Statement of significance
Introduction
Materials and methods
Study design and subjects
Data collection
MRI scanning and processing
Sleep data acquisition and analysis
EEG spectral analyses
Neuropsychological and psychopathological evaluation
Exosome extraction and quantification of Aβ42
Enzyme-linked immunosorbent assays of serum CyPA and MMP-9 levels
Intervention
Statistical analysis
Results
Demographic and clinical characteristics of the study cohorts
OSA+MCI (n = 157) | OSA-MCI (n = 118) | Control (n = 64) | P value | |
---|---|---|---|---|
Demographics | ||||
Age, years (mean ± SD) | 60.32 ± 9.87a b | 57.36 ± 11.10 | 57.28 ± 9.18 | 0.027 |
Male, n (%) | 106 (67.52) | 85 (72.03) | 38 (59.38) | 0.219 |
BMI, kg/m2 (mean ± SD) | 27.75 ± 3.83b | 28.04 ± 4.19b | 25.00 ± 3.71 | <0.001 |
Education, years, median (IQR) | 11 (3) | 12 (7) | 12 (4) | 0.105 |
Risk factors | ||||
Hypertension, n (%) | 97 (61.78)a b | 57 (48.31) | 25 (39.06) | 0.004 |
Diabetes mellitus, n (%) | 41 (26.11) | 18 (15.25) | 11 (18.75) | 0.081 |
Hyperlipidemia, n (%) | 61 (38.85)b | 38 (32.20) | 13 (20.31) | 0.028 |
Drinking, n (%) | 44 (28.03) | 36 (30.51) | 15 (23.44) | 0.598 |
Smoking, n (%) | 33 (21.02) | 31 (26.27) | 14 (21.88) | 0.575 |
Systolic blood pressure, mmHg, median (IQR) | 140 (27)b | 137 (23)b | 132 (25) | 0.013 |
Diastolic blood pressure, mmHg, median (IQR) | 85 (15)b | 85 (13)b | 80 (13) | 0.021 |
Laboratory indicators | ||||
Total cholesterol, mg/dl (mean ± SD) | 180.54 ± 45.62 | 184.41 ± 43.69 | 182.86 ± 33.25 | 0.781 |
Triglycerides, mg/dl, median (IQR) | 136.44 (101.00) | 136.00 (69.11) | 120.50 (73.54) | 0.318 |
LDL-C, mg/dl (mean ± SD) | 109.52 ± 33.63 | 110.57 ± 29.77 | 109.29 ± 30.16 | 0.966 |
Glucose, mg/dl, median (IQR) | 99.36 (30.78)a b | 94.68 (16.20) | 93.78 (15.48) | 0.001 |
Serum CyPA, ng/ml (mean ± SD) | 8.95 ± 4.49a b | 7.82 ± 4.00 | 7.09 ± 3.89 | 0.006 |
Serum MMP-9, ng/ml (mean ± SD) | 584.63 ± 208.08a b | 522.22 ± 188.15 | 494.92 ± 193.04 | 0.003 |
NDE Aβ42, pg/ml (mean ± SD) | 3.18 ± 0.65a b | 2.98 ± 0.71b | 2.76 ± 0.65 | <0.001 |
Neuropsychological test | ||||
MMSE scores, median (IQR) | 27 (4)a b | 29 (1) | 30 (1) | <0.001 |
MoCA scores, median (IQR) | 23 (4)a b | 27 (2) | 27 (3) | <0.001 |
HAMA scores, median (IQR) | 7 (8) | 6 (6) | 7 (5) | 0.297 |
HAMD scores, median (IQR) | 7 (5) | 5 (6) | 6 (5) | 0.077 |
ESS scores, median (IQR) | 9 (6)b | 8 (6)b | 5 (6) | <0.001 |
Image quantitative measurement | ||||
WMH volume, mm3, median (IQR) | 5300.71 (5342.47)a b | 4222.46 (3029.90)b | 3275.27 (1787.85) | <0.001 |
Total CSVD burden scores, median (IQR) | 1 (2)a b | 0.5 (1) | 0 (1) | <0.001 |
PSG data | ||||
AHI, events/h, median (IQR) | 33.30 (39.30)a b | 22.60 (37.58)b | 2.20 (2.48) | <0.001 |
5≤AHI<15, n (%) | 32 (20.38) | 42 (35.59) | 0 | |
15≤AHI<30, n (%) | 39 (24.84) | 28 (23.73) | 0 | |
30≤AHI, n (%) | 86 (54.78) | 48 (40.68) | 0 | 0.014 |
ODI, events/h, median (IQR) | 26.20 (34.75)b | 17.90 (27.85)b | 1.95 (2.18) | <0.001 |
TST, min (mean ± SD) | 354.41 ± 62.52 | 367.72 ± 58.65 | 364.67 ± 60.06 | 0.173 |
