Nocturnal hypoxia in ALS is related to cognitive dysfunction and can occur as clusters of desaturations.
ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ?10% of the night) and their clinical characteristics and cognitive function were compared.Compared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n?=?10, 40%) had poor memory retention (p?=?0.039) and retrieval efficiency (p?=?0.045). A cluster-of-desaturation pattern was identified in 7 patients (70%) in the Hypoxia Group.These results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation-reoxygenation (a cluster-of-desaturation pattern) during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.
Project description:Obstructive sleep apnea (OSA) is a prevalent disorder with multiple consequences including negative effects on neurocognitive function. Several domains of cognitive function are impaired in OSA patients, but the mechanisms through which this sleep disorder results in impairment are not clear. Given the well-known effects of cortisol on cognitive function, in particular memory, the dysregulating effects of OSA on cortisol levels are hypothesized as a potential pathway leading to cognitive impairment.Fifty-five participants with OSA (mean apnea-hypopnea index [AHI], 30.3) were assessed over 2 days. Over a 24-h period, blood samples were collected every 2h to examine cortisol levels. The following night, sleep was monitored with polysomnography (PSG). Participants were given a battery of neurocognitive tests, which assessed seven cognitive domains.OSA severity assessed by oxygen desaturation index (ODI) was associated with 24-h cortisol levels. AHI, ODI, and nighttime cortisol levels were associated with global deficit scores (GDS) in cognitive functioning, particularly in domains of learning, memory, and working memory (P<.05 for all). Hierarchical linear regression analysis revealed that nighttime cortisol accounted for 9-16% of variance in learning (P=.018), memory (P=.003), and working memory (P=.016) domains, though apnea severity did not significantly predict any additional variance.In our sample of patients with OSA, nocturnal cortisol levels were associated with neuropsychologic functioning above and beyond the influence of covariates and apnea severity. These findings suggest that OSA-related alterations in cortisol activity may partially explain the pathophysiology of neuropsychologic impairments in sleep apnea.
Project description:Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity.To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery.We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n = 20) were obtained during bariatric surgery.Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 +/- 29 events/hour and the median oxygen desaturation during apneic events was 4.6 +/- 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology.Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.
Project description:A critical link between amyloid-beta (A?) and hypoxia has been demonstrated in in vitro and animal studies but has not yet been proven in humans. Obstructive sleep apnea syndrome (OSAS) is a common disorder that is characterized by nocturnal intermittent hypoxaemia. This study sought to examine the association between the chronic intermittent hypoxia and A? in OSAS patients. Forty-five cognitively normal OSAS patients and forty-nine age- and gender-matched subjects diagnosed with simple snoring and not OSAS were included in the present study. Serum A?40, A?42, total tau and phosphorylated tau 181 (P-tau 181) levels were measured using ELISA kits. All subjects were evaluated with nighttime polysomnography and cognitive tests. Compared with the controls, the OSAS patients exhibited significantly higher serum A?40, A?42 and total A? levels, and each of these levels was positively correlated with the apnea-hypopnea index, the oxygen desaturation index, and the mean and lowest oxyhaemoglobin saturations in the OSAS patients. Moreover, the OSAS patients exhibited strikingly higher serum P-tau 181 levels, and these levels were positively correlated with serum A? levels. This study suggests that there is an association between chronic intermittent hypoxia and increased A? levels, implying that hypoxia may contribute to the pathogenesis of Alzheimer's disease.
