Obstructive sleep apnea affects cognition: dual effects of intermittent hypoxia on neurons

Obstructive sleep apnoea (OSA) contributes to cerebrovascular diseases and cognitive decline. Preclinical studies support the deleterious impact on the brain of intermittent hypoxia (IH), one of the main components of OSA, but heterogeneity in rodent species and brain regions studied, or induced by IH paradigms, can challenge interpretation of the studies. Hence, we conducted a systematic review and meta-analysis to evaluate the impact of IH on rodent brain oxidative stress, inflammation, apoptosis and the expression of brain-derived neurotrophic factor (BDNF) and hypoxia-inducible factor 1 (HIF-1). PubMed and Web of Science searches identified 663 articles related to IH exposure, of which 60 were included. The examined outcomes were oxidative stress, inflammation, apoptosis, HIF-1 or BDNF in brains. Standardised mean difference was used to compare studies. Metaregressions were performed to clarify the impact of IH exposure parameters, rodent characteristics or cerebral localisation on these outcomes. IH-induced oxidative stress (increased malondialdehyde (MDA) and NADPH oxidase (NOX) and decreased superoxide dismutase), increased inflammation (tumour necrosis factor-α, NF-κB and inducible nitric oxide synthase), HIF-1 and apoptosis evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labelling and cleaved caspase-3. In contrast, B-cell lymphoma 2 (BCL2) and BDNF expression were not significantly modified. Metaregressions showed that MDA, NOX and BDNF were associated with determinants of IH cycles (inspired oxygen fraction and duration of hypoxia) and some parameters depended on localisation. Rodent characteristics had little impact on the outcomes. Our meta-analysis robustly establishes that IH, independently of other confounders, has a strong effect on the brain by inducing oxidative stress, inflammation and apoptosis in rodent models. Our findings support the interest of considering and treating cerebral consequences of OSA in clinical practice.

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Is there an association between cognitive impairment and urinary adrenaline, norepinephrine, gamma-aminobutyric acid, and taurine levels in children with obstructive sleep apnea?:a case control study

Ji,

Wang,

Chen

et al. 2024

Preprint

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Background. The purpose of this study was to compare the urinary adrenaline (EPI), norepinephrine (NE), gamma-aminobutyric acid (GABA), and taurine levels between children with and without obstructive sleep apnea (OSA) and then analyze the predictive value of urinary neurotransmitters on cognitive impairment in these patients. Methods. Children aged 3–12 years were enrolled and underwent polysomnography (PSG) recording during the whole night. PedsQL and CBCL scales were used to evaluate the cognitive function of these children. Morning urine samples were collected and used to measure the abovementioned urinary neurotransmitter levels. Results. A total of 104 cases were recruited, including 30 primary snoring (PS) and 74 OSA cases. Compared with the PS group, the OSA group had a lower social function (Z=-2.506, P = 0.012), school function (T = 2.596,P = 0.011), and total PedsQL (T = 2.546, P = 0.012) scores; the OSA group also exhibited increased withdrawal (Z=-2.121, P = 0.034) and attention problem (Z=-2.176, P = 0.030) scores in the CBCL scale. A total of 39 cases were considered mild cognitive impairment(MIC) in the OSA group (PedsQL total score below 76.13), who had higher urinary EPI (F = 25.725, P < 0.001) and lower taurine (F = 9.515, P < 0.001) levels than both PS and OSA without MIC groups. Logistic regression results showed that the incidence of cognitive-behavioral impairment in OSA children with obesity was significantly higher than in OSA children who had a normal BMI (OR = 6.999, 95%CI: 1.302 ~ 37.617). High levels of urinary NE (OR = 1.023, 95%CI: 1.001–1.046) and low levels of taurine (OR = 0.985, 95%CI: 0.974–0.997) were significantly associated with cognitive-behavioral impairment in children with OSA, and their combination had a comparatively larger area under the curve (0.695), with a sensitivity of 64.1% and specificity of 68.6% (P = 0.004). Conclusions. Urinary taurine and EPI can contribute to the prediction of cognitive impairment in OSA children, and combining these two neurotransmitters may have relatively good sensitivity and specificity for the presence of cognitive impairment associated with OSA.

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Obstructive sleep apnea affects cognition: dual effects of intermittent hypoxia on neurons

Cited by 4 publications

References 149 publications

Intermittent Hypoxia Impairs Cognitive Function and Promotes Mitophagy and Lysophagy in Obstructive Sleep Apnea–Hypopnea Syndrome Rat Model

Intermittent Hypoxia Impairs Cognitive Function and Promotes Mitophagy and Lysophagy in Obstructive Sleep Apnea–Hypopnea Syndrome Rat Model

Cerebral oxidative stress, inflammation and apoptosis induced by intermittent hypoxia: a systematic review and meta-analysis of rodent data

Is there an association between cognitive impairment and urinary adrenaline, norepinephrine, gamma-aminobutyric acid, and taurine levels in children with obstructive sleep apnea?:a case control study

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