Sleep disorders and Alzheimer's disease pathophysiology: The role of the Glymphatic System. A scoping review.

BACKGROUND: Alzheimer's disease (AD) is highly intertwined with sleep disturbances throughout its whole natural history. Sleep consists of a major compound of the functionality of the glymphatic system, as the synchronized slow-wave activity during NREM facilitates cerebrospinal and interstitial long-distance mixing. OBJECTIVE: The present study undertakes a scoping review of research on the involvement of the glymphatic system in AD-related sleep disturbances. DESIGN: we searched Medline, Embase, PsychInfo and HEAL-link databases, without limitations on date and language, along with reference lists of relevant reviews and all included studies. We included in vivo, in vitro and post-mortem studies examining glymphatic implications of sleep disturbances in human populations with AD spectrum pathology. A thematic synthesis of evidence based on the extracted content was applied and presented in a narrative way. RESULTS: In total, 70 original research articles were included and were grouped as following: a) Protein aggregation and toxicity, after sleep deprivation, along with its effects on sleep architecture, b) Glymphatic Sequalae in SDB, yielding potential glymphatic markers c) Circadian Dysregulation, d) Possible Interventions. CONCLUSIONS: this review sought to provide insight into the role of sleep disturbances in AD pathogenesis, in the context of the glymphatic disruption.

The Alonissos Study: Cross-Sectional Study of the Healthcare Access and User Satisfaction in the Community of a Non-Profit-Line Greek Island.

Healthcare access and a high quality of the provided services to healthcare users are fundamental human rights according to the Alma Ata Declaration of 1978. Although 45 years have passed since then, health inequalities still exist, not only among countries but also within populations of the same country. For example, several small Greek islands have only a small Primary Healthcare Center in order to provide healthcare services to the insular population. In the current study, we investigated the level of self-reported overall, dental and mental health status and the level of satisfaction regarding the access to and the quality of the healthcare services provided by the Primary Healthcare center of Alonissos, along with registering the requirements for transportation to the mainland in order to receive such services. In this questionnaire-based cross-sectional study, 235 inhabitants of the remote Greek island of Alonissos that accounts for nearly 9% of the population participated (115 males and 120 females). The self-reported overall health status was reported to be moderate to very poor at a percentage of 31.49%, and the results were similar for dental and self-reported mental health status. Although nearly 60% of the participants reported very good/good quality of the healthcare provision, only 37.45% reported that the access to healthcare was very good/good, while around 94% had at least one visit to the mainland in order to receive proper healthcare services. Strategies for improving access to healthcare services need to be placed in remote Greek islands like Alonissos.

A novel conceptual framework for the functionality of the glymphatic system.

The glymphatic system is responsible for the clearance of the potentially harmful metabolic waste of the central nervous system. The prevalent theory is that the cerebrospinal fluid (CSF) circulates in the perivascular space (PVS) and through the astrocytes' aquaporin-4 channels (AQ-4), and it is then drained by the lymphatic vessels after mixing with interstitial fluid (ISF). However, there is little evidence supporting this hypothesis. A deeper understanding of the physiology of the glymphatic system could transform the way we understand neuropathology and our approach to treating neurological and neuropsychiatric disorders. In this review, we introduce a new conceptual framework for the functionality of the glymphatic system, offering new directions for future research. We propose that CSF and ISF exchange flow depends on arterial pulsation, respiration, posture, and sleep. PVS changes due to disrupted cerebral autoregulation, alternations of intrathoracic pressure, venous flow, and body position can also influence the glymphatic flow. The role of respiration remains controversial due to the variety of parameters that interfere with glymphatic functionality. Slow-wave sleep is important for glymphatic clearance due to neuronal electromagnetic synchronization and expansion of the interstitial space. Therefore, sleep and vascular disorders, as well as aging, may hinder glymphatic flow and induce a noxious milieu of susceptibility to neurodegenerative disorders because of metabolic waste accumulation. We lastly introduce a new idea postulating that electromagnetic induction may constitute one of the propelling forces for the convectional current and mixing of CSF and ISF.

