Kerri L. Melehan

Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature

Endothelial dysfunction is characterized by impaired endothelium-dependent vasodilatation and is an independent predictor of adverse cardiovascular consequences. The ease with which endothelial function can be assessed has led to it becoming a useful marker of cardiovascular diseases in research studies. Obstructive sleep apnea (OSA) has been independently associated with endothelial dysfunction which may explain the increased risk for cardiovascular and all-cause mortality in this population. One possible mechanism for the development of endothelial dysfunction in OSA is through the cyclical pattern of hypoxia and re-oxygenation. This creates a haemostatic imbalance in which nitric oxide bio-availability is reduced and pro-inflammatory and pro-thrombotic forces prevail. Furthermore the repair capacity of the endothelium to protect itself against this increased damage is diminished. All of these pathways contribute to vascular disease which ultimately gives rise to adverse cardiovascular consequences. This review aims to provide a critical appraisal of the cross-sectional and interventional studies which have investigated micro- and macro-vascular endothelial dysfunction in OSA with emphasis on randomised controlled studies.

Metabolic and hormonal effects of ‘catch-up’ sleep in men with chronic, repetitive, lifestyle-driven sleep restriction

Acutely restricting sleep worsens insulin sensitivity in healthy individuals whose usual sleep is normal in duration and pattern. The effect of recovery or weekend ‘catch‐up’ sleep on insulin sensitivity and metabolically active hormones in individuals with chronic sleep restriction who regularly ‘catch‐up’ on sleep at weekends is as yet unstudied.

Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire.

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinsons disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty‐six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self‐report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future.

To ED or not to ED – Is erectile dysfunction in obstructive sleep apnea related to endothelial dysfunction?

Both obstructive sleep apnea (OSA) and erectile dysfunction (ErectD) are highly prevalent and largely under diagnosed medical conditions. These disorders often co-exist, with about half of the male OSA population having ErectD and vice versa. OSA is strongly associated with an increased risk of cardiovascular mortality while ErectD has been proposed as a phenotypic marker of cardiovascular disease. This implies that the two conditions may be linked by a common pathophysiological mechanism. In this review we provide evidence supporting the hypothesis that endothelial dysfunction (EndoD) may be the common pathophysiological mechanism linking OSA with both ErectD and cardiovascular complications. EndoD is one of the earliest markers of cardiovascular disease and substantial evidence suggests that OSA independently causes EndoD. There is also strong evidence that causally links EndoD with organic ErectD. Further research should be directed at determining the value of simultaneously assessing both ErectD and OSA in patients presenting with symptoms of either condition. In both ErectD and OSA clinics, identifying both conditions could improve overall cardiovascular risk stratification whilst treatment of OSA could reduce both ErectD and cardiovascular risk.

The contribution of nocturnal sleep to the consolidation of motor skill learning in healthy ageing and Parkinson's disease.

The benefits of sleep for the consolidation of procedural motor skills are less robust in older adults, although the precise reasons for this remain unclear. To date, even less is known about these processes in older adults with neurodegenerative diseases, particularly those which impact on motor functioning. While sleep disturbance and motor symptoms are frequent disabling features of Parkinsons disease, no known studies have directly probed sleep‐dependent memory consolidation for motor skill learning in Parkinsons disease. Forty patients with idiopathic Parkinsons disease (age = 63.7 years ± 7.7; disease duration 4.1 years ± 4.4) completed a motor skill learning task pre‐ and post‐sleep and were compared to 20 age‐ and sex‐matched controls recruited from the community. Polysomnography was undertaken during the post‐training night and measures of sleep architecture were derived. Parkinsons disease patients did not demonstrate any apparent deficits in within‐session learning and overnight stabilization compared to controls, with both groups failing to demonstrate offline improvements in performance (i.e. memory consolidation). In controls, longer duration in slow wave sleep was associated with improved next‐day session learning (P = 0.007). However, in Parkinsons disease, no relationships between sleep parameters and learning measures were found. Slow wave sleep microarchitecture and the use of dopaminergic medications may contribute to impaired sleep‐dependent multi‐session acquisition of motor skill learning in Parkinsons disease.