Project description:BACKGROUND?Patients with chronic obstructive pulmonary disease (COPD) may experience sleep disordered breathing with nocturnal desaturation. An exploratory study was performed to determine whether any commonly measured clinical parameters were useful in predicting nocturnal desaturation in patients with COPD. A validation study was subsequently performed to confirm the utility of the parameter identified in the exploratory study as most useful in this regard.A total of 103 (exploratory cohort) and 200 (validation cohort) consecutive patients with COPD admitted for pulmonary rehabilitation were evaluated. Standard outcome measures including nocturnal oximetry and the 6 min walk test (6MWT) on room air with continuous pulse oximetry were assessed. Patients with sleep apnea or those undergoing long-term oxygen therapy were excluded.In the exploratory study, the mean (± SD) patient age was 70 ± 9.9 years, with forced expiratory volume in 1 s of 0.76 ± 0.34 L, which was 36 ± 16% of predicted. Body mass index, arterial oxygen tension, oxygen saturation by pulse oximetry at rest and during the 6MWT all demonstrated significant correlations with percentage of time spent with a saturation <90%. When the lowest pulse oximetry during the 6MWT was ?88%, 10 of 21 patients demonstrated a saturation <90% for at least 30% of sleep time. This measure yielded a positive likelihood ratio of 3.77 (95% CI 1.87 to 7.62) compared with those who did not reach this threshold value. The validation study confirmed similar detection characteristics.Results from the present study suggest that monitoring oxygen saturation changes during a 6MWT is useful in helping to identify COPD patients who may experience significant nocturnal desaturation.
Project description:To evaluate the effects of noninvasive ventilation (NIV) on sleep in patients with amyotrophic lateral sclerosis (ALS) after meticulous titration with polysomnography (PSG).In this prospective observational study, 24 ALS patients were admitted to the sleep laboratory during 4 nights for in-hospital NIV titration with PSG and nocturnal capnography. Questionnaires were used to assess subjective sleep quality and quality of life (QoL). Patients were readmitted after one month.In the total group, slow wave sleep and REM sleep increased and the arousal-awakening index improved. The group without bulbar involvement (non-bulbar) showed the same improvements, together with an increase in sleep efficiency. Nocturnal oxygen and carbon dioxide levels improved in the total and non-bulbar group. Except for oxygen saturation during REM sleep, no improvement in respiratory function or sleep structure was found in bulbar patients. However, these patients showed less room for improvement. Patient-reported outcomes showed improvement in sleep quality and QoL for the total and non-bulbar group, while bulbar patients only reported improvements in very few subscores.This study shows an improvement of sleep architecture, carbon dioxide, and nocturnal oxygen saturation at the end of NIV titration and after one month of NIV in ALS patients. More studies are needed to identify the appropriate time to start NIV in bulbar patients. Our results suggest that accurate titration of NIV by PSG improves sleep quality.A commentary on this article appears in this issue on page 511.
Project description:Obstructive sleep apnoea (OSA) is a sleep disorder involving repeated nocturnal desaturation and sleep fragmentation. OSA can result in decreased daytime alertness and neurocognitive dysfunction. Hypercapnia status is also related to neurocognitive dysfunction in patients with pulmonary diseases. We evaluated the effects of hypercapnia on cognitive performance and memory function in a prospective case-controlled study. We enrolled thirty-nine obese patients with OSA and collected their arterial blood samples. All the participants provided arterial blood samples, and completed two questionnaires (the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale) and six cognitive tasks (the psychomotor vigilance task [PVT], the Stroop task, the Eriksen flanker task, processing speed [DSST], and verbal and visual memory [LM&FM]), which were used to evaluate daytime sleepiness, cognitive function, and memory function within one week of a polysomnographic study. When compared to the OSA without diurnal hypoventilation, the patients with stable hypercapnia (OHS) had increased reaction times in the PVT, Stroop task, and flanker task. Hypercapnic obese patients with OSA also had comparatively significantly lower scores in the processing speed and logical memory tests. OHS had increased reaction times in the attention and cognitive function assessments, and deficits in the logical memory, when compared to those with OSA without diurnal hypoventilation.