Breathlessness and exercise with virtual reality system in long-post-coronavirus disease 2019 patients.

Long-post-coronavirus disease-2019 (COVID-19) patients tend to claim residual symptomatology from various systems, most importantly the respiratory and central nervous systems. Breathlessness and brain fog are the main complaints. The pulmonary function pattern is consistent with restrictive defects, which, in most cases, are self-resolved, while the cognitive profile may be impaired. Rehabilitation is an ongoing field for holistic management of long-post-COVID-19 patients. Virtual reality (VR) applications may represent an innovative implementation of rehabilitation. We aimed to investigate the effect of exercise with and without the VR system and to assess further breathlessness and functional fitness indicators in long-post-COVID-19 patients with mild cognitive impairment after self-selected exercise duration using the VR system. Twenty long-post-COVID-19 patients were enrolled in our study (age: 53.9 ± 9.1 years, male: 80%, body mass index: 28.1 ± 3.1 kg/m2). Participants' anthropometric data were recorded, and they underwent pulmonary functional test evaluation as well as sleep quality and cognitive assessment. The participants randomly exercised with and without a VR system (VR vs. no-VR) and, later, self-selected the exercise duration using the VR system. The results showed that exercise with VR resulted in a lower dyspnea score than exercise without VR. In conclusion, VR applications seem to be an attractive and safe tool for implementing rehabilitation. They can enhance performance during exercise and benefit patients with both respiratory and cognitive symptoms.

The Alonissos Study: Cross-Sectional Study of the Community Respiratory Health Status in a Greek Healthcare Access Underprivileged Island.

In this study, we investigated the self-reported (questionnaire-based) prevalence of Obstructive Sleep Apnoea Syndrome (OSAS) and the prevalence of Chronic Obstructive Pulmonary Diseases (COPD) in the context of demographics and adherence to the Mediterranean diet in the general population of Alonissos, a non-profit line island in Greece (i.e., with scarce boat transportation to the mainland). In this cross-sectional study, 236 inhabitants of Alonissos participated (circa 10% of the island's population), and 115 males and 121 females were evaluated with appropriate questionnaires for OSAS, COPD, and adherence to the Mediterranean diet and subsequently underwent spirometry testing to establish COPD diagnosis. The self-reported prevalence of OSAS and COPD was 9.44% and 18.8%, respectively. However, only 8.99% of the participants were diagnosed with COPD based on their spirometry testing. Adherence to the Mediterranean Diet was moderate. The high prevalence of COPD and OSAS in this underprivileged island in terms of healthcare access highlights the need for improvements in health promotion and primary healthcare provision in non-profit line Greek islands.

Tele-Exercise in Non-Hospitalized versus Hospitalized Post-COVID-19 Patients.

The purpose of our study was to investigate the effect of tele-exercise (TE) performed for 4 consecutive weeks on fitness indicators in hospitalized post-COVID-19 patients versus non-hospitalized patients. Forty COVID-19 survivors were included, and divided into two groups: non-hospitalized versus hospitalized. Body composition, anthropometric characteristics, pulmonary function tests, single-breath diffusing capacity for carbon monoxide, 6-min walk tests (6MWT) and handgrip strength tests were recorded before and after a TE regimen (3 sessions per week, 60 min each session, warm-up and cool-down with mobility exercises, aerobic exercise such as walking outdoors, and multi-joint strength exercises). Following TE, the 6-min walk distance and handgrip were increased in both groups, with a greater observed response in the non-hospitalized group (6MWT: 32.9 ± 46.6% vs. 18.5 ± 14.3%, p < 0.001; handgrip: 15.9 ± 12.3% vs. 8.9 ± 7.6%, p < 0.001). Self-assessed dyspnea and leg fatigue were reduced in both groups, while a higher percentage of reduction was observed in the non-hospitalized group (dyspnea: 62.9 ± 42.5% vs. 37.5 ± 49.0%, p < 0.05; leg fatigue: 50.4 ± 42.2% vs. 31.7 ± 45.1%, p < 0.05). Post- vs. pre-TE arterial blood pressure decreased significantly in both groups, with the hospitalized group exhibiting more prominent reduction (p < 0.001). Both groups benefited from the TE program, and regardless of the severity of the disease the non-hospitalized group exhibited a potentially diminished adaptative response to exercise, compared to the hospitalized group.

