Low Levels of Adenosine and GDNF Are Potential Risk Factors for Parkinson’s Disease with Sleep Disorders
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.1.1. Ethics Approval
2.1.2. Inclusion and Exclusion Criteria
- Aged ≥ 30 years;
- Normal listening, understanding and language expression, and could cooperate with clinicians in all neuropsychological, motor and mental behavior assessments;
- Patient or a legal representative signed the informed consent form.
- Other neurological diseases shown by imaging examination (CT or MRI), including various dementias, stroke, brain infection, tumor, or severe brain injury;
- Secondary Parkinsonian syndrome (PS) or Parkinson-plus syndrome (P-PS) caused by trauma, infection, tumor, or drugs;
- Severe systemic diseases (such as liver and kidney failure, circulatory system or blood system disorders);
- Severe mental illness (such as schizophrenia, or bipolar disorder);
- Other diseases that can cause sleep disorders (e.g., chronic poisoning, cancer pain, endocrine diseases, or urinary system diseases);
- Incomplete data.
- Understood the content and purpose of this study, willingly engaged in this study, and signed the informed consent form;
- Able to complete all scale assessments under physician guidance;
- Those with a Pittsburgh Sleep Quality Index (PSQI) ≤ 7 points.
- Long-term alcoholism, smoking, drug abuse, or bad habits that seriously affect health (e.g., gambling addiction, unprotected sex, and sexually transmitted diseases);
- A history of mental illness or sedative use;
- Incomplete data.
2.2. Sample Collection and Testing
2.3. Medical Data Gathering
2.4. Statistical Analysis
3. Results
3.1. Demographic Characteristics
3.2. Non-Motor Symptoms and Sleep Disorders
3.2.1. Cognitive and Sleep Disorders
3.2.2. Anxiety, Depression, and Sleep Disorders
3.2.3. Constipation and Sleep Disorders
3.2.4. Comparison of PDSS, ESS, RBD-SQ, and RLS among Groups
3.3. Motor Symptoms and Sleep Disorders
3.4. Antiparkinsonian Medications between PD Groups
3.5. Levels of Serum Adenosine, GDNF, and Related Neurotransmitters in Each Group
3.6. Correlation Analysis of Each Index and the PSQI Scale in PD Patients
3.6.1. The Correlations between ADO, GDNF, γ-GABA, 5-HT, Ach, and the PSQI Scale
3.6.2. The Correlations between MoCA, HAMA, HAMD, UPDRS-III, H-Y, Course of the Disease, LED, RBD-SQ, and the PSQI Scale
3.7. Risk Factors of Sleep Disturbances
3.8. The ROC Curve Analysis of Serum ADO and GDNF
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Information | HC (n = 49) | PD-NSD (n = 36) | PD-SD (n = 51) | Statistic | p |
---|---|---|---|---|---|
Age (years) | 65.57 ± 8.85 | 66.86 ± 8.9 | 67.57 ± 8.75 | 0.652 a | 0.523 |
Gender (%) | 0.279 b | 0.870 | |||
Male | 25 (51.0) | 17 (47.2) | 27 (52.9) | ||
Female | 24 (49.0) | 19 (52.8) | 24 (47.1) | ||
Education (years) | 7.00 (6.00, 9.00) | 7.50 (6.00, 9.00) | 7.00 (6.00, 9.00) | 0.029 c | 0.985 |
BMI (kg/m2) | 24.96 ± 3.19 | 24.07 ± 2.76 | 24.21 ± 3.16 | 1.119 a | 0.330 |
Smoking history (%) | 6 (12.2) | 6 (16.7) | 10 (19.6) | 1.008 b | 0.604 |
Alcohol consumption (%) | 9 (18.4) | 7 (19.4) | 10 (19.6) | 0.028 b | 0.986 |
MoCA (scores) | 26.18 ± 2.71 | 21.08 ± 4.32 * | 20.04 ± 4.97 * | 31.021 a | <0.001 |
