Cognitive Impairment In OSAHS Patients And Its Related Mechanism

Objectives:1. To evaluate the cognitive impairment status of adult patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), and to explore the relationship between sleep disturbance, nighttime intermittent hypoxia, disease severity and cognitive dysfunction.2. To determine the relationship of blood serum brain derived neurotrophic factor(BDNF) and insulin-like growth factor2(IGF-2) level with deterioration of cognitive function in patients with OSAHS and to explore the possible mechanism of cognitive impairment of OSAHS.3. To explore the effects of patient education and progressive muscle relaxation (PMR) on sleep quality, cognitive function and adherence to continuous positive air pressure(CPAP) treatment in obstructive sleep apnea/hypopnea (OSAHS) patients.Methods:1. The study sample comprised152patients with OSAHS who were used as the OSAHS group and152healthy volunteers, matched by gender (same) and age (within3years), who acted as the control group. Polysomnography(PSG) including apnea and hypopnea index(AHI), the lowest SaO2(LSO), sleep stage1to4and rapid eye movement sleep (%), the Montreal Cognitive Assessment (MoCA) and the Social Anxiety Scale (SAS) have been conducted to the sample.152OSAHS patients were randomly selected in three tertiary general hospitals—The first affiliated Hospital of Hunan Normal University, Xiangya Hospital of Central South University and The Second Xiangya Hospital of Central South University, from February2010to October2011.2. Twenty-eight male patients with OSAHS and fourteen normal men enrolled in the study. Polysomnography and neuropsychological tests including MoCA and SAS have been conducted. Blood samples were collected at6:30-7:00for measurement of blood serum BDNF and IGF-2level with Enzyme-Linked Immunosorbent Assay(ELISA). The samples were selected in the first affiliated Hospital of Hunan Normal University from February2011to October2011.3. From February2010to October2011, Seventy-six moderate and severe OSAHS patients were recruited to this study at the Second Xiangya Hospital, Central South University. All samples were randomly assigned to a control group and an education+PMR group, with38patients each group. Two groups were under CPAP treatment at home. The control group received routine health education, the education+PMR group received education and PMR intervention. Data from patient ventilator-timer recorders were used to classify patients as CPAP adherent or non-adherent at4,8and12weeks of intervention, Before and after intervention of12weeks, subjective daytime sleepiness was evaluated with the Epworth sleepiness scale (ESS), sleep quality was evaluated with the Pittsburgh Sleep Quality Index (PSQI), and the anxiety level was measured using the Social Anxiety Scale.4. Statistical analysis software Package of SPSS(version17.0) was used in all analyses, including descriptive analysis, Chi-square test, t test, analysis of variance(ANOVA), Pearson correlation coefficient analysis and multiple logistic analysis.Results:1. Analysis of the cognition of OSAHA group and control group.①The patients with cognitive dysfunction (the total score of MoCA<26) was113(74.3%) in OSAHS group and7(4.6%) in control group, respectively.The incidence of OSAHS patients with cognitive impairment was significantly higher than control group (χ2=154.699, P=0.000).②In OSAHS group, the total score of MoCA, executive function, naming, attention, calculation, language, abstraction, memory, orientation was (24.62±2.57),(3.52±1.11),(2.84±0.37),(2.41±0.49),(2.46±0.53),(2.53±0.72),(1.72±0.48),(3.51±0.77),(5.62±0.49), respectively, in control group, there were (28.81±2.45),(4.75±0.52),(2.97±0.20),(2.84±0.37),(2.82±0.39),(2.89±0.31),(1.98±0.14),(4.72±0.46),(5.95±0.21), respectively. The total score and score of every item of MoCA in OSAHS group were significantly decreased compare with control group (P<0.01).2. The correlation analysis between cognitive function of OSAHS group and their demographic data, AHI, LSO and sleep structure.①There was a negative correlation between age (r=-0.422, P=0.000) BMI (r=-0.288, P=0.000) and cognition function, it had a positive correlation with the length of schooling (r=0.443, P=0.000), and it had no correlation with gender (r=-0.046, P=0.574).