Memory Foam Pillow as an Intervention in Obstructive Sleep Apnea Syndrome: A Preliminary Randomized Study.

Specific pillow use is a seldom studied or controlled factor in the setting of sleep disordered breathing. The aim of this study was to investigate the effect of different pillows [own pillow (OP), memory foam pillow (MFP), generic laboratory pillow (LP)] on polysomnography (PSG)-derived parameters in patients with Obstructive Sleep Apnea Syndrome (OSAS). Thirty-two consecutive patients with OSAS were randomly allocated into two groups with randomized pillow usage [Group A: 3 h with LP and 3 h with OP (Age: 53.8 ± 12.5 years, BMI: 32.1 ± 4.6 kg/m2); Group B: 3 h with LP and 3 h with MFP (Age: 52.0 ± 6.3 years, BMI: 30.6 ± 2.2 kg/m2)]. Statistically significant differences between pillow types were detected in desaturation index and heart rate. In Group B (with MFP), a statistically significant decrease of 47.0 ± 15.9% was observed in snoring events (p < 0.05) and 10.6 ± 6.7% in their duration (p < 0.05) compared to LP. On the other hand, group A with OP recorded a decrease of 29.1 ± 32.1% in snoring events and 32.5 ± 33.1% in duration, but these values were not statistically significant (p > 0.05) compared to LP. These findings indicate that pillow type and usage, often uncontrolled in OSAS studies (contribution to the field), may impact several PSG parameters and are related to a snoring subtype of the syndrome. Secondly, they indicate that a focus on the treatment of the snoring OSAS subtype warrants further dedicated investigation.

Elements of Sleep Breathing and Sleep-Deprivation Physiology in the Context of Athletic Performance.

This review summarizes sleep deprivation, breathing regulation during sleep, and the outcomes of its destabilization. Breathing as an automatically regulated task consists of different basic anatomic and physiological parts. As the human body goes through the different stages of sleep, physiological changes in the breathing mechanism are present. Sleep disorders, such as obstructive sleep apnea-hypopnea syndrome, are often associated with sleep-disordered breathing and sleep deprivation. Hypoxia and hypercapnia coexist with lack of sleep and undermine multiple functions of the body (e.g., cardiovascular system, cognition, immunity). Among the general population, athletes suffer from these consequences more during their performance. This concept supports the beneficial restorative effects of a good sleeping pattern.

Physical Fitness Differences, Amenable to Hypoxia-Driven and Sarcopenia Pathophysiology, between Sleep Apnea and COVID-19.

Handgrip strength is an indirect indicator of physical fitness that is used in medical rehabilitation for its potential prognostic value. An increasing number of studies indicate that COVID-19 survivors experience impaired physical fitness for months following hospitalization. The aim of our study was to assess physical fitness indicator differences with another prevalent and hypoxia-driven disease, Obstructive Sleep Apnea Syndrome (OSAS). Our findings showed differences between post-COVID-19 and OSAS groups in cardiovascular responses, with post-COVID-19 patients exhibiting higher values for heart rate and in mean arterial blood pressure. Oxygen saturation (SpO2) was lower in post-COVID-19 patients during a six-minute walking test (6MWT), whereas the ΔSpO2 (the difference between the baseline to end of the 6MWT) was higher compared to OSAS patients. In patients of both groups, statistically significant correlations were detected between handgrip strength and distance during the 6MWT, anthropometric characteristics, and body composition parameters. In our study, COVID-19 survivors demonstrated a long-term reduction in muscle strength compared to OSAS patients. Lower handgrip strength has been independently associated with a prior COVID-19 hospitalization. The differences in muscle strength and oxygenation could be attributed to the abrupt onset of the disorder, which does not allow compensatory mechanisms to act effectively. Targeted rehabilitation focusing on such residual impairments may thus be indispensable within the setting of post-COVID-19 syndrome.

