[Association between obesity and cognition impairment in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the association between obesity and cognition impairment in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: A total of 425 eligible patients with moderate-to-severe OSAHS were screened for this retrospective study at Sleep Center, Second Affiliated Hospital, Soochow University from January 2008 to January 2013. Based on body mass index (BMI), they were categorized into normal weight (18.5 ≤ BMI<24, n = 67), mild overweight (24 ≤ BMI<26, n = 100), severe overweight (26 ≤ BMI<28, n = 134) and obese (BMI ≥ 28, n = 124) groups. They were examined by overnight polysomnography (PSG). And cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) questionnaires. MoCA scores, clinical and polysomnographic variables were compared between the groups. And the correlations between MoCA scores and clinical and PSG parameters were further evaluated by stepwise multivariate regression. Two-way analysis of variance (two-way ANOVA) was performed to examine the effects of obesity and OSAHS on MoCA score. RESULTS: The scores of MoCA progressively decreased across the spectrum from mild overweight to obese groups. The highest BMI group (obese group) had the lowest MoCA score (25.45 ± 2.35 vs 26.26 ± 2.01, 26.29 ± 2.60, 26.05 ± 2.51, P = 0.030, 0.010, 0.048). The evaluations of MoCA subdomains further revealed selective reductions. Compare to normal weight group, the score of visuospatial and executive function, memory/delayed recall significant decreased in obese and severe overweight groups (visuospatial and executive function: 4.48 ± 0.63 vs 4.07 ± 0.94, 4.13 ± 1.04, P = 0.022, 0.048; memory/delayed recall: 3.54 ± 0.90 vs 2.77 ± 1.20, 2.87 ± 1.30, P = 0.001, 0.004). Stepwise multivariate regression analysis demonstrated that MoCA scores were correlated significantly with apnea-hypopnea index (AHI), BMI, age and years of education. Two-way ANOVA revealed that both obesity and OSAHS had independent effects on MoCA score (P = 0.004). The interactions between the effect of obesity and OSAHS on cognitive score were insignificant. It indicated that the effect of BMI on cognitive function did not change with AHI. CONCLUSIONS: In OSAHS patients, obesity aggravates cognitive impairment independently of AHI. And obesity is one of the most important influencing factors of cognitive function.

[Association between serum adipocyte fatty acid binding protein level and dyslipidemia in patients with obstructive sleep apnea syndrome].

OBJECTIVE: To explore the association between serum adipocyte fatty acid binding protein (A-FABP) levels and dyslipidemia in patients with obstructive sleep apnea syndromes (OSAS). METHODS: Eighty snoring patients were monitored by overnight polysomnography (PSG) in Second Affiliated Hospital of Soochow University from November 2010 to May 2011. There were 63 males and 17 females with a mean age of (48 ± 14) years (range: 22 - 77 years). Based on the results of apnea-hypopnea index (AHI), they were divided into 3 groups: primary snoring group (AHI < 5/h, n = 19), mild-moderate OSAS group (5/h ≤ AHI ≤ 40/h, n = 22) and severe OSAS group (AHI > 40/h, n = 39). The levels of A-FABP, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured and compared between the primary snoring group and OSAS patients of different severities. And the correlations between serum A-FABP and plasma lipid as well as PSG parameters were further evaluated by partial correlation analysis. RESULTS: Compared with the primary snoring group ((15.7 ± 3.3) µg/L) and mild-moderate group ((17.3 ± 4.3) µg/L), there was a significant elevation of serum A-FABP level in the severe OSAS group ((20.4 ± 4.6) µg/L) (P = 0.001, P = 0.026). Additionally, after adjustment for body mass index and age, the serum A-FABP level showed significant positive correlations with TC, TG and LDL-C (r = 0.469, P = 0.000; r = 0.239, P = 0.035 and r = 0.366, P = 0.001). Serum A-FABP level was positively correlated with AHI and the time of oxygen saturation (SaO2) < 90% (r = 0.231, P = 0.042 and r = 0.226, P = 0.047). Nevertheless, the serum A-FABP level showed significant negative correlations with the lowest SaO2 and the mean SaO2 (r = -0.234, P = 0.039 and r = -0.270, P = 0.017). CONCLUSION: Dyslipidemia and elevated level of serum A-FABP are common in OSAS patients.

