Brain mitochondrial dysfunction and driving simulator performance in untreated obstructive sleep apnea.

It is challenging to determine which patients with obstructive sleep apnea (OSA) have impaired driving ability. Vulnerability to this neurobehavioral impairment may be explained by lower brain metabolites levels involved in mitochondrial metabolism. This study compared markers of brain energy metabolism in OSA patients identified as vulnerable vs resistant to driving impairment following extended wakefulness. 44 patients with moderate-severe OSA underwent 28hr extended wakefulness with three 90min driving simulation assessments. Using a two-step cluster analysis, objective driving data (steering deviation and crashes) from the 2nd driving assessment (22.5 h awake) was used to categorise patients into vulnerable (poor driving, n = 21) or resistant groups (good driving, n = 23). 1 H magnetic resonance spectra were acquired at baseline using two scan sequences (short echo PRESS and longer echo-time asymmetric PRESS), focusing on key metabolites, creatine, glutamate, N-acetylaspartate (NAA) in the hippocampus, anterior cingulate cortex and left orbito-frontal cortex. Based on cluster analysis, the vulnerable group had impaired driving performance compared with the resistant group and had lower levels of creatine (PRESS p = ns, APRESS p = 0.039), glutamate, (PRESS p < 0.01, APRESS p < 0.01), NAA (PRESS p = 0.038, APRESS p = 0.035) exclusively in the left orbito-frontal cortex. Adjusted analysis, higher glutamate was associated with a 21% (PRESS) and 36% (APRESS) reduced risk of vulnerable classification. Brain mitochondrial bioenergetics in the frontal brain regions are impaired in OSA patients who are vulnerable to driving impairment following sleep loss. These findings provide a potential way to identify at risk OSA phenotype when assessing fitness to drive, but this requires confirmation in larger future studies.

Clinical predictors of working memory performance in obstructive sleep apnea patients before and during extended wakefulness.

STUDY OBJECTIVES: Extended wakefulness (EW) and obstructive sleep apnea (OSA) impair working memory (WM), but their combined effects are unclear. This study examined the impact of EW on WM function in OSA patients and identified clinical predictors of WM impairment. METHODS: Following polysomnography (PSG), 56 OSA patients (mean ± SD, age 49.5 ± 8.9, apnea hypopnea index 38.1 ± 25.0) completed WM 2-back performance tasks 10 times over 24 h of wakefulness to assess average accuracy and completion times measured after 6-12 h awake (baseline) compared to 18-24 h awake (EW). Hierarchical cluster analysis classified participants with poorer versus better WM performance at baseline and during EW. Clinical predictors of performance were examined via regression and receiver operator characteristic (ROC) analyses. RESULTS: WM performance decreased following EW and showed consistent correlations with age, Epworth Sleepiness Score (ESS), total sleep time, and hypoxemia (O2 nadir and mean O2 desaturation) at baseline and with EW (all p < .01). O2 nadir and age were significant independent predictors of performance at baseline (adjusted R2 = 0.30, p < .01), while O2 nadir and ESS were predictors of WM following EW (adjusted R2 = 0.38, p < .001). ROC analysis demonstrated high sensitivity and specificity of models to predict poorer versus better performing participants at baseline (83% and 69%) and during EW (84% and 74%). CONCLUSIONS: O2 nadir, age, and sleepiness show prognostic value for predicting WM impairment in both rested and sleep-deprived OSA patients and may guide clinicians in identifying patients most at risk of impaired WM under both rested and heightened sleep pressure conditions.Clinical Trial Registration: This manuscript presents data collected as part of a larger trial-ANZCTR: Novel brain biomarkers of performance impairment in sleep apnea-https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363830, No. ACTRN12613001171707.

Sleep spindle activity correlates with implicit statistical learning consolidation in untreated obstructive sleep apnea patients.

OBJECTIVE/BACKGROUND: The aim of this study was to examine the relationship between overnight consolidation of implicit statistical learning with spindle frequency EEG activity and slow frequency delta power during non-rapid eye movement (NREM) sleep in obstructive sleep apnea (OSA). PATIENTS/METHODS: Forty-seven OSA participants completed the experiment. Prior to sleep, participants performed a reaction time cover task containing hidden patterns of pictures, about which participants were not informed. After the familiarisation phase, participants underwent overnight polysomnography. 24 h after the familiarisation phase, participants performed a test phase to assess their learning of the hidden patterns, expressed as a percentage of the number of correctly identified patterns. Spindle frequency activity (SFA) and delta power (0.5-4.5 Hz), were quantified from NREM electroencephalography. Associations between statistical learning and sleep EEG, and OSA severity measures were examined. RESULTS: SFA in NREM sleep in frontal and central brain regions was positively correlated with statistical learning scores (r = 0.41 to 0.31, p = 0.006 to 0.044). In multiple regression, greater SFA and longer sleep onset latency were significant predictors of better statistical learning performance. Delta power and OSA severity were not significantly correlated with statistical learning. CONCLUSIONS: These findings suggest spindle activity may serve as a marker of statistical learning capability in OSA. This work provides novel insight into how altered sleep physiology relates to consolidation of implicitly learnt information in patients with moderate to severe OSA.

Gender differences in obstructive sleep apnoea, insomnia and restless legs syndrome in adults - What do we know? A clinical update.

Research in sleep medicine over the last decades has involved a broad variety of sleep disorders in both men and women. Gender differences have been identified in sleep physiology as well as in the three most common sleep disorders: obstructive sleep apnoea (OSA), insomnia and restless legs syndrome (RLS). However, research on gender differences in sleep medicine appears limited. This clinical review aims to give an updated overview of gender differences, in relation to prevalence, clinical presentation, treatment and quality of life in OSA, insomnia and RLS. Future research directions in the adult population will also be discussed.