The 6-Minute Walk Test and Anthropometric Characteristics as Assessment Tools in Patients with Obstructive Sleep Apnea Syndrome. A Preliminary Report during the Pandemic.

Patients with obstructive sleep apnea syndrome (OSAS) exhibit low cardio-fitness impact, attributed to fragmented sleep architecture and associated pathophysiological sequelae. The purpose of our study was to investigate fitness indicators during 6-min walk test (6MWT) and oxidative stress markers in apnea-hypopnea index (AHI) in OSAS patients stratified by severity. A total of 37 newly diagnosed patients, comorbidity-free, were divided into two groups: (Moderate OSAS (n = 12), defined as ≥ 15 AHI < 30 events per hour; Age: 50.7 ± 7.2 years, BMI: 32.5 ± 4.0 kg/m2 vs. Severe OSAS (n = 25), defined as AHΙ ≥ 30 events per hour; Age: 46.3 ± 10.4 years, BMI: 33.3 ± 7.9 kg/m2). Measurements included demographics, anthropometric characteristics, body composition, blood sampling for reactive oxygen metabolites' levels (d-ROM) and plasma antioxidant capacity (PAT), and followed by a 6MWT. AHI was significantly associated with d-ROMs levels, chest circumference in maximal inhalation and exhalation (Δchest), neck circumference, as well as 6MWT-derived indices. In conclusion, our study determines bidirectional interrelationships between OSAS severity and anthropometrics, body composition, and fitness metrics. These findings indicate that the impact of OSAS should be evaluated well beyond polysomnography-derived parameters.

Sleep Quality's Effect on Vigilance and Perceptual Ability in Adolescent and Adult Athletes.

The aim of the study was to investigate the effect of sleep quality in cognitive domains of perceptual ability after exhausting exercise in adolescent and adult athletes. Eighty-six male professional soccer players were included in our study and divided into two groups: adolescents (age: 17.3 ± 0.2 yrs, body mass: 68.9 ± 7.9 kg, body fat: 9.9 ± 3.6 %) versus adults (age: 26.3 ± 5.2 yrs, body mass: 76.5 ± 7.2 kg, body fat: 10.3 ± 3.1 %). For each athlete, prior to cardiopulmonary exercise testing (CPET), anthropometric and morphological characteristics were recorded and Pittsburgh Sleep Quality Index (PSQI) questionnaire was answered. Immediately after CPET, all athletes underwent the perceptual ability test (PATest) for 30 sec and the sum of hits (rep/30 sec) and the time between a visual stimulus and the following stimulus (mean reaction time; RT, sec) were recorded. Oxygen uptake in maximal effort and in anaerobic threshold showed differences between hits (P=0.037) and RT (P=0.025). The variable of PSQI questionnaire "had bad dreams" showed correlation with hits (P=0.021) and RT (P=0.011) and the RT showed correlation with variables "cannot breathe comfortably" (P=0.041) and "...enthusiasm to get things done" (P=0.041). Adolescents showed poorer sleep quality (PSQI score: 5.7 ± 3.6 vs. 2.4 ± 2.6) compared to adults and slower reaction time (0.9 ± 0.1 vs. 0.8 ± 0.1 sec, P=0.029) compared to adolescent athletes with PSQI score ≥5.5. The variable of PSQI score in adolescents is related to HR in maximal effort (r = -0.364, P=0.032) and in adults is related to speed (r = -0.335, P=0.016). Perceptual ability, which requires sustained attention, vigilance, and motor coordination, is often negatively affected by restricted sleep, especially in adolescents.