[Effect of chronic intermittent hypoxia on mitochondrial function of rat genioglossus cells and intervention role of adiponectin].

OBJECTIVE: To investigate the effect of chronic intermittent hypoxia (CIH) on mitochondrial function in genioglossus cells of rats and intervention role of adiponectin (Ad). METHODS: Thirty-nine healthy male Wistar rats were randomly divided into 3 groups, normal control (NC) group, CIH group and CIH + Ad group with 13 rats in each. Rats in NC group were kept breathing normal air, while rats in both CIH and CIH + Ad groups experienced the same CIH environment (CIH 8 h/day for successive 5 weeks). However, rats in CIH + Ad group was given intravenous Ad supplement at the dosage of 10 µg, twice a week for successive 5 weeks. At the end of experiment (day 35), the levels of plasma adiponectin, mitochondrial membrane potential activities of respiratory chain complexes I and IV in mitochondrion of genioglossus cells were compared among different groups. RESULTS: Serum Ad level was significantly lower in CIH group than that in NC group [(1108 ± 112) ng/ml vs (2241 ± 121) ng/ml, P < 0.01]. Serum Ad level in CIH + Ad group [(1889 ± 119) ng/ml] was significantly higher than that in NC group but lower than that in CIH group (all P < 0.01). Mitochondrial membrane potential was significantly lower in CIH group than that in NC group [(1.82 ± 0.11) vs (2.09 ± 0.14), P < 0.01]. Mitochondrial membrane potential in CIH + Ad group (1.98 ± 0.09) was higher than that in CIH group but lower than that in NC group (all P < 0.05). The concentrations of mitochondrial respiratory chain complexes I and IV in CIH group (35.68 ± 1.73) µmol×min(-1)×mg(-1) and (2.37 ± 0.11) nmol×min(-1)×mg(-1), respectively) were the lowest but became higher from CIH + Ad group [(37.18 ± 1.95) µmol×min(-1)×mg(-1) and (2.49 ± 0.09) nmol×min(-1)×mg(-1), respectively] to NC group (39.02 ± 1.38) µmol×min(-1)×mg(-1) and (2.81 ± 0.12) nmol×min(-1)×mg(-1), respectively), with a significant difference between NC and CIH groups (P < 0.01), between CIH + Ad and CIH groups (P < 0.05), as well as between CIH + Ad and NC groups (P < 0.05). CONCLUSION: CIH could lead to hypoadiponectinemia and impaired mitochondrial function in genioglossus cells of rats. Since such changes could be partially improved by supplement of adiponectin, it was suggested that hypoadiponectinemia might be involved in CIH-induced impairment of genioglossus energy metabolism.

Correlation of Epworth Sleepiness Scale with multiple sleep latency test and its diagnostic accuracy in assessing excessive daytime sleepiness in patients with obstructive sleep apnea hypopnea syndrome.

BACKGROUND: Excessive daytime sleepiness (EDS) is often associated with obstructive sleep apnea hypopnea syndrome (OSAHS) and contributes to a number of comorbidities in these patients. Therefore, early detection of EDS is critical in disease management. We examined the association between Epworth Sleepiness Scale (ESS) and multiple sleep latency test (MSLT) and diagnostic accuracy of ESS in assessing EDS in OSAHS patients. METHODS: The ESS, MSLT and overnight polysomnography were administered to 107 Chinese patients to assess EDS and its correlations with polysomnographic parameters. The diagnostic accuracy of ESS in classifying EDS (mean sleep latency (MSL) ≤ 10 minutes) was evaluated by calculating the area under ROC curve. RESULTS: As the severity of OSAHS increased, MSL decreased with increase in ESS score. Conversely, patients with worsening EDS (shorter MSL) were characterized by advanced nocturnal hypoxaemia and sleep disruption compared to those with normal MSL, suggesting EDS is associated with more severe OSAHS. There was a negative correlation between ESS score and MSL and both moderately correlated with some polysomnographic nocturnal hypoxaemic parameters. The area under ROC curve of ESS for identifying EDS was 0.80 (95% CI: 0.71 to 0.88) and ESS score ≥ 12 provided the best predictive value with a sensitivity of 80% and specificity of 69%. CONCLUSION: The ESS score moderately correlates with MSL and our ROC study supports ESS as a screening strategy for assessing EDS in OSAHS.

