, we used a confusion-matrix chart method to assess accuracy, precision, sensitivity, and specificity of two decision-tree models based on actigraphic data in predicting disease or health status. RESULTS: Wake after sleep onset (WASO) was higher (p < 0.001) and sleep efficiency (SE) lower (p = 0.003) in MCI, and Sleep Regularity Index (SRI) was lower in AD patients compared to controls (p = 0.004). SE was lower in male AD compared to female AD (p = 0.038) and SRI lower in male AD compared to male controls (p = 0.008), male MCI (p = 0.047), but also female AD subjects (p = 0.046). Mesor was significantly lower in males in the overall population. Age reduced the dissimilarities for WASO and SE but demonstrated sex differences for amplitude (p = 0.009) in the overall population, controls (p = 0.005), and AD subjects (p = 0.034). The confusion-matrices showed good predictive power of actigraphic data. CONCLUSION: Actigraphic data could help identify disease or health status. Sex (possibly gender) differences could impact on neurodegeneration and disease trajectory with potential clinical applications.

Monitoring Neuro-Motor Recovery From Stroke With High-Resolution EEG, Robotics and Virtual Reality: A Proof of Concept.

A novel system for the neuro-motor rehabilitation of upper limbs was validated in three sub-acute post-stroke patients. The system permits synchronized cortical and kinematic measures by integrating high-resolution EEG, passive robotic device and Virtual Reality. The brain functional re-organization was monitored in association with motor patterns replicating activities of daily living (ADL). Patients underwent 13 rehabilitation sessions. At sessions 1, 7 and 13, clinical tests were administered to assess the level of motor impairment, and EEG was recorded during rehabilitation task execution. For each session and rehabilitation task, four kinematic indices of motor performance were calculated and compared with the outcome of clinical tests. Functional source maps were obtained from EEG data and projected on the real patients' anatomy (MRI data). Laterality indices were calculated for hemispheric dominance assessment. All patients showed increased participation in the rehabilitation process. Cortical activation changes during recovery were detected in relation to different motor patterns, hence verifying the system's suitability to add quantitative measures of motor performance and neural recovery to classical tests. We conclude that this system seems a promising tool for novel robot-based rehabilitation paradigms tailored to individual needs and neuro-motor responses of the patients.