Respiratory Muscle Strength as an Indicator of the Severity of the Apnea-Hypopnea Index: Stepping Towards the Distinction Between Sleep Apnea and Breath Holding.

Background and objective The aim of this study was to investigate whether the maximum inspiratory and expiratory pressure are correlated with the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea syndrome (OSAS). Methods Fifty-two patients with OSAS were divided into two groups (AHI, events/hours: <30, n=28, versus ≥30, n=24). For each patient, anthropometric characteristics, spirometry parameters, maximum inspiratory (MIP) and expiratory pressure (MEP), and cardiopulmonary function (CPF) parameters (oxygen uptake at rest (VO2), carbon dioxide output (VCO2), heart rate (HR), minute ventilation (VE), tidal volume at inspiratory (TVin) and expiratory (TVex), breath frequency (f ß), end-tidal carbon dioxide pressure (PETCO2), end-tidal oxygen pressure (PETO2), and mean arterial pressure (MAP)) in sitting position for three minutes were recorded. The independent t-test was used to measure the differences between groups (events/hours <30 versus ≥30) and Pearson correlation analysis was used for statistical comparison between parameters. Results Results showed differences between groups (AHI, events/h ≥30 versus <30) in MIP (102.0±18.3 versus 91.1±12.1 % of predicted, p=0.013) and CPF parameters TVin (0.8±0.2 versus 0.7±0.1, L, p=0.047), PETCO2 (34.6±4.2 versus 31.4±3.7, mmHg, p=0.007), and MAP (88.4±6.5 versus 82.9±6.2, mmHg, p=0.003). Pearson correlation analysis between respiratory muscle strength (MIP and MEP) and polysomnography (PSG) parameters, MIP is related to AHI (r=.332, p=0.016) and desaturation index (r=.439, p=0.001), as well as MEP to percent of REM sleep stage (r=-.564, p<0.001). Conclusion The data from the present study support that maximal inspiratory pressure relates to the severity of AHI and intermittent breath-holding during sleep increases the inspiratory muscle strength.

Obstructive Sleep Apnea Syndrome: The Effect of Acute and Chronic Responses of Exercise.

Obstructive Sleep Apnea Syndrome (OSAS) is a sleep disorder with high prevalence in general population, but alarmingly low in clinicians' differential diagnosis. We reviewed the literature on PubMed and Scopus from June 1980-2021 in order to describe the altered systematic pathophysiologic mechanisms in OSAS patients as well as to propose an exercise program for these patients. Exercise prevents a dysregulation of both daytime and nighttime cardiovascular autonomic function, reduces body weight, halts the onset and progress of insulin resistance, while it ameliorates excessive daytime sleepiness, cognitive decline, and mood disturbances, contributing to an overall greater sleep quality and quality of life.

Sleep disordered breathing from preschool to early adult age and its neurocognitive complications: A preliminary report.

OBJECTIVE: The onset and development of sleep disordered breathing (SDB) remains unclear in an age - dependent manner. Despite treatment, persistent symptoms such as snoring and excessive daytime sleepiness, as well as cognitive impairment may be present. The aim of the research was to determine the prevalence of residual symptoms of SDB in adolescence and early adulthood, the predisposing factors and its neurocognitive complications. METHODS: In the present pilot study-cohort, a questionnaire was utilized to 154 people (average age: 17.9 ± 3), who as children (mean age: 5.3 ± 1.4) had AHI ≥2.5 episodes/h. They were divided into two groups based on AHI = 5 episodes/h. Depending on the results, they were invited to undergo a repeated polysomnography (PSG) and complete the Montreal Cognitive Assessment (MoCA) test. Statistical analysis was made with IBM SPSS software. RESULTS: Out of the total, 35.7% claimed to still snore. AHI was negatively correlated to the severity of residual symptoms (Mann-Witney U test, p <0.005). According to repeated PSGs, 9/17 met the criteria for OSAS, while high BMI was associated with the severity of new AHI (chi squared test, p<0.005). Additionally, 7/16 scored below the MoCA baseline (<26/30). The characteristics of cognitive declines were mapped, with most prominent having been visuospatial, short - term memory and naming/language deficits. DISCUSSION: A significant percentage of children with sleep breathing disorder present with residual symptoms during their transition to early adulthood, as well as undiagnosed neurocognitive complications. Clinicians suspicion for the underlying neurocognitive complications is required, even in young adults, while guidelines on monitoring pediatric OSAS patients after treatment should be addressed.