Sleep latency, min, median (IQR) | 20.50 (24.00) | 19.75 (29.13) | 29.50 (34.63) | 0.210 |
Sleep efficiency, %, median (IQR) | 74.90 (21.53) | 76.90 (18.55) | 78.49 (20.72) | 0.234 |
Arousal index, events/h, median (IQR) | 20.20 (22.55)a b | 16.05 (18.70)b | 6.10 (9.20) | <0.001 |
Mean SaO2, %, median (IQR) | 94.00 (3.00)a b | 95.00 (2.25)b | 96.00 (2.00) | <0.001 |
Min SaO2, %, median (IQR) | 82.00 (12.50)b | 82.50 (13.00)b | 90.00 (4.00) | <0.001 |
T90, % , median (IQR) | 4.60 (13.65)a b | 2.45 (9.65)b | 0.00 (0.20) | <0.001 |
NREM stage 1 of TST, %, median (IQR) | 15.80 (8.65)a b | 13.00 (9.03)b | 9.35 (4.98) | <0.001 |
NREM stage 2 of TST, % (mean ± SD) | 52.09 ± 8.89 | 52.58 ± 8.20 | 51.84 ± 7.05 | 0.821 |
NREM stage 3 of TST, %, median (IQR) | 15.60 (8.40)a b | 17.75 (9.42)b | 20.15 (8.20) | <0.001 |
REM stage of TST, % (mean ± SD) | 14.21 ± 4.62b | 15.07 ± 4.77b | 17.50 ± 5.20 | <0.001 |
PSWEs in OSA+MCI patients, OSA-MCI patients, and control subjects
Adjusted relationship between PSWEs and MCI in patients with OSA
Model 0 | Model 1 | Model 2 | ||||
---|---|---|---|---|---|---|
OR (95%CIs) | P value | OR (95%CIs) | P value | OR (95%CIs) | P value | |
Total PSWEs | 1.130 (1.026–1.244) | 0.013 | 1.115 (1.009–1.231) | 0.032 | 1.119 (1.007–1.245) | 0.037 |
The PSWEs at C3/M2 in stage R | 1.385 (0.973–1.973) | 0.071 | 1.394 (0.975–1.993) | 0.069 | 1.363 (0.944–1.969) | 0.099 |
The PSWEs at C4/M1 in stage R | 1.445 (1.008–2.072) | 0.045 | 1.452 (1.009–2.090) | 0.045 | 1.436 (0.985–2.095) | 0.060 |
The PSWEs at F3/M2 in stage R | 1.360 (0.950–1.948) | 0.093 | 1.370 (0.952–1.973) | 0.090 | 1.389 (0.951–2.027) | 0.089 |
The PSWEs at F4/M1 in stage R | 1.424 (1.006–2.016) | 0.046 | 1.432 (1.005–2.039) | 0.047 | 1.454 (1.006–2.098) | 0.046 |
The PSWEs at O1/M2 in stage R | 1.415 (1.055–1.900) | 0.021 | 1.409 (1.043–1.902) | 0.025 | 1.428 (1.041–1.959) | 0.027 |
The PSWEs at O2/M1 in stage R | 1.460 (1.091–1.954) | 0.011 | 1.457 (1.082–1.962) | 0.013 | 1.470 (1.076–2.010) | 0.016 |
The PSWEs at T3/M2 in stage R | 1.382 (0.942–2.027) | 0.098 | 1.377 (0.933–2.032) | 0.107 | 1.373 (0.918–2.053) | 0.123 |
The PSWEs at T4/M1 in stage R | 1.422 (0.981–2.062) | 0.063 | 1.407 (0.964–2.053) | 0.077 | 1.397 (0.944–2.069) | 0.095 |
Model 0 | Model 1 | |||
---|---|---|---|---|
OR (95%CIs) | P value | OR (95%CIs) | P value | |
Duration ratios of PSWEs at C3/M2 in stage R | 1.067 (1.020–1.117) | 0.005 | 1.058 (1.009–1.109) | 0.019 |
Duration ratios of PSWEs at C4/M1 in stage R | 1.090 (1.038–1.145) | 0.001 | 1.091 (1.034–1.151) | 0.001 |
Duration ratios of PSWEs at F3/M2 in stage R | 1.084 (1.038–1.132) | <0.001 | 1.084 (1.033–1.137) | 0.001 |
Duration ratios of PSWEs at F4/M1 in stage R | 1.078 (1.033–1.124) | <0.001 | 1.074 (1.026–1.124) | 0.002 |
Duration ratios of PSWEs at O1/M2 in stage R | 1.062 (1.030–1.096) | <0.001 | 1.063 (1.027–1.099) | <0.001 |
Duration ratios of PSWEs at O2/M1 in stage R | 1.060 (1.027–1.094) | <0.001 | 1.058 (1.022–1.095) | 0.001 |