Project description:INTRODUCTION:Functional magnetic resonance imaging (fMRI) studies enable the investigation of neural correlates underlying behavioral performance. We investigate the working memory (WM) function of patients with untreated obstructive sleep apnea (OSA) from the view point of task positive and default mode networks (TPN and DMN, respectively) and compare the results to those of healthy controls (HC). METHODS:A parametric fMRI experiment with 4 levels of visuospatial N-back task was used to investigate the pattern of cortical activation in 17 men with untreated moderate or severe OSA and 7 age-matched HC. Categorical and parametrical analysis of the data was performed. Multiple regression analysis of fMRI data of OSA patients was performed with AHI, nocturnal desaturation time, and BMI as covariates. RESULTS:OSA patients demonstrate compensatory spatial recruitment of the TPN (maximal at 3-back) and of the DMN (maximal at 2-back). HC had a different patten of spatial recruitment and deactivation of the DMN at the maximal load of task (3-back). Nocturnal desaturation had significant positive correlation with BOLD signal in bilateral frontal, temporal, and occipital regions, and negative correlations in bilateral frontal and left parietal regions; whereas BMI showed only negative correlations with BOLD signal, predominantly in the PFC. AHI was positively correlated with BOLD signal in bilateral frontal regions. CONCLUSION:Both TPN and DMN are affected in OSA patients, with nocturnal desaturation affecting both networks; whereas BMI appears to be the major negative factor influencing the TPN and has a significant negative correlation with behavioral performance.
Project description:Sleep apnea has been related to brain changes such as atrophy. However, which component of sleep apnea, the apnea-hypopnea index (AHI), nocturnal oxygen desaturation or arousals, can explain this association is unclear. In this large population-based study (n=681, mean age 62.1 years), we investigated the associations of AHI, nocturnal oxygen desaturation and arousals with global and regional gray matter and white matter volumes and with white matter lesion volumes. All participants underwent one night of polysomnography and MRI scanning of their brain. Gray matter, white matter and white matter lesion volumes adjusted for intracranial volume were studied as markers of brain atrophy. Nocturnal oxygen desaturation was related to whole brain white matter atrophy independent of covariates (multivariable adjusted B=-8.3, 95% CI=-16.7; -0.02). This association was most prominently reflected in the association between more oxygen desaturation and a smaller white matter parietal volume (B=-3.95 ml, 95% CI=-6.02; -1.88). Furthermore, oxygen desaturation was related to a smaller hippocampus (B=-0.22 ml, 95% CI=-0.42; -0.01). Although a higher AHI was related to smaller parietal gray (B=-0.05, 95% CI=-0.09; -0.004) and white matter (B=-0.06, 95% CI=-0.12; -0.10) volumes, these associations disappeared when adding oxygen desaturation to the model. We did not find a relation between arousals and gray and white matter brain atrophy and white matter lesion volumes. This suggests that oxygen desaturation mainly explains the association between sleep apnea and brain damage.
Project description:Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 h a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT.The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is double blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy. The follow-up period is intended to last at least 3 years.The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight.Current Controlled Trials ISRCTN50085100 ; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010).
Project description:BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) suffer from hypoventilation, which can easily worsen during sleep. This study evaluated the efficacy of capnography monitoring in patients with ALS for assessing nocturnal hypoventilation and predicting good compliance with subsequent noninvasive ventilation (NIV) treatment. METHODS: Nocturnal monitoring and brief wake screening by capnography/pulse oximetry, functional scores, and other respiratory signs were assessed in 26 patients with ALS. Twenty-one of these patients were treated with NIV and had their treatment compliance evaluated. RESULTS: Nocturnal capnography values were reliable and strongly correlated with the patients' respiratory symptoms (R(2)?= 0.211-0.305, p = 0.004-0.021). The duration of nocturnal hypercapnea obtained by capnography exhibited a significant predictive power for good compliance with subsequent NIV treatment, with an area-under-the-curve value of 0.846 (p = 0.018). In contrast, no significant predictive values for nocturnal pulse oximetry or functional scores for nocturnal hypoventilation were found. Brief waking supine capnography was also useful as a screening tool before routine nocturnal capnography monitoring. CONCLUSION: Capnography is an efficient tool for assessing nocturnal hypoventilation and predicting good compliance with subsequent NIV treatment of ALS patients, and may prove useful as an adjunctive tool for assessing the need for NIV treatment in these patients.