The Reciprocal Association between Fitness Indicators and Sleep Quality in the Context of Recent Sport Injury.

The purpose of the study is to investigate whether the oxygen uptake and heart rate at rest, in Greek professional soccer players, are affected by recent injuries, as well as how sleep quality is affected. Forty-two male professional soccer players were included in the study and divided into two groups: injurygroup (n = 22, age: 21.6 ± 5.4 years, body fat: 11.0 ± 3.9%, total body water: 64.0 ± 2.5%) and no-injurygroup (n = 20, age: 24.2 ± 5.6 years, body fat: 10.1 ± 2.8%, total body water: 64.3 ± 1.8%). The oxygen uptake at rest (VO2resting, mL/min/kg) and heart rate (HR, bpm) were recorded in the upright position for 3 min, and the predicted values were calculated. One hour before, the athletes answered the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The results showed a difference between groups (injurygroup vs. no-injurygroup) in VO2resting (7.5 ± 1.4 vs. 5.5 ± 1.2 mL/min/kg, p < 0.001) and percent of predicted values (92.5 ± 17.2 vs. 68.3 ± 14.6%, p < 0.001) and HR, such as beats per min (100.6 ± 12.8 vs. 93.1 ± 4.6 bpm, p = 0.001), percent of predicted values (50.7 ± 6.4 vs. 47.6 ± 2.8%, p = 0.003) and sleep quality score (PSQI: 4.9 ± 2.2 vs. 3.1 ± 0.9, p = 0.005). Anthropometric characteristics were not different between groups. Oxygen consumption and heart rate at rest are affected by the systemic adaptations due to injury. These pathophysiological changes probably relate to increased blood flow in an attempt to restore the injury area.

Alzheimer's Disease in Patients with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a disorder with high prevalence among adults and is an independent risk factor for various diseases, especially those affecting the central nervous system (CNS). Continuous positive airway pressure (CPAP) is usually the optimal choice of treatment for OSAS. Alzheimer's disease (AD) is a neurodegenerative disease affecting a large proportion of the elderly population. The purpose of this study was to collect information concerning the two pathological entities and investigate the effectiveness of CPAP in the treatment of AD. MATERIALS AND METHODS: In this review, Twenty articles were found concerning OSAS and AD, of which one article was about treatment with donepezil and seven articles considered treatment with CPAP. RESULTS: Serious OSAS and short sleep duration are associated with a high risk of developing dementia. Respiratory distress during sleep is associated with developing mild cognitive impairment at younger ages. The cerebrovascular damage of AD patients is correlated with the severity of OSAS. Lower cerebrospinal fluid levels are associated with memory disturbances and oxygen saturation parameters in patients with OSAS-AD. Continuous use of CPAP is related to the delayed onset of cognitive impairment and is suggested as an effective method of protecting cognitive function, depression, sleep quality and architecture, and daytime sleepiness in AD patients with good compliance. Treatment of CPAP patients with OSAS-AD is suggested as an effective method of protecting cognitive function. CONCLUSION: Clinicians dealing with AD patients should consider CPAP treatment when OSAS coexists.