HAMD (scores) | 3.00 (2.00, 5.00) | 5.50 (2.25, 8.75) * | 11.00 (6.00, 21.00) *,# | 47.003 c | <0.001 |
HAMA (scores) | 3.00 (2.00, 5.00) | 6.00 (2.25, 9.75) * | 10.00 (5.00, 17.00) *,# | 45.217 c | <0.001 |
RBD-SQ (scores) | 2.00 (1.00, 3.00) | 2.50 (1.00, 8.00) * | 4.00 (2.00, 7.00) * | 16.746 c | <0.001 |
ESS (scores) | 3.00 (2.00, 5.00) | 5.50 (2.25, 9.00) * | 9.00 (3.00, 14.00) *,# | 27.448 c | <0.001 |
RLS, case (%) | 3 (6.1) | 6 (16.7) | 13 (25.5) * | 6.922 b | 0.031 |
Constipation, case (%) | 14 (28.6) | 21 (58.3) * | 31(60.8) * | 12.266 b | 0.002 |
UPDRS-III (scores) | NA | 22.67 ± 12.97 | 30.98 ± 16.26 | 2.547 d | 0.013 |
NMSS (scores) | NA | 21.00 (15.25, 64.00) | 41.00 (20.00, 74.00) | −1.599 e | 0.110 |
Phenotype (%) | 0.746 b | 0.689 | |||
TD | NA | 20 (55.6) | 24 (47.1) | ||
PIGD | NA | 11 (30.6) | 20 (39.2) | ||
Indeterminate | NA | 5 (13.9) | 7 (13.7) | ||
Disease duration (months) | NA | 54.00 (26.75, 72.00) | 66.00 (48.00, 82.00) | −1.452 e | 0.146 |
PDSS (scores) | NA | 129.00 (102.00, 139.00) | 79.00 (72.00, 81.00) | −7.110 e | <0.001 |
H-Y (on-stage) | NA | 2.00 (1.00, 2.50) | 2.50 (2.00, 3.00) | −2.716 e | <0.001 |
Drug | PD-NSD (n = 36) | PD-SD (n = 51) | Z/χ2 | p |
---|---|---|---|---|
LED (mg) | 412.50 (337.50, 596.88) | 425.00 (337.50, 575.00) | −0.108 | 0.914 |
Levodopa/benserazide (%) | 32 (88.9) | 48 (94.1) | 0.233 | 0.629 |
Dopamine agonist (%) | 24 (66.7) | 38 (74.5) | 0.634 | 0.426 |
MAO-B inhibitors (%) | 12 (33.3) | 20 (39.2) | 0.314 | 0.575 |
Amantadine hydrochloride (%) | 4 (11.1) | 12 (23.5) | 2.168 | 0.141 |
Test Indexes | HC (n = 49) | PD-NSD (n = 36) | PD-SD (n = 51) | F | p |
---|---|---|---|---|---|
ADO (ng/mL) | 19.07 ± 4.16 | 16.96 ± 3.01 * | 13.18 ± 3.31 *,# | 34.792 | <0.001 |
GDNF (pg/mL) | 453.56 ± 141.26 | 392.81 ± 85.08 * | 287.55 ± 85.92 *,# | 29.619 | <0.001 |
5-HT (ng/mL) | 167.61 ± 14.88 | 164.08 ± 13.33 | 160.9 ± 10.52 * | 3.351 | 0.038 |
γ-GABA (ng/mL) | 43.68 ± 2.84 | 39.22 ± 2.79 * | 37.21 ± 2.94 *,# | 66.045 | <0.001 |
Ach (ng/mL) | 72.36 ± 8.53 | 69.64 ± 5.99 | 67.78 ± 7.50 * | 4.657 | 0.011 |
Indicators | PSQI Total Score | Component 1 | Component 2 | Component 3 | Component 4 | Component 5 | Component 6 | Component 7 | |
---|---|---|---|---|---|---|---|---|---|
GDNF | r | −0.485 ** | −0.375 ** | −0.340 ** | −0.381 ** | −0.428 ** | −0.164 | −0.315 ** | −0.175 |
p | <0.001 | <0.001 | 0.001 | <0.001 | <0.001 | 0.128 | 0.003 | 0.105 | |
5-HT | r | −0.029 | 0.110 | 0.074 | −0.154 | −0.078 | −0.053 | 0.114 | −0.039 |
p | 0.793 | 0.308 | 0.497 | 0.154 | 0.470 | 0.625 | 0.292 | 0.720 | |
ADO | r | −0.657 ** | −0.479 ** | −0.492 ** | −0.494 ** | −0.438 ** | −0.108 | −0.502 ** | −0.484 ** |
p | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.318 | <0.001 | <0.001 | |
γ-GABA | r | −0.526 ** | −0.510 ** | −0.351 ** | −0.325 ** | −0.277 ** | −0.131 | −0.468 ** | −0.583 ** |
p | <0.001 | <0.001 | 0.001 | 0.002 | 0.009 | 0.226 | <0.001 | <0.001 | |
Ach | r | −0.191 | −0.280 ** | −0.138 | −0.053 | −0.050 | −0.209 | −0.123 | −0.149 |
p | 0.076 | 0.009 | 0.204 | 0.628 | 0.643 | 0.052 | 0.256 | 0.169 |
Indicators | PSQI Total Score | Component 1 | Component 2 | Component 3 | Component 4 | Component 5 | Component 6 | Component 7 | |