Duration ratios of PSWEs at T3/M2 in stage R | 1.108 (1.052–1.166) | <0.001 | 1.109 (1.048–1.174) | <0.001 |
Duration ratios of PSWEs at T4/M1 in stage R | 1.102 (1.049–1.158) | <0.001 | 1.105 (1.046–1.166) | <0.001 |
Relative independent factors affecting PSWEs in patients with OSA
Total PSWEs | PSWEs at F4/M1 in stage R | PSWEs at O1/M2 in stage R | PSWEs at O2/M1 in stage R | |||||
---|---|---|---|---|---|---|---|---|
β (SE) | P value | β (SE) | P value | β (SE) | P value | β (SE) | P value | |
NDE Aβ42 | 0.106 (0.228) | 0.076 | 0.047 (0.065) | 0.440 | 0.060 (0.075) | 0.323 | 0.063 (0.076) | 0.296 |
WMH volume | 0.206 (0.000) | 0.001 | 0.039 (0.000) | 0.527 | 0.089 (0.000) | 0.146 | 0.066 (0.000) | 0.281 |
Total CSVD burden | 0.087 (0.144) | 0.137 | 0.031 (0.041) | 0.606 | 0.078 (0.049) | 0.189 | 0.089 (0.050) | 0.133 |
ESS | 0.136 (0.034) | 0.025 | 0.076 (0.010) | 0.222 | 0.036 (0.011) | 0.558 | 0.018 (0.011) | 0.763 |
AHI | 0.037 (0.007) | 0.546 | 0.076 (0.002) | 0.221 | 0.035 (0.002) | 0.564 | 0.031 (0.002) | 0.618 |
ODI | −0.015 (0.007) | 0.809 | 0.045 (0.002) | 0.464 | −0.001 (0.002) | 0.989 | −0.005 (0.002) | 0.941 |
Mean SaO2 | −0.351 (0.048) | <0.001 | −0.229 (0.014) | <0.001 | −0.174 (0.017) | 0.004 | −0.174 (0.017) | 0.004 |
Min SaO2 | −0.069 (0.014) | 0.263 | −0.105 (0.004) | 0.094 | −0.008 (0.005) | 0.897 | −0.011 (0.005) | 0.855 |
T90 | 0.129 (0.009) | 0.031 | 0.122 (0.003) | 0.046 | 0.089 (0.003) | 0.141 | 0.087 (0.003) | 0.151 |
Association between PSWEs and serum CyPA and MMP-9 levels
Correlation between PSWEs and cognitive performance in patients with OSA
Total PSWEs | PSWEs at F4/M1 in stage R | PSWEs at O1/M2 in stage R | PSWEs at O2/M1 in stage R | |||||
---|---|---|---|---|---|---|---|---|
r | P value | r | P value | r | p value | r | P value | |
Total MoCA scores | −0.310 | <0.001 | −0.201 | 0.001 | −0.203 | 0.001 | −0.208 | 0.001 |
Visuoexecutive | −0.212 | <0.001 | −0.128 | 0.034 | −0.160 | 0.008 | −0.190 | 0.002 |
Naming | −0.291 | <0.001 | −0.200 | 0.001 | −0.196 | 0.001 | −0.184 | 0.002 |
Attention | −0.168 | 0.005 | −0.133 | 0.028 | −0.087 | 0.151 | −0.079 | 0.190 |
Language | −0.205 | 0.001 | −0.140 | 0.020 | −0.125 | 0.038 | −0.146 | 0.016 |
Abstraction | −0.153 | 0.011 | −0.125 | 0.039 | −0.072 | 0.234 | −0.079 | 0.194 |
Delayed recall | −0.223 | <0.001 | −0.086 | 0.154 | −0.125 | 0.039 | −0.119 | 0.048 |
Orientation | −0.259 | <0.001 | −0.171 | 0.004 | −0.184 | 0.002 | −0.179 | 0.003 |
Alterations in the occurrence of PSWEs and serum CyPA and MMP-9 levels after CPAP intervention
Baseline | Follow-up | P value | |
---|---|---|---|
Total PSWEs | 3.5 (3.2) | 3.1 (2.5) | <0.001 |
PSWEs in stage R | |||
C3/M2, median (IQR) | 0.4 (0.9) | 0.4 (0.7) | 0.033 |
C4/M1, median (IQR) | 0.3 (0.6) | 0.3 (0.6) | 0.043 |
F3/M2, median (IQR) | 0.3 (0.9) | 0.3 (0.6) | 0.026 |
F4/M1, median (IQR) | 0.3 (0.8) | 0.3 (0.6) | 0.017 |
O1/M2, median (IQR) | 1.0 (1.3) | 0.6 (0.7) | 0.040 |
O2/M1, median (IQR) | 1.0 (1.2) | 0.7 (0.7) | 0.044 |
T3/M2, median (IQR) | 0.3 (0.6) | 0.3 (0.6) | 0.022 |
T4/M1, median (IQR) | 0.3 (0.7) | 0.4 (0.5) | 0.028 |