②There was a close negative correlation between AHI and the total score of MoCA (r=-0.546, P=0.000), there was a positive correlation with LSO (r=0.554,P=0.000), S3+S4(r=0.229,P=0.004) and REM(r=0.214, P=0.008), and it had no correlation with S1+S2(r=-0.085, P=0.296)③Among all items of MoCA, the score of attention (r=-0.182, P=0.025) and abstraction (r=-0.187, P=0.021) were negative correlated with S1+S2, the score of executive function (r=0.191, P=0.018), naming (r=0.257, P=0.001),memory (r=0.170, P=0.037) was positive correlated with S3+S4, it had a positive correlation between executive function (r=0.175, P=0.031), abstraction (r=0.312, P=0.000) and REM.3. The analysis of cognitive function in different severity of OSAHS patients.①Of152OSAHS patients, there were mild OSAHS with28, moderate with40, and severe with84based on their AHI. The incidence of cognitive impairment among mild, moderate, and severe OSAHS patients was36%,73%,88%, respectively. The incidence of cognitive dysfunction was significantly different in patients with various severities of OSAHSC χ2=30.304, P=0.000), among groups, there was a significant difference between the incidence of moderate group and mild group, severe group and moderate group in pairwise comparison after adjusting P value.②The total score of MoCA in mild, moderate, severe group was (26.64±1.37),(25.00±2.91),(23.77±2.29), respectively, it had statistical significance (F=16.496, P=0.000), among groups, there was a significant difference between the score of moderate group and mild group, severe group and mild group, severe group and moderate group in pairwise comparison (P<0.05).③In all items of MoCA, there were four items including executive function (F=4.523, P=0.012),naming (F=8.512, P=0.000),calculating (F=5.618, P=0.004) and memory (F=23.536, P=0.000), their score was significantly different in patients with various severities of OSAHS. The pairwise comparison result showed that there was significant different between severe group and mild group in executive function (P<0.05), there was significant different between severe and mild group, severe and moderate group in naming (P<0.05), there was significant different between severe and mild group, moderate and mild group in calculating and orientation (P<0.05), there was significant different among mild, moderate and severe groups in memory (P<0.05) 4. The analysis of anxiety in OSAHS patients①There were64(42.1%) OSAHS patients fulfilled criteria for anxiety, and10(9.9%) in control group. The SAS score of OSAHS group and control group was (47.50±9.57) and (40.50±6.007), respectively. SAS score was significantly different between two groups (t=7.636, P=0.000).②The score of SAS was close positive correlation with AHI (r=0.430, P=0.000) and S1+S2(r=0.196,P=0.016), it was negative correlation with S3+S4(r=-0.177, P=0.029) and REM (r=-0.278, P=0.001).③There was close negative correlation between the total score of MoCA(r=-0.343,P=0.000), executive function (r=-0.214, P=0.008), calculation (r=-0.195, P=0.016), abstraction (r=-0.325, P=0.000), memory (r=-0.246, P=0.002) and SAS in OSAHS patients.5. Multiple factors analysis showed that the length of schooling (X3), SAS score (X5) and AHI (X6) came into the regression equation.≥13years (X3) of education was a protective factor (OR<1;95%CI<1). SAS score and AHI were risk factors (OR>1;95%CI>1). The possibility of OSAHS patients with cognitive dysfunction (education≥13years, X3) was0.12times more than that of others (education<9years, X3)(95%CI:0.04,0.38). The possibility of OSAHS anxiety patients with cognitive impairment was5.25times more than that of others (95%CI:2.02,13.64). With the increases of abnormal AHI, the risk of cognitive impairment in OSAHS patients had also grown (OR=2.08;95%CI:1.21,3.55). Logistic regression equation:logitP=-2.257+0.688X32-2.160X33+1.658X5+0.731X6.6. The analysis of the blood serum BDNF level①The blood serum BDNF level of OSAHS group and control group was (5.01±0.61) ng/ml,(7.27±0.68) ng/ml, respectively, the blood serum BDNF level of OSAHS patients was significantly decreased compare with the control group (t=-10.912, P=0.000).②The MoCA score of subjects was significantly positive associated with their blood serum BDNF level (r=0.544,P=0.000).It had no significantly correlation with age (r=-0.307, P=0.054), BMI (r=-0.274, P=0.079) and the length of schooling (r=0.113, P=0.475)③The blood serum BDNF level of subjects was significantly negative associated with AHI (r=-0.607,P=0.000) and S1+S2(r=-0.768, P=0.000), It was significantly positive associated with the LSO (r=0.566, P=0.000), S3+S4(r=0.778,P=0.000) and REM (r=0.575, P=0.000), and it had no significantly correlation with age (r=0.072, P=0.653), BMI (r=-0.020,P=0.900) and the length of schooling (r=-0.010, P=0.952)7. The analysis of the blood serum IGF-2level①The blood serum IGF-2level of OSAHS group and control group was (0.97±0.46) ng/ml,(0.44±0.15) ng/ml, respectively, there was significant difference between the two groups (t=5.587, P=0.000).