---|---|---|---|---|---|---|---|---|---|
MoCA | r | −0.164 | −0.216 * | 0.050 | −0.095 | −0.127 | −0.242 * | −0.045 | −0.229 * |
p | 0.130 | 0.044 | 0.644 | 0.380 | 0.240 | 0.024 | 0.679 | 0.033 | |
HAMA | r | 0.536 ** | 0.418 ** | 0.264 * | 0.460 ** | 0.356 ** | 0.168 | 0.336 ** | 0.468 ** |
p | <0.001 | <0.001 | 0.014 | <0.001 | 0.001 | 0.121 | 0.001 | <0.001 | |
HAMD | r | 0.469 ** | 0.396 ** | 0.289 ** | 0.370** | 0.335 ** | 0.193 | 0.269 * | 0.255 * |
p | <0.001 | <0.001 | 0.007 | <0.001 | 0.002 | 0.073 | 0.012 | 0.017 | |
UPDRS-III | r | 0.400 ** | 0.334 ** | 0.432 ** | 0.246 * | 0.270 * | 0.027 | 0.280 ** | 0.231 * |
p | <0.001 | 0.002 | <0.001 | 0.022 | 0.011 | 0.802 | 0.009 | 0.031 | |
H-Y stage | r | 0.434 ** | 0.316 ** | 0.115 | 0.261 * | 0.354 ** | 0.326 ** | 0.248 * | 0.452 ** |
p | <0.001 | 0.003 | 0.288 | 0.015 | 0.001 | 0.002 | 0.020 | <0.001 | |
The course of disease | r | 0.064 | −0.003 | 0.014 | 0.083 | 0.108 | −0.137 | 0.084 | 0.014 |
p | 0.557 | 0.976 | 0.899 | 0.442 | 0.321 | 0.207 | 0.439 | 0.894 | |
LED | r | 0.205 | 0.273 * | 0.059 | 0.108 | 0.044 | 0.101 | 0.202 | 0.322 ** |
p | 0.056 | 0.011 | 0.590 | 0.319 | 0.684 | 0.351 | 0.061 | 0.002 | |
RBD-SQ | r | 0.178 | 0.070 | −0.100 | 0.060 | 0.208 | 0.224 * | 0.099 | 0.339 ** |
p | 0.100 | 0.521 | 0.359 | 0.581 | 0.053 | 0.037 | 0.361 | 0.001 |
Factors | B | SE | Waldχ2 | p | OR (95% CI) |
---|---|---|---|---|---|
GDNF | −0.017 | 0.005 | 12.404 | <0.001 | 0.983 (0.974~0.993) |
ADO | −0.577 | 0.211 | 7.464 | 0.006 | 0.562 (0.371~0.85) |
γ-GABA | 0.441 | 0.246 | 3.202 | 0.074 | 1.554 (0.959~2.519) |
HAMD | 0.128 | 0.059 | 4.709 | 0.030 | 1.137 (1.013~1.277) |
HAMA | 0.001 | 0.072 | 0.001 | 0.984 | 1.001 (0.87~1.153) |
UPDRS-III | 0.001 | 0.025 | 0.002 | 0.963 | 1.001 (0.953~1.052) |
H-Y stage | −0.096 | 0.393 | 0.059 | 0.807 | 0.909 (0.421~1.962) |
Constant | −3.211 | 7.317 | 0.193 | 0.661 | - |
Parameter | GDNF | ADO | ADO + GDNF |
---|---|---|---|
AUC 95% CI | 0.815 0.723~0.906 | 0.780 0.685~0.875 | 0.883 0.808~0.959 |
SE | 0.047 | 0.048 | 0.039 |
p | <0.001 | <0.001 | <0.001 |
The threshold value | 305.205 | 13.000 | 0.570 |
Sensitivity (%) | 62.7 | 49.0 | 82.4 |
Specificity (%) | 91.7 | 94.4 | 83.3 |
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Wang, L.; Gao, Z.; Chen, G.; Geng, D.; Gao, D. Low Levels of Adenosine and GDNF Are Potential Risk Factors for Parkinson’s Disease with Sleep Disorders. Brain Sci. 2023, 13, 200. https://doi.org/10.3390/brainsci13020200
Wang L, Gao Z, Chen G, Geng D, Gao D. Low Levels of Adenosine and GDNF Are Potential Risk Factors for Parkinson’s Disease with Sleep Disorders. Brain Sciences. 2023; 13(2):200. https://doi.org/10.3390/brainsci13020200
Chicago/Turabian StyleWang, Li, Zheng Gao, Gang Chen, Deqin Geng, and Dianshuai Gao. 2023. "Low Levels of Adenosine and GDNF Are Potential Risk Factors for Parkinson’s Disease with Sleep Disorders" Brain Sciences 13, no. 2: 200. https://doi.org/10.3390/brainsci13020200
APA StyleWang, L., Gao, Z., Chen, G., Geng, D., & Gao, D. (2023). Low Levels of Adenosine and GDNF Are Potential Risk Factors for Parkinson’s Disease with Sleep Disorders. Brain Sciences, 13(2), 200. https://doi.org/10.3390/brainsci13020200