Changes in genioglossus and their association with serum adiponectin levels in rats subjected to chronic intermittent hypoxia.

BACKGROUND: The genioglossus (GG) is involved in the maintenance of an open airway for effective breathing. Although the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) was closely associated with GG dysfunction, its causes and possible treatment have not been elucidated. The aim of the study was to investigate the effects of chronic intermittent hypoxia (CIH) on serum adiponectin levels, electromyograph (EMG) activity and ultrastructure of GG, as well as the effect of an adiponectin supplement in anesthetized rats. METHODS: Forty-two healthy male Wistar rats were randomly divided into normal control (A), CIH (B) and adiponectin treatment (C) groups, 14 rats in each group. CIH was performed eight hours per day for five weeks in both groups B and C. Group C received transvenous injection of adiponectin at the dosage of 10 microg per injection, twice a week for five weeks. At the end of the 5th week the GG EMG voltage was measured and compared among the three groups. Transmission electron microscope was used to observe the ultrastructure of the GG. RESULTS: CIH caused significant hypoadiponectinemia, weakened activity of GG EMG at both baseline and hypoxia stimulation, and induced ultrastructural pathological changes, such as, myofibril discontinuities, lysis of myofilament, edema of mitochondria and disruption of cristae, vacuolus and lysis of some mitochondria. Venous supplement of adiponectin improved the above pathological changes resulting from CIH. CONCLUSION: CIH resulted in pathological changes in GG's EMG and ultrastructure, which could be improved by supplement of adiponectin and be associated with hypoadiponectinemia caused by CIH.

[Effect of chronic intermittent hypoxia on genioglossus and its intervention by adiponectin].

OBJECTIVE: To investigate the effects of chronic intermittent hypoxia (CIH) on electromyograph (EMG) and ultrastructure of genioglossus (GG) and the interventive effects with adiponectin supplement. METHODS: Forty-two healthy male Wistar rats were randomly divided into normal control (A), CIH (B) and adiponectin treatment (C) groups with 14 rats in each. CIH was performed 8 hours per day for 5 weeks in both group B and C. In group C, transvenous injection of adiponectin of 10 microg dosage each time, twice a week for 5 weeks. While in group A and B, transvenous injection of saline was performed twice a week for 5 weeks. At the beginning of 6th week the GG EMG voltages were measured before, during and following hypoxia stimulation by inserted bipolar needle electrodes and compared among three groups. Transmission electron microscope was used for observation of ultrastructure of GG. RESULTS: The serum adiponectin level in group B (1226.0 +/- 112.0) ng/ml (x(-) +/- s) was significantly lower than that in group A (2491.8 +/- 117.9) ng/ml, q = 38.2, P < 0.01), and adiponectin level in group C (1988.3 +/- 114.7) ng/ml was significantly higher than that in group B (q = 23.0, P < 0.01). Comparison of GG EMG activity showed that the baseline amplitude of GG EMG before hypoxia stimulation was significantly lower in group B than that in both group A and group C (all P < 0.01). At the 5th min of hypoxia stimulation the GG EMG activities were significantly enhanced among three groups (all P < 0.01). Such an enhancement was the most evident in group A but the least remarkable in group B, with a significant difference among three groups (q(ab) = 17.5; q(ac) = 8.9; q(bc) = 8.6, all P < 0.01). 15 min, 30 min and 45 min after hypoxia stimulation the amplitude of GG EMG remained at relative higher levels in group A and C, significantly higher than that in group B (all P < 0.01). CIH could cause significant ultrastructural pathological changes such as myofibril discontinuities, lysis of myofilament, edema of mitochondria and disruption of cristae, vacuoles and lysis of some mitochondria in group B. Venous supplement of adiponectin could improve pathological changes resulting from CIH. CONCLUSIONS: CIH could resulted in pathological changes in EMG and ultrastructure of GG, which might be associated with hypoadiponectinemia caused by CIH.