②The MoCA score of subjects was significantly negative associated with their blood serum IGF-2level (r=-0.483, P=0.001), It had no significantly correlation with age (r=0.060, P=0.705), BMI (r=-0.071, P=0.656) and the length of schooling (r=-0.009, P=0.953).③The blood serum IGF-2level of subjects was significantly positive associated with AHI (r=0.483, P=0.001), S1+S2(r=0.549, P=0.000), It was significantly negative associated with LSO (r=-0.449, P=0.003), S3+S4(r=-0.612,P=0.000) and REM (r=-0.395, P=0.010), and it had no significantly different with age (r=0.060, P=0.705), BMI (r=-0.071, P=0.656) and the length of schooling (r=-0.009, P=0.953)8. An analysis on the effects of patients education combined with progressive muscle relaxation (PMR)①Education+PMR group showed31.6%,31.5%and31.5%improvement in adherence over control group at4,8, and12weeks of intervention, respectively. The adherence rate of Education+PMR group was significantly higher than that of control group at4(x2=10.483, P=0.001),8(x2=9.212, P=0.002) and12weeks (x2=8.143, P=0.004) of intervention.②At4,8and12weeks of intervention, the average CPAP usage time of Education+PMR group was (6.50±0.17) hours,(5.74±0.21) hours,(5.47±0.20) hours, respectively, the control group was (5.30±0.24) hours,(4.64±0.15) hours,(3.68±0.17) hours, respectively. The CPAP usage of Education+PMR group at4weeks (t=17.865,P=0.000),8weeks (t=18.578, P=0.000),12weeks(t=30.052, P=0.000)were significantly improved compared with control group.③At12weeks of intervention, the score of ESS (14.79±2.96VS8.05±2.78),PSQI (12.55±2.53VS6.26±1.93) and SAS (48.29±10.17VS40.89±8.80) of Education+PMR group was significantly decreased (P<0.01), the MoCA score (24.13±1.66VS26.39±1.82, P<0.05) was significantly increased. for control group, the score of ESS (14.13±2.51VS10.13±2.18) and PSQI (11.76±2.07VS7.74±1.96) significantly decreased (P<0.05), the MoCA score was significantly increased (23.92±1.95VS25.87±1.36, P <0.05), there was no significant difference in SAS score between before and after intervention.④The Education+PMR group showed greater descending range of ESS, PSQI and SAS score compared with the control group at12weeks of intervention, there was significant difference between the reduction value of ESS (6.74±1.62VS4.00±0.81, t=-9315,p=0.000), PSQI (6.29±1=.57VS4.03±0.72,t=-8.062,p=0.000) and SAS score (7.39±3.42VS3.82±1.33,t=-6.009,p=0.000) between the two groups. There was no significant difference in the added value of MoCA between the two groups at12weeks of intervention (2.26±1.77VS1.95±1.21, P=0.366)Conclusion:1. Approximately75%OSAHS patients showed varying severities of cognitive impairment. Cognitive impairment in OSAHS patients was associated with nighttime intermittent hypoxia/hypopnea and sleep disturbance. The severity of cognitive impairment in OSAHS patients was related to AHI and the degree of nighttime intermittent hypoxia/hypopnea. The more sever nighttime intermittent hypoxia/hypopnea was, the more serious the cognitive impairment was. So was the executive function, memory and attention. About40%patients with OSAHS presented anxiety, which resulted from nighttime apnea/hypopnea, sleep disturbance and cognitive dysfunction. OSAHS patients with anxiety were more prone to appear cognitive impairment.2. The blood serum BDNF level in OSAHS patients was lower than that of healthy people. Nocturnal hypoxia and the deprivation of slow wave sleep and REM may be the reason that leads to the decrease of serum BDNF in patients with OSAHS. The blood serum BDNF in OSAHS patients decreases may be the factor contributing to cognitive impairment in OSAHS patients. The blood serum IGF-2level in OSAHS patients was higher than that of healthy people. The increase of serum BDNF in patients with OSAHS may be related to cognition, nocturnal hypoxia and the deprivation of slow wave sleep and REM. It is possible for IGF-2to play an important role in the mechanism of cognitive impairment in patients with OSAHS.3. Combined intervention with patient education and PMR can significantly improve sleep quality and anxiety. It can significantly improve CPAP adherence in OSAHS patients for at least12weeks. The intervention paradigm may serve as an important reference for future studies on CPAP adherence.