Prevalence of patent foramen ovale and its impact on oxygen desaturation in obstructive sleep apnea

BACKGROUND A possible association between patent foramen ovale (PFO) and obstructive sleep apnea has been suggested (OSA), whereby right-to-left shunting may exacerbate the severity of nocturnal oxygen desaturation. However, the interaction between these two conditions has not been well characterised. METHODS A case-control study was conducted to evaluate the epidemiological association between PFO and OSA. Subjects were recruited prospectively from a sleep laboratory population, and 102 OSA subjects (mean age 51.5 ± 13 years) were compared to 50 controls without OSA (mean age 49.9 ± 12.4). The presence and size of right-to-left shunting were determined by contrast transcranial Doppler ultrasonography with Valsalva provocation. Using the 21,749 obstructive breathing events recorded at polysomnography from the OSA group, a mixed-effects linear regression model was developed to evaluate the impact of right-to-left shunting on nocturnal oxygen desaturation (ΔSpO2). RESULTS A higher prevalence of PFO was present in the OSA group compared to the control group (47.1% vs. 26.0%, OR 2.53, CI 1.20 to 5.31, p=0.014). From the regression model, right-to-left shunt size did not exert a significant influence on the severity of ΔSpO2 (coefficient 0.85, CI -0.62 to 2.32, p=0.254); whereas sleep state, event type, body position, event duration, awake oxygen saturation, apnea-hypopnea index and body mass index were all independent predictors of ΔSpO2. CONCLUSION A higher prevalence of PFO is found in OSA subjects. However, the degree of right-to-left shunting, characterised by Valsalva provocation, is not associated with an increased severity of nocturnal oxygen desaturation.

Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo‐controlled study

Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre‐specified at 8, 11 and 13 nmol/L. This was a randomized placebo‐controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep‐related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep‐related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing.

Methodology for the assessment of sleep

This chapter provides an overview of the assessment methods used to examine sleep. We focus on techniques that are commonly employed to diagnose sleep disorders, evaluate treatment response, and summarize investigative methods adopted by sleep scientists. This chapter covers the following practices: polysomnography, actigraphy, brain imaging, hormone assessment, and subjective measures including self-report questionnaires and sleep diaries. These measures enable sleep scientists to further understand the role of sleep in human behavior.

Investigating the night-to-night variability of REM without atonia in Parkinson's disease

OBJECTIVES Rapid eye movement (REM) sleep behaviour disorder is frequently observed in Parkinsons disease and is characterized electrophysiologically by the absence of atonia during REM sleep. However, the night-to-night variability of REM sleep without atonia is yet to be determined in Parkinsons disease. METHODS Using polysomnography, this study measured the variability of REM sleep without atonia across two consecutive nights, using the REM atonia index in 38 patients with Parkinsons disease. RESULTS The intraclass correlation coefficient between the REM sleep atonia index across two nights was 0.816 (F = 9.795, p < 0.001) and the difference between the two nights was 4.7% (standard deviation (SD) 8.2). CONCLUSION The REM atonia index demonstrated low variability across two consecutive nights of PSG. Furthermore, the diagnosis of REM sleep behaviour disorder based on this electrophysiological marker and other clinical variables was in agreement across the two nights.

Randomized Trial of CPAP and Vardenafil on Erectile and Arterial Function in Men With Obstructive Sleep Apnea and Erectile Dysfunction

Context Erectile function is important for life satisfaction and often impaired in men with obstructive sleep apnea (OSA). Uncontrolled studies show that treating OSA with continuous positive airway pressure (CPAP) improves erectile function. Phosphodiesterase type 5 inhibitors (e.g., vardenafil) are the first-line therapy for erectile dysfunction (ED), but may worsen OSA. Objective To assess the effects of CPAP and vardenafil on ED. Design Sixty-one men with moderate-to-severe OSA and ED were randomized to 12 weeks of CPAP or sham CPAP, and 10 mg daily vardenafil or placebo in a two-by-two factorial design. Main Outcome Measures International Index of Erectile Function (primary end point), treatment and relationship satisfaction, sleep-related erections, sexual function, endothelial function, arterial stiffness, quality of life, and sleep-disordered breathing. Results CPAP increased the frequency of sleep-related erections, overall sexual satisfaction, and arterial stiffness but did not change erectile function or treatment or relationship satisfaction. Vardenafil did not alter erectile function, endothelial function, arterial stiffness, or sleep-disordered breathing, but did improve overall self-esteem and relationship satisfaction, other aspects of sexual function, and treatment satisfaction. Adherent CPAP improved erectile function, sexual desire, overall sexual, self-esteem, relationship, and treatment satisfaction, as well as sleepiness, and quality of life. Adherent vardenafil use did not consistently change nocturnal erection quality. Conclusion CPAP improves overall sexual satisfaction, sleep-related erections, and arterial stiffness. Low-dose daily vardenafil improves certain aspects of sexual function and did not worsen OSA. Adherent CPAP or vardenafil use further improves ED and quality of life.